Datasets:

keirp
/

open-web-math-dev

Dataset card Data Studio Files Files and versions Community

Split (1)

train · 2.95M rows

url stringlengths 14 1.76k	text stringlengths 100 1.02M	metadata stringlengths 1.06k 1.1k
http://science.sciencemag.org/content/309/5736/917	Report # Probing the Ultrafast Charge Translocation of Photoexcited Retinal in Bacteriorhodopsin See allHide authors and affiliations Science 05 Aug 2005: Vol. 309, Issue 5736, pp. 917-920 DOI: 10.1126/science.1111482 ## Abstract The ultrafast evolution of the electric field within bacteriorhodopsin was measured by monitoring the absorption changes of a tryptophan residue after excitation of retinal. The Trp absorption decreases within the first 200 femtoseconds and then recovers on time scales typical for retinal isomerization and vibrational relaxation. A model of excitonic coupling between retinal and tryptophans shows that the signal reflects a gradual rise of the retinal difference dipole moment, which precedes and probably drives isomerization. The results suggest an intimate connection between the progressive dipole moment change and the retinal skeletal changes reported over the same time scale. View Full Text	{"extraction_info": {"found_math": false, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.8144617676734924, "perplexity": 7199.5355541508125}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2018-47/segments/1542039743216.58/warc/CC-MAIN-20181116214920-20181117000920-00525.warc.gz"}
https://publikationen.bibliothek.kit.edu/1000037298	Electroweak Processes in the Standard Model and Beyond: Backgrounds to Higgs Physics and Semileptonic Decay Modes Feigl, Bastian Abstract: This thesis describes several aspects of electroweak processes at the Large Hadron Collider. In the first part an analysis of supersymmetry induced backgrounds to the production of a SM-like Higgs boson in the MSSM is performed. The possible influence of BSM effects on the data-driven determination of non-BSM backgrounds is discussed in the second part of this thesis. Finally, the implementation of semileptonic decay modes for processes involving several electroweak gauge bosons is discussed. Zugehörige Institution(en) am KIT Institut für Theoretische Physik (ITP) Publikationstyp Hochschulschrift Jahr 2013 Sprache Englisch Identifikator KITopen ID: 1000037298 Verlag Karlsruhe Abschlussart Dissertation Fakultät Fakultät für Physik (PHYSIK) Institut Institut für Theoretische Physik (ITP) Prüfungsdaten 15.11.2013 Referent/Betreuer Prof. D. Zeppenfeld KIT – Die Forschungsuniversität in der Helmholtz-Gemeinschaft KITopen Landing Page	{"extraction_info": {"found_math": false, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.8589240312576294, "perplexity": 9680.67653380518}, "config": {"markdown_headings": false, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.3, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2018-34/segments/1534221213508.60/warc/CC-MAIN-20180818075745-20180818095745-00057.warc.gz"}
http://quant.stackexchange.com/questions?pagesize=50&sort=newest	# All Questions 1 view ### delta of a swaption using Bringo I struggeling with calculating the delta of a swaption. In the interest rate case I usually mess around with the multiple cash flows over time so that the discounting is more complex than in the ... 17 views ### Connection between implied volatily and implied probability I am reading some lecture notes about Black-Scholes (BS) option pricing. Since the BS-formula is not supported by observed data because of the dependence of the implied volatility on the strik and ... 20 views ### How to learn QuantLib-python at first? In my project, I have to get the delta of up and out call option (with vol surface). I found out that QuantLib might help me on that. Since my main language is python and I don't know well about C++, ... 30 views ### Legitimate input parameters for Nelson Siegel Svensson model I had previously asked this question and have come to better understand the answer with regards to setting the input parameters for the Non-Linear Optimization problem that provides the NSS ... 33 views ### Rebalancing portfolio weights I have a matrix of returns and weights for every time period. ... 19 views ### Compound Discounting(?) I am a programmer interning at a small contract furniture company. This company receives multiple discounts from the manufacturers, and I am trying to calculate the end discount. For example, the ... 15 views ### Understanding portfolio weights and purchasing stock in modern portfolio theory Recently I've been learning about the markowitz algorithm. It's pretty interesting, but I'm curious how we apply this in practice. Lets say I have some optimal portfolio: $R_p = x_aR_a + x_bR_b$ ... 34 views ### About the boundary conditions of the Black-Scholes-Merton PDE I have a question about the solution of the Black-Scholes PDE for the European call option when I read the book Stochastic Calculus for Finance II of Steven E.Shreve. Let $c(t,x)$ be the value of the ... 40 views ### Calculating discount factors using Nelson Siegel Svensson model I am trying to understand how to calculate the discount factors $disc(TTM)$ mentioned on Page 9 of this pdf. When I'm calculating the discount factors, mentioned each bond has its own cash flow and ... 18 views 28 views 29 views ### optimization with absolute constraints Suppose I have an optimization where I need to impose ADV-like constraint (for a case where Shorting is allowed): $\max \mu'w - \lambda w'\Sigma w$ $\|w\| \le V$ $Aw = 0$ and I want to use a ... 40 views ### Correlation Between 2 Portfolios I have a set of assets, n. I'm trying to find the correlation between 2 portfolios, say x and y, where x is nested in, or, a sub-set of y. That is, x is a portfolio based on a sub-set of n, while y is ... 46 views ### Newbie Quant: Bulding price feeder to securities master db First of all, warm hello to all. I am newbie and i admit it, but with at least 15+ years of exp in C++. Working in IB - derivatives mainly, but unfortunately on the business side not trading at all. ... 43 views ### Careers in finance for postgraduates? [on hold] Having read through similar topics, I see these questions are often poorly received, so apologies if this is not the place to ask (would appreciate if someone could redirect me). I shall try to be as ... 63 views 111 views ### Are all stocks and stock indexes just white noise In the paper Super-Whiteness of Returns Spectra from Erhard Reschenhofer of University of Vienna it is commented the following "Until the late 70’s the spectral densities of stock returns and stock ... 137 views ### Is there any research on pyramiding techniques of entering/exiting a trend? I am looking for any research about optimal strategies for gradually building (scaling in) positions inside a trend as well as optimal gradual exit strategies on pullbacks/reversals to minimise ... 64 views ### How to discretize a GBM under P- and Q-measures? Under the P-measure, a geometric Brownian motion can be specified using the following SDE: $$dS_t=\mu S_tdt+\sigma S_tdW_t^P$$ and its Euler discretization is S_{t+\Delta t}=S_t + \mu S_t \Delta ... 60 views ### Spot price and volatility has a correlation of -1, why? A stock option trader taught me yesterday that the correlation between the spot price of asset X and the variance of asset X is approximately -1. Can anyone give me a explanation why this is true? 81 views ### Momentum - Statistical Argument In their seminal paper Jegadeesh and Titman (1993) develop a statistical model to infer where moment comes from. In practice they setup the following: $r_{it}=\mu_i + b_i f_t +e_{it}$ ...	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 1, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.6110259294509888, "perplexity": 1687.5294532431324}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2015-32/segments/1438042986444.39/warc/CC-MAIN-20150728002306-00049-ip-10-236-191-2.ec2.internal.warc.gz"}
https://workforce.libretexts.org/Courses/Diablo_Valley_College/Econ_101%3A_Economics_of_Public_Issues/07%3A_Monopoly_Power/7.03%3A_Antitrust_Laws/7.3.03%3A_Regulation-_Protecting_People_from_the_Market	# 7.3.3: Regulation- Protecting People from the Market • Contributed by Learning Objective 1. Compare the public interest and public choice theories of regulation. 2. Discuss the costs and benefits of consumer protection laws. 3. Discuss the pros and cons of the trend toward deregulation over the last quarter century. Antitrust policies are primarily concerned with limiting the accumulation and use of market power. Government regulation is used to control the choices of private firms or individuals. Regulation may constrain the freedom of firms to enter or exit markets, to establish prices, to determine product design and safety, and to make other business decisions. It may also limit the choices made by individuals. In general terms, there are two types of regulatory agencies. One group attempts to protect consumers by limiting the possible abuse of market power by firms. The other attempts to influence business decisions that affect consumer and worker safety. Regulation is carried out by more than 50 federal agencies that interpret the applicable laws and apply them in the specific situations they find in real-world markets. Table 16.2 “Selected Federal Regulatory Agencies and Their Missions” lists some of the major federal regulatory agencies, many of which are duplicated at the state level. Table 16.2 Selected Federal Regulatory Agencies and Their Missions ## Theories of Regulation Competing explanations for why there is so much regulation range from theories that suggest regulation protects the public interest to those that argue regulation protects the producers or serves the interests of the regulators. The distinction corresponds to our discussion in the last chapter of the public interest versus the public choice understanding of government policy in general. ## The Public Interest Theory of Regulation The public interest theory of regulation holds that regulators seek to find market solutions that are economically efficient. It argues that the market power of firms in imperfectly competitive markets must be controlled. In the case of natural monopolies (discussed in an earlier chapter), regulation is viewed as necessary to lower prices and increase output. In the case of oligopolistic industries, regulation is often advocated to prevent cutthroat competition. The public interest theory of regulation also holds that firms may have to be regulated in order to guarantee the availability of certain goods and services—such as electricity, medical facilities, and telephone service—that otherwise would not be profitable enough to induce unregulated firms to provide them in a given community. Firms providing such goods and services are often granted licenses and franchises that prevent competition. The regulatory authority allows the firm to set prices above average cost in the protected market in order to cover losses in the target community. In this way, the firms are allowed to earn, indeed are guaranteed, a reasonable rate of return overall. Proponents of the public interest theory also justify regulation of firms by pointing to externalities, such as pollution, that are not taken into consideration when unregulated firms make their decisions. As we have seen, in the absence of property rights that force the firms to consider all of the costs and benefits of their decisions, the market may fail to allocate resources efficiently. ## The Public Choice Theory of Regulation The public interest theory of regulation assumes that regulations serve the interests of consumers by restricting the harmful actions of business firms. That assumption, however, is now widely challenged by advocates of the public choice theory of regulation, which rests on the premise that all individuals, including public servants, are driven by self-interest. They prefer the capture theory of regulation, which holds that government regulations often end up serving the regulated firms rather than their customers. Competing firms always have an incentive to collude or operate as a cartel. The public is protected from such collusion by a pervasive incentive for firms to cheat. Capture theory asserts that firms seek licensing and other regulatory provisions to prevent other firms from entering the market. Firms seek price regulation to prevent price competition. In this view, the regulators take over the role of policing cartel pricing schemes; individual firms in a cartel would be incapable of doing so themselves. Because it is practically impossible for the regulatory authorities to have as much information as the firms they are regulating, and because these authorities often rely on information provided by those firms, the firms find ways to get the regulators to enforce regulations that protect profits. The regulators get “captured” by the very firms they are supposed to be regulating. In addition to its use of the capture theory, the public choice theory of regulation argues that employees of regulatory agencies are not an exception to the rule that people are driven by self-interest. They maximize their own satisfaction, not the public interest. This insight suggests that regulatory agencies seek to expand their bureaucratic structure in order to serve the interests of the bureaucrats. As the people in control of providing government protection from the rigors of the market, bureaucrats respond favorably to lobbyists and special interests. Public choice theory views the regulatory process as one in which various groups jockey to pursue their respective interests. Firms might exploit regulation to limit competition. Consumers might seek lower prices or changes in products. Regulators themselves might pursue their own interests in expanding their prestige or incomes. The abstract goal of economic efficiency is unlikely to serve the interest of any one group; public choice theory does not predict that efficiency will be a goal of the regulatory process. Regulation might improve on inefficient outcomes, but it might not. ## Consumer Protection Every day we come into contact with regulations designed to protect consumers from unsafe products, unscrupulous sellers, or our own carelessness. Seat belts are mandated in cars and airplanes; drivers must provide proof of liability insurance; deceptive advertising is illegal; firms cannot run “going out of business” sales forever; electrical and plumbing systems in new construction must be inspected and approved; packaged and prepared foods must carry certain information on their labels; cigarette packages must warn users of the dangers involved in smoking; gasoline stations must prevent gas spillage; used-car odometers must be certified as accurate. The list of regulations is seemingly endless. There are often very good reasons behind consumer protection regulation, and many economists accept such regulation as a legitimate role and function of government agencies. But there are costs as well as benefits to consumer protection. ## The Benefits of Consumer Protection Consumer protection laws are generally based on one of two conceptual arguments. The first holds that consumers do not always know what is best for them. This is the view underlying government efforts to encourage the use of merit goods and discourage the use of demerit goods. The second suggests that consumers simply do not have sufficient information to make appropriate choices. Laws prohibiting the use of certain products are generally based on the presumption that not all consumers make appropriate choices. Drugs such as cocaine and heroin are illegal for this reason. Children are barred from using products such as cigarettes and alcohol on grounds they are incapable of making choices in their own best interest. Other regulations presume that consumers are rational but may not have adequate information to make choices. Rather than expect consumers to determine whether a particular prescription drug is safe and effective, for example, federal regulations require the Food and Drug Administration to make that determination for them. The benefit of consumer protection occurs when consumers are prevented from making choices they would regret if they had more information. A consumer who purchases a drug that proves ineffective or possibly even dangerous will presumably stop using it. By preventing the purchase in the first place, the government may save the consumer the cost of learning that lesson. One problem in assessing the benefits of consumer protection is that the laws themselves may induce behavioral changes that work for or against the intent of the legislation. For example, requirements for childproof medicine containers appear to have made people more careless with medicines. Requirements that mattresses be flame-resistant may make people more careless about smoking in bed. In some cases, then, the behavioral changes attributed to consumer protection laws may actually worsen the problem the laws seek to correct. An early study on the impact of seat belts on driving behavior indicated that drivers drove more recklessly when using seat belts, presumably because the seat belts made them feel more secure (Peltzman, S., 1975). A recent study, however, found that this was not the case and suggests that use of seat belts may make drivers more safety-conscious (Cohen, A., and Liran Einan, 2003). In any event, these “unintended” behavioral changes can certainly affect the results achieved by these laws. ## The Cost of Consumer Protection Regulation aimed at protecting consumers can benefit them, but it can also impose costs. It adds to the cost of producing goods and services and thus boosts prices. It also restricts the freedom of choice of individuals, some of whom are willing to take more risks than others. Those who demand, and are willing to pay the price for, high-quality, safe, warranted products can do so. But some argue that people who demand and prefer to pay (presumably) lower prices for lower-quality products that may have risks associated with their use should also be allowed to exercise this preference. By increasing the costs of goods, consumer protection laws may adversely affect the poor, who are forced to purchase higher-quality products; the rich would presumably buy higher-quality products in the first place. To assess whether a particular piece of consumer protection is desirable requires a careful look at how it stacks up against the marginal decision rule. The approach of economists is to attempt to determine how the costs of a particular regulation compare to its benefits. Economists W. Mark Crain and Thomas D. Hopkins estimated the cost of consumer protection regulation in 2001 and found that the total cost was $843 billion, or$7,700 per household in the United States (Crain, W. M., and Thomas D. Hopkins, 2001). ## Deregulating the Economy Concern that regulation might sometimes fail to serve the public interest prompted a push to deregulate some industries, beginning in the late 1970s. In 1978, for example, Congress passed the Airline Deregulation Act, which removed many of the regulations that had prevented competition in the airline industry. Safety regulations were not affected. The results of deregulation included a substantial reduction in airfares, the merger and consolidation of airlines, and the emergence of frequent flier plans and other marketing schemes designed to increase passenger miles. Not all the consequences of deregulation were applauded, however. Many airlines, unused to the demands of a competitive, unprotected, and unregulated environment, went bankrupt or were taken over by other airlines. Large airlines abandoned service to small and midsized cities, and although most of these routes were picked up by smaller regional airlines, some consumers complained about inadequate service. Nevertheless, the more competitive airline system today is probably an improvement over the highly regulated industry that existed in the 1970s. It is certainly cheaper. Table 16.3 “Improvement in Consumer Welfare from Deregulation” suggests that the improvements in consumer welfare from deregulation through the 1990s have been quite substantial across a broad spectrum of industries that have been deregulated. Table 16.3 Improvement in Consumer Welfare from Deregulation Industry Improvements Airlines Average fares are roughly 33% lower in real terms since deregulation, and service frequently has improved significantly. Less-than-truckload trucking Average rates per vehicle mile have declined at least 35% in real terms since deregulation, and service times have improved significantly. Truckload trucking Average rates per vehicle mile have declined by at least 75% in real terms since deregulation, and service times have improved significantly. Railroads Average rates per ton-mile have declined more than 50% in real terms since deregulation, and average transit time has fallen more than 20%. Banking Consumers have benefited from higher interest rates on deposits, from better opportunities to manage risk, and from more banking offices and automated teller machines. Natural gas Average prices for residential customers have declined at least 30% in real terms since deregulation, and average prices for commercial and industrial customers have declined more than 30%. In addition, service has been more reliable as shortages have been almost completely eliminated. Economist Clifford Winston found substantial benefits from deregulation in the five industries he studied—airlines, trucking, railroads, banking, and natural gas. But there are forces working in the opposite direction as well. Many businesses continue to turn to the government for protection from competition. Public choice theory suggests that more, not less, regulation is often demanded by firms threatened with competition at home and abroad. More and more people seem to demand environmental protection, including clear air, clean water, and regulation of hazardous waste and toxic waste. Indeed, as incomes rise over time, there is evidence that the demand for safety rises. This market phenomenon began before the birth of regulatory agencies and can be seen in the decline in unintentional injury deaths over the course of the last hundred years (Viscusi, W. K., 2002). And there is little reason to expect less demand for regulations in the areas of civil rights, handicapped rights, gay rights, medical care, and elderly care. The basic test of rationality—that marginal benefits exceed marginal costs—should guide the formulation of regulations. While economists often disagree about which, if any, consumer protection regulations are warranted, they do tend to agree that market incentives ought to be used when appropriate and that the most cost-effective policies should be pursued. ## Key Takeaways • Federal, state, and local governments regulate the activities of firms and consumers. • The public interest theory of regulation asserts that regulatory efforts act to move markets closer to their efficient solutions. • The public choice theory of regulation argues that regulatory efforts serve private interests, not the public interest. • Consumer protection efforts may sometimes be useful, but they tend to produce behavioral responses that often negate the effort at protection. • Deregulation efforts through the 1990s generally produced large gains in consumer welfare, though demand for more regulation is rising in certain areas, especially finance. ### Try It! The deregulation of the airline industry has generally led to lower fares and increased quantities produced. Use the model of demand and supply to show this change. What has happened to consumer surplus in the market? (Hint: You may want to refer back to the earlier discussion of consumer surplus.) Case in Point: Do Consumer Protection Laws Protect Consumers? Figure 16.3 Economist W. Kip Viscusi of the Harvard Law School has long advocated economic approaches to health and safety regulations. Economic approaches recognize 1) behavioral responses to technological regulations; 2) performance-oriented standards as opposed to command-and-control regulations; and 3) the opportunity cost of regulations. Below are some examples of how these economic approaches would improve health and safety policy. Behavioral responses: Consider the requirement, imposed in 1972, that aspirin containers have childproof caps. That technological change seemed straightforward enough. But, according to Mr. Viscusi, the result has not been what regulators expected. Mr. Viscusi points out that childproof caps are more difficult to open. They thus increase the cost of closing the containers properly. An increase in the cost of any activity reduces the quantity demanded. So, childproof caps result in fewer properly closed aspirin containers. Mr. Viscusi calls the response to childproof caps a “lulling effect.” Parents apparently think of containers as safer and are, as a result, less careful with them. Aspirin containers, as well as other drugs with childproof caps, tend to be left open. Mr. Viscusi says that the tragic result is a dramatic increase in the number of children poisoned each year. Hence, he urges government regulators to take behavioral responses into account when promulgating technological solutions. He also advocates well-articulated hazard warnings that give consumers information on which to make their own choices. Performance-oriented standards: Once a health and safety problem has been identified, the economic approach would be to allow individuals or firms discretion in how to address the problem as opposed to mandating a precise solution. Flexibility allows a standard to be met in a less costly way and can have greater impact than command-and-control approaches. Mr. Viscusi cites empirical evidence that worker fatality rates would be about one-third higher were it not for the financial incentives firms derive from creating a safer workplace and thereby reducing the workers’ compensation premiums they pay. In contrast, empirical estimates of the impact of OSHA regulations, most of which are of the command-and-control type, range from nil to a five to six percent reduction in worker accidents that involve days lost from work. Opportunity cost of regulations: Mr. Viscusi has estimated the cost per life saved on scores of regulations. Some health and safety standards have fairly low cost per life saved. For example, car seat belts and airplane cabin fire protection cost about $100,000 per life saved. Automobile side impact standards and the children’s sleepwear flammability ban, at about$1 million per life saved, are also fairly inexpensive. In contrast, the asbestos ban costs $131 million per life saved, regulations concerning municipal solid waste landfills cost about$23 billion per life saved, and regulations on Atrazine/alachlor in drinking water cost a whopping \$100 billion per life saved. “A regulatory system based on sound economic principles would reallocate resources from the high-cost to the low-cost regulations. That would result in more lives saved at the same cost to society.” ### Answer to Try It! Problem Deregulation of the airline industry led to sharply reduced fares and expanded output, suggesting that supply increased. That should significantly increase consumer surplus. Specifically, the supply curve shifted from S1 to S2. Consumer surplus is the difference between the total benefit received by consumers and total expenditures by consumers. Before deregulation, when the price was B and the quantity was Q1, the consumer surplus was BCD. The lower rates following deregulation reduced the price to consumers to, say, F, and increased the quantity to Q2 on the graph, thereby increasing consumer surplus to FCG. Figure 16.4 ## References Cohen, A., and Liran Einan, “The Effects of Mandatory Seat Belt Laws on Driving Behaviour and Traffic Fatalities,” Review of Economics and Statistics 85:4 (November 2003): 828–43. Crain, W. M., and Thomas D. Hopkins, “The Impact of Regulatory Costs on Small Firms,” Report for the Office of Advocacy, U.S. Small Business Administration, Washington, D.C., RFP No. SBAHQ-00-R-0027, October 2001, p. 1. Peltzman, S., “The Effects of Automobile Safety Regulations,” Journal of Political Economy 83 (August 1975): 677–725. Viscusi, W. K., “Safety at Any Price?” Regulation, Fall 2002: 54–63.	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.16142137348651886, "perplexity": 3370.6652200288695}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2020-10/segments/1581875145443.63/warc/CC-MAIN-20200221045555-20200221075555-00236.warc.gz"}
https://malegislature.gov/Laws/GeneralLaws/PartIII/TitleIV/Chapter255E/Section6	# General Laws ## Section 6 License suspension or revocation; notice and hearing Section 6. The commissioner may suspend or revoke any license issued pursuant to this chapter if said commissioner finds that: (i) the licensee has violated any provision of this chapter or any rule or regulation adopted hereunder, or any other law applicable to the conduct of its business; or (ii) any fact or condition exists which, if it had existed at the time of the original application for such license, would have warranted the commissioner in refusing to issue such license. Except as provided in section seven, no license shall be revoked or suspended except after notice and a hearing thereon pursuant to chapter thirty A. A licensee may surrender a license by delivering to the commissioner written notice that it thereby surrenders such license, but such surrender shall not affect the civil or criminal liability of the licensee for acts committed before such surrender. No revocation, suspension or surrender of any license shall impair or affect the obligation of any pre-existing lawful contract between the licensee and any person.	{"extraction_info": {"found_math": false, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.8816289901733398, "perplexity": 11637.649057711731}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2015-22/segments/1432207930259.97/warc/CC-MAIN-20150521113210-00123-ip-10-180-206-219.ec2.internal.warc.gz"}
http://benstanhope.blogspot.com/2010/12/is-god-bound-by-laws-of-logic.html	## Wednesday, December 1, 2010 ### Is God bound by the laws of logic? I wrote these proofs to settle a disagreement with my philosophy professor. He came to agree they were true. Since there is very little good information on this subject on the web and such a question is so vital to constructing a proper theology I have posted them here: The Law of non-contradiction:1) When one says “God is not bound to the laws of logic” they are stating that it is false to say that “God is bound to the laws of logic”. 2) The law of non-contradiction is a law of logic. 3) If God is “not bound to” the laws of logic then God is not “bound” to the law of non-contradiction (from 2). 4) The law of non-contradiction affirms that “something cannot be both true and false at the same time and in the same sense”. 5) If God is not bound by the law of non-contradiction (from 3) then it is possible for God to be bound by the laws of logic and not be bound by the laws logic at the same time and in the same sense (from 4). 6) The one who says “God is not bound by the laws of logic” is stating that it is false to say that “God is bound by the laws of logic.”(from 1) 7) Therefore, the one who says “God is not bound by laws of logic” assumes that God is bound by the law of non-contradiction in order for his statement to be true and the negating statement to be false (from 4 and 5). 8) Therefore, the one who says “God is not bound by the laws of logic” is assuming that God is bound by a law of logic (i.e. the law of non-contradiction). The Law of Identity (a richly satisfying spectacle): 1) When one says “God is not bound by the laws of logic” they are assuming that God is God in order to say that He is not bound by the laws of logic (i.e. God is not my dog which is quite bound by the laws of logic). 2) The law of identity is a law of logic 3) If God is not bound by the laws of logic then God is not bound by the law of identity (from 2). 4) The law of identity states that “Everything is what it is and not another thing”. 5) If God is not bound by the law of identity (from 3) then God needn’t be God and can be “other things” (from 4). 6) When one says “God is not bound by the laws of logic” they are assuming that God is God and not other things in order to say that He is not bound by the laws of logic (from 1). 7) Therefore, the one who says “God is not bound by the laws of logic” assumes that God is bound by a law of logic (i.e. law of non-contradiction) in order to deny that he is bound by the laws of logic. The Law of the excluded middle:1) When one says “God is not bound by the laws of logic” they are assuming their statement is true. 2) The law of the excluded middle is a law of logic. 3) The law of the excluded middle states “a proposition is either true or false”. 4) If God is not bound by the laws of logic then God is not bound by the law of the excluded middle (from 2). 5) If God is not bound by the law of the excluded middle (from 2) then propositions about God can be neither true nor false. 6) The statement “God is not bound by the laws of logic” is a proposition which claims to be true (from 1). 7) Therefore, the person who says “God is not bound by the laws of logic” is assuming that God is bound by the law of the excluded middle (from 3 and 4) in order to claim their statement is true and/or that it’s negation is false One might object by saying that God created the laws of logic and currently subjugates Himself under them, but this appears to be self-defeating as well: -Who created the laws of logic? The person here assumes the law of identity before it was created. (For that matter why would God create the laws of logic if there were no laws of logic withholding the existence of the laws of logic?) - When God was not subjugating Himself to logic is it true that He was not subjugating Himself to logic (excluded middle is presupposed). - To say the laws of logic didn’t exist is to assume that the law of non-contradiction did; otherwise, the laws of logic would have existed and would have not existed at the same time. You cannot refute logic without presupposing it. 1. On behalf of Grand Master Ashra Kwesi we would like to challenge you to a online debate on our internet radio show. Please email us if you except you will be givin a call in number time and date thank you. Much respect 2. If a concept is not bound by the laws of logic then the concept is illogical. The concept of god is illogical. A concept can't be logical and illogical at the same time. You can't have it both ways 3. What about dialetheism? The liar paradox is one of many examples that seems to fly in the face of this assumption. Whilst I'm not saying that this implies there is a god of any kind, I am suggesting that there are limits to what we can infer from logic alone. 4. "You can't refute logic without presupposing it." Well, you also can't "prove" logic without presupposing it. That's the tricky thing about logic. As soon as you start asking questions about whether or not logic is true, you hit a brick wall.	{"extraction_info": {"found_math": false, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.9054563641548157, "perplexity": 553.6673374600807}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 20, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2014-35/segments/1408500814701.13/warc/CC-MAIN-20140820021334-00030-ip-10-180-136-8.ec2.internal.warc.gz"}
https://indico.bnl.gov/event/17432/timetable/?view=standard_inline_minutes	# Ciro Riccio: T2K recent results and future prospects US/Eastern Small seminar room Description T2K (Tokai to Kamioka) is a Japan based long-baseline neutrino oscillation experiment designed to measure (anti-)neutrino flavor oscillations. A neutrino beam peaked around 0.6 GeV is produced in Tokai and directed toward the water Cherenkov detector Super-Kamiokande, which is located 295 km away. A complex of near detectors is located at 280 m and is used to constrain the flux and cross-section uncertainties. In 2014, T2K has started a campaign to measure the phase $\delta_{CP}$, an unknown element of the Pontecorvo-Maki-Nakagawa-Sakata matrix, that can provide a test of the violation or conservation of the CP symmetry in the lepton sector. To achieve this goal, T2K is taking data with a neutrino and antineutrino enhanced beam investigating asymmetries in the electron neutrino and antineutrino appearance probabilities. One of the largest systematic uncertainties affecting neutrino oscillation measurements comes from limited knowledge of (anti-)neutrino-nucleus interactions. The T2K experiment has a wide range of neutrino cross-section measurements using detectors in its near detector complex. In this seminar an overview of the latest T2K neutrino oscillation and cross-section measurements are presented as well as its future prospects, which are characterized by an intense program of upgrades. The agenda of this meeting is empty	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.9689631462097168, "perplexity": 1983.7292773143686}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2023-14/segments/1679296949678.39/warc/CC-MAIN-20230331175950-20230331205950-00070.warc.gz"}
https://www.snapsolve.com/solutions/-1678596309723137	Home/Class 10/Science/ ## QuestionScienceClass 10 एक न्यूरॉन की संरचना ड्रा करें और इसकी व्याख्या करें फंक्शन। Diagrammatic representation of neuron- $$(i)$$Neuron is the structural unit of the nervous system. $$(ii)$$ It serves the purpose of transmission of messages between organs and parts of nervous system$$-$$brain and spinal cord for the transmission of message or information takes place mainly in the form of electrical signals. $$(iii)$$Neuron is differentiated into $$3$$ regions $$-$$ Cyton (cell body), Axon and Nerve endings. $$(iv)$$Cyton consist of nucleus and cytoplasm and is responsible for the growth and development of cell. $$(v)$$ Many dendrites extend from cyton and are responsible for taking up messages from the nerve ending of other neuron. $$(vi)$$ The message then travels through the axon and reach the nerve endings. $$(vii)$$The junction between two neurons is known as synapse. $$(viii)$$As the message approaches synapse the nerve endings release a neuro-transmitter known as acetylcholine which helps in relaying message to the dendrites of other neuron. 4.6 4.6 Correct30 Incorrect0 Still Have Question?	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 1, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.677704930305481, "perplexity": 7259.422673396517}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 5, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2021-49/segments/1637964363445.41/warc/CC-MAIN-20211208053135-20211208083135-00087.warc.gz"}
http://gmatclub.com/forum/letters-of-recommendation-avg-length-113678.html	Find all School-related info fast with the new School-Specific MBA Forum It is currently 31 May 2016, 00:54 ### GMAT Club Daily Prep #### Thank you for using the timer - this advanced tool can estimate your performance and suggest more practice questions. We have subscribed you to Daily Prep Questions via email. Customized for You we will pick new questions that match your level based on your Timer History Track every week, we’ll send you an estimated GMAT score based on your performance Practice Pays we will pick new questions that match your level based on your Timer History # Events & Promotions ###### Events & Promotions in June Open Detailed Calendar # Letters of Recommendation - Avg Length? Author Message TAGS: ### Hide Tags Senior Manager Joined: 20 Jun 2010 Posts: 488 Concentration: Strategy, Economics Schools: Chicago (Booth) - Class of 2014 Followers: 14 Kudos [?]: 78 [0], given: 27 Letters of Recommendation - Avg Length? [#permalink] ### Show Tags 15 May 2011, 08:04 For those of you who have experience with this... How long should my letters of recommendation be? I want to be clear in my expectations when speaking to my recommenders. Some of the schools I am applying to have templates/forms (e.g. CBS) while others ask for an open letter (e.g. Kellogg). So for something like CBS, how l long should a response be for a single question (i.e. Comment on your observations of the applicant’s ethical behavior.) And then how about for a non-template letter? Thanks, Michael _________________ Manager Status: Darden Class of 2013 Joined: 15 Nov 2010 Posts: 103 Location: Israel Schools: Duke (R1-int/WL), UCLA (R1), Haas (R2-int/WL-ding), Cornell - R3 (Accepted with ), , Darden Class of 2013 (R2) WE 1: 4 years non profit management WE 2: 2 years real estate Followers: 1 Kudos [?]: 3 [0], given: 1 Re: Letters of Recommendation - Avg Length? [#permalink] ### Show Tags 15 May 2011, 08:42 MDF wrote: For those of you who have experience with this... How long should my letters of recommendation be? I want to be clear in my expectations when speaking to my recommenders. Some of the schools I am applying to have templates/forms (e.g. CBS) while others ask for an open letter (e.g. Kellogg). So for something like CBS, how l long should a response be for a single question (i.e. Comment on your observations of the applicant’s ethical behavior.) And then how about for a non-template letter? Thanks, Michael It's hard to average it since some schools have 9 questions (Hass) and some 3 (Darden), but anyway it shouldn't be more than 2 pages long. Current Student Joined: 16 Jul 2010 Posts: 153 Location: Los Angeles, CA Schools: UCLA Anderson FEMBA Class of 2014 Followers: 3 Kudos [?]: 17 [0], given: 4 Re: Letters of Recommendation - Avg Length? [#permalink] ### Show Tags 15 May 2011, 08:44 I would agree, no more than 2 pages. Also, there's a great thread on rec. letters and making 'packets' for your recommenders to refresh them on what they should write about. Make sure they write the right school name Senior Manager Joined: 20 Jun 2010 Posts: 488 Concentration: Strategy, Economics Schools: Chicago (Booth) - Class of 2014 Followers: 14 Kudos [?]: 78 [0], given: 27 Re: Letters of Recommendation - Avg Length? [#permalink] ### Show Tags 15 May 2011, 08:58 thisguy310 wrote: I would agree, no more than 2 pages. Also, there's a great thread on rec. letters and making 'packets' for your recommenders to refresh them on what they should write about. Make sure they write the right school name Thank you! Could you please point me in the direction of this thread? I'm having trouble locating it via the search engine... _________________ Current Student Joined: 16 Jul 2010 Posts: 153 Location: Los Angeles, CA Schools: UCLA Anderson FEMBA Class of 2014 Followers: 3 Kudos [?]: 17 [0], given: 4 Re: Letters of Recommendation - Avg Length? [#permalink] ### Show Tags 15 May 2011, 20:11 1 This post was BOOKMARKED Senior Manager Joined: 20 Jun 2010 Posts: 488 Concentration: Strategy, Economics Schools: Chicago (Booth) - Class of 2014 Followers: 14 Kudos [?]: 78 [0], given: 27 Re: Letters of Recommendation - Avg Length? [#permalink] ### Show Tags 18 May 2011, 06:34 thisguy310 wrote: Thank you! This is great! _________________ Non-Human User Joined: 01 Oct 2013 Posts: 451 Followers: 59 Kudos [?]: 10 [0], given: 0 Re: Letters of Recommendation - Avg Length? [#permalink] ### Show Tags 18 Aug 2014, 13:46 Hello from the GMAT Club MBAbot! Thanks to another GMAT Club member, I have just discovered this valuable topic, yet it had no discussion for over a year. I am now bumping it up - doing my job. I think you may find it valuable (esp those replies with Kudos). Want to see all other topics I dig out? Follow me (click follow button on profile). You will receive a summary of all topics I bump in your profile area as well as via email. Joined: 07 Mar 2012 Posts: 364 Followers: 17 Kudos [?]: 226 [0], given: 0 Re: Letters of Recommendation - Avg Length? [#permalink] ### Show Tags 19 Aug 2014, 08:00 Expert's post Most letters of recommendation are 2-4 pages long. One page recommendations are usually too short to demonstrate and highlight the significant nature of the relationship. Of course, sticking to the school's instructions is always a good advice! For more MBA Recommendations tips: http://www.aringo.com/MBA_Recommendations_Process.htm Re: Letters of Recommendation - Avg Length? [#permalink] 19 Aug 2014, 08:00 Similar topics Replies Last post Similar Topics: Recommendation letter length? 5 10 Aug 2011, 06:01 4 Recommendation letters 4 29 Jan 2010, 00:11 Length of recommendation letter 0 26 Sep 2009, 10:59 Recommendation letters 2 03 Dec 2008, 21:56 Recommendation letters 1 22 Aug 2006, 19:38 Display posts from previous: Sort by	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.25996482372283936, "perplexity": 11355.608388687018}, "config": {"markdown_headings": true, "markdown_code": false, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2016-22/segments/1464051196108.86/warc/CC-MAIN-20160524005316-00149-ip-10-185-217-139.ec2.internal.warc.gz"}
https://kevinkotze.github.io/if-6-carry/	In most cases we find that the covered interest rate parity condition holds. Therefore, when using forward contracts to try to derive an arbitrage profit, the evidence suggests that the difference between the spot and forward foreign exchange rates is equivalent to the interest rate differentials in the respective countries. However, there is substantial evidence which suggests that the future spot foreign exchange rate changes do not move one-for-one with interest rate differentials in most countries. This may suggest that the uncovered interest rate parity may not hold and the empirical failure of this condition has been documented in a number of studies that go back to Fama (1984). In addition, the evidence also suggests that the forward rate may not provide an unbiased estimate of the future spot rate. In has been suggested that in many cases we observe that the spot exchange rate would usually move by an amount that is less than what would be suggested by the forward exchange rate. This condition is termed a forward bias and the apparent failure of the unbiasedness hypothesis suggests that interest rate differentials may contain information about future spot exchange rates that could be profitably exploited. Both academic analysts and foreign exchange professionals have explored models that link future exchange rate changes to interest rate differentials and other easily available information (such as past exchange rates) to predict future exchange rates. In this section we consider the application of a particular investment strategy that seeks to exploit the forward bias. As a part of this analysis we also provide a number of possible explanations as to why this condition may exist. # 1 The Forward Bias and Carry Trades To exploit the forward bias, we can use the regression for the unbiasedness hypothesis to find a value for the expected return on a forward position. If the expected return is positive (negative), a relatively simple investment strategy would be to go long (short) in a particular currency. While some professional currency managers possibly follow such quantitative strategies, apparent deviations from the unbiasedness hypothesis made a much less sophisticated trade popular, namely the carry trade. If the unbiasedness hypothesis does not hold then it would suggest that the interest rate differentials are not necessarily related to the future movements in exchange rates. This would imply that we could possibly set up trades to benefit from this phenomena. The simplest way of doing so would be to make use of a carry trade investment strategy, where we would wish to: • Borrow in low interest rate currencies (termed funding currencies) • Invest in high interest rate currencies (termed target currencies) The strategy is called carry as the carry represents the interest rate differential between the high- and the low-yield currencies. If the exchange rate does not change in value, the investor simply earns the carry (i.e. the difference between the interest rates). Since the covered interest rate parity condition suggests that the forward premium is equal to the interest rate differential between the domestic and foreign currencies $$({F_t - S_t})/{S_t} = ({i_t - i^{\star}_t})/({1 + i^{\star}_t})$$, we could earn a similar return by taking an uncovered forward position in the high interest rate currencies. Once again, the naive idea is that the investor earns the forward discount (i.e. the carry) if the future spot rate happens to equal the current spot rate as the difference between the current spot and forward rates is equivalent to the interest rate differential. The main funding currencies would include those from the highly stable developed world that pay relatively low rates of interest (such as the USD, JPY, and CHF), while the main target currencies include those that provide higher interest rates. In most cases you would want to avoid those currencies that are highly unstable to mitigate some of the risk factors and as such potential target currencies could include the AUD and NZD. Carry Trade Opportunity To consider a hypothetical example of where a carry trade, suppose the following conditions are given: • Spot exchange rate for USDZAR is R14.00 • Three-month forward exchange rate for USDZAR is R14.20 • The interest rate in South Africa is higher than in the United States Hence, the rand is trading at an annualised premium in the forward market of: $\begin{eqnarray} \left[ 1+\left(\frac{14.20 - 14.00}{14.00}\right) \right]^4 -1 = 5.84\% \end{eqnarray}$ From covered interest rate parity condition, we know that this is approximately the interest rate differential between 3-month rand and dollar external currency market investments. Since the dollar is relatively more expensive in the forward market, we would buy rand forward, hoping the spot exchange rate will not change by much. Our eventual return can be decomposed as follows: $\begin{eqnarray} fmr_{t+1} = s_{t+1} - fp_t = s_{t+1} + (1+ 0.0584)^{\frac{1}{4}} -1 = 143 \; \text{basis points} \end{eqnarray}$ Hence the forward discount or carry of 143 basis points is the cushion on the trade. As long as the rand does not depreciate by more than 143 basis points over the next 3 months, we will come out ahead. Of course, if the unbiasedness hypothesis holds then the rand would depreciate by exactly 143 basis points and we will break even (if there are no transaction costs). Exploiting the forward bias with a carry trade investment strategy simply implies that you invest in currencies with high forward discounts (or high interest rates) relative to other currencies. These trades have been implemented successfully by many investors over the past decade, as a number of hedge funds and other professional investors have started to view investing in currencies as an asset class in its own right. One of the most popular strategies among such investors is the carry trade and Galati, Heath, and McGuire (2007) have noted that carry trade activity has increased significantly over the first decade of the 21st century.1 Given the size of the interest rate differentials that have existed between countries, this should not be surprising. For example, Doskov and Swinkels (2015) consider the interest rate differentials between the four highest yielding and four lowest yielding currencies over the period 1901 to 2012, which at times was greater than 12%. This result is displayed in Figure 1. Figure 1: Source: Doskov and Swinkels (2015) Galati, Heath, and McGuire (2007) consider the relative profitability of this trading strategy after looking at the main funding and target currencies. They note that between 2002 and 2007, official interest rates were lowest in Japan and Switzerland. For this reason, the yen and Swiss franc are among the most commonly cited funding currencies. The Australian dollar, the New Zealand dollar and sterling have appreciated steadily and have been cited as popular target currencies, although a number of other currencies are often used as well (e.g. the Brazilian real and the South African rand). From 2004 and prior to the imposition of quantitative easing, the normalisation of policy rates from historically low levels in the United States has moved the US dollar from being a funding currency to a potential target. The respective interest rates of these currencies is displayed in Figure 2. Figure 2: Source: Galati, Heath, and McGuire (2007) It has also been suggested that carry trade schemes may potentially affect currency values by putting upward (downward) pressure on target (funding) currencies. For example, Galati, Heath, and McGuire (2007) note that when the demand for currencies that provide high interest rates increases, this would result in an appreciation in the value of the currency. However, at some point in time investors may become nervous and they would choose to cover their positions with a forward contract. As the increase in demand for forward contracts would give rise to an expected depreciation in the value of the currency, this could affect expectations about the relative stability of the country that provides the higher interest rate. Such a change in the price of these contracts may foster conditions that give rise to a self-fulfilling prophecy, where there are concerns regarding the relative financial instability of the target country. In addition, there have also been instances when the low-interest (funding) currencies have experienced sudden and relative large appreciations in value. For example, the value of the CHF has appreciated strongly in recent times (partly due to concerns about the value of the USD). Hence, if the CHF was used as a funding currency then the investor would have realised a significant loss at the point when the carry trade unwinds. To see how carry trades have potentially affected the value of a currency, consider the case of Australia, where Galati and Melvin (2004) note that during the period where the interest rate differential (between funding and targeting country) increased, the turnover in the foreign exchange market for these currencies increased by a particularly large amount. This is illustrated in Figure 3, for transactions that involved the US and Australian dollars. Note also that value of the Australian dollar increased over this period, as demand for the target currency increased. This would also suggest that those who invested in such a carry trade scheme would have made a significant profit. Figure 3: Source: Galati and Melvin (2004) Following the widespread acceptance of the carry trade, it is now viewed as one of the standard currency strategies. For example, in 2006, Deutsche Bank created a carry trade index, easily investable for all types of investors, including retail investors, at a fixed fee. Deutsche Bank’s strategy involves making a diversified investment in equally weighted long or short positions in 10 possible currencies versus the U.S. dollar. The 10 currencies are the euro and the currencies of Australia, Canada, Denmark, Great Britain, Japan, New Zealand, Norway, Sweden, and Switzerland. The strategy involves going long in the three currencies that trade at the steepest forward discounts versus the U.S. dollar (that is, currencies traded in countries where money market yields are higher than those in the United States) and going short in the three currencies that trade at the highest forward premiums versus the U.S. dollar (that is, currencies traded in countries where money market yields are lower than those in the United States). The long or short positions are determined at the beginning of each month and are closed at the end of each month. # 2 Measures of Investment Success To investigate the relative profitably of various trading strategies, we could make use of a number of useful measures that are discussed below. ## 2.1 Sharpe Ratios and Leverage The relative success or failure of a trading strategy may be measured by the economic profits or returns that it generates. However, as different investment strategies may be associated with different degrees of risk, it is customary to compare the risk-adjusted returns of the respective investment strategies. The Sharpe ratio is one such measure of risk-adjusted returns, which essentially represents the excess return per unit of volatility (as measured by the standard deviation). Hence, we could make use of the expression $\begin{eqnarray} \text{Sharpe ratio}=\frac{\text{Average excess return}}{\text{Standard deviation of excess return}} \end{eqnarray}$ Correcting for the volatility of returns is especially important for currency strategies, as they often employ leverage}, which would affect the relative risk and return of an investment. For example, as a forward contract does not require any upfront investment and is just a bilateral contract with a bank, it would imply that the amount of capital that an investor could put at risk may be greater than the amount of capital that they potentially own. Since banks want ensure that their counterparties can deliver on their contracts, the investor would typically need to assure the bank that they have sufficient capital to absorb potential losses. This amount of available capital would usually be invested in relatively riskless securities, such as high-quality Treasury bills. Note that as the potential losses are going to less than the principle investment amount (in almost every case) the bank would only require that the investor would have access to sufficient capital to cover the potential loss and not the principle investment. Since most carry trades originate from the funding currency country, we can consider the case of an American investor. For example, if there is exactly $1 invested in a Treasury bill for every dollar bought or sold in the forward foreign exchange market, the excess return on the trading strategy, that is, the return over and above the return on the Treasury bill, equals the return on capital at risk. If forward contracts pertain to more dollars than there are in a riskless account, the trading strategy uses leverage. For example, if for every$1 in the riskless account, $2 of forward contracts are made, the leverage ratio is 100%: $\begin{eqnarray} \text{Leverage} = \frac{\text{Capital at risk - Capital owned}}{\text{Capital owned}} =\frac{\2 - \1}{\1} = 100\% \end{eqnarray}$ Using leverage in a trading strategy scales up both its returns and its risk, which implies that we should focus on the risk-return trade-off when considering whether or not these trading strategies are profitable. ## 2.2 Empirical findings Burnside, Eichenbaum, and Rebelo (2012) consider a carry-trade strategy that combines individual-currency carry trades into an equally-weighted portfolio. They use monthly data for 20 currencies, where all portfolios are constructed such that the U.S. dollar is the domestic currency. Figure 4 displays the cumulative returns to investing in the carry and momentum strategies and in the U.S. stock market. The investment period spans March 1976 to January 2012. Two features of Figure 4 are worth noting. Firstly, the cumulative returns of the strategy is almost as high as the cumulative return to investing in stocks. Secondly, the cumulative returns to the stock market are much more volatile than those of the currency portfolios. Figure 4: Source: Burnside, Eichenbaum, and Rebelo (2012) In addition, the summary statistics in Table 5 show that the carry-trade strategy has an average annualized payoff of 4.5%, with a standard deviation of 5.2%, and a Sharpe ratio of 0.86. The Sharpe ratios of this strategy is higher than that of the stock market. The average excess return to the U.S. stock market over our sample period is 6.5%, with a standard deviation of 15.8% and a Sharpe ratio only equal to 0.41. These results are in line with those of Bekaert and Hodrick (2012) who suggest that the Sharpe ratio in the U.S. stock market is often estimated to be 0.30 to 0.40, where the average annualized excess return is between 5% and 6% and the annualized standard deviation is 15%. They also note that studies find that regression-based foreign exchange strategies produce Sharpe ratios similar and even higher than those available in stock markets, offering a reason for the increase in popularity of this trading strategy. Carry Trade Stock Market Excess return 4.5% 6.5% Standard deviation 5.2% 15.8% Sharpe ratio 0.86 0.41 Table 1: Returns, Risk and Sharpe Ratios The high Sharpe ratio of the carry-trade strategy reflects the large gains from diversifying across carry-trade strategies for individual currencies, where the benefits from this diversification reduce the volatility of payoffs by more than 50%. Since the average payoff is not affected, the Sharpe ratio of the portfolio doubles relative to the average Sharpe ratio of individual carry trades.2 Another striking feature of the Burnside, Eichenbaum, and Rebelo (2012) study is that they are able to show that the payoffs to carry trade strategy are uncorrelated with stock market returns. Hence, this currency-trading strategy would provide a natural source of diversification when combined with a broad portfolio of U.S. stocks. Although these results present quite a strong argument in favour of the use of this strategy, it is important to note that past performance need not repeat itself and that currency investing is risky. In particular, as the distribution for changes in the value of currencies exhibit fat tails, extreme outcomes (both positive and negative) are certainly possible, which would make the investment relatively risky. With this in mind it is worth noting that during the recent global financial crisis the Deutsche Bank carry trade index declined by more than 20% over a short period of time. This would imply that those currency funds with a 3-to-1 leverage ratio (which is not uncommon) would have generated a negative return of -80%. This feature is particularly evident in the study that is presented Rosenberg (2013), which looks at a shorter sample. Figure 5: Source: Rosenberg (2013) However, if one is able to stay in the market, then one could have made a significant return on investment, as is evident from the long-term return has been shown in Figure 7. Figure 6: Source: Doskov and Swinkels (2015) # 3 Risk Premiums and the Unbiased Hypothesis Earlier we noted that an investment strategy which is based on the covered interest rate parity condition has very little or no risk, while a carry trade investment strategy is associated with substantial risk. Therefore, one may suggest that positive returns that have been provided by the carry trade investment strategy (on average) may constitute payment for the difference in the risk premium of these investments. For example, let us consider the case where a bank believes that the rand is undervalued. If the forward discount on the rand relative to the dollar be 2% (which would be equivalent to the interest rate differential) and the bank believes that the rand is expected to appreciate by 3%, the risk premium would be given as $\begin{eqnarray} rp_t = \mathbb{E}_t \big[ fmr_{t+1} \big] = \mathbb{E}_t \big[ s_{t+1} - fp_t \big] = 3\% - (- 2\%) = 5\% \end{eqnarray}$ Note that the risk premium is the aggregate of the expected rate of appreciation and the forward discount. For this forecast to be consistent with a risk explanation, we must believe that the volatility of the rand would imply that it is so risky that it not only offers a 2% interest rate premium but also is expected to appreciate by 3%. Hence, it offers a 5% expected excess return to investors. Is this plausible (or sustainable) and could it be used to explain the potential forward bias? ## 3.1 The Variability of the Risk Premium The volatilities of forward premiums on the major currencies are about 3% (on an annualized basis). It turns out that the regression evidence implies that both the volatilities of expected exchange rate changes and risk premiums are often (much) larger than the volatilities of forward premiums. The reason for this may be derived from the regression $\begin{eqnarray} \mathbb{E}_t \big[ s_{t+1} \big] = \phi_1 +\phi_2 fp_t \end{eqnarray}$ where the variance of expected exchange rate changes is $\begin{eqnarray} \mathsf{var} \Big[ \mathbb{E}_t \big[ s_{t+1} \big] \Big] = \mathsf{var} \Big[ \phi_1 +\phi_2 fp_t \Big] = \phi_2^2 \mathsf{var} \Big[ fp_t \Big] \end{eqnarray}$ Hence, if $$\phi^2 > 1$$, which is the case for all pairs involving the yen and dollar, the expected exchange rate changes are more variable than forward premiums. To find the variance of the risk premium, recall that the risk premium is simply the expected forward market return. Therefore, $\begin{eqnarray} rp_t = \mathbb{E}_t \big[ fmr_{t+1} \big] = \mathbb{E}_t \big[ s_{t+1} - fp_t \big] = \phi_1 +( \phi_2 - 1) fp_t \end{eqnarray}$ Hence, $\begin{eqnarray} \mathsf{var} \big[ rp_{t} \big] = ( \phi_2 -1)^2 \mathsf{var} \big[ fp_t \big] \end{eqnarray}$ Consequently, as long as $$\phi_2$$ is negative, which is the case for all currencies, the implied variance of the risk premium is not only larger than the variance of the forward premium, but it is also larger than the implied variance of the expected exchange rate changes. If risk premiums are more variable than expected currency appreciation, it may be that a particular movement in the interest rate is driven by a change in the risk premium than by a change in the expected rate of appreciation of the currency. This is counter-intuitive to most economists, who think that most of the forward premium variation reflects expected currency depreciation. A number of economists have argued that survey data on forecasts of rates of appreciation from market professionals are closely related to forward premiums.3 Therefore, the survey data forecasts of rates of appreciation may be biased as well. However, there are multiple problems with survey data as they may not have the proper incentive to tell the truth. In addition, faced with a disparity of forecasts, the method that is used to represent the market’s} forecast may be called into question. Typically, the median forecast is chosen, however, as we are interested in the marginal investor’s expectation this may not be an accurate representation. Nevertheless, basic formal models of risk, such as the CAPM, have a hard time generating risk premiums as variable as implied by the regressions.4 The recent global crisis has rekindled interest in the dynamics and economic sources of carry trade returns. In general we find that the carry trade appears to have attractive long-run returns that trickle in slowly as the carry more than compensates for the depreciation of the high-yielding currencies. However, there are periods where we experience sudden and steep movements in exchange rates, where the low-yield currencies appreciate sharply. This would expose those who are looking to benefit from a carry trade when it unwinds. When considering the distribution of the strategy’s returns we note that they are not normal, but exhibit fat tails and negative skewness. Most investors obviously dislike such return properties, and recent studies have focused on these properties of carry trade returns to provide new risk-based explanations. Unwinds of the carry trade tend to happen as a result of economic crises, and it is conceivable that people become dramatically more risk averse when they might lose their job or face large investment losses. Investors would usually refer to a flight to quality} that occurs during such periods. Since the returns to carry trades are correlated with such macroeconomic risks, they command a positive risk premium.5 Other research focuses on the behaviour of traders. Brunnermeier, Nagel, and Pedersen (2009) stress that when a carry trade unwinds, investment managers face margin calls and may have difficulty funding their levered positions. Their clients may withdraw money as well. These forces would subsequently cause the managers to unwind their positions, selling the high-yield currencies and buying the low-yield currencies. In doing so, they exacerbate the losses on the carry trade. If the unwinding process is bad enough, the investment managers may go out of business. Knowing that this might happen causes an insufficient allocation of risky capital to the carry trade, keeping the returns higher than they should be. This explanation combines the presence of risk premiums with the idea of limits to arbitrage we encountered before. The new explanations also rely on the fact that there are infrequent disastrous returns to the carry trade. These events by themselves can provide a potential explanation of the forward bias, as we discuss in what follows. ## 3.2 Further empirical evidence and theoretical explanations ### 3.2.1 Unstable Coefficients Figure 8 presents rolling estimates of the slope coefficients from the regression model to characterize its dynamic features over time. $\begin{eqnarray} s_{t+1} = \phi_1 + \phi_2 fp_t + \varepsilon_{t+1} \tag{3.1} \end{eqnarray}$ The first estimate uses the first $$5$$ years of monthly data. The next estimate results from rolling the data forward by 1 month and re-estimating the regression, again with 5 years of data. Figure 7: Source: Bekaert and Hodrick (2012) In the regression analysis of the unbiasedness hypothesis, the estimates of the slope coefficient, $$\phi_2$$, are very far from 1, but Figure 8 indicates that there is dramatic instability in these coefficients across 5-year intervals. During the major appreciation of the dollar relative to the other major currencies in the early 1980s, the estimated slope coefficient decreased from -5 to -10. Clearly, this was probably because of the unexpectedly strong appreciation of the dollar and not a response to an increase in the variability of risk premiums. The large carry trade unwinds in the 2007 to 2008 period increased the coefficients towards 1. This evidence indicates a potential problem with the assumption of rational expectations underlying the statistical analysis. In the following section we explain how this might happen. ### 3.2.2 Peso Problems A phenomenon called the peso problem arises when rational investors anticipate events, typically dramatic, that do not occur during the sample or at least do not occur with the frequency that investors expect. Peso problems invalidate statistical inference conducted under the rational expectations assumption based on data drawn from the period. The peso problem got its name from considering problems that would have arisen in analysing Mexico’s experience with fixed exchange rates. During 1955 to 1975, the Mexican authorities successfully pegged the USDMXP exchange rate at MXP 12 per USD. Now suppose we assume that the market sets the forward rate in such a way that it is an unbiased predictor of the future spot rate, where we assume that the unbiasedness hypothesis holds. To determine whether a statistician would conclude that the forward rate is an unbiased or a biased predictor in this case we could perform the following calculation. Let $$S_{\text{peg}}$$ be the USDMXP exchange rate at which the Mexican authorities are currently pegging, and $$S_{\text{dev}} >S_{\text{peg}}$$ is the rate that the Mexican authorities will choose if they devalue the peso. Suppose that the market knows $$S_{\text{dev}}$$ and let $$p_t$$ be the probability that the market assigns to the event that the peso will be devalued during the next month. Then, the 1-month forward rate is an unbiased predictor of the future spot rate when it is the probability-weighted average of the two possible events: $\begin{eqnarray} F_t = \mathbb{E}_t \big[ S_{t+1} \big] = (1 - p_t ) S_{\text{peg}} + (p_t ) S_{\text{dev}} \end{eqnarray*}$ The forward rate is the probability of no devaluation multiplied by the current exchange rate plus the probability of a devaluation multiplied by the new exchange rate. As the market’s assessment of the strength of the government’s commitment to the peg changes over time, $$p_t$$ will change, and so will the forward rate. As long as the devaluation does not materialize, the dollar will trade at a forward premium relative to the peso (in pesos per dollar, $$F_t > S_{\text{peg}}$$), and peso money market investments will carry higher interest rates than dollar investments. Suppose the Mexican authorities successfully peg the peso to the dollar between time $$T_0$$ and time $$T_2$$, when they eventually devalue the peso. Suppose also that the market knew during the time period between $$T_0$$ and $$T_2$$ that the Mexican authorities might devalue the peso at any time. If the statistician takes data from an interval of time during which no devaluation occurs, say, between $$T_0$$ and $$T_1$$, where $$T_1 < T_2$$, and compares forward rates with realized future spot rates, she will conclude that the forward rate is a biased predictor of the future spot rate. During the statistician’s sample, the realized future spot rate is always below the forward rate. Hence, the statistician rejects the null hypothesis that the forward rate is an unbiased predictor of the future spot rate. The statistician has rejected the null hypothesis, but the null hypothesis is true. How did the statistician go wrong? In other words, what led to the peso problem in this case? When we do statistical analysis on a financial time series using the rational expectations assumption, we assume that a reasonably long sample of returns is representative of the true distribution of returns that investors thought they faced when they made their investments. For the forward market example, we would assume that the ex post spot rates reflect all the possible events that investors thought might happen when they entered into their forward contracts. If there are important events that investors thought might happen but that did not happen, or if relatively rare events happened too frequently, the historical sample means, variances, and correlations in the data may tell us very little about the means, variances, and correlations of returns that investors thought they faced. The historical means, variances, and correlations may also be relatively uninformative about the moments that investors will face in the future. It is in this sense that the past performance of foreign investments may be poor indicators of the returns that investors can expect in the future. In the case of the Mexican peso, even though the forward rate seemed to be a biased predictor of the future spot rate over 20 years, the devaluation eventually occurred in 1976, thereby validating the prediction embedded in the forward rate. For the peso problem to explain the evidence regarding carry trade returns and the forward bias we discussed before, the peso events must be anticipated by market participants and, when they occur, they should wipe out the gains accrued before so that excess returns from currency speculation average out to zero. Burnside et al. (2008) claim that even the 2008 disastrous returns do not suffice to make this true. They argue that carry traders can hedge the downside risk using options without sacrificing all their returns, which is inconsistent with a strict interpretation of the peso problem. However, they can explain the carry trade returns if they assume agents become very risk averse when an unwind happens. It appears that time-varying risk premiums remain critical to explain speculative currency returns. ### 3.2.3 Carry Trades and Currency Crashes Another useful empirical insight is provided by Brunnermeier, Nagel, and Pedersen (2009) trace the evolution of a typical carry-trade cycle from the gradual buildup of speculative positions in long high-yield/short low-yield carry-trade strategies to the forced unwinding of those positions when the volatility regime shifts and liquidity conditions tighten. They suggest that in a typical carry-trade cycle, an initial widening in high-yield/low yield interest rate spreads tends to attract capital into the high-yield market. To gain that confidence, investors often rely on successful back-tests of risky strategies before they are ready to commit meaningful amounts of capital to the trade. As evidence accumulates that the uptrend in carry-trade returns appears sustainable, only then will more capital be committed to the trade. This wait-and-see approach gives rise to a gradual adjustment in portfolio allocations, which in turn gives rise to a gradual increase in the capital inflows into the target currency. Given the steady increase in inflows one would observe trend-persistence in positive excess returns that may be earned on foreign exchange carry trades. This gradual build-up then places carry-trade investors in a vulnerable position in which a sudden shock might force investors to unwind these speculative positions, thereby precipitating a crash in carry-trade returns. While it is often the case that capital tends to move slowly into carry trades, the exit from carry trade positions tends to be rapid. This would imply that there is a strong link between currency carry trades and currency crashes that are associated with the sudden unwinding of these positions. In many respects, this is not dissimilar to the herding and fire-sale behaviour that is evident on many financial markets. Consistent with models in which the erosion of capital increases insurance premia, we find that the price of protecting against a crash in the aftermath of one increases despite the fact that a subsequent crash is less likely. Furthermore, they note that currency crashes are positively correlated with increases in implied stock market volatility and indicators of funding illiquidity. This could be the outcome of a setting in which higher volatility leads to lower available speculator capital due to higher margins and capital requirements, inducing traders to cut back on their carry trade activities. Moreover, we find that a higher volatility could be used to predict higher carry returns going forward and that controlling for this effect reduces the foreign exchange return predictability of interest rates. Finally, their finding that currencies with similar interest rates comove with each other, after controlling for other effects, suggests that carry trades affect exchange rate movements. In summary, they argue that the results of their investigation are consistent with the view that macroeconomic fundamentals determine which currencies have high and low interest rates and that they also influence the value of currencies in the long-run. They also suggest that illiquidity and capital immobility could lead to short-run currency underreaction to changes in economic fundamentals and occasional currency crashes due to liquidity crises. # 4 Conclusion Understanding the rationale for widely-used currency strategies is important as they affect exchange rate movements, which has normative and positive implications of capital flows. In addition, the profitability of simple currency-trading strategies presents perhaps even more of a challenge to traditional asset-pricing theory and there are still a number of unresolved questions that need to be answered. In an interesting investigation, Burnside, Eichenbaum, and Rebelo (2012) suggest that the failure of UIP is not surprising from a theoretical perspective as it would require for agents to be risk neutral. So, a natural explanation for both the failure of UIP and the profitability of the carry trade strategy is the presence of a risk premium that compensates investors for the covariance between the payoffs to the currency strategies and their stochastic discount factor. However, they note that the profitability of these strategies is not a compensation for risk, as measured in conventional portfolio management theory. The rationale for this is that the covariance between the payoffs from this strategy and those from conventional investments is not statistically significant. In addition, the authors find that the skewness of the carry-trade payoffs is statistically insignificant, and possibly less skewed than the payoffs to the U.S. stock market. Furthermore, the dangers associated with the fat tails of the currency strategies are also much less pronounced than those associated with the stock market. This area of research has important implications for our understanding of macroeconomic and financial events and it has been suggested that we need to incorporate realistic financial frictions into modern modelling frameworks, while also allowing for heterogeneity in expectations and disagreement among agents. # 5 References Bekaert, Geert. 1996. “The Time Variation of Risk and Return in Foreign Exchange Markets: A General Equilibrium.” Review of Financial Studies 9: 427–70. ———. 2011. “Valuing Currency Management: TOM Vs. U.S. Commerce Bank.” 100310. Columbia CaseWorks. Bekaert, Geert, and Robert J. Hodrick. 2012. International Financial Management. New York: Prentice Hall. Brunnermeier, Markus K., Stefan Nagel, and Lasse H. Pedersen. 2009. “Carry Trades and Currency Crashes.” In NBER Macroeconomics Annual 2008, Volume 23, 313–47. NBER Chapters. National Bureau of Economic Research, Inc. Burnside, Craig, Martin Eichenbaum, and Sergio Rebelo. 2012. “Understanding the Profitability of Currency-Trading Strategies.” Research Summary 3. NBER Reporter 2012. Vol. Number 3. National Bureau of Economic Research. Burnside, Craig, Martin Eichenbaum, Isaac Kleshchelski, and Sergio Rebelo. 2006. “The Returns to Currency Speculation.” WP 12489. NBER. ———. 2008. “Do Peso Problems Explain the Returns to the Carry Trade?” NBER Working Paper. Chinn, Menzie, and Jeffrey A. Frankel. 2002. “Monetary Policy, Capital Flows and Financial Market Developments in the Era of Financial Globalisation: Essays in Honour of Max Fry.” In, edited by Bill Allen and David Dickinson. London: Routledge. Doskov, Nikolay, and Laurens Swinkels. 2015. “Empirical Evidence on the Currency Carry Trade, 1900-2012.” Journal of International Money and Finance 51: 370–89. Fama, Eugene F. 1984. “Forward and Spot Exchange Rates.” Journal of Monetary Economics 14 (3): 319–38. Frankel, Jeffrey A., and Kenneth Froot. 1990. “International Business Reader.” In, edited by D. Das. Oxford: Oxford University Press. Galati, Gabriele, and M. Melvin. 2004. “Why Has Fx Trading Surged? Explaining the 2004 Triennial Survey.” BIS Quarterly Review. Bank of International Settlements. Galati, Gabriele, Alexandra Heath, and Patrick McGuire. 2007. “Evidence of Carry Trade Activity.” BIS Quarterly Review 3: 27–41. Giovannini, Alberto, and Philippe Jorion. 1989. “The Time-Variation of Risk and Return in the Foreign-Exchange Stock Markets.” Journal of Finance 44 (2): 307–25. Rosenberg, Michael R. 2013. The Carry Trade: Theory, Strategy, and Risk Management. Bloomberg. Verdelhan, Adrien. 2010. “A Habit-Based Explanation of the Exchange Rate Risk Premium.” Journal of Finance 65: 123–45. 1. Bekaert (2011) suggests that assets under management in currency related funds grew from under$5 billion to over \$25 billion between 2000 and the end of 2007. 2. See, Burnside et al. (2006) for the benefits of diversification gains that may be achieved with carry trade strategies. 3. See, Frankel and Froot (1990) and Chinn and Frankel (2002). 4. See, for example, Bekaert (1996) and Giovannini and Jorion (1989). 5. See, Verdelhan (2010) for a recent example of such a model.	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 2, "mathjax_display_tex": 1, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.6004146337509155, "perplexity": 1642.4805662613824}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2020-24/segments/1590347422803.50/warc/CC-MAIN-20200602033630-20200602063630-00377.warc.gz"}
http://www.ck12.org/book/CK-12-Basic-Algebra-Concepts/section/12.9/	<img src="https://d5nxst8fruw4z.cloudfront.net/atrk.gif?account=iA1Pi1a8Dy00ym" style="display:none" height="1" width="1" alt="" /> # 12.9: Clearing Denominators in Rational Equations Difficulty Level: Basic Created by: CK-12 0% Progress Practice Clearing Denominators in Rational Equations Progress 0% Suppose that you had 24 quarts of juice to equally distribute to each member of your class. However, 10 members of your class were absent, so the amount of juice distributed to each person increased by 15\begin{align} \frac {1}{5}\end{align} of a quart. How many people are in your class? What equation could you set up to find the answer to this question? In this Concept, you'll learn how to solve rational equations by clearing denominators so that you can solve problems like this one. ### Guidance Solving by Clearing Denominators When a rational equation has several terms, it may not be possible to use the method of cross products. A second method to solve rational equations is to clear the fractions by multiplying the entire equation by the least common multiple of the denominators. #### Example A Solve 5x1x=4\begin{align}5x-\frac{1}{x}=4\end{align}. Solution: Start by clearing the denominators. In this case, there is only one denominator, x\begin{align}x\end{align}. This means that x\begin{align}x\end{align} is the LCM of all the denominators, since there is only one denominator. Simply multiply the whole equation by that denominator, x\begin{align}x\end{align}. Then solve for x\begin{align}x\end{align} using methods learned previously. Clear the denominator.This is quadratic, so make one side equal to zero.Factor.Use the Zero Product Property to solve for the variable.5x1x5x215x24x1(5x+1)(x1)x=15 or x=4=4x=0=0=1 #### Example B Solve 3x+24x5=2x23x10\begin{align}\frac{3}{x+2}-\frac{4}{x-5}=\frac{2}{x^2-3x-10}\end{align}. Solution: Factor all denominators and find the least common multiple. 3x+2LCM4x52(x+2)(x5)=(x+2)(x5) Multiply all terms in the equation by the LCM and cancel the common terms. (x+2)(x5)3x+2(x+2)(x5)4x5(x+2)(x5)3x+2(x+2)(x5)4x5=(x+2)(x5)2(x+2)(x5)=(x+2)(x5)2(x+2)(x5) Now solve and simplify. 3x+24x52x23x10=325+24255=0.003=2(25)23(25)10=0.003 #### Example C A group of friends decided to pool their money together and buy a birthday gift that cost $200. Later 12 of the friends decided not to participate any more. This meant that each person paid$15 more than the original share. How many people were in the group to start? Solution: Let x=\begin{align}x=\end{align} the number of friends in the original group Number of People Gift Price Share Amount Original group x\begin{align}x\end{align} 200 200x\begin{align}\frac{200}{x}\end{align} Later group x12\begin{align}x-12\end{align} 200 200x12\begin{align}\frac{200}{x-12}\end{align} ### Answers for Explore More Problems To view the Explore More answers, open this PDF file and look for section 12.9. Basic 8 , 9 ## Date Created: Feb 24, 2012 Aug 20, 2015 You can only attach files to Modality which belong to you If you would like to associate files with this Modality, please make a copy first.	{"extraction_info": {"found_math": true, "script_math_tex": 28, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.4744550287723541, "perplexity": 1543.028237771942}, "config": {"markdown_headings": true, "markdown_code": false, "boilerplate_config": {"ratio_threshold": 0.3, "absolute_threshold": 20, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2015-48/segments/1448398448389.58/warc/CC-MAIN-20151124205408-00236-ip-10-71-132-137.ec2.internal.warc.gz"}
https://cstheory.stackexchange.com/questions/11139/contract-preservation-using-grammars	# Contract preservation using grammars I am exploring using annotated grammars to formalize and enforce parts of contracts between nodes in a distributed application. I've found a number of articles on languages for specifying fairly general types of contracts, mostly based around the idea of a contract as a state machine; and others (mostly object-capability schemes) based around the idea of identifying a "safe" subset of a language; but none that use a grammar as the specification of the contract. I was wondering how attempts to formalize contracts tend to fail, and what else should one keep in mind. Below are details of the particular kind of contract I am trying to enforce. Given a BNF grammar for part of HTML: HTML ::== (Text \| Link); Text ::== ("&" \| "<" \| """ \| [^&<"])+; Link ::== "<a" Href? ">" Text "</a>"; Href ::== "href=\"" Text+ "\""; I can infer which strings are in the language and which are not, and the structure of a parse tree, but by adding annotations thus HTML ::== (Text \| Link); Text ::== @String((@CharValue{"&"}"&" \| @CharValue{"<"}"<" \| @CharValue{"\""}""" \| [^&<"]))+; Link ::== "<a" Href? ">" Text? "</a>"; Href ::== " href=\"" @Embeds{URI}Text+ "\""; I can infer additional facts: 1. That plain text can be encoded/decoded by replacing "&" with "&", etc. and that a string can be encoded as a string that matches the Text non-terminal. 2. That the URI grammar should be recursively applied to the content of the href post-decoding. From this I hope to generate several artifacts: 1. Encoders. An encoder for non-terminal T is a 'a -> T string function that encodes a data value. 2. Sanitizers. A function T string -> T string that produces a similar string that falls in a subset of the language that is well-handled by many different implementations and which does not contain high-power instructions. 3. A template context propagator. A function string * context -> string * context which takes a string from a trusted source and the context before the string (context is a type describing a set of prefixes of strings in the language) and produces a string in the well-handled subset of the language and the context after that string is appended to any of the prefixes described by the input context. This is useful for composing a string from trusted and untrusted code. With these tools, I hope to be able to enforce the contract that any powerful instructions which are parsed by the receiver of a network message composed using these tools are instructions that are present in snippets of code authored by the message sender, and not instructions authored by a provider of untrusted data. If the sender uses the derived tools to encode or sanitize all untrusted data appropriately, and uses the template propagation algorithm to choose encoders/sanitizers appropriate to the context of the buffer on which the message is being built, then high-power instructions in the buffer must have come from a privileged source. If the recipient receives a message over a secure channel, and uses the same grammar to parse and decode the message, then it can be confident of the provenance of the instructions it receives. So the annotated grammar serves as a formal description of a contract, and the tools move the burden of preserving the contract from the application author to the grammar author. Since there are many application authors who tend to know the well-tested parts of a language, a much smaller number of language specialists who know the poorly tested parts of the grammars as well should be able to make applications robust against code injection. (I'm not in theory; please regard this as a placeholder answer.) 1. Is this a research-level question? You may have more luck at cs.stackexchange.com. 2. The reason you haven't found much relevant literature may be your choice of keywords. The terms contract and communication often refer to describing patterns of interaction formed by message passing as a whole, usually abstracting away from the contents of the messages; your contracts, on the other hand, are limitations on the possible contents of individual messages. That subject is better known as validation, and indeed, grammars are routinely used for that purpose. 3. Your example uses HTML as the language to restrict, and introduces a BNF for describing it. Don't do that if you can avoid it; SGML and XML were invented for a reason. They take away the need for you to describe how to recognize syntax trees in strings, so a grammar merely needs to describe a set of allowable trees. XML is a well-established and well-supported standard, and so are several grammar definition formalisms for XML-based languages: XML Schema, Relax-NG, DTDs, Schematron. 4. Your example also introduces a technique for describing entity encoding and decoding. SGML and XML come equipped with such a technique, and it is applied in HTML, so why not just use that? (Not that I'm happy with how that works, but it's standard: if you have an XML language, the mechanism is there for you to use.) 5. I'm puzzled by @Embeds{URI} - why isn't URI simply a nonterminal? I can see that its grammar isn't that of HTML, but that of URIs, but XML has a way of dealing with that already: XIncludes and namespaces. (Not that I'm happy with how that works, but it's standard: if you have an XML language, the mechanism is there for you to use.) 6. I don't understand your sanitizers or template context propagators. If you do need a more general annotation mechanism that can be used both to constrain syntax and to interpret it, have a look at stuff such as attribute grammars, affix grammars and definite clause grammars. I'm not aware of a pendant for XML, but XSLT can be used in a similar way. 7. If the point of sanitizers and template context propagators really is to restrict the HTML language, why not just override the grammar for some nonterminals in the HTML grammar with your own, more restrictive definitions? Both XML Schema and Relax NG support this, although I must add that they don't provide any support for limiting such overrides to defining restrictions only. An alternative is to use Schematron, in which syntactic constraints are a language construct. 8. HTML is an odd choice of language for an example - in a typical web application, there is no great need to constrain the HTML being sent (largely owing to the language being used for markup only and being SGML/XML-based) while it is imperative to put very clear constraints on the messages being accepted in the opposite direction, the HTTP requests. But those are usually simple and don't really use a standard language, unless you put something like SOAP on top. So I'm curious what sort of application you have in mind for this. To summarize: yes, there is a lot of support for what you want to do (if I'm not too mistaken about your sanitizers and propagators), especially when the languages you use are XML-based. • Taking your points one at a time. 3. SGML and XML don't help with sanitization of HTML -- taking a string of noisy HTML in and producing a string of HTML without powerful instructions that is in the XHTML-like subset that is handled similarly by all major browsers. There are reasons why the HTML5 specification does not use either to describe HTML -- they can't handle the reality of what browsers do. – Mike Samuel May 7 '12 at 22:53 • 4. I want to make sure encodings faithfully represent the dual of what parsers produce when they decode. XML languages are just one kind of language that I have to deal with, so are not a substitute for reliable encoder generation. Encoders are currently hand-written for each library language and are often buggy and inconsistent as a result. This work is attempting to provide a way to produce encoders of consistent quality for many platforms based on a specification that can be understood by message language experts. – Mike Samuel May 7 '12 at 22:58 • 5. Because all of the URIs in the following are the same <a href="O'Reilly.html">, <a href="O'Reilly.html">, <a href="O&APOS;Reilly.html">, <a href="O'Reilly.html">. I don't want to specify a grammar for a URI and a grammar for a URI embeded in HTML , and a grammar for a URI embedded in CSS, and a grammar for a URI embedded in CSS embedded in HTML (<a style="background: url('O\27 Reilly& al.css')">). – Mike Samuel May 7 '12 at 23:01 • 6. There is a glossary which defines terms like sanitizers and contexts. In short, templates combine trusted and untrusted data and the context propagation parses small snippets of trusted content so it can figure out the appropriate encoders/sanitizers to use for the untrusted content to preserve the security properties in that same tech report. – Mike Samuel May 7 '12 at 23:03 • I think a blog or something like IRC would be a better environment for this discussion. – reinierpost May 21 '12 at 7:43	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 1, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.26086845993995667, "perplexity": 1687.6575299403244}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.3, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2019-47/segments/1573496671548.98/warc/CC-MAIN-20191122194802-20191122223802-00399.warc.gz"}
http://science.sciencemag.org/content/324/5929/888	PerspectiveOcean Science # Ice Sheet Stability and Sea Level See allHide authors and affiliations Science 15 May 2009: Vol. 324, Issue 5929, pp. 888-889 DOI: 10.1126/science.1173958 ## Summary Volume changes in the Antarctic Ice Sheet are poorly understood, despite the importance of the ice sheet to sea-level and climate variability. Over both millennial and shorter time scales, net water influx to the ice sheet (mainly snow accumulation) nearly balances water loss through ice calving and basal ice shelf melting at the ice sheet margins (1). However, there may be times when parts of the West Antarctic Ice Sheet (WAIS) are lost to the oceans, thus raising sea levels. On page 901 of this issue, Bamber et al. (2) calculate the total ice volume lost to the oceans from an unstable retreat of WAIS, which may occur if the part of the ice sheet that overlies submarine basins is ungrounded and moves to a new position down the negative slope (see the figure).	{"extraction_info": {"found_math": false, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.9210615754127502, "perplexity": 3282.133204096456}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2018-22/segments/1526794863626.14/warc/CC-MAIN-20180520151124-20180520171124-00211.warc.gz"}
https://www.physicsforums.com/threads/using-cross-product-to-find-angle-between-two-vectors.510814/	# Using cross product to find angle between two vectors 1. ### yayscience 5 1. The problem statement, all variables and given/known data Find the angle between \begin{align} \vec{A} = 10\hat{y} + 2\hat{z} \\ and \\ \vec{B} = -4\hat{y}+0.5\hat{z} \end{align} using the cross product. The answer is given to be 161.5 degrees. 2. Relevant equations $$\left\| \vec{A} \times \vec{B} \right\| = \left\| \vec{A} \right\| \left\| \vec{B} \right\|sin(\theta)$$ 3. The attempt at a solution $$\left\| \vec{A} \times \vec{B} \right\| =$$ $$\left\| \begin{array}{ccc} \hat{x} & \hat{y} & \hat{z} \\ 0 & 10 & 2 \\ 0 & -4 & 0.5 \end{array} \right\| = \left\| 13\hat{x} \right\| = 13$$ The magnitude of A cross B is 13. Next we find the magnitude of vectors A and B: $$\left\| \vec{A} \right\| = \sqrt{10^2+2^2} = \sqrt{104} = 10.198039$$ and $$\left\| \vec{B} \right\| = \sqrt{(-4)^2+(\frac{1}{2})^2} = \sqrt{16.25} = 4.0311289$$ multiplying the previous two answers we get: 41.109609 So now we should have: $$\frac{13}{41.109609} = sin(\theta)$$ Solving for theta, we get: 18.434951 degrees. This is frustrating: 180-18.434951 = the correct answer. I'm not quite sure where I'm going wrong here. I must be making the same mistake repeatedly. Another problem was the same thing, but with the numbers changed, and I also got the 180-{the answer I was getting} = {the correct answer}, but when I tried the example using the SAME methodology, I got the correct answer. Can someone please share some relevant wisdom in my direction? 2. ### ehild 12,091 sin(alpha)=sin(180-alpha) Plot the two vectors and you will see what angle they enclose. ehild 3. ### I like Serena 6,193 You might use the sign of the inner dot product to see which angle you have. 4. ### yayscience 5 I can plot them, and I can see the angle, but I'm interested in calculating the angle. When I use the dot product I get the correct result, but I cannot see where my mistake is while using the cross product. 5. ### ehild 12,091 There is no mistake, you get the sine of the angle, but there are two angles between 0 and pi with the same sine. ehild 6. ### yayscience 5 Oh wow; I didn't even consider that the answer wasn't unique. Thanks!	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 1, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.9958646297454834, "perplexity": 806.1888048176183}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2015-18/segments/1429246656168.61/warc/CC-MAIN-20150417045736-00146-ip-10-235-10-82.ec2.internal.warc.gz"}
http://hal.in2p3.fr/in2p3-01337069	# Measurements of the Mass and Isotopic Yields of the 233U(nth,f) Reaction by the Lohengrin Spectrometer 4 ACEN - Aval du cycle et Energie Nucléaire CENBG - Centre d'Etudes Nucléaires de Bordeaux Gradignan Abstract : Analysis and results of the measurements of the independent isotopic and mass fission yields for the 233U(nth,f) reaction are presented, which were performed at the Lohengrin recoil mass spectrometer in ILL. The spectrometer separates the fission products according to their mass to ion charge ratio and kinetic energy to ion charge ratio. Mass yields were obtained by means of an ionisation chamber after separation by the spectrometer. Isotopic yields were determined by placing two high-purity Germanium clover detectors downstream the spectrometer. An innovative analysis method developed for the Lohengrin spectrometer is presented, from which the final results are independent from the previous evaluations, which is usually not the case. Type de document : Article dans une revue Nuclear Data Sheets, Elsevier, 2014, 119, pp.328-330. 〈10.1016/j.nds.2014.08.090〉 http://hal.in2p3.fr/in2p3-01337069 Contributeur : Emmanuelle Vernay <> Soumis le : vendredi 24 juin 2016 - 14:14:29 Dernière modification le : jeudi 11 janvier 2018 - 06:26:26 ### Citation F. Martin, C. Sage, G. Kessedjian, O. Sérot, C. Amouroux, et al.. Measurements of the Mass and Isotopic Yields of the 233U(nth,f) Reaction by the Lohengrin Spectrometer. Nuclear Data Sheets, Elsevier, 2014, 119, pp.328-330. 〈10.1016/j.nds.2014.08.090〉. 〈in2p3-01337069〉 ### Métriques Consultations de la notice	{"extraction_info": {"found_math": false, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.9258403778076172, "perplexity": 10927.56512500081}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2018-05/segments/1516084891705.93/warc/CC-MAIN-20180123012644-20180123032644-00659.warc.gz"}
https://hal-ens-lyon.archives-ouvertes.fr/ensl-01585049v3	# Root Separation for Trinomials 2 MC2 - Modèles de calcul, Complexité, Combinatoire LIP - Laboratoire de l'Informatique du Parallélisme Abstract : We give a separation bound for the complex roots of a trinomial $f \in \mathbb{Z}[X]$. The logarithm of the inverse of our separation bound is polynomial in the size of the sparse encoding of $f$; in particular, it is polynomial in $\log (\deg f)$. It is known that no such bound is possible for 4-nomials (polynomials with 4 monomials). For trinomials, the classical results (which are based on the degree of $f$ rather than the number of monomials) give separation bounds that are exponentially worse. As an algorithmic application, we show that the number of real roots of a trinomial $f$ can be computed in time polynomial in the size of the sparse encoding of~$f$. The same problem is open for 4-nomials. Keywords : Document type : Journal articles Domain : Cited literature [18 references] https://hal-ens-lyon.archives-ouvertes.fr/ensl-01585049 Contributor : Pascal Koiran Connect in order to contact the contributor Submitted on : Wednesday, October 24, 2018 - 3:09:30 PM Last modification on : Saturday, September 11, 2021 - 3:18:59 AM Long-term archiving on: : Friday, January 25, 2019 - 2:11:13 PM ### Files revised.pdf Files produced by the author(s) ### Identifiers • HAL Id : ensl-01585049, version 3 • ARXIV : 1709.03294 ### Citation Pascal Koiran. Root Separation for Trinomials. Journal of Symbolic Computation, Elsevier, In press. ⟨ensl-01585049v3⟩ Record views	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.7667942047119141, "perplexity": 2229.77425786963}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2021-49/segments/1637964363791.16/warc/CC-MAIN-20211209091917-20211209121917-00363.warc.gz"}
http://arxitics.com/articles/1901.03318	## arXiv Analytics ### arXiv:1901.03318 [cond-mat.stat-mech]AbstractReferencesReviewsResources #### Thermodynamics of majority-logic decoding in information erasure Published 2019-01-10Version 1 We investigate the performance of majority-logic decoding in both reversible and finite-time information erasure processes performed on macroscopic bits that contain $N$ microscopic binary units. While we show that for reversible erasure protocols single-unit transformations are more efficient than majority-logic decoding, the latter is found to offer several benefits for finite-time erasure processes: Both the minimal erasure duration for a given erasure and the minimal erasure error for a given erasure duration are reduced, if compared to a single unit. Remarkably, the majority-logic decoding is also more efficient in both the small erasure error and fast erasure region. These benefits are also preserved under the optimal erasure protocol that minimizes the dissipated heat. Our work therefore shows that majority-logic decoding can lift the precision-speed-efficiency trade-off in information erasure processes.	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.69951993227005, "perplexity": 3060.8041780256613}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2019-13/segments/1552912201707.53/warc/CC-MAIN-20190318211849-20190318233849-00528.warc.gz"}
https://thosgood.com/blog/2021/09/24/some-questions-about-analytic-geometry/	# Some questions about complex-analytic geometry ###### 24th September, 2021 Despite being an analytic/algebraic geometer by name (and title, and qualification, and academic upbringing, and …), there are so many gaps in my knowledge, even when it comes to simple foundational things. One thing which I have always tried to do during my academic “career”, however, is to be the person who asks the first stupid question, so that others can feel less nervous about asking their (certainly less stupid) questions. Thus: this blog post. I am going to explain what I do know, talk about what I don’t, and then ask some semi-concrete questions that I’m hoping people will be able to help me out with! # The algebraic dictionary In the case of algebraic geometry, we have a nice dictionary which lets us translate between the language of sheaves, of bundles, and of modules. I’m sure that many of you will have seen at least the first and last column of this table before; the middle one talks about what sort of resolutions we can find. Sheaves Bundles¹ Modules² locally free vector bundles finitely generated and projective coherent complexes of vector bundles finitely generated quasi-coherent complexes of vector bundles arbitrary ¹ For quasi-projective Noetherian schemes. ² For Noetherian affine schemes. Of course, there are some very important caveats here, noted above (i.e. we need to be working over sufficiently nice spaces in order for these correspondences to hold). Note that here we can write a quasi-coherent sheaf as a (filtered) colimit of its coherent subsheaves, hence the fact that it can also be resolved by a complex of vector bundles (just maybe a really really big and unwieldy one). # The analytic dictionary Now, I don’t really work very much in the algebraic setting: I’m more interested in the case of holomorphic things on Stein spaces, and so on. So here’s my attempt at filling in the analogous table. Sheaves Bundles Modules locally free vector bundles ??? coherent complexes of vector bundles on the Čech nerve ??? “quasi-coherent” ??? ??? As you can see, it is far from complete, but let’s start with the things that I do know (since this won’t take very long to talk about). It is still the case that locally free sheaves on a complex-analytic manifold correspond to vector bundles, and, by the results of Green’s 1980 thesis (or mine), we can show that coherent (analytic) sheaves (on a complex-analytic manifold) can be resolved, not quite by complexes of vector bundles, but by a sort of up-to-homotopy version of this, namely Green complexes, or complexes of vector bundles on the Čech nerve. For the last row of the “Bundles” column, things get a bit complicated. Indeed, it’s not really universally accepted (as far as I know) what “the” “good” definition of quasi-coherent even is in the complex-analytic case. The reason why we don’t really want to use the same definition as in the algebraic case (i.e. having a local presentation) is that such objects are not very well behaved at all. For example, as mentioned above, we know that any quasi-coherent algebraic sheaf is the filtered colimit of its coherent subsheaves, but the analogous statement in the analytic setting is very much not true. In particular, there exist quasi-coherent (in the sense of the algebraic definition) analytic sheaves on Stein spaces that have non-zero first sheaf cohomology. This is bad, because any coherent analytic sheaf on a Stein space has zero higher sheaf cohomology, and so there is absolutely no hope of recovering such quasi-coherent sheaves as colimits of their coherent subsheaves. (Indeed, it’s really bad, because it’s not just that we don’t quite recover the quasi-coherent sheaf from the colimit, but we’re really far away from doing so, because we’re trying to get something non-zero from a bunch of things that are zero!) There is the notion of Fréchet quasi-coherence, which I have read is a good substitute, but I don’t fully understand why, nor if it is somehow “the” good substitute (indeed, I haven’t even fully internalised the definition, since it really is something quite analytic). Theorem 4.3.6 in Spectral Decompositions and Analytic Sheaves tells us the following: Let X be a finite-dimensional Stein space, and let \mathscr{F} be a Fréchet \mathscr{O}_X-module. The following conditions are equivalent: 1. \mathscr{F} is quasi-coherent; 2. \mathscr{F} admits globally topologically free resolutions on the left; 3. \mathscr{F} is acyclic on X and admits, locally on X, topologically free resolutions to the left. Here, when they write “quasi-coherent”, they mean “Fréchet quasi-coherent”. So maybe this is useful somehow, because it characterises this notion of quasi-coherence in terms of a resolution property, but I’m not sure if that answers my question or not. Indeed, I’m (yet again) still not entirely sure what these “globally topologically free resolutions” look like, and how they might relate to things that I already know. Then, of course, there’s the elephant in the room (or dictionary, I suppose): what goes in the right-hand column? That is, what even is \operatorname{Spec} in the analytic setting? I know that this can be sort of understood through the framework of analytic spaces, in the sense of Grauert et al, but I can’t quite complete the whole story in my head from what I’ve read. I’ve been meaning to read Brian Conrad’s “Relative ampleness in rigid geometry”, since I think this might hold some answers, but I’ve been too scared by the appearance of the word “rigid” in the title to actually properly dive in… # Questions Anyway, there you go: there are lots of things that I, having a PhD in complex-analytic geometry stuff, really should know the answer to, but don’t. Here are my “precise” questions: 1. How can I fill in this analytic dictionary? 2. In fact, what even is \operatorname{Spec} in the analytic setting? 3. Is Fréchet quasi-coherent the good thing to put in the analytic dictionary? That is, what analogous properties does Fréchet quasi-coherence satisfy to make it the “right” notion? e.g. does it arise as the right Kan extension of the pseudofunctor from commutative rings to categories which sends a ring to the category of modules over that ring? 4. More specifically, is it true that Fréchet quasi-coherent sheaves can be recovered as filtered colimits of their coherent subsheaves? Sadly I still haven’t set up comments on this blog (it’s on my (ever-growing) to-do list), so having a conversation might be a bit tricky, but Twitter might be a good place to do this (on this thread, for example), or you can just drop me an email — I’d love to hear from anybody!	{"extraction_info": {"found_math": false, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.8491066098213196, "perplexity": 539.0628345032757}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 5, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2022-49/segments/1669446710712.51/warc/CC-MAIN-20221129232448-20221130022448-00083.warc.gz"}
http://www.ima.umn.edu/geoscience/spring/g11.html	HOME » PROGRAMS/ACTIVITIES » Annual Thematic Program IMA Workshop Pint Process Modeling and Seismological Applications of Statistics June 10-14, 2002 Mathematics in Geosciences, September 2001 - June 2002 Organizers: Frederic Paik Schoenberg Department of Statistics University of California-Los Angeles [email protected] David R. Brillinger Department of Statistics University of California-Berkeley [email protected] Bruce A. Bolt Department of Geology and Geophysics University of California-Berkeley [email protected] Statistical methods have proven to be useful in many seismology applications, such as estimation of seismic hazard, assessment of earthquake prediction schemes, and quantification of uncertainties in estimates of earthquake locations or magnitudes. However, there is still much room for further application of statistics in seismology. In particular, much dialog is needed in order for statistical models and methods to be better understood and made more accessible to seismologists. In addition, applied statisticians and point process theorists need to better understand which assumptions may be reasonable, and which statistical methods are useful under conditions appropriate to seismological problems. This workshop will focus heavily on getting seismologists and other applied earth scientists to learn useful statistical methods and concepts, and on getting statisticians to focus on problems that are of real practical interest. We will experiment with creative ways to get the two groups talking about the overlap of theory and application. The workshop will focus on several topics, which will be explored in sequence. The topics are listed below. The examination of each topic will be broken up into three parts. The first part will be a tutorial, in which concepts, methods and applications relevant to the topic are surveyed. A purpose of the tutorial is to attempt to bridge the gap between the seismological and statistical and/or mathematical communities and to ensure that all participants can agree on a common terminology. The tutorial will be followed by several lectures, which will have a more technical focus, emphasizing statistical issues of contemporary interest and recent developments with potential seismological applications. Finally, each topic will conclude with an interdisciplinary forum. The forum will provide an opportunity for a statistician or seismologist to present a cutting-edge research problem and provide an opportunity for another participant to respond and for the audience to participate in the discussion. As an illustration, a seismologist could present a new class of problem, discuss its statistical issues, and survey methods of addressing those issues, and a statistician might suggest refinements that may improve upon those methods. Alternatively, a statistician might discuss a new class of models or methods of potential use in seismology, and a seismologist might respond with insights on the nature of how assumptions or methods might be modified in order for statistical methods or results to be more broadly applicable to seismological problems. The workshop will conclude with a panel discussion of what has been learned and a formulation of how in the future we can examine problems of interest both to seismologists and statisticians. In particular, the panel will report on the following three questions: a) What problems in seismology most deserve immediate attention and how can statisticians help in addressing them; b) What useful statistical methods can be built around assumptions germane to the real world; c) How can we bridge the communication gap between seismologists and statisticians and mathematicians and nurture an ongoing dialog. The daily topics will include the following. 1) Introduction to earthquakes. This topic will motivate the workshop. Seismic hazard estimation will be examined as a paradigm of a problem in the Earth Sciences for which there already is a repertoire of statistical methodology and substantial room for improvement in the use of statistics. 2) The role of randomness' in seismology. While seismologists traditionally describe earthquakes via deterministic, physical models, applied statisticians have increasingly explored the use of stochastic, or "random" models for earthquake behavior. It is important to explore questions such as: Which characteristics of earthquakes may usefully described as "random"? What roles can stochastic point process or time series models play in addressing useful seismological problems? In particular, questions of scale come into play, as deterministic models may be useful in describing phenomena which, on a relatively macroscopic scale, appear to behave randomly, and vice versa. 3) Time series versus point processes. The main stochastic models used for describing earthquakes come from the areas of time series and point processes. Time series models are generally used in describing random processes that appear to be sampled at discrete time points. Point processes are useful for modeling random processes that appear at irregularly spaced times, and which may conceivably occur anywhere in a continuum of possible times. Rather little attention has been given to how these two classes of models compare, and in which applications to use one type of model as opposed to the other. These questions will motivate an introduction and discussion of the two types of models in a context that will be both useful and accessible to seismologists and other earth scientists. In addition, special attention will focus on conditional rate (or conditional intensity) models for point process, which have proven useful in describing earthquake occurrences but whose descriptions are rather intricate. 4) Statistical models for seismological processes. Seismologists have predominantly explored physical models in describing earthquakes. Such models are generally deterministic descriptions of physical phenomena and how they interact within a closed and well-defined environment, and typically are expressed as differential equations, ordinary or partial (e.g. Newton's laws of motion). By contrast, statistical models are often used to describe observations of phenomena which are thought to have some inherent variability or which are observed with incomplete information, such as data recorded with error or events occurring at an irregular and uncertain pattern of locations and times. (Sometimes the statistical model incorporates the mathematical solution to a physical model, but in many situations this is not entirely possible.) Statistical models may be especially useful in quantifying uncertainties related to previously observed phenomena as well as to forecasts of future events. We will explore examples of these models in detail, and discuss how they may be used to address basic seismological problems of concern. Of particular interest are point process models including stress-release processes and other state-space models, branching processes, renewal processes, and mixture models. Special attention will be paid to issues involving spatial-temporal marked point processes and their applications to seismological data. 5) Evaluation of statistical models. Many different statistical models can and indeed have frequently been used to describe the same seismological phenomena. Thus, given a statistical model, a very important and basic question is: how adequately does the model describe the data (observations or simulations) to which it applies, and how does the fit of the model in question compare to competing statistical models? We will survey methods, both graphical and numerical, for assessing goodness-of-fit for stochastic models for seismological processes. Further, we will discuss practical implications, including which types of models appear to fit well to which seismic datasets, and what can be deduced in terms of construction of confidence intervals, standard errors, and statistical tests. Keywords: Risk assessment, seismic hazard estimation, prediction, point process (theory and applications), marked point process, earthquakes, insurance WORKSHOP SCHEDULE Monday Tuesday Wednesday Thursday Friday MONDAY, JUNE 10 All talks are in Lecture Hall EE/CS 3-180 unless otherwise noted. Theme: Introduction to earthquakes Chair: Bruce Bolt 8:15 am Coffee and Registration Reception Room EE/CS 3-176 9:15 am Douglas N. Arnold, Robert Gulliver, and Frederic Paik Schoenberg Welcome and Introduction 9:30 am Tutorial: Bruce Bolt University of California-Berkeley Earthquake Morphology 10:30 am Coffee Break Reception Room EE/CS 3-176 11:00 am Forum: "Are earthquakes random?" (Abstract) 11:00 am Frederic Paik Schoenberg, presents Yan Y. Kagan work Transparencies (Email questions to [email protected]) 11:10 am David R. Brillinger, University of California, Berkeley rejoins 11:15 am Brillinger presents 11:25 am Schoenberg rejoins 11:30 am Discussion led by Discussants: Robert Nadeau, William Newman 12:00 pm Lunch Break 1:30 pm Norm Abrahamson Pacific Gas & Electric Company, San Francisco, CA Methodology for Evaluation of Characteristic Earthquake Models Using Paleoseismic Measurements of Fault Slip from Sites with Multiple Earthquakes 2:20 pm Discussion 2:30 pm Coffee Break Reception Room EE/CS 3-176 3:00 pm James W. Dewey U.S. Geological Survey Mapping Earthquake Shaking and Earthquake Damage 3:50 pm Discussion 4:00 pm Second Chances (Bruce Bolt, moderator) 4:30 pm IMA Tea/Poster Session A variety of appetizers and beverages will be served. 400 Lind Hall 1. K. Borovkov University of Melbourne and Mark S. Bebbington Massey University A stochastic two-node stress transfer model reproducing Omori's law 2. Steven C. Jaume College of Charleston and Mark S. Bebbington Massey University Accelerating Moment Release in Modified Stress Release Models of Regional Seismicity Slides: html pdf powerpoint 3. Alexey A. Lyubushin Russian Academy of Sciences http://www.ima.umn.edu/~lyubushi/ Multidimensional Wavelet Analysis of Point Processes 4. Renata Rotondi CNR - IMATI, Milano, Italy and E. Varini Universiat "L. Bocconi", Milano, Italy Bayesian Analysis of a Marked Point Process: Application in Seismic Hazard Assessment 5. Renata Rotondi CNR - IMATI, Milano, Italy Renewal processes for great events: Bayesian nonparametric interevent time density estimation 6. Daniel R.H. O'Connell U.S. Bureau of Reclamation, Denver, Colorado Do You Live in a Bad Neighborhood?: Maybe Site-Specific PSHA is an Oxymoron 7. Sung Eun Kim University of Cincinnati Robert H. Shumway University of California, Davis Multiple Infrasound Arrays Processing 8 Yosihiko Ogata Institute of Statistical Mathematics, Tokyo Demonstrations of space-time seismicity analysis (Poster) 9 Maura Murru Istituto Nazionale di Geofisica e Vulcanologia Bath's Law and the Gutenberg-Richter Relation pdf html doc TUESDAY, JUNE 11 All talks are in Lecture Hall EE/CS 3-180 unless otherwise noted. Theme: Uses of time series & point process models in seismology Chair: David R. Brillinger 9:00 am Coffee Reception Room EE/CS 3-176 9:30 am David R. Brillinger University of California, Berkeley Uses of point process and time series models in seismic risk analysis (Tutorial) Slides 10:30 am Coffee Break Reception Room EE/CS 3-176 11:00 am David Harte Statistics Research Associates, Wellington, New Zealand Interpretation and Uses of Fractal Dimensions in Modelling Earthquake Data Slides: pdf postscript 11:50 am Discussion 12:00 pm Lunch Break 2:00 pm Didier Sornette Institute of Geophysics and Planetary Physics and Department of Earth and Space Science at UCLA and LPMC at University of Nice, France Renormalized Omori Law, Conditional Foreshocks, Spatial Diffusion and Earthquake Prediction with the Etas Model 2:50 pm Discussion 3:00 pm Second Chances (David Brillinger, moderator) WEDNESDAY, JUNE 12 All talks are in Lecture Hall EE/CS 3-180 unless otherwise noted. Theme: Stochastic models for earthquake occurrences Chair: David Vere-Jones 9:00 am Coffee Reception Room EE/CS 3-176 9:30 am Tutorial: David Vere-Jones Victoria University, New Zealand Stochastic models for earthquake occurrences Tutorial Slides 10:30 am Coffee Break Reception Room EE/CS 3-176 11:00 am Forum: "Which models are acceptable?" (Abstract) 11:00 am Renata Rotondi, CNR/IAMI, Milan presents 11:10 am Daryl Daley, Australian National University rejoins 11:15 am Daley presents 11:25 am Rotondi rejoins 11:30 am Discussion led by Discussants: Alexey Lyubushin, Greg Anderson 12:00 pm Lunch Break 1:30 pm Stephen L. Rathbun Pennsylvania State University A Marked Spatio-Temporal Point Process Model for California Earthquakes Slides.pdf Slides.html 2:20 pm Discussion 2:30 pm Coffee Break Reception Room EE/CS 3-176 3:00 pm David Vere-Jones (on behalf of Yan Y. Kagan) Transparencies (Email questions to [email protected]) Earthquake Occurrence: Statistical Analysis, Stochastic Modeling, Mathematical Challenges Based to a large degree on the joint paper (Kagan and Vere-Jones, Lecture Notes in Statistics 114, C.C. Heyde et al. eds., New York, Springer, pp. 398-425, 1996) Presentation Slides Debate Contribution Slides Set 1 Debate Contribution Slides Set 2 3:50 pm Discussion 4:00 pm Second Chances (David Vere-Jones, moderator) THURSDAY, JUNE 13 All talks are in Lecture Hall EE/CS 3-180 unless otherwise noted. Theme: Point process models Chair: Yosihiko Ogata 9:00 am Coffee Reception Room EE/CS 3-176 9:30 am Tutorial by Yosihiko Ogata Institute of Statistical Mathematics, Tokyo Analysis of Seismic Activity Through Point-Process Modeling Tutorial Slides 10:30 am Coffee Break Reception Room EE/CS 3-176 11:00 am Valerie Isham University College, London Applications of point process models in hydrology Slides 11:50 am Discussion 12:00 pm Lunch Break 2:00 pm Pierre Brémaud INRIA/ENS A review of recent results on Hawkes processes 2:50 pm Discussion 3:00 pm Second Chances (Yosihiko Ogata, moderator) 6:00 pm Workshop Dinner Gardens of Salonika 19 N.E. 5th Street, Minneapolis FRIDAY, JUNE 14 All talks are in Lecture Hall EE/CS 3-180 unless otherwise noted. Theme: Evaluation of statistical models for earthquakes Chair: Frederic Paik Schoenberg 9:00 am Coffee Reception Room EE/CS 3-176 9:30 am Tutorial: Frederic Paik Schoenberg University of California, Los Angeles Evaluation of statistical models for earthquakes Slides 10:30 am Coffee Break Reception Room EE/CS 3-176 11:00 am Forum: "Which models seem most promising?" (Abstract) 11:00 am Yosihiko Ogata, Institute of Statistical Mathematics, presents Forum Slides 11:10 am David Vere-Jones, Victoria University, New Zealand rejoins 11:15 am Vere-Jones presents 11:25 am Ogata rejoins 11:30 am Discussion led by Discussants: Steven Jaume, Dan O'Connell 12:00 pm Lunch Break 1:30 pm Lothar Heinrich Universität Augsburg Testing the Poisson Hypothesis and Higher-Order Normal Approximation for Statistics of Poisson-Based Point Process Models Slides 2:20 pm Discussion 2:30 pm Coffee Break Reception Room EE/CS 3-176 3:00 pm Mark S. Bebbington Massey University, New Zealand More ways to burn CPU: A macedoine of tests, scores and validation Slides 3:50 pm Discussion 4:00 pm Second Chances (Frederic Paik Schoenberg, moderator) Monday Tuesday Wednesday Thursday Friday #### LIST OF CONFIRMED PARTICIPANTS As of 6/4/2002 ta Name Department Affiliation Norm Abrahamson &PG&E Greg Anderson US Geological Survey Doug Arnold Institute for Mathematics & its Applications Mark Bebbington Institute of Information Sci & Tech. Massey University Bruce A Bolt Geology & Geophysics University of California-Berkeley W. John Braun Statistics & Actuarial Science University of Western Ontario Pierre Bremaud Institute of Communications Systems Ecole Polytechnique Fédérale de Lausanne David R. Brillinger Statistics University of California, Berkeley Daryl Daley Centre for Mathematics and its Applications Australian National University James Dewey Geologic Hazards Team U.S. Geological Survey Licia Faenza Geophysics University of Bologna Robert Gulliver Institute for Mathematics & its Applications David Harte Statistics Research Associates Limited Victoria University Lothar Heinrich Institut fur Mathematik Universitat Augsburg Valerie Isham Statistical Science University College London Steven C. Jaume Geology College of Charleston Sung Eun Kim Mathematical Sciences University of Cincinnati Anna Maria Lombardi Alexey Lyubushin Institute of Physics of the Earth Russian Academy of Sciences Maura Murru Istituto Nazionale di Geofisica e Vulcanologia Roger Musson Global Seismology and Geomagnetism British Geological Survey Robert Nadeau Earth Sciences Lawrence Berkeley National Lab William I. Newman Earth and Space Sciences, Physics and Astronomy, and Mathematics University of California, Los Angeles Dan O'Connell Seismotectonics Group U.S. Bureau of Reclamation Yosihiko Ogata The Institute of Statistical Mathematics Stephen L Rathbun Statistics - Eberly College of Science The Pennsylvania State University Enders Anthony Robinson Earth and Environmental Engineering Columbia University, Henry Krumb School of Mines Renata Rotondi CNR IMATI Fadil Santosa Institute for Mathematics & its Applications Michael W. Smiley Mathematics Iowa State University Didier Sornette Earth and Space Sciences University of California, Los Angeles Robert Uhrhammer Seismological Laboratory University of California - Berkeley David Vere-Jones Mathematics and Computing Sciences Victoria University Connect With Us: Go © 2015 Regents of the University of Minnesota. All rights reserved. The University of Minnesota is an equal opportunity educator and employer Last modified on October 06, 2011 Twin Cities Campus: Parking & Transportation Maps & Directions Directories Contact U of M Privacy	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 1, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.22890996932983398, "perplexity": 8928.657416733711}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2015-32/segments/1438042988312.76/warc/CC-MAIN-20150728002308-00166-ip-10-236-191-2.ec2.internal.warc.gz"}
http://www.gnu.org/software/gsl/manual/html_node/Simulated-Annealing-algorithm.html	### 25.1 Simulated Annealing algorithm The simulated annealing algorithm takes random walks through the problem space, looking for points with low energies; in these random walks, the probability of taking a step is determined by the Boltzmann distribution, p = e^{-(E_{i+1} - E_i)/(kT)} if E_{i+1} > E_i, and p = 1 when E_{i+1} <= E_i. In other words, a step will occur if the new energy is lower. If the new energy is higher, the transition can still occur, and its likelihood is proportional to the temperature T and inversely proportional to the energy difference E_{i+1} - E_i. The temperature T is initially set to a high value, and a random walk is carried out at that temperature. Then the temperature is lowered very slightly according to a cooling schedule, for example: T -> T/mu_T where \mu_T is slightly greater than 1. The slight probability of taking a step that gives higher energy is what allows simulated annealing to frequently get out of local minima.	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 1, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.9225342869758606, "perplexity": 619.4337646558192}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2015-11/segments/1424936463453.54/warc/CC-MAIN-20150226074103-00161-ip-10-28-5-156.ec2.internal.warc.gz"}
http://two-sheds.blogspot.com/2007_02_01_archive.html	February 25, 2007 371 Years of Treason On September 22nd, 1776, on his way to the gallows, Nathan Hale proclaimed his only regret to be that he "had but one life to lose for my country." Since then, it has been all downhill for Connecticut in terms of loyalty. A spy for the Revolutionary forces, Hale was caught behind enemy lines and executed for his role prior to the Battle of Long Island. He was America's first espionage agent, but is celebrated almost entirely for his famous last words -- which differ in their few vague accounts and which most scholars believe to be a repetition of a phrase he did not come up with himself. In any case, for being this sort of fearless, patriotic Christ-figure, Nathan Hale is honored far and wide with postage stamps, statues, and an obscene number of elementary schools. [Incidentally, the primary witness to this speech was a British Colonel John Montresor. Despite the distinctiveness of this name and the modest notoriety he achieved for his role in the war he seems to bear no relation to the Montresor of Poe's Cask of Amontillado. Not that this would make any literary sense either.] Since Hale uttered his celebrated line, Connecticut history has been nothing but a parade of backstabbers and turncoats. In fact, I will demonstrate that treachery is the state's most basic identity. Let us consider some notable historical figures in the intervening time. Not more than four years later, Benedict Arnold was thwarted in his plot to surrender West Point to the British. That would be the Connecticut-born, Benedict Arnold, synonymous with betrayal. That one is too obvious, how about something more obscure? The Hale execution story was popularized primarily by one man, William Hull, then a lower-level army officer who heard of Hale's bravery while meeting with a British officer the following day. By the War of 1812 he had worked his way up to the level of general, commanding the northwestern army. Facing what he thought (erroneously) to be vastly superior British forces approaching Fort Detroit, he promptly surrendered THE ENTIRE NORTHWESTERN ARMY. Despite popularizing Hale's all edged speech Hull did not seem willing to regret that he didn't even bother to try losing his life to defend the whole Midwest. Few subordinates believed this action to be even remotely necessary, and a court marshall agreed. Hull was ordered to be shot, and only spared at the last minute by President Madison. In modern politics, we have Joe Lieberman, Bush's shadow. Go-to guy for really misguided Iraq War ideas and repetition of corrosive "people who criticize the war hate the soldiers" type rhetoric. Who lost the Democratic primary and then stabbed the party that supported his entire career in the back by running as the Independent/Connecticut for Lieberman nominee. Who periodically threatens to break his promise and side with his real soul-mates in the Senate, overturning the intention of the people who voted for him with the expectation that he wouldn't do that. Not to mention the fact that almost none of the positions he espouses are held by the actual people of his constituency in a state that dumped all but one of its Republican representitives last November. Classic Connecticut. [ Speaking of which, someone with an excellent sense of humor actually joined Joe's nominal "Connecticut for Lieberman" party. He called the Secretary of State, found out that no one, not even the Senator, had bothered to become a member of the party named after himself. As the only member of the Connecticut for Lieberman Party, Dr. John Orman held a convention at his house, nominated himself for chairman, seconded his own nomination and voted for himself. He then adopted a number of party rules, including "If you run under Connecticut for Lieberman, you must actually join our party."and "If any CFL candidate loses our party's nomination in a primary, that candidate must bolt our party, form a new party and work to defeat our party endorsed candidate."] Speaking of people who love the President, need I remind you that no one is working harder to further the terrorists' goal of fomenting terror in America and the rest of the world than Connecticut-born George W. Bush himself? Freaking out the country with vague threats, doing the enemy's job by building up the danger they pose and keeping them constantly in the limelight, while at the same time wasting vast resources and efforts fighting people who are not them. Not to mention the obvious stuff like allowing bin Laden to avoid capture and creating a generation of impoverished displaced Muslims who hate America. Whether or not he's actually trying to, it is hard to deny that he's helping the enemy at this point. Now to more important matter, baseball. Connecticut has always been the least authentic part of New England, or so it seems to the rest of us. In the "real" New England states like Rhode Island and Massachusetts, I think that the source of our unease with Connecticut is their non-allegiance to the Red Sox, and to a lesser extent, the Patriots. We just don't know how to deal with people who call themselves NEer's but don't support the very thing that unifies our region. This intrepid blogger could write a book on Red Sox-Yankees dynamics in CT, and frequently laments the grating fact that the New England Sports Network, which carries the Sox, does not serve Fairfield Country. Is it too much to expect a channel that calls itself the New England Sports Network to operate in, you know, New England?! In any case, it is merely symptomatic of a larger problem, the overflow of fair-weather baseball fans into what is rightly our dominion. Here is how it is supposed to work- Officially designated Red Sox Area: New England. Officially designated Yankees area: NY, NJ, remote regions of the country with losing teams and poor baseball knowledge, much of Japan. Oh, and I forgot, BOS: Dominican Republic, NYY: Nicaragua. But Connecticutters are not content to stick to the pre-arrangement. Instead, many of the weak-willed betrayers of western Conn. took it upon themselves to divide up the state as they wish. The NY Times published a fascinating summary of the boarder dispute last summer. Which all brings us back to Hale, who was, at the very least, a patriot who has inspired millions to serve our nation with his brave demeanor. But is it surprising, after all this, that Connecticut's official state hero is a spy? Who probably didn't come up with or actually utter the very words for which he was immortalized? And what of Conn.'s familiar appellation: The Nutmeg State? Astute knowers of trivia will recognize that this handle refers to the shrewd practice of peddling fake wooden nutmeg to southerners and similarly dimwitted fellow residents. So ingrained is Connecticut's deceitful nature that the state's nickname itself celebrates their own duplicity! Quad erat demonstratum. So next time you are enjoying the manatee exhibit at Mystic Aquarium, watch your back. What shocks me about an electron in a Penning trap is... I saw this the other night and laughed fairly hard. It was inserted directly into the middle of an interview, which was proceeding not unnormally up to this point. I wish people really talked this way. I also wish I could find the article it is from. Seconds later, this happened. Update: Some goons took down the YouTube video but it is still available here. Update II: I think that previous update no longer works. Now it is here. Update II.V: As of Jan 2010 the only place I can find it is here. Update III: The link in update II may still work, but either way, here is the transcript, courtesy of mettadata. Jim Carrey: I was just reading this incredible paper on the stochastic phase-shifting of the parametrically-driven electron in a Penning trap; and apparently, a bistability arises dynamically in the specific parametrically-driven systems, because the phase $\psi$ of the electron’s steady-state oscillation can either have the two values separated by $\pi$. (…) Conan O’Brien: You know, it’s funny, what shocks me about an electron in a Penning trap is that most amplitude collapses are accompanied by a phase flip. Given that the rate of escape from the trap depends exponentially on an activation energy $\textit{E}$ as the diffusion constant $\textit{D}$ approaches $\textit{T}_{n}$ and $\rho$ approaches $\epsilon^\textit{-E/D}$. JC: Absolutely. No question there. Max Weinberg: I don’t know about that, Conan. Have you considered that the parametric driving force excites a nearly-resonant electron oscillation at the drive frequency, $\omega_{d}/3=\omega_{z}+\epsilon$? It’s a classic example of the period-doubling that occurs when a linear oscillator is strongly driven. JC: Max. Did you just say that $\omega_{d}/3=\omega_{z}+\epsilon$? MW: Yeah. CB: (Laughs). It’s actually $\omega_{d}/2=\omega_{z}+\epsilon$! Wow, Max. Max, you know nothing about quantum physics! MW: You’re right. February 24, 2007 Colloquium Drawing of the Week 6 "3 if by air" Properly viewed by opening this up in a different tab. February 23, 2007 timeline An unusual thing just happened. For whatever reason the cable TV hiccuped, but continued to broadcast a still image of the screen without sound. This itself isn't so strange, no one can know the ways of the TV network malfunctions, but it certainly led to a bizarre learning experience. When it stopped I just sort of stared at it for about 7 seconds, looked around the room to see if anything was moving, then automatically checked my watch. The seconds were ticking by, confirming my original suspicion that it was the television that had ceased to work properly, not the passage of time. I know this sounds like I'm just being smart-alecky, but it was my actual, unthinking, reaction. I had a 99% certainty about it being a cable problem, but some part of me wanted to rule out the time-freeze alternative decisively. No matter how sober and evidence-based your style of thinking may be, you can never stop these funny little quirks from slipping in there. February 22, 2007 Magnet-ism This is a lazy post. First, a video of a ferrofluid, a liquid with creepy nanoscale magnets suspended in it. Who ever said physics wasn't evil? Speaking of evil, here is a famous frog levitating in a magnetic field. Everything is diamagnetic if the external field is strong enough...but only frogs are unlucky enough to get used in these experiments. February 19, 2007 Silver Lining In honor of President's day, a reminder that even the worst deciders had redeeming qualities...or at least hidden talents. Also, no post about lousy presidents would be complete without a mention of the Simpsons tribute to the Mediocre Presidents. February 17, 2007 Science vs. Faith, a summary It's flowchart time. This clever one contrasts the scientific method with the, um, non-scientific one. I love it when people who think they are being open-minded say things to the effect of "science and religion each have much to teach the other." Unthinking reverence for outlandish stories that make no sense? It would certainly make peer-review less painful. [via BoingBoing] February 15, 2007 The Dryyyyyy Cracker! The Matsuzaka Era has finally arrived. "I would like my first batter, if he is listening, please try and not hit the ball." That's a wit as dry as the Asahi he's pitching. February 12, 2007 ATHF plot Exclusive behind-the-scenes footage of the planning of that terrorist plot in Boston last month. February 8, 2007 Two Years Biennial of this outstanding blog. 158 posts, a bunch of nifty improvements like rotating banners and quotes, and virtually nothing of real substance. I think we all know the appropriate phrase to use here. February 7, 2007 Too legit to...slow down I've been meaning to photograph this sign for months. February 5, 2007 The Moon Rulz 28 day time lapse of Earth's satellite. [Via Backreaction from Wikipedia - Moon] Seeing the moon like this is so exciting that it just makes me want to ditch NASA's funding of actual science and send manned missions there again! February 4, 2007 To Err is human The goal of terrorism is to terrorize. I don't think I have heard a single person point this out anywhere in the news once in the past 6 years. Killing people is the strategy: you murder 100 people to scare 100 million. Then you induce an over-reaction that makes everyone think about you all the time. If you freak out at the drop of a hat and make everyone's life inconvenient you are doing their job for them. Vigilance is half of the anti-terror response, the other half is refusing to be terrorized. Only traitors try to make us afraid of terrorists. That is why last week's fiasco in Boston is so disturbing. Not merely because our crack police forces shut down the city for an hour because anything with "wires" and "batteries" is an incendiary device (I know if I was making a bomb I would try to light it up and put it in conspicuous places). Or even because as a they are now attempting to scapegoat the two loopy art-house types who planted the ads, to cover up their own incompetence and shame. But because we have now reached the point where we are flying off the handle when anyone even hints at the idea of a terrorist plot--which of course, gives terrorists exactly what they want without even lifting a finger. During last summer's thwarted, and probably overstated liquid bombing freak-out the worst thing I heard anywhere in the news was some guy they interviewed while chucking his souvenir maple syrup saying that it was "better safe than dead." Not only is this an obviously false dichotomy, it is a pathetic, surrendering attitude. You know what the right attitude towards terrorists is? That they should go fuck themselves. That we're not changing anything (other than smart security measures), or obsessing about them. I don't care "why they hate us," or how they decided that violent tactics were a justifiable method of forcing their medieval religious views on us, or what some dipshit retired CIA pion thinks their next target might be. I don't want to hear about how they have a "warped" belief system, that doesn't represent the "real" Islam. All I care about is not giving them what they want, which is for old ladies to be forced to pour out bottles of wine at airports and for everyone else to consider this "necessary." Nothing is more helpful than broadcasting our reactionary hysteria and fear to show them that they are accomplishing their objective. This might be the best thing I have read on this topic so far. Back after the 9/11 attack I remember thinking that there was something not quite right with all the weepiness on soft news programs. I couldn't put my finger on why it didn't seem quite right then, but I get it now. Obviously some sentimental stories were necessary and cathartic, but generally speaking, your assignment as a citizen after a terrorist incident is to be unshaken and unterrorized, to show the criminals that their tactics are a failue. To be defiant and unmoved. As for sensationalistic news coverage that overstates the danger and importance of these people, you get an F. This Egyptian magazine article is dead on. "Keep terrorists out of the headlines: If we can agree that the goal of terrorism is to terrorize, nothing suits the murderers’ purposes better than horrific images rehashed again and again on page one. If you work in media, be responsible." Look at how London reacted to that bus bombing, carrying on normally despite their anger. Stiff upper lip and all that. But back to the phoney incident. It just illustrates how everyone, even all this time after 9/11 isn't getting the point. Oh, and the way the media and the embarrassed Massachusetts authorities are throwing around the word "hoax?" Maybe they should look at a definition of the word, since it has to include, you know, an intent to make people think those lite-brite's were bombs. As a silver lining, it seems that the advertising worked, if not in the way it was intended too, and the whole event has produced some decent comedy. At least this incident might throw some light on the ridiculousness of this type of knee-jerk overreacton...but I'm not holding my breath. Colloquium Drawing of the Week 4 "Boston Sucks, the Moon Rules!" Part 4 of my award-winning series. Inspired by recent events. The Ottauquechee River To the left of the photo there is a sign that says "No one allowed on Dam." I don't think there is much risk of that anytime soon. February 2, 2007 Winter of my Discontent I hate Febuary more than any other time of the year. That is all. February 1, 2007 Wikipedathon Update I just wrote about a fun hobby: connecting two random wikipedia articles through other linked articles. Unsurprisingly, this must not be as new as I thought it was, as there is actually an outstanding online program that can find the shortest path for you. So friends, from now on, you are on the honor system.	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 10, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.18423137068748474, "perplexity": 3428.4023172154416}, "config": {"markdown_headings": false, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 20, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2017-34/segments/1502886107490.42/warc/CC-MAIN-20170821041654-20170821061654-00571.warc.gz"}
https://www.tampabay.com/archive/1994/10/27/hubble-finding-answers/	Our coronavirus coverage is free for the first 24 hours. Find the latest information at tampabay.com/coronavirus. Please consider subscribing or donating. 1. Archive Astronomers are closing in on two of the most elusive statistics ever _ the age and size of the universe. The Hubble Space Telescope has yielded observations that show it can establish a cosmic yardstick and determine how fast the universe is expanding, scientists say. The results also renew a long-standing paradox in which the universe appears to be younger than some of its stars. That impossibility suggests scientists will have to revise theories of the cosmos. One goal of the Hubble telescope is to make observations that would let scientists accurately measure the distances to faraway objects. The cosmic map now is like a roadmap without a distance scale; scientists know how various distances compare but don't know just what those distances are. With an accurate distance scale, scientists could determine how fast the universe is expanding. And that rate could be combined with some scientific assumptions to estimate the age of the universe. A team of scientists trained the Hubble telescope on a distant galaxy called M100. In today's issue of the journal, Nature, researchers report that the observations let them estimate with good precision that the M100 galaxy is some 56-million light-years away. A light-year is the distance light travels in one year, about 5.9-trillion miles. The finding let the scientists make a rough estimate of the rate of expansion of the universe, a long-debated number called the Hubble constant. More observations are needed to reach a more precise estimate, they said. The new estimate of the expansion rate implies that the universe is a relatively young 8-billion years old. The age becomes 12-billion years old if one assumes the universe contains far less matter than many theorists believe. Some prior age estimates have ranged up to 16-billion years, said Barry Madore, an astronomy professor at the California Institute of Technology and a member of the research team.	{"extraction_info": {"found_math": false, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.8328336477279663, "perplexity": 1180.08875727152}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2020-29/segments/1593655934052.75/warc/CC-MAIN-20200711161442-20200711191442-00040.warc.gz"}
https://bildungsportal.sachsen.de/opal/auth/RepositoryEntry/29467738129;jsessionid=5CF7B0BF8DE1C5AE1124E2573C9A0545.opalN9?0	## Introduction to Nonlocal Operators TU Dresden \| Sommersemester 2021 Introduction to Nonlocal Operators Dr. Guy F. Foghem G. and PhD David Garza Padilla (Applied Analysis Group of Prof. S. Neukamm) In this course, we will study the well-posedness of certain classes of nonlocal problems involving integrodifferential operators of Lévy type, that generalize the fractional Laplace operator. The prototype problems we will study, include IntegroDifferential Equations (IDEs) with Dirichlet type condition and/or Neumann type condition. In the area of Partial Differential Equations (PDEs), these two prototype problems are very similar to the Dirichlet and Neumann boundary problems for the Laplace operator. Classical Sobolev spaces play a decisive role in the study of weak solutions associated with the aforementioned boundary values problems and many other PDEs. However, due to the fact that integrodifferential operators are nonlocal (i.e., do not preserve the support), the corresponding Dirichlet and/or Neumann type conditions are assigned on the complement of the underlying domains. Hereby contrasting with the Dirichlet and the Neumann problems for the Laplace operator where the conditions are set on the boundary. Thus, the type of IDEs under consideration in this course underscores the need to introduce and to study some new tailored made "nonlocal Sobolev type spaces". Another objective of this lecture consists of showing that solutions to a certain class of elliptic PDEs are limits of solutions to elliptic IDEs. Prerequisites: (Will be offered in the first part of the lecture) • Basics on Sobolev spaces, • Basics on functional analysis and variational methods (e.g. Lax-Milgram). Topics: (Main part) • Characterization of (elliptic) integrodifferential operators, • Nonlocal Sobolev spaces and applications to IntegroDierential Equations (IDEs), • Convergence from nonlocal elliptic IDEs to local elliptic PDEs. Main references: The lecture will be based on the recent (open access) monograph: $$L^2$$-Theory for nonlocal operators on domains. For the prerequisites we will use Brezis' book: Haim Brezis. Functional analysis, Sobolev spaces, and partial differential equations. Springer. Science & Business Media, 2010. Target group: Master students (mathematics, physics) and PhD-students. Language: The course will be taught in English. Teaching concept: The lecture will be taught remotely via Zoom, in the synchronous format 3+1 (3 h lectures + 1h exercise). Please register on the OPAL platform where further detailed information will be posted.	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 1, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.7457426190376282, "perplexity": 1410.4281962388504}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2021-17/segments/1618038084765.46/warc/CC-MAIN-20210415095505-20210415125505-00489.warc.gz"}
http://mathhelpforum.com/calculus/35351-divergent-sequences.html	Math Help - divergent sequences 1. divergent sequences is it possible for both the summation of (x sub n) and (y sub n) to be divergent and the summation of (x sub n ysubn) be convergent? 2. Hello, One of the best examples is to take $(x_n)=\sum \frac{1}{n}$ and $(y_n)=\sum \frac{-1}{n}$ The two are known to be divergent.. Though the summation is equal to 0 and convergent.	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 2, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.9497089385986328, "perplexity": 1307.6214477700785}, "config": {"markdown_headings": false, "markdown_code": false, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 5, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2015-18/segments/1429246660493.3/warc/CC-MAIN-20150417045740-00035-ip-10-235-10-82.ec2.internal.warc.gz"}
https://www.deepdyve.com/lp/ou_press/one-bit-compressive-sensing-of-dictionary-sparse-signals-k1l3bdmQC9	# One-bit compressive sensing of dictionary-sparse signals One-bit compressive sensing of dictionary-sparse signals Abstract One-bit compressive sensing has extended the scope of sparse recovery by showing that sparse signals can be accurately reconstructed even when their linear measurements are subject to the extreme quantization scenario of binary samples—only the sign of each linear measurement is maintained. Existing results in one-bit compressive sensing rely on the assumption that the signals of interest are sparse in some fixed orthonormal basis. However, in most practical applications, signals are sparse with respect to an overcomplete dictionary, rather than a basis. There has already been a surge of activity to obtain recovery guarantees under such a generalized sparsity model in the classical compressive sensing setting. Here, we extend the one-bit framework to this important model, providing a unified theory of one-bit compressive sensing under dictionary sparsity. Specifically, we analyze several different algorithms—based on convex programming and on hard thresholding—and show that, under natural assumptions on the sensing matrix (satisfied by Gaussian matrices), these algorithms can efficiently recover analysis–dictionary-sparse signals in the one-bit model. 1. Introduction The basic insight of compressive sensing is that a small number of linear measurements can be used to reconstruct sparse signals. In traditional compressive sensing, we wish to reconstruct an $$s$$-sparse1 signal $${\bf x} \in \mathbb{R}^N$$ from linear measurements of the form $$\label{meas} {\bf y} = {\bf A}{\bf x} \in \mathbb{R}^m \qquad\text{(or its corrupted version {\bf y} = {\bf A}{\bf x} + {\bf e})},$$ (1.1) where $${\bf A}$$ is an $$m\times N$$ measurement matrix. A significant body of work over the past decade has demonstrated that the $$s$$-sparse (or nearly $$s$$-sparse) signal $${\bf x}$$ can be accurately and efficiently recovered from its measurement vector $${\bf y} = {\bf A}{\bf x}$$ when $${\bf A}$$ has independent Gaussian entries, say, and when $$m \asymp s\log(N/s)$$ [1,12,15]. This basic model has been extended in several directions. Two important ones—which we focus on in this work—are (a) extending the set of signals to include the larger and important class of dictionary- sparse signals, and (b) considering highly quantized measurements as in one-bit compressive sensing. Both of these settings have important practical applications and have received much attention in the past few years. However, to the best of our knowledge, they have not been considered together before. In this work, we extend the theory of one-bit compressive sensing to dictionary-sparse signals. Below, we briefly review the background on these notions, set up notation and outline our contributions. 1.1 One-bit measurements In practice, each entry $$y_i = \langle {\bf a}_i, {\bf x}\rangle$$ (where $${\bf a}_i$$ denotes the $$i$$th row of $${\bf A}$$) of the measurement vector in (1.1) needs to be quantized. That is, rather than observing $${\bf y}={\bf A}{\bf x}$$, one observes $${\bf y} = Q({\bf A}{\bf x})$$ instead, where $$Q: \mathbb{R}^m \rightarrow \mathscr{A}$$ denotes the quantizer that maps each entry of its input to a corresponding quantized value in an alphabet $$\mathscr{A}$$. The so-called one-bit compressive sensing [5] problem refers to the case when $$\|\mathscr{A}\| = 2$$, and one wishes to recover $${\bf x}$$ from its heavily quantized (one bit) measurements $${\bf y} = Q({\bf A}{\bf x})$$. The simplest quantizer in the one-bit case uses the alphabet $$\mathscr{A} = \{-1, 1\}$$ and acts by taking the sign of each component as $$\label{eq:quantized} y_i = Q(\langle {\bf a}_i, {\bf x}\rangle) = \mathrm{sgn}(\langle {\bf a}_i, {\bf x}\rangle),$$ (1.2) which we denote in shorthand by $${\bf y} = \mathrm{sgn}({\bf A}{\bf x})$$. Since the publication of [5] in 2008, several efficient methods, both iterative and optimization based, have been developed to recover the signal $${\bf x}$$ (up to normalization) from its one-bit measurements (see e.g. [17–19,24,25,30]). In particular, it is shown [19] that the direction of any $$s$$-sparse signal $${\bf x}$$ can be estimated by some $$\hat{{\bf x}}$$ produced from $${\bf y}$$ with accuracy $$\left\\| \frac{{\bf x}}{\\|{\bf x}\\|_2} - \frac{\hat{{\bf x}}}{\\|\hat{{\bf x}}\\|_2}\right\\|_2 \leq \varepsilon$$ when the number of measurements is at least $$m = {\it {\Omega}}\left(\frac{s \ln(N/s)}{\varepsilon} \right)\!.$$ Notice that with measurements of this form, we can only hope to recover the direction of the signal, not the magnitude. However, we can recover the entire signal if we allow for thresholded measurements of the form $$\label{eq:quantizeddither} y_i = \mathrm{sgn}(\langle {{{\bf a}_i}}, {{{\bf x}}} \rangle - \tau_i).$$ (1.3) In practice, it is often feasible to obtain quantized measurements of this form, and they have been studied before. Existing works using measurements of the form (1.3) have also allowed for adaptive thresholds; that is, the $$\tau_i$$ can be chosen adaptively based on $$y_j$$ for $$j < i$$. The goal of those works was to improve the convergence rate, i.e. the dependence on $$\varepsilon$$ in the number of measurements $$m$$. It is known that a dependence of $${\it {\Omega}}(1/\varepsilon)$$ is necessary with non-adaptive measurements, but recent work on Sigma-Delta quantization [28] and other schemes [2,20] have shown how to break this barrier using measurements of the form (1.3) with adaptive thresholds. In this article, we neither focus on the decay rate (the dependence on $$\varepsilon$$) nor do we consider adaptive measurements. However, we do consider non-adaptive measurements both of the form (1.2) and (1.3). This allows us to provide results on reconstruction of the magnitude of signals, and the direction. 1.2 Dictionary sparsity Although the classical setting assumes that the signal $${\bf x}$$ itself is sparse, most signals of interest are not immediately sparse. In the straightforward case, a signal may be instead sparse after some transform; for example, images are known to be sparse in the wavelet domain, sinusoidal signals in the Fourier domain, and so on [9]. Fortunately, the classical framework extends directly to this model, since the product of a Gaussian matrix and an orthonormal basis is still Gaussian. However, in many practical applications, the situation is not so straightforward, and the signals of interest are sparse, not in an orthonormal basis, but rather in a redundant (highly overcomplete) dictionary; this is known as dictionary sparsity. Signals in radar and sonar systems, for example, are sparsely represented in Gabor frames, which are highly overcomplete and far from orthonormal [13]. Images may be sparsely represented in curvelet frames [6,7], undecimated wavelet frames [29] and other frames, which by design are highly redundant. Such redundancy allows for sparser representations and a wider class of signal representations. Even in the Fourier domain, utilizing an oversampled DFT allows for much more realistic and practical signals to be represented. For these reasons, recent research has extended the compressive sensing framework to the setting, where the signals of interest are sparsified by overcomplete tight frames (see e.g. [8,14,16,27]). Throughout this article, we consider a dictionary $${\bf D} \in \mathbb{R}^{n \times N}$$, which is assumed to be a tight frame, in the sense that ${\bf D} {\bf D}^* = {\bf I}_n.$ To distinguish between the signal and its sparse representation, we write $${\bf f}\in\mathbb{R}^n$$ for the signal of interest and $${\bf f}={\bf D}{\bf x}$$, where $${\bf x}\in\mathbb{R}^N$$ is a sparse coefficient vector. We then acquire the samples of the form $${\bf y} = {\bf A}{\bf f} = {\bf A}{\bf D}{\bf x}$$ and attempt to recover the signal $${\bf f}$$. Note that, due to the redundancy of $${\bf D}$$, we do not hope to be able to recover a unique coefficient vector $${\bf x}$$. In other words, even when the measurement matrix $${\bf A}$$ is well suited for sparse recovery, the product $${\bf A}{\bf D}$$ may have highly correlated columns, making recovery of $${\bf x}$$ impossible. With the introduction of a non-invertible sparsifying transform $${\bf D}$$, it becomes important to distinguish between two related but distinct notions of sparsity. Precisely, we say that $${\bf f}$$ is $$s$$-synthesis sparse if $${\bf f} = {\bf D} {\bf x}$$ for some $$s$$-sparse $${\bf x} \in \mathbb{R}^N$$; $${\bf f}$$ is $$s$$-analysis sparse if $${\bf D}^* {\bf f} \in \mathbb{R}^N$$ is $$s$$-sparse. We note that analysis sparsity is a stronger assumption, because, assuming analysis sparsity, one can always take $${\bf x} = {\bf D}^* {\bf f}$$ in the synthesis sparsity model. See [11] for an introduction to the analysis-sparse model in compressive sensing (also called the analysis cosparse model). Instead of exact sparsity, it is often more realistic to study effective sparsity. We call a coefficient vector $${\bf x} \in \mathbb{R}^N$$ effectively $$s$$-sparse if $$\\|{\bf x}\\|_1 \le \sqrt{s} \\|{\bf x}\\|_2,$$ and we say that $${\bf f}$$ is effectively $$s$$-synthesis sparse if $${\bf f} = {\bf D} {\bf x}$$ for some effectively $$s$$-sparse $${\bf x} \in \mathbb{R}^N$$; $${\bf f}$$ is effectively $$s$$-analysis sparse if $${\bf D}^* {\bf f} \in \mathbb{R}^N$$ is effectively $$s$$-sparse. We use the notation \begin{align} {\it {\Sigma}}^N_s & \mbox{for the set of $s$-sparse coefficient vectors in $\mathbb{R}^N$, and} \\ {\it {\Sigma}}_s^{N,{\rm eff}} & \mbox{for the set of effectively $s$-sparse coefficient vectors in $\mathbb{R}^N$.} \end{align} We also use the notation $$B_2^n$$ for the set of signals with $$\ell_2$$-norm at most $$1$$ (i.e. the unit ball in $$\ell_2^n$$) and $$S^{n-1}$$ for the set of signals with $$\ell_2$$-norm equal to $$1$$ (i.e. the unit sphere in $$\ell_2^n$$). It is now well known that, if $${\bf D}$$ is a tight frame and $${\bf A}$$ satisfies analogous conditions to those in the classical setting (e.g. has independent Gaussian entries), then a signal $${\bf f}$$ which is (effectively) analysis- or synthesis sparse can be accurately recovered from traditional compressive sensing measurements $${\bf y} = {\bf A} {\bf f} = {\bf A}{\bf D}{\bf x}$$ (see e.g. [4,8,10,14,16,22,23,27]). 1.3 One-bit measurements with dictionaries: our setup In this article, we study one-bit compressive sensing for dictionary-sparse signals. Precisely, our aim is to recover signals $${\bf f} \in \mathbb{R}^n$$ from the binary measurements $$y_i = \mathrm{sgn} \langle {\bf a}_i, {\bf f} \rangle \qquad i=1,\ldots,m,$$ or $$y_i = \mathrm{sgn} \left(\langle {\bf a}_i, {\bf f} \rangle - \tau_i \right) \qquad i = 1,\ldots,m,$$ when these signals are sparse with respect to a dictionary $${\bf D}$$. As in Section 1.2, there are several ways to model signals that are sparse with respect to $${\bf D}$$. In this work, two different signal classes are considered. For the first one, which is more general, our results are based on convex programming. For the second one, which is more restrictive, we can obtain results using a computationally simpler algorithm based on hard thresholding. The first class consists of signals $${\bf f} \in ({\bf D}^)^{-1} {\it {\Sigma}}_s^{N,\rm{eff}}$$ that are effectively $$s$$-analysis sparse, i.e. they satisfy $$\label{Assumption} \\|{\bf D}^ {\bf f}\\|_1 \le \sqrt{s} \\|{\bf D}^* {\bf f}\\|_2.$$ (1.4) This occurs, of course, when $${\bf D}^* {\bf f}$$ is genuinely sparse (analysis sparsity) and this is realistic if we are working, e.g. with piecewise-constant images, since they are sparse after application of the total variation operator. We consider effectively sparse signals since genuine analysis sparsity is unrealistic when $${\bf D}$$ has columns in general position, as it would imply that $${\bf f}$$ is orthogonal to too many columns of $${\bf D}$$. The second class consists of signals $${\bf f} \in {\bf D}({\it {\Sigma}}_s^N) \cap ({\bf D}^)^{-1} {\it {\Sigma}}_{\kappa s}^{N, \rm{eff}}$$ that are both $$s$$-synthesis sparse and $$\kappa s$$-analysis sparse for some $$\kappa \ge 1$$. This will occur as soon as the signals are $$s$$-synthesis sparse, provided we utilize suitable dictionaries $${\bf D} \in \mathbb{R}^{n \times N}$$. One could take, for instance, the matrix of an equiangular tight frame when $$N = n + k$$, $$k = {\rm constant}$$. Other examples of suitable dictionaries found in [21] include harmonic frames again with $$N = n + k$$, $$k = {\rm constant}$$, as well as Fourier and Haar frames with constant redundancy factor $$N/n$$. Figure 1 summarizes the relationship between the various domains we deal with. Fig. 1 View largeDownload slide The coefficient, signal and measurement domains. Fig. 1 View largeDownload slide The coefficient, signal and measurement domains. 1.4 Contributions Our main results demonstrate that one-bit compressive sensing is viable even when the sparsifying transform is an overcomplete dictionary. As outlined in Section 1.1, we consider both the challenge of recovering the direction $${\bf f}/\\|{\bf f}\\|_2$$ of a signal $${\bf f}$$, and the challenge of recovering the entire signal (direction and magnitude). Using measurements of the form $$y_i = \mathrm{sgn}\langle {\bf a}_i, {\bf f} \rangle$$, we can recover the direction but not the magnitude; using measurements of the form $$y_i = \mathrm{sgn}\left(\langle {\bf a}_i, {\bf f} \rangle - \tau_i \right)$$, we may recover both. In (one-bit) compressive sensing, two standard families of algorithms are (a) algorithms based on convex programming, and (b) algorithms based on thresholding. In this article, we analyze algorithms from both classes. One reason to study multiple algorithms is to give a more complete landscape of this problem. Another reason is that the different algorithms come with different trade-offs (between computational complexity and the strength of assumptions required), and it is valuable to explore this space of trade-offs. 1.4.1 Recovering the direction First, we show that the direction of a dictionary-sparse signal can be estimated from one-bit measurements of the type $$\mathrm{sgn}({\bf A} {\bf f})$$. We consider two algorithms: our first approach is based on linear programming, and our second is based on hard thresholding. The linear programming approach is more computationally demanding, but applies to a broader class of signals. In Section 3, we prove that both of these approaches are effective, provided the sensing matrix $${\bf A}$$ satisfies certain properties. In Section 2, we state that these properties are in fact satisfied by a matrix $${\bf A}$$ populated with independent Gaussian entries. We combine all of these results to prove the statement below. As noted above, the different algorithms require different definitions of ‘dictionary sparsity’. In what follows, $$\gamma, C, c$$ refer to absolute numerical constants. Theorem 1 (Informal statement of direction recovery) Let $$\varepsilon \,{>}\, 0$$, let $$m \,{\ge}\, C \varepsilon^{-7} s \ln(eN/s)$$ and let $${\bf A} \in \mathbb{R}^{m \times n}$$ be populated by independent standard normal random variables. Then, with failure probability at most $$\gamma \exp(-c \varepsilon^2 m)$$, any dictionary-sparse2 signal $${\bf f} \in \mathbb{R}^n$$ observed via $${\bf y} = \mathrm{sgn}({\bf A} {\bf f})$$ can be approximated by the output $$\widehat{{\bf f}}$$ of an efficient algorithm with error $$\left\\| \frac{{\bf f}}{\\|{\bf f}\\|_2} - \frac{\widehat{{\bf f}}}{\\|\widehat{{\bf f}}\\|_2} \right\\|_2 \le \varepsilon.$$ 1.4.2 Recovering the whole signal By using one-bit measurements of the form $$\mathrm{sgn}({\bf A} {\bf f} - \boldsymbol{\tau})$$, where $$\tau_1,\ldots,\tau_m$$ are properly normalized Gaussian random thresholds, we are able to recover not just the direction, but also the magnitude of a dictionary-sparse signal $${\bf f}$$. We consider three algorithms: our first approach is based on linear programming, our second approach on second-order cone programming and our third approach on hard thresholding. Again, there are different trade-offs to the different algorithms. As above, the approach based on hard thresholding is more efficient, whereas the approaches based on convex programming apply to a broader signal class. There is also a trade-off between linear programming and second-order cone programming: the second-order cone program requires knowledge of $$\\|{\bf f}\\|_2,$$ whereas the linear program does not (although it does require a loose bound), but the second-order cone programming approach applies to a slightly larger class of signals. We show in Section 4 that all three of these algorithms are effective when the sensing matrix $${\bf A}$$ is populated with independent Gaussian entries, and when the thresholds $$\tau_i$$ are also independent Gaussian random variables. We combine the results of Section 4 in the following theorem. Theorem 2 (Informal statement of signal estimation) Let $$\varepsilon, r, \sigma > 0$$, let $$m \ge C \varepsilon^{-9} s \ln(eN/s)$$, and let $${\bf A} \in \mathbb{R}^{m \times n}$$ and $$\boldsymbol{\tau} \in \mathbb{R}^m$$ be populated by independent mean-zero normal random variables with variance $$1$$ and $$\sigma^2$$, respectively. Then, with failure probability at most $$\gamma \exp(-c \varepsilon^2 m)$$, any dictionary-sparse$$^2$$ signal $${\bf f} \in \mathbb{R}^n$$ with $$\\|{\bf f}\\|_2 \le r$$ observed via $${\bf y} = \mathrm{sgn}({\bf A} {\bf f} - \boldsymbol{\tau})$$ is approximated by the output $$\widehat{{\bf f}}$$ of an efficient algorithm with error $$\left\\| {\bf f} - \widehat{{\bf f}} \right\\|_2 \le \varepsilon r.$$ We have not spelled out the dependence of the number of measurements and the failure probability on the parameters $$r$$ and $$\sigma$$: as long as they are roughly the same order of magnitude, the dependence is absorbed in the constants $$C$$ and $$c$$ (see Section 4 for precise statements). As outlined earlier, an estimate of $$r$$ is required to implement the second-order cone program, but the other two algorithms do not require such an estimate. 1.5 Discussion and future directions The purpose of this work is to demonstrate that techniques from one-bit compressive sensing can be effective for the recovery of dictionary-sparse signals, and we propose several algorithms to accomplish this for various notions of dictionary sparsity. Still, some interesting future directions remain. First, we do not believe that the dependence on $$\varepsilon$$ above is optimal. We do believe instead that a logarithmic dependence on $$\varepsilon$$ for the number of measurements (or equivalently an exponential decay in the oversampling factor $$\lambda = m / (s \ln(eN/s))$$ for the recovery error) is possible by choosing the thresholds $$\tau_1,\ldots,\tau_m$$ adaptively. This would be achieved by adjusting the method of [2], but with the strong proviso of exact sparsity. Secondly, it is worth asking to what extent the trade-offs between the different algorithms reflect reality. In particular, is it only an artifact of the proof that the simpler algorithm based on hard thresholding applies to a narrower class of signals? 1.6 Organization The remainder of the article is organized as follows. In Section 2, we outline some technical tools upon which our results rely, namely some properties of Gaussian random matrices. In Section 3, we consider recovery of the direction $${\bf f}/\\|{\bf f}\\|$$ only and we propose two algorithms to achieve it. In Section 4, we present three algorithms for the recovery of the entire signal $${\bf f}$$. Finally, in Section 5, we provide proofs for the results outlined in Section 2. 2. Technical ingredients In this section, we highlight the theoretical properties upon which our results rely. Their proofs are deferred to Section 5 so that the reader does not lose track of our objectives. The first property we put forward is an adaptation to the dictionary case of the so-called sign product embedding property (the term was coined in [18], but the result originally appeared in [25]). Theorem 3 ($${\bf D}$$-SPEP) Let $$\delta > 0$$, let $$m \ge C \delta^{-7} s \ln(eN/s)$$ and let $${\bf A} \in \mathbb{R}^{m \times n}$$ be populated by independent standard normal random variables. Then, with failure probability at most $$\gamma \exp(-c \delta^2 m)$$, the renormalized matrix $${\bf A}':= (\sqrt{2/\pi}/m) {\bf A}$$ satisfies the $$s$$th-order sign product embedding property adapted to $${\bf D} \in \mathbb{R}^{n \times N}$$ with constant $$\delta$$ — $${\bf D}$$-SPEP$$(s,\delta)$$ for short—i.e. $$\label{SPEP} \left\| \langle {\bf A}' {\bf f}, \mathrm{sgn}({\bf A}' {\bf g}) \rangle - \langle {\bf f}, {\bf g} \rangle \right\| \le \delta$$ (2.1) holds for all $${\bf f}, {\bf g} \in {\bf D}({\it {\Sigma}}^N_s) \cap S^{n-1}$$. Remark 1 The power $$\delta^{-7}$$ is unlikely to be optimal. At least in the non-dictionary case, i.e. when $${\bf D} = {\bf I}_n$$, it can be reduced to $$\delta^{-2}$$, see [3]. As an immediate consequence of $${\bf D}$$-SPEP, setting $${\bf g} = {\bf f}$$ in (2.1) allows one to deduce a variation of the classical restricted isometry property adapted to $${\bf D}$$, where the inner norm becomes the $$\ell_1$$-norm (we mention in passing that this variation could also be deduced by other means). Corollary 1 ($${\bf D}$$-RIP$$_1$$) Let $$\delta \,{>}\, 0$$, let $$m \,{\ge}\, C \delta^{-7} s \,{\ln}\,(eN/s)$$ and let $${\bf A} \in \mathbb{R}^{m \times n}$$ be populated by independent standard normal random variables. Then, with failure probability at most $$\gamma \exp(-c \delta^2 m)$$, the renormalized matrix $${\bf A}':= (\sqrt{2/\pi}/m) {\bf A}$$ satisfies the $$s$$th-order $$\ell_1$$-restricted isometry property adapted to $${\bf D} \in \mathbb{R}^{n \times N}$$ with constant $$\delta$$ — $${\bf D}$$-RIP$$_{1}(s,\delta)$$ for short—i.e. $$(1-\delta) \\| {\bf f}\\|_2 \le \\| {\bf A}' {\bf f} \\|_1 \le (1+\delta) \\|{\bf f}\\|_2$$ (2.2) holds for all $${\bf f} \in {\bf D}({\it {\Sigma}}_s^N)$$. The next property we put forward is an adaptation of the tessellation of the ‘effectively sparse sphere’ (see [26]) to the dictionary case. In what follows, given a (non-invertible) matrix $${\bf M}$$ and a set $$K$$, we denote by $${\bf M}^{-1} (K)$$ the preimage of $$K$$ with respect to $${\bf M}$$. Theorem 4 (Tessellation) Let $$\varepsilon > 0$$, let $$m \ge C \varepsilon^{-6} s \ln(eN/s)$$ and let $${\bf A} \in \mathbb{R}^{m \times n}$$ be populated by independent standard normal random variables. Then, with failure probability at most $$\gamma \exp(-c \varepsilon^2 m)$$, the rows $${\bf a}_1,\ldots,{\bf a}_m \in \mathbb{R}^n$$ of $${\bf A}$$$$\varepsilon$$-tessellate the effectively $$s$$-analysis-sparse sphere—we write that $${\bf A}$$ satisfies $${\bf D}$$-TES$$(s,\varepsilon)$$ for short—i.e. $$\label{Tes} [{\bf f},{\bf g} \in ({\bf D}^)^{-1}({\it {\Sigma}}_{s}^{N,{\rm eff}}) \cap S^{n-1} : \; \mathrm{sgn} \langle {\bf a}_i, {\bf f} \rangle = \mathrm{sgn} \langle {\bf a}_i, {\bf g} \rangle \mbox{for all} i =1,\ldots,m] \Longrightarrow [\\|{\bf f} - {\bf g}\\|_2 \le \varepsilon].$$ (2.3) 3. Signal estimation: direction only In this whole section, given a measurement matrix $${\bf A} \in \mathbb{R}^{m \times n}$$ with rows $${\bf a}_1,\ldots,{\bf a}_m \in \mathbb{R}^n$$, the signals $${\bf f} \in \mathbb{R}^n$$ are acquired via $${\bf y} = \mathrm{sgn}({\bf A} {\bf f}) \in \{-1,+1\}^m$$, i.e. $$y_i = \mathrm{sgn} \langle {\bf a}_i, {\bf f} \rangle \qquad i = 1,\ldots,m.$$ Under this model, all $$c {\bf f}$$ with $$c>0$$ produce the same one-bit measurements, so one can only hope to recover the direction of $${\bf f}$$. We present two methods to do so, one based on linear programming and the other one based on hard thresholding. 3.1 Linear programming Given a signal $${\bf f} \in \mathbb{R}^n$$ observed via $${\bf y} = \mathrm{sgn} ({\bf A} {\bf f})$$, the optimization scheme we consider here consists in outputting the signal $${\bf f}_{\rm lp}$$ solution of $$\label{LPforDir} \underset{{{\bf h} \in \mathbb{R}^n}}{\rm minimize}\, \\| {\bf D}^* {\bf h}\\|_1 \qquad \mbox{subject to} \quad \mathrm{sgn}({\bf A} {\bf h}) = {\bf y} \quad \\|{\bf A} {\bf h}\\|_1 = 1.$$ (3.1) This is in fact a linear program (and thus may be solved efficiently), since the condition $$\mathrm{sgn}({\bf A} {\bf h}) = {\bf y}$$ reads $$y_i ({\bf A} {\bf h})_i \ge 0 \qquad \mbox{for all} i = 1,\ldots, m,$$ and, under this constraint, the condition $$\\|{\bf A} {\bf h}\\|_1 = 1$$ reads $$\sum_{i=1}^m y_i ({\bf A} {\bf h})_i = 1.$$ Theorem 5 If $${\bf A} \,{\in}\, \mathbb{R}^{m \times n}$$ satisfies both $${\bf D}$$-TES$$(36s,\varepsilon)$$ and $${\bf D}$$-RIP$$_1(25s,1/5)$$, then any effectively $$s$$-analysis-sparse signal $${\bf f} \in ({\bf D}^)^{-1}{\it {\Sigma}}_s^{N,{\rm eff}}$$ observed via $${\bf y} = \mathrm{sgn}({\bf A} {\bf f})$$ is directionally approximated by the output $${\bf f}_{\rm lp}$$ of the linear program (3.1) with error $$\left\\| \frac{{\bf f}}{\\|{\bf f}\\|_2} - \frac{{\bf f}_{\rm lp}}{\\|{\bf f}_{\rm lp}\\|_2} \right\\|_2 \le \varepsilon.$$ Proof. The main step is to show that $${\bf f}_{\rm lp}$$ is effectively $$36s$$-analysis sparse when $${\bf D}$$-RIP$$_1(t,\delta)$$ holds with $$t= 25s$$ and $$\delta=1/5$$. Then, since both $${\bf f}/\\|{\bf f}\\|_2$$ and $${\bf f}_{\rm lp} / \\|{\bf f}_{\rm lp}\\|_2$$ belong to $$({\bf D}^)^{-1}{\it {\Sigma}}_{36 s}^{N,{\rm eff}} \cap S^{n-1}$$ and have the same sign observations, $${\bf D}$$-TES$$(36s,\varepsilon)$$ implies the desired conclusion. To prove the effective analysis sparsity of $${\bf f}_{\rm lp}$$, we first estimate $$\\|{\bf A} {\bf f}\\|_1$$ from below. For this purpose, let $$T_0$$ denote an index set of $$t$$ largest absolute entries of $${\bf D}^* {\bf f}$$, $$T_1$$ an index set of next $$t$$ largest absolute entries of $${\bf D}^* {\bf f}$$, $$T_2$$ an index set of next $$t$$ largest absolute entries of $${\bf D}^* {\bf f}$$, etc. We have \begin{align} \\|{\bf A} {\bf f} \\|_1 & = \\|{\bf A} {\bf D} {\bf D}^ {\bf f}\\|_1 = \left\\| {\bf A} {\bf D} \left(\sum_{k \ge 0} ({\bf D}^{\bf f})_{T_k} \right) \right\\|_1 \ge \\|{\bf A} {\bf D} \left(({\bf D}^ {\bf f})_{T_0} \right)\!\\|_1 - \sum_{k \ge 1} \\|{\bf A} {\bf D} \left(({\bf D}^* {\bf f})_{T_k} \right)\!\\|_1\\ & \ge (1-\delta) \\|{\bf D} \left(({\bf D}^* {\bf f})_{T_0} \right)\!\\|_2 - \sum_{k \ge 1} (1+\delta) \\|{\bf D} \left(({\bf D}^* {\bf f})_{T_k} \right)\!\\|_2, \end{align} where the last step used $${\bf D}$$-RIP$$_1(t,\delta)$$. We notice that, for $$k \ge 1$$, $$\\|{\bf D} \left(({\bf D}^ {\bf f})_{T_k} \right)\!\\|_2 \le \\| ({\bf D}^* {\bf f})_{T_k}\! \\|_2 \le \frac{1}{\sqrt{t}} \\| ({\bf D}^* {\bf f})_{T_{k-1}}\!\\|_1,$$ from where it follows that $$\label{LowerAf} \\|{\bf A} {\bf f}\\|_1 \ge (1-\delta) \\|{\bf D} \left(({\bf D}^* {\bf f})_{T_0}\right)\!\\|_2 - \frac{1+\delta}{\sqrt{t}} \\|{\bf D}^* {\bf f} \\|_1.$$ (3.2) In addition, we observe that \begin{align} \\|{\bf D}^ {\bf f} \\|_2 & = \\|{\bf f}\\|_2 = \\|{\bf D} {\bf D}^* {\bf f}\\|_2 = \left\\| {\bf D} \left(\sum_{k \ge 0} ({\bf D}^* {\bf f})_{T_k} \right) \right\\|_2 \le \left\\| {\bf D} \left(({\bf D}^* {\bf f})_{T_0} \right) \right\\|_2 + \sum_{k \ge 1} \left\\| {\bf D} \left(({\bf D}^* {\bf f})_{T_k} \right) \right\\|_2\\ & \le \left\\| {\bf D} \left(({\bf D}^* {\bf f})_{T_0} \right) \right\\|_2 + \frac{1}{\sqrt{t}} \\|{\bf D}^* {\bf f} \\|_1. \end{align} In view of the effective sparsity of $${\bf D}^ {\bf f}$$, we obtain $$\\|{\bf D}^* {\bf f}\\|_1 \le \sqrt{s} \\|{\bf D}^* {\bf f}\\|_2 \le \sqrt{s}\left\\| {\bf D} \left(({\bf D}^* {\bf f})_{T_0} \right) \right\\|_2 + \sqrt{s/t} \\|{\bf D}^* {\bf f} \\|_1,$$ hence $$\label{LowerDDT0} \left\\| {\bf D} \left(({\bf D}^ {\bf f})_{T_0} \right) \right\\|_2 \ge \frac{1- \sqrt{s/t}}{\sqrt{s}} \\|{\bf D}^* {\bf f} \\|_1.$$ (3.3) Substituting (3.3) in (3.2) yields $$\label{LowerAf2} \\|{\bf A} {\bf f}\\|_1 \ge \left((1-\delta)(1-\sqrt{s/t}) - (1+\delta)(\sqrt{s/t}) \right) \frac{1}{\sqrt{s}} \\|{\bf D}^* {\bf f}\\|_1 = \frac{2/5}{\sqrt{s}} \\|{\bf D}^* {\bf f}\\|_1,$$ (3.4) where we have used the values $$t = 25s$$ and $$\delta=1/5$$. This lower estimate for $$\\|{\bf A} {\bf f} \\|_1$$, combined with the minimality property of $${\bf f}_{\rm lp}$$, allows us to derive that $$\label{UpperDfhat} \\|{\bf D}^ {\bf f}_{\rm lp} \\|_1 \le \\|{\bf D}^({\bf f}/ \\|{\bf A} {\bf f}\\|_1)\\|_1 = \frac{\\|{\bf D}^ {\bf f}\\|_1}{\\|{\bf A} {\bf f} \\|_1} \le (5/2) \sqrt{s}.$$ (3.5) Next, with $$\widehat{T}_0$$ denoting an index set of $$t$$ largest absolute entries of $${\bf D}^* {\bf f}_{\rm lp}$$, $$\widehat{T}_1$$ an index set of next $$t$$ largest absolute entries of $${\bf D}^* {\bf f}_{\rm lp}$$, $$\widehat{T}_2$$ an index set of next $$t$$ largest absolute entries of $${\bf D}^* {\bf f}_{\rm lp}$$, etc., we can write \begin{align} 1 & = \\|{\bf A} {\bf f}_{\rm lp} \\|_1 = \\|{\bf A} {\bf D} {\bf D}^ {\bf f}_{\rm lp} \\|_1 = \left\\| {\bf A} {\bf D} \left(\sum_{k \ge 0} ({\bf D}^* {\bf f}_{\rm lp})_{\widehat{T}_k} \right) \right\\|_1 \le \sum_{k \ge 0} \left\\| {\bf A} {\bf D} \left(({\bf D}^* {\bf f}_{\rm lp})_{\widehat{T}_k} \right) \right\\|_1\\ & \le \sum_{k \ge 0} (1+\delta) \left\\| {\bf D} \left(({\bf D}^* {\bf f}_{\rm lp})_{\widehat{T}_k} \right) \right\\|_2 = (1+\delta) \left[\!\left\\| ({\bf D}^* {\bf f}_{\rm lp})_{\widehat{T}_0} \right\\|_2 + \sum_{k \ge 1} \!\left\\| ({\bf D}^* {\bf f}_{\rm lp})_{\widehat{T}_k} \right\\|_2 \right]\\ & \le (1+\delta) \left[\\|{\bf D}^* {\bf f}_{\rm lp} \\|_2 + \frac{1}{\sqrt{t}} \\|{\bf D}^* {\bf f}_{\rm lp}\\|_1 \right] \le (1+\delta) \left[\\|{\bf D}^* {\bf f}_{\rm lp} \\|_2 + (5/2)\sqrt{s/t} \right]. \end{align} This chain of inequalities shows that $$\label{LowerDfhat} \\|{\bf D}^* {\bf f}_{\rm lp} \\|_2 \ge \frac{1-(5/2)\sqrt{s/t}}{1+\delta} = \frac{5}{12}.$$ (3.6) Combining (3.5) and (3.6), we obtain $$\\|{\bf D}^* {\bf f}_{\rm lp} \\|_1 \le 6 \sqrt{s} \\|{\bf D}^* {\bf f}_{\rm lp} \\|_2.$$ In other words, $${\bf D}^* {\bf f}_{\rm lp}$$ is effectively $$36s$$-sparse, which is what was needed to conclude the proof. □ Remark 2 We point out that if $${\bf f}$$ was genuinely, instead of effectively, $$s$$-analysis sparse, then a lower bound of the type (3.4) would be immediate from the $${\bf D}$$-RIP$$_1$$. We also point out that our method of proving that the linear program outputs an effectively analysis-sparse signal is new even in the case $${\bf D} = {\bf I}_n$$. In fact, it makes it possible to remove a logarithmic factor from the number of measurements in this ‘non-dictionary’ case, too (compare with [24]). Furthermore, it allows for an analysis of the linear program (3.1) only based on deterministic conditions that the matrix $${\bf A}$$ may satisfy. 3.2 Hard thresholding Given a signal $${\bf f} \in \mathbb{R}^n$$ observed via $${\bf y} = \mathrm{sgn} ({\bf A} {\bf f})$$, the hard thresholding scheme we consider here consists in constructing a signal $${\bf f}_{\rm ht} \in \mathbb{R}^n$$ as $$\label{HTforDir} {\bf f}_{\rm ht} = {\bf D} {\bf z}, \qquad \mbox{where} {\bf z} := H_t({\bf D}^* {\bf A}^* {\bf y}).$$ (3.7) Our recovery result holds for $$s$$-synthesis-sparse signals that are also effectively $$\kappa s$$-analysis sparse for some $$\kappa \ge 1$$ (we discussed in Section 1 some choices of dictionaries $${\bf D}$$ making this happen). Theorem 6 If $${\bf A} \in \mathbb{R}^{m \times n}$$ satisfies $${\bf D}$$-SPEP$$(s+t,\varepsilon/8)$$, $$t = \lceil 16 \varepsilon^{-2} \kappa s \rceil$$, then any $$s$$-synthesis-sparse signal $${\bf f} \in {\bf D}({\it {\Sigma}}_s^N)$$ with $${\bf D}^* {\bf f} \in {\it {\Sigma}}_{\kappa s}^{N,{\rm eff}}$$ observed via $${\bf y} = \mathrm{sgn} ({\bf A} {\bf f})$$ is directionally approximated by the output $${\bf f}_{\rm ht}$$ of the hard thresholding (3.7) with error $$\left\\| \frac{{\bf f}}{\\|{\bf f}\\|_2} - \frac{{\bf f}_{\rm ht}}{\\|{\bf f}_{\rm ht}\\|_2} \right\\|_2 \le \varepsilon.$$ Proof. We assume without loss of generality that $$\\|{\bf f}\\|_2 = 1$$. Let $$T=T_0$$ denote an index set of $$t$$ largest absolute entries of $${\bf D}^* {\bf f}$$, $$T_1$$ an index set of next $$t$$ largest absolute entries of $${\bf D}^* {\bf f}$$, $$T_2$$ an index set of next $$t$$ largest absolute entries of $${\bf D}^* {\bf f}$$, etc. We start by noticing that $${\bf z}$$ is a better $$t$$-sparse approximation to $${\bf D}^* {\bf A}^* {\bf y} = {\bf D}^* {\bf A}^* \mathrm{sgn}({\bf A} {\bf f})$$ than $$[{\bf D}^* {\bf f}]_T$$, so we can write $$\\| {\bf D}^* {\bf A}^* \mathrm{sgn}({\bf A} {\bf f}) - {\bf z} \\|_2^2 \le \\|{\bf D}^* {\bf A}^* \mathrm{sgn}({\bf A} {\bf f}) - [{\bf D}^* {\bf f}]_T \\|_2^2,$$ i.e. $$\\| ({\bf D}^* {\bf f} - {\bf z}) - ({\bf D}^* {\bf f} - {\bf D}^* {\bf A}^* \mathrm{sgn}({\bf A} {\bf f})) \\|_2^2 \le \\| ({\bf D}^* {\bf f} - {\bf D}^* {\bf A}^* \mathrm{sgn}({\bf A} {\bf f})) - [{\bf D}^* {\bf f}]_{\overline{T}} \\|_2^2.$$ Expanding the squares and rearranging gives \begin{align} \label{Term1} \\|{\bf D}^* {\bf f} - {\bf z} \\|_2^2 & \le 2 \langle {\bf D}^* {\bf f} - {\bf z}, {\bf D}^* {\bf f} - {\bf D}^* {\bf A}^* \mathrm{sgn}({\bf A} {\bf f}) \rangle \\ \end{align} (3.8) \begin{align} \label{Term2} & - 2 \langle [{\bf D}^* {\bf f}]_{\overline{T}} , {\bf D}^* {\bf f} - {\bf D}^* {\bf A}^* \mathrm{sgn}({\bf A} {\bf f}) \rangle \\ \end{align} (3.9) \begin{align} \label{Term3} & + \\| [{\bf D}^* {\bf f}]_{\overline{T}} \\|_2^2. \end{align} (3.10) To bound (3.10), we invoke [15, Theorem 2.5] and the effective analysis sparsity of $${\bf f}$$ to derive $$\\| [{\bf D}^* {\bf f}]_{\overline{T}} \\|_2^2 \le \frac{1}{4t} \\| {\bf D}^* {\bf f} \\|_1^2 \le \frac{\kappa s}{4t} \\| {\bf D}^* {\bf f} \\|_2^2 = \frac{\kappa s}{4t} \\|{\bf f} \\|_2^2 = \frac{\kappa s}{4t}.$$ To bound (3.8) in absolute value, we notice that it can be written as \begin{align} 2 \| \langle {\bf D} {\bf D}^ {\bf f} - {\bf D} {\bf z}, &{\bf f} - {\bf A}^* \mathrm{sgn}({\bf A} {\bf f}) \rangle \| = 2 \| \langle {\bf f} - {\bf f}_{\rm ht}, {\bf f} - {\bf A}^* \mathrm{sgn}({\bf A} {\bf f}) \rangle \| \\ & = 2 \| \langle {\bf f} - {\bf f}_{\rm ht}, {\bf f} \rangle - \langle {\bf A} ({\bf f} - {\bf f}_{\rm ht}), \mathrm{sgn}({\bf A} {\bf f}) \rangle \| \le 2 \varepsilon' \\|{\bf f} - {\bf f}_{\rm ht} \\|_2, \end{align} where the last step followed from $${\bf D}$$-SPEP$$(s+t,\varepsilon')$$, $$\varepsilon' := \varepsilon /8$$. Finally, (3.9) can be bounded in absolute value by \begin{align} 2 & \sum_{k \ge 1} \| \langle [{\bf D}^* {\bf f}]_{T_k}, {\bf D}^({\bf f} - {\bf A}^ \mathrm{sgn}({\bf A} {\bf f})) \rangle \| = 2 \sum_{k \ge 1} \| \langle {\bf D}([{\bf D}^* {\bf f}]_{T_k}), {\bf f} - {\bf A}^* \mathrm{sgn}({\bf A} {\bf f}) \rangle \| \\ & = 2 \sum_{k \ge 1} \| \langle {\bf D}([{\bf D}^* {\bf f}]_{T_k}), {\bf f} \rangle - \langle {\bf A} ({\bf D}([{\bf D}^* {\bf f}]_{T_k})), \mathrm{sgn}({\bf A} {\bf f}) \rangle \| \le 2 \sum_{k \ge 1} \varepsilon' \\| {\bf D}([{\bf D}^* {\bf f}]_{T_k}) \\|_2\\ & \le 2 \varepsilon' \sum_{k \ge 1} \\| [{\bf D}^* {\bf f}]_{T_k} \\|_2 \le 2 \varepsilon' \sum_{k \ge 1} \frac{\\| [{\bf D}^* {\bf f}]_{T_{k-1}} \\|_1}{\sqrt{t}} \le 2 \varepsilon' \frac{\\|{\bf D}^* {\bf f}\\|_1}{\sqrt{t}} \le 2 \varepsilon' \frac{\sqrt{\kappa s} \\|{\bf D}^* {\bf f}\\|_2}{\sqrt{t}} = 2 \varepsilon' \sqrt{\frac{\kappa s}{t}}. \end{align} Putting everything together, we obtain $$\\|{\bf D}^ {\bf f} - {\bf z} \\|_2^2 \le 2 \varepsilon' \\|{\bf f} - {\bf f}_{\rm ht}\\|_2 + 2 \varepsilon' \sqrt{\frac{\kappa s}{t}} + \frac{\kappa s}{4t}.$$ In view of $$\\|{\bf f} - {\bf f}_{\rm ht}\\|_2 = \\|{\bf D} ({\bf D}^* {\bf f} - {\bf z}) \\|_2 \le \\|{\bf D}^* {\bf f} - {\bf z}\\|_2$$, it follows that $$\\|{\bf f} - {\bf f}_{\rm ht}\\|_2^2 \le 2 \varepsilon' \\|{\bf f} - {\bf f}_{\rm ht}\\|_2 + 2 \varepsilon' \sqrt{\frac{\kappa s}{t}} + \frac{\kappa s}{4t}, \quad \mbox{i.e.} \; (\\|{\bf f} - {\bf f}_{\rm ht}\\|_2 - \varepsilon')^2 \le {\varepsilon'}^2 + 2 \varepsilon' \sqrt{\frac{\kappa s}{t}} + \frac{\kappa s}{4t} \le \left(\varepsilon' \hspace{-0.5mm}+\hspace{-0.5mm} \sqrt{\frac{\kappa s}{t}} \right)^2 \hspace{-1mm}.$$ This implies that $$\\|{\bf f} - {\bf f}_{\rm ht}\\|_2 \le 2 \varepsilon' + \sqrt{\frac{\kappa s}{t}}.$$ Finally, since $${\bf f}_{\rm ht}/\\|{\bf f}_{\rm ht}\\|_2$$ is the best $$\ell_2$$-normalized approximation to $${\bf f}_{\rm ht}$$, we conclude that $$\left\\| {\bf f} - \frac{{\bf f}_{\rm ht}}{\\|{\bf f}_{\rm ht}\\|_2} \right\\|_2 \le \\|{\bf f} - {\bf f}_{\rm ht}\\|_2 + \left\\| {\bf f}_{\rm ht} - \frac{{\bf f}_{\rm ht}}{\\|{\bf f}_{\rm ht}\\|_2} \right\\|_2 \le 2 \\|{\bf f} - {\bf f}_{\rm ht}\\|_2 \le 4 \varepsilon' + 2 \sqrt{\frac{\kappa s}{t}}.$$ The announced result follows from our choices of $$t$$ and $$\varepsilon'$$. □ 4. Signal estimation: direction and magnitude Since information of the type $$y_i = \mathrm{sgn} \langle {\bf a}_i,{\bf f} \rangle$$ can at best allow one to estimate the direction of a signal $${\bf f} \in \mathbb{R}^n$$, we consider in this section information of the type $$y_i = \mathrm{sgn}(\langle {\bf a}_i, {\bf f} \rangle - \tau_i) \qquad i = 1,\ldots,m ,$$ for some thresholds $$\tau_1,\ldots,\tau_m$$ introduced before quantization. In the rest of this section, we give three methods for recovering $${\bf f}$$ in its entirety. The first one is based on linear programming, the second one on second-order code programming and the last one on hard thresholding. We are going to show that using these algorithms, one can estimate both the direction and the magnitude of dictionary-sparse signal $${\bf f} \in \mathbb{R}^n$$ given a prior magnitude bound such as $$\\| {\bf f} \\|_2 \le r$$. We simply rely on the previous results by ‘lifting’ the situation from $$\mathbb{R}^n$$ to $$\mathbb{R}^{n+1}$$, in view of the observation that $${\bf y} = \mathrm{sgn} ({\bf A} {\bf f} - \boldsymbol{\tau})$$ can be interpreted as The following lemma will be equally useful when dealing with linear programming, second-order cone programming or hard thresholding schemes. Lemma 1 For $$\widetilde{{\bf f}}, \widetilde{{\bf g}} \in \mathbb{R}^{n+1}$$ written as $$\widetilde{{\bf f}} := \begin{bmatrix} {\bf f}_{[n]} \\ \hline f_{n+1} \end{bmatrix} \qquad \mbox{and} \qquad \widetilde{{\bf g}} =: \begin{bmatrix} {\bf g}_{[n]} \\ \hline g_{n+1} \end{bmatrix}$$ with $$\widetilde{{\bf f}}_{[n]}, \widetilde{{\bf g}}_{[n]} \in \mathbb{R}^n$$ and with $$f_{n+1} \not= 0$$, $$g_{n+1} \not= 0$$, one has $$\left\\| \frac{{\bf f}_{[n]}}{f_{n+1}} - \frac{{\bf g}_{[n]}}{g_{n+1}} \right\\|_2 \le \frac{\\|\widetilde{{\bf f}}\\|_2 \\|\widetilde{{\bf g}}\\|_2}{\|f_{n+1}\|\|g_{n+1}\|} \left\\| \frac{\widetilde{{\bf f}}}{\\|\widetilde{{\bf f}}\\|_2} - \frac{\widetilde{{\bf g}}}{\\|\widetilde{{\bf g}}\\|_2} \right\\|_2.$$ Proof. By using the triangle inequality in $$\mathbb{R}^n$$ and Cauchy–Schwarz inequality in $$\mathbb{R}^2$$, we can write \begin{align} \left\\| \frac{{\bf f}_{[n]}}{f_{n+1}} - \frac{{\bf g}_{[n]}}{g_{n+1}} \right\\|_2 & = \\|\widetilde{{\bf f}}\\|_2 \left\\| \frac{1/f_{n+1}}{\\|\widetilde{{\bf f}}\\|_2} {\bf f}_{[n]} - \frac{1/g_{n+1}}{\\|\widetilde{{\bf f}}\\|_2} {\bf g}_{[n]} \right\\|_2\\ & \le \\|\widetilde{{\bf f}}\\|_2 \left(\frac{1}{f_{n+1}} \left\\| \frac{{\bf f}_{[n]}}{\\| \widetilde{{\bf f}} \\|_2} - \frac{{\bf g}_{[n]}}{\\|\widetilde{{\bf g}}\\|_2} \right\\|_2 + \left\| \frac{1/g_{n+1}}{\\|\widetilde{{\bf f}}\\|_2} - \frac{1/f_{n+1}}{\\|\widetilde{{\bf g}}\\|_2} \right\| \\|{\bf g}_{[n]}\\|_2 \right)\\ & = \\|\widetilde{{\bf f}}\\|_2 \left(\frac{1}{f_{n+1}} \left\\| \frac{{\bf f}_{[n]}}{\\| \widetilde{{\bf f}} \\|_2} - \frac{{\bf g}_{[n]}}{\\|\widetilde{{\bf g}}\\|_2} \right\\|_2 + \frac{\\|{\bf g}_{[n]}\\|_2}{\|f_{n+1}\| \|g_{n+1}\|} \left\| \frac{f_{n+1}}{\\|\widetilde{{\bf f}}\\|_2} - \frac{g_{n+1}}{\\|\widetilde{{\bf g}}\\|_2} \right\| \right)\\ & \le \\|\widetilde{{\bf f}}\\|_2 \left[\frac{1}{\|f_{n+1}\|^2} + \frac{\\|{\bf g}_{[n]}\\|_2^2}{\|f_{n+1}\|^2 \|g_{n+1}\|^2} \right]^{1/2} \left[\left\\| \frac{{\bf f}_{[n]}}{\\| \widetilde{{\bf f}} \\|_2} - \frac{{\bf g}_{[n]}}{\\|\widetilde{{\bf g}}\\|_2} \right\\|_2^2 + \left\| \frac{f_{n+1}}{\\|\widetilde{{\bf f}}\\|_2} - \frac{g_{n+1}}{\\|\widetilde{{\bf g}}\\|_2} \right\|^2 \right]^{1/2}\\ & = \\|\widetilde{{\bf f}}\\|_2 \left[\frac{\\|\widetilde{{\bf g}}\\|_2^2}{\|f_{n+1}\|^2 \|g_{n+1}\|^2} \right]^{1/2} \left\\| \frac{\widetilde{{\bf f}}}{\\|\widetilde{{\bf f}}\\|_2} - \frac{\widetilde{{\bf g}}}{\\|\widetilde{{\bf g}}\\|_2} \right\\|_2, \end{align} which is the announced result. □ 4.1 Linear programming Given a signal $${\bf f} \in \mathbb{R}^n$$ observed via $${\bf y} = \mathrm{sgn} ({\bf A} {\bf f} - \boldsymbol{\tau})$$ with $$\tau_1,\ldots,\tau_m \sim \mathscr{N}(0,\sigma^2)$$, the optimization scheme we consider here consists in outputting the signal $$\label{Defflp} {\bf f}_{\rm LP} = \frac{\sigma}{\widehat{u}} \widehat{{\bf h}} \in \mathbb{R}^n,$$ (4.1) where $$\widehat{{\bf h}} \in \mathbb{R}^{n}$$ and $$\widehat{u} \in \mathbb{R}$$ are solutions of $$\label{OptProg} \underset{{\bf h} \in \mathbb{R}^n, u \in \mathbb{R}}{\rm minimize \;} \; \\|{\bf D}^* {\bf h} \\|_1 + \|u\| \qquad \mbox{subject to} \quad \mathrm{sgn}({\bf A} {\bf h} - u \boldsymbol{\tau} / \sigma) = {\bf y}, \quad \\|{\bf A} {\bf h} - u \boldsymbol{\tau} / \sigma \\|_1 = 1.$$ (4.2) Theorem 7 Let $$\varepsilon, r, \sigma > 0$$, let $$m \ge C (r/\sigma+\sigma/r)^6 \varepsilon^{-6} s \ln(eN/s)$$ and let $${\bf A} \in \mathbb{R}^{m \times n}$$ be populated by independent standard normal random variables. Furthermore, let $$\tau_1,\ldots,\tau_m$$ be independent normal random variables with mean zero and variance $$\sigma^2$$ that are also independent from the entries of $${\bf A}$$. Then, with failure probability at most $$\gamma \exp(-c m \varepsilon^2 r^2 \sigma^2/(r^2+\sigma^2)^2)$$, any effectively $$s$$-analysis sparse $${\bf f} \in \mathbb{R}^n$$ satisfying $$\\|{\bf f}\\|_2 \le r$$ and observed via $${\bf y} = \mathrm{sgn}({\bf A} {\bf f} - \boldsymbol{\tau})$$ is approximated by $${\bf f}_{\rm LP}$$ given in (4.1) with error $$\left\\| {\bf f}- {\bf f}_{\rm LP} \right\\|_2 \le \varepsilon r.$$ Proof. Let us introduce the ‘lifted’ signal $$\widetilde{{\bf f}} \in \mathbb{R}^{n+1}$$, the ‘lifted’ tight frame $$\widetilde{{\bf D}} \in \mathbb{R}^{(n+1)\times (N+1)}$$, and the ‘lifted’ measurement matrix $$\widetilde{{\bf A}} \in \mathbb{R}^{m \times (N+1)}$$ defined as $$\tilde{\mathbf{f}}:=\left[\!\!\!\frac{\ \ \ \mathbf{f}\ \ }{\sigma}\!\!\!\right],\quad \tilde{\mathbf{D}}:=\left[\!\!\begin{array}{c\|c} \mathbf{D} & \mathbf{0}\\\hline \mathbf{0} & \mathbf{1} \end{array}\!\!\right],\quad \tilde{\mathbf{A}}:= \left[\begin{array}{c\|c} & -\tau_1/\sigma\\ \mathbf{A} & \vdots \\ & -\tau_m/\sigma\end{array}\right].$$ (4.3) First, we observe that $$\widetilde{{\bf f}}$$ is effectively $$(s+1)$$-analysis sparse (relative to $$\widetilde{{\bf D}}$$), since , hence $$\frac{\\|\widetilde{{\bf D}}^* \widetilde{{\bf f}}\\|_1}{\\|\widetilde{{\bf D}}^* \widetilde{{\bf f}}\\|_2} = \frac{\\|{\bf D}^* {\bf f} \\|_1 + \sigma}{\sqrt{\\|{\bf D}^* {\bf f}\\|_2^2+\sigma^2}} \le \frac{\sqrt{s} \\|{\bf D}^* {\bf f}\\|_2 + \sigma}{\sqrt{\\|{\bf D}^* {\bf f}\\|_2^2+\sigma^2}} \le \sqrt{s+1}.$$ Next, we observe that the matrix $$\widetilde{{\bf A}} \in \mathbb{R}^{m \times (n+1)}$$, populated by independent standard normal random variables, satisfies $$\widetilde{{\bf D}}$$-TES$$(36(s+1),\varepsilon')$$, $$\varepsilon' := \dfrac{r \sigma}{2(r^2 + \sigma^2)} \varepsilon$$ and $$\widetilde{{\bf D}}$$-RIP$$_1(25(s+1),1/5)$$ with failure probability at most $$\gamma \exp(-c m {\varepsilon'}^2) + \gamma' \exp(-c' m) \le \gamma'' \exp(-c'' m \varepsilon^2 r^2 \sigma^2 / (r^2 + \sigma^2)^2)$$, since $$m \ge C {\varepsilon'}^{-6} (s+1) \ln(eN/(s+1))$$ and $$m \ge C (1/5)^{-7} (s+1) \ln(e N / (s+1))$$ are ensured by our assumption on $$m$$. Finally, we observe that $${\bf y} = \mathrm{sgn}(\widetilde{{\bf A}} \widetilde{{\bf f}})$$ and that the optimization program (4.2) reads $$\underset{\widetilde{{\bf h}} \in \mathbb{R}^{n+1}}{\rm minimize \;} \\|\widetilde{{\bf D}}^* \widetilde{{\bf h}} \\|_1 \qquad \mbox{subject to} \quad \mathrm{sgn}(\widetilde{{\bf A}} \widetilde{{\bf h}}) = {\bf y}, \quad \\|\widetilde{{\bf A}} \widetilde{{\bf h}} \\|_1 = 1.$$ Denoting its solution as , Theorem 5 implies that $$\left\\| \frac{\widetilde{{\bf f}}}{\\|\widetilde{{\bf f}}\\|_2} - \frac{\widetilde{{\bf g}}}{\\|\widetilde{{\bf g}}\\|_2} \right\\|_2 \le \varepsilon'.$$ In particular, looking at the last coordinate, this inequality yields $$\left\| \frac{\sigma}{\\|\widetilde{{\bf f}}\\|_2} - \frac{g_{n+1}}{\\|\widetilde{{\bf g}}\\|_2} \right\| \le \varepsilon', \qquad \mbox{hence} \qquad \frac{\|g_{n+1}\|}{\\|\widetilde{{\bf g}}\\|_2} \ge \frac{\sigma}{\\|\widetilde{{\bf f}}\\|_2} - \varepsilon' \ge \frac{\sigma}{\sqrt{r^2+\sigma^2}} - \frac{\sigma}{2 \sqrt{r^2 + \sigma^2}} = \frac{\sigma}{2 \sqrt{r^2 + \sigma^2}}.$$ In turn, applying Lemma 1 while taking $${\bf f} = {\bf f}_{[n]}$$ and $${\bf f}_{\rm LP} = (\sigma/g_{n+1}) {\bf g}_{[n]}$$ into consideration gives $$\left\\| \frac{{\bf f}}{\sigma} - \frac{{\bf f}_{\rm LP}}{\sigma} \right\\|_2 \le \frac{\\| \widetilde{{\bf f}} \\|_2}{\sigma} \frac{\\| \widetilde{{\bf g}} \\|_2}{\|g_{n+1}\|} \varepsilon' \le \frac{\\| \widetilde{{\bf f}} \\|_2}{\sigma} \frac{2\sqrt{r^2+\sigma^2}}{\sigma} \frac{r \sigma}{2(r^2 + \sigma^2)} \varepsilon = \frac{\\| \widetilde{{\bf f}} \\|_2}{\sigma} \frac{r}{\sqrt{r^2+\sigma^2}} \varepsilon,$$ so that $$\\| {\bf f} - {\bf f}_{\rm LP} \\|_2 \le \\|\widetilde{{\bf f}}\\|_2 \frac{r}{\sqrt{r^2+\sigma^2}} \varepsilon \le r \varepsilon.$$ This establishes the announced result. □ Remark 3 The recovery scheme (4.2) does not require an estimation of $$r$$ to be run. The recovery scheme presented next does require such an estimation. Moreover, it is a second-order cone program instead of a simpler linear program. However, it has one noticeable advantage, namely that it applies not only to signals satisfying $$\\|{\bf D}^* {\bf f}\\|_1 \le \sqrt{s}\\|{\bf D}^{\bf f}\\|_2$$ and $$\\|{\bf D}^{\bf f}\\|_2 \le r$$, but also more generally to signals satisfying $$\\|{\bf D}^* {\bf f}\\|_1 \le \sqrt{s} r$$ and $$\\|{\bf D}^{\bf f}\\|_2 \le r$$. For both schemes, one needs $$\sigma$$ to be of the same order as $$r$$ for the results to become meaningful in terms of number of measurement and success probability. However, if $$r$$ is only upper-estimated, then one could choose $$\sigma \ge r$$ and obtain a weaker recovery error $$\\|{\bf f} - \widehat{{\bf f}}\\|_2 \le \varepsilon \sigma$$ with relevant number of measurement and success probability. 4.2 Second-order cone programming Given a signal $${\bf f} \in \mathbb{R}^n$$ observed via $${\bf y} = \mathrm{sgn} ({\bf A} {\bf f} - \boldsymbol{\tau})$$ with $$\tau_1,\ldots,\tau_m \sim \mathscr{N}(0,\sigma^2)$$, the optimization scheme we consider here consists in outputting the signal $$\label{Deffcp} {\bf f}_{\rm CP} = \underset{{\bf h} \in \mathbb{R}^n}{\rm {\rm argmin}\, \;} \; \\|{\bf D}^ {\bf h}\\|_1 \qquad \mbox{subject to} \quad \mathrm{sgn}({\bf A} {\bf h} - \boldsymbol{\tau}) = {\bf y}, \quad \\|{\bf h}\\|_2 \le r.$$ (4.4) Theorem 8 Let $$\varepsilon, r, \sigma > 0$$, let $$m \ge C (r/\sigma + \sigma/r)^6(r^2/\sigma^2+1) \varepsilon^{-6} s \ln(eN/s)$$ and let $${\bf A} \in \mathbb{R}^{m \times n}$$ be populated by independent standard normal random variables. Furthermore, let $$\tau_1,\ldots,\tau_m$$ be independent normal random variables with mean zero and variance $$\sigma^2$$ that are also independent from $${\bf A}$$. Then, with failure probability at most $$\gamma \exp(- c' m \varepsilon^2 r^2 \sigma^2 / (r^2+\sigma^2)^2)$$, any signal $${\bf f} \in \mathbb{R}^n$$ with $$\\|{\bf f}\\|_2 \le r$$, $$\\|{\bf D}^* {\bf f}\\|_1 \le \sqrt{s} r$$ and observed via $${\bf y} = \mathrm{sgn}({\bf A} {\bf f} - \boldsymbol{\tau})$$ is approximated by $${\bf f}_{\rm CP}$$ given in (4.4) with error $$\left\\| {\bf f}- {\bf f}_{\rm CP} \right\\|_2 \le \varepsilon r.$$ Proof. We again use the notation (4.3) introducing the ‘lifted’ objects $$\widetilde{{\bf f}}$$, $$\widetilde{{\bf D}}$$ and $$\widetilde{{\bf A}}$$. Moreover, we set . We claim that $$\widetilde{{\bf f}}$$ and $$\widetilde{{\bf g}}$$ are effectively $$s'$$-analysis sparse, $$s' := (r^2 / \sigma^2 + 1)(s+1)$$. For $$\widetilde{{\bf g}}$$, this indeed follows from $$\\| \widetilde{{\bf D}}^* \widetilde{{\bf g}} \\|_2 = \\|\widetilde{{\bf g}}\\|_2 = \sqrt{\\|{\bf f}_{\rm CP}\\|_2^2 + \sigma^2} \ge \sigma$$ and $$\\|\widetilde{{\bf D}}^* \widetilde{{\bf g}}\\|_1 = \left\\| \begin{bmatrix} {\bf D}^* {\bf f}_{\rm CP} \\ \hline \sigma \end{bmatrix} \right\\|_1 = \\| {\bf D}^* {\bf f}_{\rm CP}\\|_1 + \sigma \le \\| {\bf D}^* {\bf f} \\|_1 + \sigma \le \sqrt{s} r + \sigma \le \sqrt{r^2 + \sigma^2} \sqrt{s+1}.$$ We also notice that $$\widetilde{{\bf A}}$$ satisfies $$\widetilde{{\bf D}}$$-TES$$(s', \varepsilon')$$, $$\varepsilon' \,{:=}\, \dfrac{r \sigma}{r^2 + \sigma^2} \varepsilon$$, with failure probability at most $$\gamma \exp(-c m {\varepsilon'}^2) \le \gamma \exp(- c' m \varepsilon^2 r^2 \sigma^2 / (r^2+\sigma^2)^2)$$, since $$m \ge C {\varepsilon'}^{-6} s' \ln(eN/s')$$ is ensured by our assumption on $$m$$. Finally, we observe that both $$\widetilde{{\bf f}}/ \\|\widetilde{{\bf f}}\\|_2$$ and $$\widetilde{{\bf g}}/ \\|\widetilde{{\bf g}}\\|_2$$ are $$\ell_2$$-normalized effectively $$s'$$-analysis sparse and have the same sign observations $$\mathrm{sgn}(\widetilde{{\bf A}} \widetilde{{\bf f}}) = \mathrm{sgn}(\widetilde{{\bf A}} \widetilde{{\bf g}}) = {\bf y}$$. Thus, $$\left\\| \frac{\widetilde{{\bf f}}}{\\|\widetilde{{\bf f}}\\|_2} - \frac{\widetilde{{\bf g}}}{\\|\widetilde{{\bf g}}\\|_2} \right\\|_2 \le \varepsilon'.$$ In view of Lemma 1, we derive $$\left\\| \frac{{\bf f}}{\sigma} - \frac{{\bf f}_{\rm CP}}{\sigma} \right\\|_2 \le \frac{r^2 + \sigma^2}{\sigma^2} \varepsilon', \qquad \mbox{hence} \qquad \\|{\bf f} - {\bf f}_{\rm CP}\\|_2 \le \frac{r^2 + \sigma^2}{\sigma} \varepsilon' = r \varepsilon.$$ This establishes the announced result. □ 4.3 Hard thresholding Given a signal $${\bf f} \in \mathbb{R}^N$$ observed via $${\bf y} = \mathrm{sgn}({\bf A} {\bf f} - \boldsymbol{\tau})$$ with $$\tau_1,\ldots,\tau_m \sim \mathscr{N}(0,\sigma^2)$$, the hard thresholding scheme we consider here consists in outputting the signal $$\label{fht} {\bf f}_{\rm HT} = \frac{-\sigma^2}{\langle \boldsymbol{\tau}, {\bf y} \rangle} {\bf D} {\bf z}, \qquad {\bf z} = H_{t-1}({\bf D}^* {\bf A}^* {\bf y}).$$ (4.5) Theorem 9 Let $$\varepsilon, r, \sigma > 0$$, let $$m \ge C \kappa (r/\sigma+\sigma/r)^9 \varepsilon^{-9} s \ln(eN/s)$$ and let $${\bf A} \in \mathbb{R}^{m \times n}$$ be populated by independent standard normal random variables. Furthermore, let $$\tau_1,\ldots,\tau_m$$ be independent normal random variables with mean zero and variance $$\sigma^2$$ that are also independent from the entries of $${\bf A}$$. Then, with failure probability at most $$\gamma \exp(-c m \varepsilon^2 r^2 \sigma^2/(r^2+\sigma^2)^2)$$, any $$s$$-synthesis-sparse and effectively $$\kappa s$$-analysis-sparse signal $${\bf f} \in \mathbb{R}^n$$ satisfying $$\\|{\bf f}\\|_2 \le r$$ and observed via $${\bf y} = \mathrm{sgn}({\bf A} {\bf f} - \boldsymbol{\tau})$$ is approximated by $${\bf f}_{\rm HT}$$ given in (4.5) for $$t:=\lceil 16 (\varepsilon'/8)^{-2} \kappa (s+1) \rceil$$ with error $$\left\\| {\bf f}- {\bf f}_{\rm HT} \right\\|_2 \le \varepsilon r.$$ Proof. We again use the notation (4.3) for the ‘lifted’ objects $$\widetilde{{\bf f}}$$, $$\widetilde{{\bf D}}$$ and $$\widetilde{{\bf A}}$$. First, we notice that $$\widetilde{{\bf f}}$$ is $$(s+1)$$-synthesis sparse (relative to $$\widetilde{{\bf D}}$$), as well as effectively $$\kappa (s+1)$$-analysis sparse, since satisfies $$\frac{\\|\widetilde{{\bf D}}^* \widetilde{{\bf f}}\\|_1}{\\|\widetilde{{\bf D}}^* \widetilde{{\bf f}}\\|_2} = \frac{\\|{\bf D}^* {\bf f}\\|_1 + \sigma}{\sqrt{\\|{\bf D}^{\bf f}\\|_2^2 + \sigma^2}} \le \frac{\sqrt{\kappa s}\\|{\bf D}^ {\bf f}\\|_2 + \sigma}{\sqrt{\\|{\bf D}^{\bf f}\\|_2^2 +\sigma^2}} \le \sqrt{\kappa s + 1} \le \sqrt{\kappa (s+1)}.$$ Next, we observe that the matrix $$\widetilde{{\bf A}}$$, populated by independent standard normal random variables, satisfies $$\widetilde{{\bf D}}$$-SPEP$$(s+1+t,\varepsilon'/8)$$, $$\varepsilon ' := \dfrac{r \sigma}{2(r^2 + \sigma^2)} \varepsilon$$, with failure probability at most $$\gamma \exp(-c m {\varepsilon'}^2 r^2)$$, since $$m \ge C (\varepsilon'/8)^{-7} (s+1+t) \ln(e(N+1)/(s+1+t))$$ is ensured by our assumption on $$m$$. Finally, since $${\bf y} = \mathrm{sgn}(\widetilde{{\bf A}} \widetilde{{\bf f}})$$, Theorem 5 implies that $$\left\\| \frac{\widetilde{{\bf f}}}{\\|\widetilde{{\bf f}}\\|_2} - \frac{\widetilde{{\bf g}}}{\\|\widetilde{{\bf g}}\\|_2} \right\\|_2 \le \varepsilon',$$ where $$\widetilde{{\bf g}} \in \mathbb{R}^{n+1}$$ is the output of the ‘lifted’ hard thresholding scheme. i.e. $$\widetilde{{\bf g}} = \widetilde{{\bf D}} \widetilde{{\bf z}}, \qquad \widetilde{{\bf z}} = H_{t} (\widetilde{{\bf D}}^\widetilde{{\bf A}}^* {\bf y}).$$ In particular, looking at the last coordinate, this inequality yields $$\label{LBg} \left\| \frac{\sigma}{\\|\widetilde{{\bf f}}\\|_2} - \frac{g_{n+1}}{\\|\widetilde{{\bf g}}\\|_2} \right\| \le \varepsilon', \quad \mbox{hence} \quad \frac{\|g_{n+1}\|}{\\|\widetilde{{\bf g}}\\|_2} \ge \frac{\sigma}{\\|\widetilde{{\bf f}}\\|_2} - \varepsilon' \ge \frac{\sigma}{\sqrt{r^2+\sigma^2}} - \frac{\sigma}{2 \sqrt{r^2 + \sigma^2}} = \frac{\sigma}{2 \sqrt{r^2 + \sigma^2}}.$$ (4.6) Now let us also observe that $$\widetilde{{\bf z}} = H_{t} \left(\begin{bmatrix} {\bf D}^* {\bf A}^* {\bf y} \\ \hline - \langle \boldsymbol{\tau},{\bf y} \rangle / \sigma \end{bmatrix} \right) = \left\{ \begin{matrix} \begin{bmatrix} H_{t}({\bf D}^* {\bf A}^* {\bf y}) \\ \hline 0 \end{bmatrix}, \\ \mbox{or}\hspace{30mm}\\ \begin{bmatrix} H_{t-1}({\bf D}^* {\bf A}^* {\bf y}) \\ \hline - \langle \boldsymbol{\tau},{\bf y} \rangle / \sigma \end{bmatrix} , \end{matrix} \right. \quad \mbox{hence} \quad \widetilde{{\bf g}} = \widetilde{{\bf D}} \widetilde{{\bf z}} = \left\{ \begin{matrix} \begin{bmatrix} {\bf D}(H_{t}({\bf D}^* {\bf A}^* {\bf y})) \\ \hline 0 \end{bmatrix}, \\ \mbox{or}\hspace{35mm}\\ \begin{bmatrix} {\bf D}(H_{t-1}({\bf D}^* {\bf A}^* {\bf y})) \\ \hline - \langle \boldsymbol{\tau},{\bf y} \rangle / \sigma \end{bmatrix}. \end{matrix} \right.$$ In view of (4.6), the latter option prevails. It is then apparent that $${\bf f}_{\rm HT} = \sigma {\bf g}_{[n]} / g_{n+1}$$. Lemma 1 gives $$\left\\| \frac{{\bf f}}{\sigma} - \frac{{\bf f}_{\rm HT}}{\sigma} \right\\|_2 \le \frac{\\| \widetilde{{\bf f}} \\|_2}{\sigma} \frac{\\| \widetilde{{\bf g}} \\|_2}{\|g_{n+1}\|} \varepsilon' \le \frac{\\| \widetilde{{\bf f}} \\|_2}{\sigma} \frac{2\sqrt{r^2+\sigma^2}}{\sigma} \frac{r \sigma}{2(r^2 + \sigma^2)} \varepsilon = \frac{\\| \widetilde{{\bf f}} \\|_2}{\sigma} \frac{r}{\sqrt{r^2+\sigma^2}} \varepsilon,$$ so that $$\\| {\bf f} - {\bf f}_{\rm HT} \\|_2 \le \\|\widetilde{{\bf f}}\\|_2 \frac{r}{\sqrt{r^2+\sigma^2}} \varepsilon \le r \varepsilon.$$ This establishes the announced result. □ 5. Postponed proofs and further remarks This final section contains the theoretical justification of the technical properties underlying our results, followed by a few points of discussion around them. 5.1 Proof of $${\mathbf D}$$-$${\rm SPEP}$$ The Gaussian width turns out to be a useful tool in our proofs. For a set $$K \subseteq \mathbb{R}^n$$, it is defined by $$w(K) = \mathbb{E} \left[\sup_{{\bf f} \in K} \langle {\bf f}, {\bf g} \rangle \right], \qquad {\bf g} \in \mathbb{R}^n \mbox{is a standard normal random vector}.$$ We isolate the following two properties. Lemma 2 Let $$K \subseteq \mathbb{R}^n$$ be a linear space and $$K_1,\ldots,K_L \subseteq \mathbb{R}^n$$ be subsets of the unit sphere $$S^{n-1}$$. (i) $$k / \sqrt{k+1} \le w(K \cap S^{n-1}) \le \sqrt{k} \qquad k:= \dim (K)$$; (ii) $$\displaystyle{w \left(K_1 \cup \ldots \cup K_L \right) \le \max \left\{w(K_1),\ldots,w(K_L) \right\} + 3 \sqrt{\ln(L)}}$$. Proof. (i) By the invariance under orthogonal transformation (see [25, Proposition 2.1]3), we can assume that $$K = \mathbb{R}^k \times \left\{(0,\ldots,0) \right\}$$. We then notice that $$\sup_{{\bf f} \in K \cap S^{n-1}} \langle {\bf f}, {\bf g} \rangle = \\|(g_1,\ldots,g_k)\\|_2$$ is the $$\ell_2$$-norm of a standard normal random vector of dimension $$k$$. We invoke, e.g. [15, Proposition 8.1] to derive the announced result. (ii) Let us introduce the non-negative random variables $$\xi_\ell := \sup_{{\bf f} \in K_\ell} \langle {\bf f} , {\bf g} \rangle \quad \ell = 1,\ldots, L ,$$ so that the Gaussian widths of each $$K_\ell$$ and of their union take the form $$w(K_\ell) = \mathbb{E}(\xi_\ell) \quad \ell = 1,\ldots, L \qquad \mbox{and} \qquad w \left(K_1 \cup \cdots \cup K_L \right) = \mathbb{E} \left(\max_{\ell = 1, \ldots, L} \xi_\ell \right).$$ By the concentration of measure inequality (see e.g. [15, Theorem 8.40]) applied to the function $$F: {\bf x} \in \mathbb{R}^n \mapsto \sup_{{\bf f} \in K_\ell} \langle {\bf f}, {\bf x} \rangle$$, which is a Lipschitz function with constant $$1$$, each $$\xi_\ell$$ satisfies $$\mathbb{P}(\xi_\ell \ge \mathbb{E}(\xi_\ell) + t) \le \exp \left(-t^2/2 \right)\!.$$ Because each $$\mathbb{E}(\xi_\ell)$$ is no larger than $$\max_\ell \mathbb{E}(\xi_\ell) = \max_\ell w(K_\ell) =: \omega$$, we also have $$\mathbb{P} (\xi_\ell \ge \omega + t) \le \exp \left(-t^2/2 \right)\!.$$ Setting $$v:= \sqrt{2 \ln(L)}$$, we now calculate \begin{align} \mathbb{E} \left(\max_{\ell =1,\ldots, L} \xi_\ell \right) & = \int_0^\infty \mathbb{P} \left(\max_{\ell =1,\ldots, L} \xi_\ell \ge u \right) \,{\rm{d}}u = \left(\int_0^{\omega+v} + \int_{\omega+v}^\infty \right) \mathbb{P} \left(\max_{\ell = 1,\ldots, L} \xi_\ell \ge u \right) \,{\rm{d}}u\\ & \le \int_0^{\omega + v} 1\, {\rm{d}}u + \int_{\omega + v}^\infty \sum_{\ell=1}^L \mathbb{P} \left(\xi_\ell \ge u \right) \,{\rm{d}}u = \omega + v + \sum_{\ell=1}^L \int_v^\infty \mathbb{P} \left(\xi_\ell \ge \omega + t \right) \,{\rm{d}}t\\ & \le \omega + v + L \int_v^\infty \exp \left(-t^2/2 \right)\, {\rm{d}}t \le \omega + v + L \frac{\exp(-v^2/2)}{v} \\ & = \omega + \sqrt{2 \ln(L)} + L \frac{1/L}{\sqrt{2 \ln(L)}} \le \omega + c \sqrt{\ln(L)}, \end{align} where $$c=\sqrt{2} + (\sqrt{2} \ln(2))^{-1} \le 3$$. We have shown that $$w \left(K_1 \cup \cdots \cup K_L \right) \le \max_{\ell} w(K_\ell) + 3 \sqrt{\ln(L)}$$, as desired. □ We now turn our attention to proving the awaited theorem. Proof of Theorem 3. According to [25, Proposition 4.3], with $${\bf A}' := (\sqrt{2/\pi}/m) {\bf A}$$, we have $$\left\| \langle {\bf A}' {\bf f}, \mathrm{sgn}({\bf A}' {\bf g}) \rangle - \langle {\bf f}, {\bf g} \rangle \right\| \le \delta,$$ for all $${\bf f},{\bf g} \in {\bf D}({\it {\Sigma}}_s^N) \cap S^{n-1}$$ provided $$m \ge C \delta^{-7} w({\bf D}({\it {\Sigma}}_s^N) \cap S^{n-1})^2$$, so it is enough to upper bound $$w({\bf D}({\it {\Sigma}}_s^N) \cap S^{n-1})$$ appropriately. To do so, with $${\it {\Sigma}}_S^N$$ denoting the space $$\{{\bf x} \in \mathbb{R}^N: {\rm supp}({\bf x}) \subseteq S \}$$ for any $$S \subseteq \{1,\ldots, N \}$$, we use Lemma 2 to write \begin{align} w({\bf D}({\it {\Sigma}}_s^N) \cap S^{n-1}) & = w \bigg(\bigcup_{\|S\|=s} \left\{{\bf D}({\it {\Sigma}}_S^N) \cap S^{n-1} \right\} \bigg) \underset{(ii)}{\le} \max_{\|S\|=s} w({\bf D}({\it {\Sigma}}_S^N) \cap S^{n-1}) + 3 \sqrt{\ln \left(\binom{N}{s} \right)}\\ & \underset{(i)}{\le} \sqrt{s} + 3 \sqrt{s \ln \left(eN/s \right)} \le 4 \sqrt{s \ln \left(eN/s \right)}. \end{align} The result is now immediate. □ 5.2 Proof of TES We propose two approaches for proving Theorem 4. One uses again the notion of Gaussian width, and the other one relies on covering numbers. The necessary results are isolated in the following lemma. Lemma 3 The set of $$\ell_2$$-normalized effectively $$s$$-analysis-sparse signals satisfies (i) $$\displaystyle{w \left(({\bf D}^)^{-1}({\it {\Sigma}}_s^{N,{\rm eff}}) \cap S^{n-1} \right)} \le C \sqrt{s \ln(eN/s)},$$ (ii) $$\displaystyle{\mathscr{N} \left(({\bf D}^)^{-1}({\it {\Sigma}}_s^{N,{\rm eff}}) \cap S^{n-1} , \rho \right) \le \binom{N}{t}\left(1 + \frac{8}{\rho} \right)^t, \qquad t := \lceil 4 \rho^{-2}} s \rceil.$$ Proof. (i) By the definition of the Gaussian width for $$\mathscr{K}_s: = ({\bf D}^)^{-1}({\it {\Sigma}}_s^{N,{\rm eff}}) \cap S^{n-1}$$, with $${\bf g} \in \mathbb{R}^n$$ denoting a standard normal random vector, $$\label{slep} w(\mathscr{K}_s) = \mathbb{E} \left[\sup_{\substack{{\bf D}^ {\bf f} \in {\it {\Sigma}}_s^{N,{\rm eff}} \\ \\|{\bf f}\\|_2 = 1}} \langle {\bf f} , {\bf g} \rangle \right] = \mathbb{E} \left[\sup_{\substack{{\bf D}^* {\bf f} \in {\it {\Sigma}}_s^{N,{\rm eff}} \\ \\|{\bf D}^* {\bf f}\\|_2 = 1}} \langle {\bf D} {\bf D}^* {\bf f} , {\bf g} \rangle \right] \le \mathbb{E} \left[\sup_{\substack{{\bf x} \in {\it {\Sigma}}_s^{N,{\rm eff}} \\ \\|{\bf x}\\|_2 = 1}} \langle {\bf D} {\bf x} , {\bf g} \rangle \right].$$ (5.1) In view of $$\\|{\bf D}\\|_{2 \to 2} = 1$$, we have, for any $${\bf x},{\bf x}' \in {\it {\Sigma}}_s^{N,{\rm eff}}$$ with $$\\|{\bf x}\\|_2 = \\|{\bf x}'\\|_2 =1$$, \begin{align} \mathbb{E} \left(\langle {\bf D} {\bf x}, {\bf g} \rangle - \langle {\bf D} {\bf x}', {\bf g}' \rangle \right)^2 &= \mathbb{E} \left[\langle {\bf D} {\bf x}, {\bf g} \rangle ^2 \right] + \mathbb{E} \left[\langle {\bf D} {\bf x}', {\bf g}' \rangle ^2 \right] = \\|{\bf D} {\bf x}\\|_2^2 + \\|{\bf D} {\bf x}'\\|_2^2 \le \\|{\bf x}\\|_2^2 + \\|{\bf x}'\\|_2^2\\ &= \mathbb{E} \left(\langle {\bf x}, {\bf g} \rangle - \langle {\bf x}', {\bf g}' \rangle \right)^2. \end{align} Applying Slepian’s lemma (see e.g. [15, Lemma 8.25]), we obtain $$w(\mathscr{K}_s) \le \mathbb{E} \left[\sup_{\substack{{\bf x} \in {\it {\Sigma}}_s^{N,{\rm eff}} \\ \\|{\bf x}\\|_2 = 1}} \langle {\bf x} , {\bf g} \rangle \right] =w({\it {\Sigma}}_s^{N,{\rm eff}} \cap S^{n-1}).$$ The latter is known to be bounded by $$C s \ln (eN/s)$$, see [25, Lemma 2.3]. (ii) The covering number $$\mathscr{N}(\mathscr{K}_s,\rho)$$ is bounded above by the maximal number $$\mathscr{P}(\mathscr{K}_s,\rho)$$ of elements in $$\mathscr{K}_s$$ that are separated by a distance $$\rho$$. We claim that $$\mathscr{P} (\mathscr{K}_s, \rho) \le \mathscr{P}({\it {\Sigma}}_t^N \cap B_2^N, \rho/2)$$. To justify this claim, let us consider a maximal $$\rho$$-separated set $$\{{\bf f}^1,\ldots,{\bf f}^L\}$$ of signals in $$\mathscr{K}_s$$. For each $$i$$, let $$T_i \subseteq \{1, \ldots, N \}$$ denote an index set of $$t$$ largest absolute entries of $${\bf D}^* {\bf f}^i$$. We write $$\rho < \\|{\bf f}^i - {\bf f}^j \\|_2 = \\|{\bf D}^* {\bf f}^i - {\bf D}^* {\bf f}^j \\|_2 \le \\|({\bf D}^* {\bf f}^i)_{T_i} - ({\bf D}^* {\bf f}^j)_{T_j} \\|_2 + \\| ({\bf D}^* {\bf f}^i)_{\overline{T_i}} \\|_2 + \\| ({\bf D}^* {\bf f}^j)_{\overline{T_j}} \\|_2.$$ Invoking [15, Theorem 2.5], we observe that $$\\| ({\bf D}^* {\bf f}^i)_{\overline{T_i}} \\|_2 \le \frac{1}{2\sqrt{t}} \\|{\bf D}^* {\bf f}^i \\|_1 \le \frac{\sqrt{s}}{2 \sqrt{t}} \\|{\bf D}^* {\bf f}^i \\|_2 = \frac{\sqrt{s}}{2 \sqrt{t}},$$ and similarly for $$j$$ instead of $$i$$. Thus, we obtain $$\rho < \\|({\bf D}^* {\bf f}^i)_{T_i} - ({\bf D}^* {\bf f}^j)_{T_j} \\|_2 + \sqrt{\frac{s}{t}} \le \\|({\bf D}^* {\bf f}^i)_{T_i} - ({\bf D}^* {\bf f}^j)_{T_j} \\|_2 + \frac{\rho}{2}, \quad \mbox{i.e.} \; \\|({\bf D}^* {\bf f}^i)_{T_i} - ({\bf D}^* {\bf f}^j)_{T_j} \\|_2 > \frac{\rho}{2}.$$ Since we have uncovered a set of $$L = \mathscr{P}(\mathscr{K}_s,\rho)$$ points in $${\it {\Sigma}}_t^N \cap B_2^N$$ that are $$(\rho/2)$$ separated, the claimed inequality is proved. We conclude by recalling that $$\mathscr{P}({\it {\Sigma}}_t^N \cap B_2^N, \rho/2)$$ is bounded above by $$\mathscr{N}({\it {\Sigma}}_t^N \cap B_2^N, \rho/4)$$, which is itself bounded above by $$\dbinom{N}{t} \left(1 + \dfrac{2}{\rho/4} \right)^t$$. □ We can now turn our attention to proving the awaited theorem. Proof of Theorem 4. With $$\mathscr{K}_s = ({\bf D}^)^{-1}({\it {\Sigma}}_s^{N,{\rm eff}}) \cap S^{n-1}$$, the conclusion holds when $$m \ge C \varepsilon^{-6} w(\mathscr{K}_s)^2$$ or when $$m \ge C \varepsilon^{-1} \ln (\mathscr{N}(\mathscr{K}_s,c \varepsilon))$$, according to [26, Theorem 1.5] or to [3, Theorem 1.5], respectively. It now suffices to call upon Lemma 3. Note that the latter option yields better powers of $$\varepsilon^{-1}$$, but less pleasant failure probability. □ 5.3 Further remarks We conclude this theoretical section by making two noteworthy comments on the sign product embedding property and the tessellation property in the dictionary case. Remark 4 $${\bf D}$$-SPEP cannot hold for arbitrary dictionary $${\bf D}$$ if synthesis sparsity was replaced by effective synthesis sparsity. This is because the set of effectively $$s$$-synthesis-sparse signals can be the whole space $$\mathbb{R}^n$$. Indeed, let $${\bf f} \in \mathbb{R}^n$$ that can be written as $${\bf f} = {\bf D} {\bf u}$$ for some $${\bf u} \in \mathbb{R}^N$$. Let us also pick an $$(s-1)$$-sparse vector $${\bf v} \in \ker {\bf D}$$—there are tight frames for which this is possible, e.g. the concatenation of two orthogonal matrices. For $$\varepsilon > 0$$ small enough, we have $$\frac{\\|{\bf v} + \varepsilon {\bf u} \\|_1}{\\|{\bf v} + \varepsilon {\bf u}\\|_2} \le \frac{\\|{\bf v}\\|_1 + \varepsilon \\|{\bf u}\\|_1}{\\|{\bf v}\\|_2 - \varepsilon \\|{\bf u}\\|_2} \le \frac{\sqrt{s-1} \\|{\bf v}\\|_2 + \varepsilon \\|{\bf u}\\|_1}{\\|{\bf v}\\|_2 - \varepsilon \\|{\bf u}\\|_2} \le \sqrt{s},$$ so that the coefficient vector $${\bf v} + \varepsilon {\bf u}$$ is effectively $$s$$-sparse, hence so is $$(1/\varepsilon){\bf v} + {\bf u}$$. It follows that $${\bf f} = {\bf D}((1/\varepsilon){\bf v} + {\bf u})$$ is effectively $$s$$-synthesis sparse. Remark 5 Theorem 3 easily implies a tessellation result for $${\bf D}({\it {\Sigma}}_s^N) \,\cap\, S^{n-1}$$, the ‘synthesis-sparse sphere’. Precisely, under the assumptions of the theorem (with a change of the constant $$C$$), $${\bf D}$$-SPEP$$(2s,\delta/2)$$ holds. Then, one can derive $$[{\bf g},{\bf h} \in {\bf D}({\it {\Sigma}}_s) \cap S^{n-1} : \; \mathrm{sgn}({\bf A} {\bf g}) = \mathrm{sgn}({\bf A} {\bf h})] \Longrightarrow [\\|{\bf g} - {\bf h}\\|_2 \le \delta].$$ To see this, with $$\boldsymbol{\varepsilon} := \mathrm{sgn}({\bf A} {\bf g}) = \mathrm{sgn}({\bf A} {\bf h})$$ and with $${\bf f} := ({\bf g}-{\bf h})/\\|{\bf g}-{\bf h}\\|_2 \in {\bf D}({\it {\Sigma}}_{2s}) \cap S^{n-1}$$, we have $$\left\| \frac{\sqrt{2/\pi}}{m} \langle {\bf A} {\bf f} , \boldsymbol{\varepsilon}\rangle - \langle {\bf f}, {\bf g} \rangle \right\| \le \frac{\delta}{2}, \qquad \left\| \frac{\sqrt{2/\pi}}{m} \langle {\bf A} {\bf f} , \boldsymbol{\varepsilon} \rangle - \langle {\bf f}, {\bf h} \rangle \right\| \le \frac{\delta}{2},$$ so by the triangle inequality $$\|\langle {\bf f}, {\bf g} - {\bf h} \rangle\| \le \delta$$, i.e. $$\\|{\bf g} -{\bf h}\\|_2 \le \delta$$, as announced. Acknowledgements The authors would like to thank the AIM SQuaRE program that funded and hosted our initial collaboration. Funding NSF grant number [CCF-1527501], ARO grant number [W911NF-15-1-0316] and AFOSR grant number [FA9550-14-1-0088] to R.B.; Alfred P. Sloan Fellowship and NSF Career grant number [1348721 to D.N.]; NSERC grant number [22R23068 to Y.P.]; and NSF Postdoctoral Research Fellowship grant number [1400558 to M.W.]. Footnotes 1 A signal $${\bf x} \in \mathbb{R}^N$$ is called $$s$$-sparse if $$\\|{\bf x}\\|_0 := \|\mathrm{supp}({\bf x})\| \leq s \ll N$$. 2 Here, ‘dictionary sparsity’ means effective $$s$$-analysis sparsity if $$\widehat{{\bf f}}$$ is produced by convex programming and genuine $$s$$-synthesis sparsity together with effective $$\kappa s$$-analysis sparsity if $$\widehat{{\bf f}}$$ is produced by hard thresholding. 3 In particular, [25, Proposition 2.1] applies to the slightly different notion of mean width defined as $$\mathbb{E} \left[\sup_{{\bf f} \in K - K} \langle {\bf f}, {\bf g} \rangle \right]$$. References 1. ( 2016) Compressive Sensing webpage. http://dsp.rice.edu/cs (accessed 24 June 2016). 2. Baraniuk R., Foucart S., Needell D., Plan Y. & Wootters M. ( 2017) Exponential decay of reconstruction error from binary measurements of sparse signals. IEEE Trans. Inform. Theory, 63, 3368– 3385. Google Scholar CrossRef Search ADS 3. Bilyk D. & Lacey M. T. ( 2015) Random tessellations, restricted isometric embeddings, and one bit sensing. arXiv preprint arXiv:1512.06697. 4. Blumensath T. ( 2011) Sampling and reconstructing signals from a union of linear subspaces. IEEE Trans. Inform. Theory, 57, 4660– 4671. Google Scholar CrossRef Search ADS 5. Boufounos P. T. & Baraniuk R. G. ( 2008) 1-Bit compressive sensing. Proceedings of the 42nd Annual Conference on Information Sciences and Systems (CISS), IEEE, pp. 16– 21. 6. Candès E. J., Demanet L., Donoho D. L. & Ying L. ( 2000) Fast discrete curvelet transforms. Multiscale Model. Simul., 5, 861– 899. Google Scholar CrossRef Search ADS 7. Candès E. J. & Donoho D. L. ( 2004) New tight frames of curvelets and optimal representations of objects with piecewise $$C^2$$ singularities. Comm. Pure Appl. Math., 57, 219– 266. Google Scholar CrossRef Search ADS 8. Candès E. J., Eldar Y. C., Needell D. & Randall P. ( 2010) Compressed sensing with coherent and redundant dictionaries. Appl. Comput. Harmon. Anal., 31, 59– 73. Google Scholar CrossRef Search ADS 9. Daubechies I. ( 1992) Ten Lectures on Wavelets . Philadelphia, PA: SIAM. Google Scholar CrossRef Search ADS 10. Davenport M., Needell D. & Wakin M. B. ( 2012) Signal space CoSaMP for sparse recovery with redundant dictionaries. IEEE Trans. Inform. Theory, 59, 6820– 6829. Google Scholar CrossRef Search ADS 11. Elad M., Milanfar P. & Rubinstein R. ( 2007) Analysis versus synthesis in signal priors. Inverse Probl., 23, 947. Google Scholar CrossRef Search ADS 12. Eldar Y. C. & Kutyniok G. ( 2012) Compressed Sensing: Theory and Applications . Cambridge, UK: Cambridge University Press. Google Scholar CrossRef Search ADS 13. Feichtinger H. & Strohmer T. (eds.) ( 1998) Gabor Analysis and Algorithms . Boston, MA: Birkhäuser. Google Scholar CrossRef Search ADS 14. Foucart S. ( 2016) Dictionary-sparse recovery via thresholding-based algorithms. J. Fourier Anal. Appl., 22, 6– 19. Google Scholar CrossRef Search ADS 15. Foucart S. & Rauhut H. ( 2013) A Mathematical Introduction to Compressive Sensing . Basel, Switzerland: Birkhäuser. Google Scholar CrossRef Search ADS 16. Giryes R., Nam S., Elad M., Gribonval R. & Davies M. E. ( 2014) Greedy-like algorithms for the cosparse analysis model. Linear Algebra Appl., 441, 22– 60. Google Scholar CrossRef Search ADS 17. Gopi S., Netrapalli P., Jain P. & Nori A. ( 2013) One-bit compressed sensing: Provable support and vector recovery. Proceedings of the 30th International Conference on Machine Learning (ICML), Atlanta GA, 2013, pp. 154– 162. 18. Jacques L., Degraux K. & De Vleeschouwer C. ( 2013) Quantized iterative hard thresholding: bridging 1-bit and high-resolution quantized compressed sensing. Proceedings of the 10th International Conference on Sampling Theory and Applications (SampTA), Bremen, Germany, pp. 105– 108. 19. Jacques L., Laska J. N., Boufounos P. T. & Baraniuk R. G. ( 2013) Robust 1-bit compressive sensing via binary stable embeddings of sparse vectors. IEEE Trans. Inform. Theory, 59, 2082– 2102. Google Scholar CrossRef Search ADS 20. Knudson K., Saab R. & Ward R. ( 2016) One-bit compressive sensing with norm estimation. IEEE Trans. Inform. Theory, 62, 2748– 2758. Google Scholar CrossRef Search ADS 21. Krahmer F., Needell D. & Ward R. ( 2015) Compressive sensing with redundant dictionaries and structured measurements. SIAM J. Math. Anal., 47, 4606– 4629. Google Scholar CrossRef Search ADS 22. Nam S., Davies M. E., Elad M. & Gribonval R. ( 2013) The cosparse analysis model and algorithms. Appl. Comput. Harmon. Anal., 34, 30– 56. Google Scholar CrossRef Search ADS 23. Peleg T. & Elad M. ( 2013) Performance guarantees of the thresholding algorithm for the cosparse analysis model. IEEE Trans. Inform. Theory, 59, 1832– 1845. Google Scholar CrossRef Search ADS 24. Plan Y. & Vershynin R. ( 2013a) One-bit compressed sensing by linear programming. Comm. Pure Appl. Math., 66, 1275– 1297. Google Scholar CrossRef Search ADS 25. Plan Y. & Vershynin R. ( 2013b) Robust 1-bit compressed sensing and sparse logistic regression: a convex programming approach. IEEE Trans. Inform. Theory, 59, 482– 494. Google Scholar CrossRef Search ADS 26. Plan Y. & Vershynin R. ( 2014) Dimension reduction by random hyperplane tessellations. Discrete Comput. Geom., 51, 438– 461. Google Scholar CrossRef Search ADS 27. Rauhut H., Schnass K. & Vandergheynst P. ( 2008) Compressed sensing and redundant dictionaries. IEEE Trans. Inform. Theory, 54, 2210– 2219. Google Scholar CrossRef Search ADS 28. Saab R., Wang R. & Yilmaz Ö. ( 2016) Quantization of compressive samples with stable and robust recovery. Applied and Computational Harmonic Analysis, to appear. 29. Starck J.-L., Elad M. & Donoho D. ( 2004) Redundant multiscale transforms and their application for morphological component separation. Advances in Imaging and Electron Physics, 132, 287– 348. Google Scholar CrossRef Search ADS 30. Yan M., Yang Y. & Osher S. ( 2012) Robust 1-bit compressive sensing using adaptive outlier pursuit., IEEE Trans. Signal Process., 60, 3868– 3875. Google Scholar CrossRef Search ADS © The authors 2017. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) For permissions, please e-mail: journals. [email protected] http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Information and Inference: A Journal of the IMA Oxford University Press # One-bit compressive sensing of dictionary-sparse signals , Volume 7 (1) – Mar 1, 2018 22 pages /lp/ou_press/one-bit-compressive-sensing-of-dictionary-sparse-signals-k1l3bdmQC9 Publisher Oxford University Press © The authors 2017. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved. ISSN 2049-8764 eISSN 2049-8772 D.O.I. 10.1093/imaiai/iax009 Publisher site See Article on Publisher Site ### Abstract Abstract One-bit compressive sensing has extended the scope of sparse recovery by showing that sparse signals can be accurately reconstructed even when their linear measurements are subject to the extreme quantization scenario of binary samples—only the sign of each linear measurement is maintained. Existing results in one-bit compressive sensing rely on the assumption that the signals of interest are sparse in some fixed orthonormal basis. However, in most practical applications, signals are sparse with respect to an overcomplete dictionary, rather than a basis. There has already been a surge of activity to obtain recovery guarantees under such a generalized sparsity model in the classical compressive sensing setting. Here, we extend the one-bit framework to this important model, providing a unified theory of one-bit compressive sensing under dictionary sparsity. Specifically, we analyze several different algorithms—based on convex programming and on hard thresholding—and show that, under natural assumptions on the sensing matrix (satisfied by Gaussian matrices), these algorithms can efficiently recover analysis–dictionary-sparse signals in the one-bit model. 1. Introduction The basic insight of compressive sensing is that a small number of linear measurements can be used to reconstruct sparse signals. In traditional compressive sensing, we wish to reconstruct an $$s$$-sparse1 signal $${\bf x} \in \mathbb{R}^N$$ from linear measurements of the form $$\label{meas} {\bf y} = {\bf A}{\bf x} \in \mathbb{R}^m \qquad\text{(or its corrupted version {\bf y} = {\bf A}{\bf x} + {\bf e})},$$ (1.1) where $${\bf A}$$ is an $$m\times N$$ measurement matrix. A significant body of work over the past decade has demonstrated that the $$s$$-sparse (or nearly $$s$$-sparse) signal $${\bf x}$$ can be accurately and efficiently recovered from its measurement vector $${\bf y} = {\bf A}{\bf x}$$ when $${\bf A}$$ has independent Gaussian entries, say, and when $$m \asymp s\log(N/s)$$ [1,12,15]. This basic model has been extended in several directions. Two important ones—which we focus on in this work—are (a) extending the set of signals to include the larger and important class of dictionary- sparse signals, and (b) considering highly quantized measurements as in one-bit compressive sensing. Both of these settings have important practical applications and have received much attention in the past few years. However, to the best of our knowledge, they have not been considered together before. In this work, we extend the theory of one-bit compressive sensing to dictionary-sparse signals. Below, we briefly review the background on these notions, set up notation and outline our contributions. 1.1 One-bit measurements In practice, each entry $$y_i = \langle {\bf a}_i, {\bf x}\rangle$$ (where $${\bf a}_i$$ denotes the $$i$$th row of $${\bf A}$$) of the measurement vector in (1.1) needs to be quantized. That is, rather than observing $${\bf y}={\bf A}{\bf x}$$, one observes $${\bf y} = Q({\bf A}{\bf x})$$ instead, where $$Q: \mathbb{R}^m \rightarrow \mathscr{A}$$ denotes the quantizer that maps each entry of its input to a corresponding quantized value in an alphabet $$\mathscr{A}$$. The so-called one-bit compressive sensing [5] problem refers to the case when $$\|\mathscr{A}\| = 2$$, and one wishes to recover $${\bf x}$$ from its heavily quantized (one bit) measurements $${\bf y} = Q({\bf A}{\bf x})$$. The simplest quantizer in the one-bit case uses the alphabet $$\mathscr{A} = \{-1, 1\}$$ and acts by taking the sign of each component as $$\label{eq:quantized} y_i = Q(\langle {\bf a}_i, {\bf x}\rangle) = \mathrm{sgn}(\langle {\bf a}_i, {\bf x}\rangle),$$ (1.2) which we denote in shorthand by $${\bf y} = \mathrm{sgn}({\bf A}{\bf x})$$. Since the publication of [5] in 2008, several efficient methods, both iterative and optimization based, have been developed to recover the signal $${\bf x}$$ (up to normalization) from its one-bit measurements (see e.g. [17–19,24,25,30]). In particular, it is shown [19] that the direction of any $$s$$-sparse signal $${\bf x}$$ can be estimated by some $$\hat{{\bf x}}$$ produced from $${\bf y}$$ with accuracy $$\left\\| \frac{{\bf x}}{\\|{\bf x}\\|_2} - \frac{\hat{{\bf x}}}{\\|\hat{{\bf x}}\\|_2}\right\\|_2 \leq \varepsilon$$ when the number of measurements is at least $$m = {\it {\Omega}}\left(\frac{s \ln(N/s)}{\varepsilon} \right)\!.$$ Notice that with measurements of this form, we can only hope to recover the direction of the signal, not the magnitude. However, we can recover the entire signal if we allow for thresholded measurements of the form $$\label{eq:quantizeddither} y_i = \mathrm{sgn}(\langle {{{\bf a}_i}}, {{{\bf x}}} \rangle - \tau_i).$$ (1.3) In practice, it is often feasible to obtain quantized measurements of this form, and they have been studied before. Existing works using measurements of the form (1.3) have also allowed for adaptive thresholds; that is, the $$\tau_i$$ can be chosen adaptively based on $$y_j$$ for $$j < i$$. The goal of those works was to improve the convergence rate, i.e. the dependence on $$\varepsilon$$ in the number of measurements $$m$$. It is known that a dependence of $${\it {\Omega}}(1/\varepsilon)$$ is necessary with non-adaptive measurements, but recent work on Sigma-Delta quantization [28] and other schemes [2,20] have shown how to break this barrier using measurements of the form (1.3) with adaptive thresholds. In this article, we neither focus on the decay rate (the dependence on $$\varepsilon$$) nor do we consider adaptive measurements. However, we do consider non-adaptive measurements both of the form (1.2) and (1.3). This allows us to provide results on reconstruction of the magnitude of signals, and the direction. 1.2 Dictionary sparsity Although the classical setting assumes that the signal $${\bf x}$$ itself is sparse, most signals of interest are not immediately sparse. In the straightforward case, a signal may be instead sparse after some transform; for example, images are known to be sparse in the wavelet domain, sinusoidal signals in the Fourier domain, and so on [9]. Fortunately, the classical framework extends directly to this model, since the product of a Gaussian matrix and an orthonormal basis is still Gaussian. However, in many practical applications, the situation is not so straightforward, and the signals of interest are sparse, not in an orthonormal basis, but rather in a redundant (highly overcomplete) dictionary; this is known as dictionary sparsity. Signals in radar and sonar systems, for example, are sparsely represented in Gabor frames, which are highly overcomplete and far from orthonormal [13]. Images may be sparsely represented in curvelet frames [6,7], undecimated wavelet frames [29] and other frames, which by design are highly redundant. Such redundancy allows for sparser representations and a wider class of signal representations. Even in the Fourier domain, utilizing an oversampled DFT allows for much more realistic and practical signals to be represented. For these reasons, recent research has extended the compressive sensing framework to the setting, where the signals of interest are sparsified by overcomplete tight frames (see e.g. [8,14,16,27]). Throughout this article, we consider a dictionary $${\bf D} \in \mathbb{R}^{n \times N}$$, which is assumed to be a tight frame, in the sense that ${\bf D} {\bf D}^ = {\bf I}_n.$ To distinguish between the signal and its sparse representation, we write $${\bf f}\in\mathbb{R}^n$$ for the signal of interest and $${\bf f}={\bf D}{\bf x}$$, where $${\bf x}\in\mathbb{R}^N$$ is a sparse coefficient vector. We then acquire the samples of the form $${\bf y} = {\bf A}{\bf f} = {\bf A}{\bf D}{\bf x}$$ and attempt to recover the signal $${\bf f}$$. Note that, due to the redundancy of $${\bf D}$$, we do not hope to be able to recover a unique coefficient vector $${\bf x}$$. In other words, even when the measurement matrix $${\bf A}$$ is well suited for sparse recovery, the product $${\bf A}{\bf D}$$ may have highly correlated columns, making recovery of $${\bf x}$$ impossible. With the introduction of a non-invertible sparsifying transform $${\bf D}$$, it becomes important to distinguish between two related but distinct notions of sparsity. Precisely, we say that $${\bf f}$$ is $$s$$-synthesis sparse if $${\bf f} = {\bf D} {\bf x}$$ for some $$s$$-sparse $${\bf x} \in \mathbb{R}^N$$; $${\bf f}$$ is $$s$$-analysis sparse if $${\bf D}^* {\bf f} \in \mathbb{R}^N$$ is $$s$$-sparse. We note that analysis sparsity is a stronger assumption, because, assuming analysis sparsity, one can always take $${\bf x} = {\bf D}^* {\bf f}$$ in the synthesis sparsity model. See [11] for an introduction to the analysis-sparse model in compressive sensing (also called the analysis cosparse model). Instead of exact sparsity, it is often more realistic to study effective sparsity. We call a coefficient vector $${\bf x} \in \mathbb{R}^N$$ effectively $$s$$-sparse if $$\\|{\bf x}\\|_1 \le \sqrt{s} \\|{\bf x}\\|_2,$$ and we say that $${\bf f}$$ is effectively $$s$$-synthesis sparse if $${\bf f} = {\bf D} {\bf x}$$ for some effectively $$s$$-sparse $${\bf x} \in \mathbb{R}^N$$; $${\bf f}$$ is effectively $$s$$-analysis sparse if $${\bf D}^* {\bf f} \in \mathbb{R}^N$$ is effectively $$s$$-sparse. We use the notation \begin{align} {\it {\Sigma}}^N_s & \mbox{for the set of $s$-sparse coefficient vectors in $\mathbb{R}^N$, and} \\ {\it {\Sigma}}_s^{N,{\rm eff}} & \mbox{for the set of effectively $s$-sparse coefficient vectors in $\mathbb{R}^N$.} \end{align} We also use the notation $$B_2^n$$ for the set of signals with $$\ell_2$$-norm at most $$1$$ (i.e. the unit ball in $$\ell_2^n$$) and $$S^{n-1}$$ for the set of signals with $$\ell_2$$-norm equal to $$1$$ (i.e. the unit sphere in $$\ell_2^n$$). It is now well known that, if $${\bf D}$$ is a tight frame and $${\bf A}$$ satisfies analogous conditions to those in the classical setting (e.g. has independent Gaussian entries), then a signal $${\bf f}$$ which is (effectively) analysis- or synthesis sparse can be accurately recovered from traditional compressive sensing measurements $${\bf y} = {\bf A} {\bf f} = {\bf A}{\bf D}{\bf x}$$ (see e.g. [4,8,10,14,16,22,23,27]). 1.3 One-bit measurements with dictionaries: our setup In this article, we study one-bit compressive sensing for dictionary-sparse signals. Precisely, our aim is to recover signals $${\bf f} \in \mathbb{R}^n$$ from the binary measurements $$y_i = \mathrm{sgn} \langle {\bf a}_i, {\bf f} \rangle \qquad i=1,\ldots,m,$$ or $$y_i = \mathrm{sgn} \left(\langle {\bf a}_i, {\bf f} \rangle - \tau_i \right) \qquad i = 1,\ldots,m,$$ when these signals are sparse with respect to a dictionary $${\bf D}$$. As in Section 1.2, there are several ways to model signals that are sparse with respect to $${\bf D}$$. In this work, two different signal classes are considered. For the first one, which is more general, our results are based on convex programming. For the second one, which is more restrictive, we can obtain results using a computationally simpler algorithm based on hard thresholding. The first class consists of signals $${\bf f} \in ({\bf D}^)^{-1} {\it {\Sigma}}_s^{N,\rm{eff}}$$ that are effectively $$s$$-analysis sparse, i.e. they satisfy $$\label{Assumption} \\|{\bf D}^ {\bf f}\\|_1 \le \sqrt{s} \\|{\bf D}^* {\bf f}\\|_2.$$ (1.4) This occurs, of course, when $${\bf D}^* {\bf f}$$ is genuinely sparse (analysis sparsity) and this is realistic if we are working, e.g. with piecewise-constant images, since they are sparse after application of the total variation operator. We consider effectively sparse signals since genuine analysis sparsity is unrealistic when $${\bf D}$$ has columns in general position, as it would imply that $${\bf f}$$ is orthogonal to too many columns of $${\bf D}$$. The second class consists of signals $${\bf f} \in {\bf D}({\it {\Sigma}}_s^N) \cap ({\bf D}^)^{-1} {\it {\Sigma}}_{\kappa s}^{N, \rm{eff}}$$ that are both $$s$$-synthesis sparse and $$\kappa s$$-analysis sparse for some $$\kappa \ge 1$$. This will occur as soon as the signals are $$s$$-synthesis sparse, provided we utilize suitable dictionaries $${\bf D} \in \mathbb{R}^{n \times N}$$. One could take, for instance, the matrix of an equiangular tight frame when $$N = n + k$$, $$k = {\rm constant}$$. Other examples of suitable dictionaries found in [21] include harmonic frames again with $$N = n + k$$, $$k = {\rm constant}$$, as well as Fourier and Haar frames with constant redundancy factor $$N/n$$. Figure 1 summarizes the relationship between the various domains we deal with. Fig. 1 View largeDownload slide The coefficient, signal and measurement domains. Fig. 1 View largeDownload slide The coefficient, signal and measurement domains. 1.4 Contributions Our main results demonstrate that one-bit compressive sensing is viable even when the sparsifying transform is an overcomplete dictionary. As outlined in Section 1.1, we consider both the challenge of recovering the direction $${\bf f}/\\|{\bf f}\\|_2$$ of a signal $${\bf f}$$, and the challenge of recovering the entire signal (direction and magnitude). Using measurements of the form $$y_i = \mathrm{sgn}\langle {\bf a}_i, {\bf f} \rangle$$, we can recover the direction but not the magnitude; using measurements of the form $$y_i = \mathrm{sgn}\left(\langle {\bf a}_i, {\bf f} \rangle - \tau_i \right)$$, we may recover both. In (one-bit) compressive sensing, two standard families of algorithms are (a) algorithms based on convex programming, and (b) algorithms based on thresholding. In this article, we analyze algorithms from both classes. One reason to study multiple algorithms is to give a more complete landscape of this problem. Another reason is that the different algorithms come with different trade-offs (between computational complexity and the strength of assumptions required), and it is valuable to explore this space of trade-offs. 1.4.1 Recovering the direction First, we show that the direction of a dictionary-sparse signal can be estimated from one-bit measurements of the type $$\mathrm{sgn}({\bf A} {\bf f})$$. We consider two algorithms: our first approach is based on linear programming, and our second is based on hard thresholding. The linear programming approach is more computationally demanding, but applies to a broader class of signals. In Section 3, we prove that both of these approaches are effective, provided the sensing matrix $${\bf A}$$ satisfies certain properties. In Section 2, we state that these properties are in fact satisfied by a matrix $${\bf A}$$ populated with independent Gaussian entries. We combine all of these results to prove the statement below. As noted above, the different algorithms require different definitions of ‘dictionary sparsity’. In what follows, $$\gamma, C, c$$ refer to absolute numerical constants. Theorem 1 (Informal statement of direction recovery) Let $$\varepsilon \,{>}\, 0$$, let $$m \,{\ge}\, C \varepsilon^{-7} s \ln(eN/s)$$ and let $${\bf A} \in \mathbb{R}^{m \times n}$$ be populated by independent standard normal random variables. Then, with failure probability at most $$\gamma \exp(-c \varepsilon^2 m)$$, any dictionary-sparse2 signal $${\bf f} \in \mathbb{R}^n$$ observed via $${\bf y} = \mathrm{sgn}({\bf A} {\bf f})$$ can be approximated by the output $$\widehat{{\bf f}}$$ of an efficient algorithm with error $$\left\\| \frac{{\bf f}}{\\|{\bf f}\\|_2} - \frac{\widehat{{\bf f}}}{\\|\widehat{{\bf f}}\\|_2} \right\\|_2 \le \varepsilon.$$ 1.4.2 Recovering the whole signal By using one-bit measurements of the form $$\mathrm{sgn}({\bf A} {\bf f} - \boldsymbol{\tau})$$, where $$\tau_1,\ldots,\tau_m$$ are properly normalized Gaussian random thresholds, we are able to recover not just the direction, but also the magnitude of a dictionary-sparse signal $${\bf f}$$. We consider three algorithms: our first approach is based on linear programming, our second approach on second-order cone programming and our third approach on hard thresholding. Again, there are different trade-offs to the different algorithms. As above, the approach based on hard thresholding is more efficient, whereas the approaches based on convex programming apply to a broader signal class. There is also a trade-off between linear programming and second-order cone programming: the second-order cone program requires knowledge of $$\\|{\bf f}\\|_2,$$ whereas the linear program does not (although it does require a loose bound), but the second-order cone programming approach applies to a slightly larger class of signals. We show in Section 4 that all three of these algorithms are effective when the sensing matrix $${\bf A}$$ is populated with independent Gaussian entries, and when the thresholds $$\tau_i$$ are also independent Gaussian random variables. We combine the results of Section 4 in the following theorem. Theorem 2 (Informal statement of signal estimation) Let $$\varepsilon, r, \sigma > 0$$, let $$m \ge C \varepsilon^{-9} s \ln(eN/s)$$, and let $${\bf A} \in \mathbb{R}^{m \times n}$$ and $$\boldsymbol{\tau} \in \mathbb{R}^m$$ be populated by independent mean-zero normal random variables with variance $$1$$ and $$\sigma^2$$, respectively. Then, with failure probability at most $$\gamma \exp(-c \varepsilon^2 m)$$, any dictionary-sparse$$^2$$ signal $${\bf f} \in \mathbb{R}^n$$ with $$\\|{\bf f}\\|_2 \le r$$ observed via $${\bf y} = \mathrm{sgn}({\bf A} {\bf f} - \boldsymbol{\tau})$$ is approximated by the output $$\widehat{{\bf f}}$$ of an efficient algorithm with error $$\left\\| {\bf f} - \widehat{{\bf f}} \right\\|_2 \le \varepsilon r.$$ We have not spelled out the dependence of the number of measurements and the failure probability on the parameters $$r$$ and $$\sigma$$: as long as they are roughly the same order of magnitude, the dependence is absorbed in the constants $$C$$ and $$c$$ (see Section 4 for precise statements). As outlined earlier, an estimate of $$r$$ is required to implement the second-order cone program, but the other two algorithms do not require such an estimate. 1.5 Discussion and future directions The purpose of this work is to demonstrate that techniques from one-bit compressive sensing can be effective for the recovery of dictionary-sparse signals, and we propose several algorithms to accomplish this for various notions of dictionary sparsity. Still, some interesting future directions remain. First, we do not believe that the dependence on $$\varepsilon$$ above is optimal. We do believe instead that a logarithmic dependence on $$\varepsilon$$ for the number of measurements (or equivalently an exponential decay in the oversampling factor $$\lambda = m / (s \ln(eN/s))$$ for the recovery error) is possible by choosing the thresholds $$\tau_1,\ldots,\tau_m$$ adaptively. This would be achieved by adjusting the method of [2], but with the strong proviso of exact sparsity. Secondly, it is worth asking to what extent the trade-offs between the different algorithms reflect reality. In particular, is it only an artifact of the proof that the simpler algorithm based on hard thresholding applies to a narrower class of signals? 1.6 Organization The remainder of the article is organized as follows. In Section 2, we outline some technical tools upon which our results rely, namely some properties of Gaussian random matrices. In Section 3, we consider recovery of the direction $${\bf f}/\\|{\bf f}\\|$$ only and we propose two algorithms to achieve it. In Section 4, we present three algorithms for the recovery of the entire signal $${\bf f}$$. Finally, in Section 5, we provide proofs for the results outlined in Section 2. 2. Technical ingredients In this section, we highlight the theoretical properties upon which our results rely. Their proofs are deferred to Section 5 so that the reader does not lose track of our objectives. The first property we put forward is an adaptation to the dictionary case of the so-called sign product embedding property (the term was coined in [18], but the result originally appeared in [25]). Theorem 3 ($${\bf D}$$-SPEP) Let $$\delta > 0$$, let $$m \ge C \delta^{-7} s \ln(eN/s)$$ and let $${\bf A} \in \mathbb{R}^{m \times n}$$ be populated by independent standard normal random variables. Then, with failure probability at most $$\gamma \exp(-c \delta^2 m)$$, the renormalized matrix $${\bf A}':= (\sqrt{2/\pi}/m) {\bf A}$$ satisfies the $$s$$th-order sign product embedding property adapted to $${\bf D} \in \mathbb{R}^{n \times N}$$ with constant $$\delta$$ — $${\bf D}$$-SPEP$$(s,\delta)$$ for short—i.e. $$\label{SPEP} \left\| \langle {\bf A}' {\bf f}, \mathrm{sgn}({\bf A}' {\bf g}) \rangle - \langle {\bf f}, {\bf g} \rangle \right\| \le \delta$$ (2.1) holds for all $${\bf f}, {\bf g} \in {\bf D}({\it {\Sigma}}^N_s) \cap S^{n-1}$$. Remark 1 The power $$\delta^{-7}$$ is unlikely to be optimal. At least in the non-dictionary case, i.e. when $${\bf D} = {\bf I}_n$$, it can be reduced to $$\delta^{-2}$$, see [3]. As an immediate consequence of $${\bf D}$$-SPEP, setting $${\bf g} = {\bf f}$$ in (2.1) allows one to deduce a variation of the classical restricted isometry property adapted to $${\bf D}$$, where the inner norm becomes the $$\ell_1$$-norm (we mention in passing that this variation could also be deduced by other means). Corollary 1 ($${\bf D}$$-RIP$$_1$$) Let $$\delta \,{>}\, 0$$, let $$m \,{\ge}\, C \delta^{-7} s \,{\ln}\,(eN/s)$$ and let $${\bf A} \in \mathbb{R}^{m \times n}$$ be populated by independent standard normal random variables. Then, with failure probability at most $$\gamma \exp(-c \delta^2 m)$$, the renormalized matrix $${\bf A}':= (\sqrt{2/\pi}/m) {\bf A}$$ satisfies the $$s$$th-order $$\ell_1$$-restricted isometry property adapted to $${\bf D} \in \mathbb{R}^{n \times N}$$ with constant $$\delta$$ — $${\bf D}$$-RIP$$_{1}(s,\delta)$$ for short—i.e. $$(1-\delta) \\| {\bf f}\\|_2 \le \\| {\bf A}' {\bf f} \\|_1 \le (1+\delta) \\|{\bf f}\\|_2$$ (2.2) holds for all $${\bf f} \in {\bf D}({\it {\Sigma}}_s^N)$$. The next property we put forward is an adaptation of the tessellation of the ‘effectively sparse sphere’ (see [26]) to the dictionary case. In what follows, given a (non-invertible) matrix $${\bf M}$$ and a set $$K$$, we denote by $${\bf M}^{-1} (K)$$ the preimage of $$K$$ with respect to $${\bf M}$$. Theorem 4 (Tessellation) Let $$\varepsilon > 0$$, let $$m \ge C \varepsilon^{-6} s \ln(eN/s)$$ and let $${\bf A} \in \mathbb{R}^{m \times n}$$ be populated by independent standard normal random variables. Then, with failure probability at most $$\gamma \exp(-c \varepsilon^2 m)$$, the rows $${\bf a}_1,\ldots,{\bf a}_m \in \mathbb{R}^n$$ of $${\bf A}$$$$\varepsilon$$-tessellate the effectively $$s$$-analysis-sparse sphere—we write that $${\bf A}$$ satisfies $${\bf D}$$-TES$$(s,\varepsilon)$$ for short—i.e. $$\label{Tes} [{\bf f},{\bf g} \in ({\bf D}^)^{-1}({\it {\Sigma}}_{s}^{N,{\rm eff}}) \cap S^{n-1} : \; \mathrm{sgn} \langle {\bf a}_i, {\bf f} \rangle = \mathrm{sgn} \langle {\bf a}_i, {\bf g} \rangle \mbox{for all} i =1,\ldots,m] \Longrightarrow [\\|{\bf f} - {\bf g}\\|_2 \le \varepsilon].$$ (2.3) 3. Signal estimation: direction only In this whole section, given a measurement matrix $${\bf A} \in \mathbb{R}^{m \times n}$$ with rows $${\bf a}_1,\ldots,{\bf a}_m \in \mathbb{R}^n$$, the signals $${\bf f} \in \mathbb{R}^n$$ are acquired via $${\bf y} = \mathrm{sgn}({\bf A} {\bf f}) \in \{-1,+1\}^m$$, i.e. $$y_i = \mathrm{sgn} \langle {\bf a}_i, {\bf f} \rangle \qquad i = 1,\ldots,m.$$ Under this model, all $$c {\bf f}$$ with $$c>0$$ produce the same one-bit measurements, so one can only hope to recover the direction of $${\bf f}$$. We present two methods to do so, one based on linear programming and the other one based on hard thresholding. 3.1 Linear programming Given a signal $${\bf f} \in \mathbb{R}^n$$ observed via $${\bf y} = \mathrm{sgn} ({\bf A} {\bf f})$$, the optimization scheme we consider here consists in outputting the signal $${\bf f}_{\rm lp}$$ solution of $$\label{LPforDir} \underset{{{\bf h} \in \mathbb{R}^n}}{\rm minimize}\, \\| {\bf D}^* {\bf h}\\|_1 \qquad \mbox{subject to} \quad \mathrm{sgn}({\bf A} {\bf h}) = {\bf y} \quad \\|{\bf A} {\bf h}\\|_1 = 1.$$ (3.1) This is in fact a linear program (and thus may be solved efficiently), since the condition $$\mathrm{sgn}({\bf A} {\bf h}) = {\bf y}$$ reads $$y_i ({\bf A} {\bf h})_i \ge 0 \qquad \mbox{for all} i = 1,\ldots, m,$$ and, under this constraint, the condition $$\\|{\bf A} {\bf h}\\|_1 = 1$$ reads $$\sum_{i=1}^m y_i ({\bf A} {\bf h})_i = 1.$$ Theorem 5 If $${\bf A} \,{\in}\, \mathbb{R}^{m \times n}$$ satisfies both $${\bf D}$$-TES$$(36s,\varepsilon)$$ and $${\bf D}$$-RIP$$_1(25s,1/5)$$, then any effectively $$s$$-analysis-sparse signal $${\bf f} \in ({\bf D}^)^{-1}{\it {\Sigma}}_s^{N,{\rm eff}}$$ observed via $${\bf y} = \mathrm{sgn}({\bf A} {\bf f})$$ is directionally approximated by the output $${\bf f}_{\rm lp}$$ of the linear program (3.1) with error $$\left\\| \frac{{\bf f}}{\\|{\bf f}\\|_2} - \frac{{\bf f}_{\rm lp}}{\\|{\bf f}_{\rm lp}\\|_2} \right\\|_2 \le \varepsilon.$$ Proof. The main step is to show that $${\bf f}_{\rm lp}$$ is effectively $$36s$$-analysis sparse when $${\bf D}$$-RIP$$_1(t,\delta)$$ holds with $$t= 25s$$ and $$\delta=1/5$$. Then, since both $${\bf f}/\\|{\bf f}\\|_2$$ and $${\bf f}_{\rm lp} / \\|{\bf f}_{\rm lp}\\|_2$$ belong to $$({\bf D}^)^{-1}{\it {\Sigma}}_{36 s}^{N,{\rm eff}} \cap S^{n-1}$$ and have the same sign observations, $${\bf D}$$-TES$$(36s,\varepsilon)$$ implies the desired conclusion. To prove the effective analysis sparsity of $${\bf f}_{\rm lp}$$, we first estimate $$\\|{\bf A} {\bf f}\\|_1$$ from below. For this purpose, let $$T_0$$ denote an index set of $$t$$ largest absolute entries of $${\bf D}^* {\bf f}$$, $$T_1$$ an index set of next $$t$$ largest absolute entries of $${\bf D}^* {\bf f}$$, $$T_2$$ an index set of next $$t$$ largest absolute entries of $${\bf D}^* {\bf f}$$, etc. We have \begin{align} \\|{\bf A} {\bf f} \\|_1 & = \\|{\bf A} {\bf D} {\bf D}^ {\bf f}\\|_1 = \left\\| {\bf A} {\bf D} \left(\sum_{k \ge 0} ({\bf D}^{\bf f})_{T_k} \right) \right\\|_1 \ge \\|{\bf A} {\bf D} \left(({\bf D}^ {\bf f})_{T_0} \right)\!\\|_1 - \sum_{k \ge 1} \\|{\bf A} {\bf D} \left(({\bf D}^* {\bf f})_{T_k} \right)\!\\|_1\\ & \ge (1-\delta) \\|{\bf D} \left(({\bf D}^* {\bf f})_{T_0} \right)\!\\|_2 - \sum_{k \ge 1} (1+\delta) \\|{\bf D} \left(({\bf D}^* {\bf f})_{T_k} \right)\!\\|_2, \end{align} where the last step used $${\bf D}$$-RIP$$_1(t,\delta)$$. We notice that, for $$k \ge 1$$, $$\\|{\bf D} \left(({\bf D}^ {\bf f})_{T_k} \right)\!\\|_2 \le \\| ({\bf D}^* {\bf f})_{T_k}\! \\|_2 \le \frac{1}{\sqrt{t}} \\| ({\bf D}^* {\bf f})_{T_{k-1}}\!\\|_1,$$ from where it follows that $$\label{LowerAf} \\|{\bf A} {\bf f}\\|_1 \ge (1-\delta) \\|{\bf D} \left(({\bf D}^* {\bf f})_{T_0}\right)\!\\|_2 - \frac{1+\delta}{\sqrt{t}} \\|{\bf D}^* {\bf f} \\|_1.$$ (3.2) In addition, we observe that \begin{align} \\|{\bf D}^ {\bf f} \\|_2 & = \\|{\bf f}\\|_2 = \\|{\bf D} {\bf D}^* {\bf f}\\|_2 = \left\\| {\bf D} \left(\sum_{k \ge 0} ({\bf D}^* {\bf f})_{T_k} \right) \right\\|_2 \le \left\\| {\bf D} \left(({\bf D}^* {\bf f})_{T_0} \right) \right\\|_2 + \sum_{k \ge 1} \left\\| {\bf D} \left(({\bf D}^* {\bf f})_{T_k} \right) \right\\|_2\\ & \le \left\\| {\bf D} \left(({\bf D}^* {\bf f})_{T_0} \right) \right\\|_2 + \frac{1}{\sqrt{t}} \\|{\bf D}^* {\bf f} \\|_1. \end{align} In view of the effective sparsity of $${\bf D}^ {\bf f}$$, we obtain $$\\|{\bf D}^* {\bf f}\\|_1 \le \sqrt{s} \\|{\bf D}^* {\bf f}\\|_2 \le \sqrt{s}\left\\| {\bf D} \left(({\bf D}^* {\bf f})_{T_0} \right) \right\\|_2 + \sqrt{s/t} \\|{\bf D}^* {\bf f} \\|_1,$$ hence $$\label{LowerDDT0} \left\\| {\bf D} \left(({\bf D}^ {\bf f})_{T_0} \right) \right\\|_2 \ge \frac{1- \sqrt{s/t}}{\sqrt{s}} \\|{\bf D}^* {\bf f} \\|_1.$$ (3.3) Substituting (3.3) in (3.2) yields $$\label{LowerAf2} \\|{\bf A} {\bf f}\\|_1 \ge \left((1-\delta)(1-\sqrt{s/t}) - (1+\delta)(\sqrt{s/t}) \right) \frac{1}{\sqrt{s}} \\|{\bf D}^* {\bf f}\\|_1 = \frac{2/5}{\sqrt{s}} \\|{\bf D}^* {\bf f}\\|_1,$$ (3.4) where we have used the values $$t = 25s$$ and $$\delta=1/5$$. This lower estimate for $$\\|{\bf A} {\bf f} \\|_1$$, combined with the minimality property of $${\bf f}_{\rm lp}$$, allows us to derive that $$\label{UpperDfhat} \\|{\bf D}^ {\bf f}_{\rm lp} \\|_1 \le \\|{\bf D}^({\bf f}/ \\|{\bf A} {\bf f}\\|_1)\\|_1 = \frac{\\|{\bf D}^ {\bf f}\\|_1}{\\|{\bf A} {\bf f} \\|_1} \le (5/2) \sqrt{s}.$$ (3.5) Next, with $$\widehat{T}_0$$ denoting an index set of $$t$$ largest absolute entries of $${\bf D}^* {\bf f}_{\rm lp}$$, $$\widehat{T}_1$$ an index set of next $$t$$ largest absolute entries of $${\bf D}^* {\bf f}_{\rm lp}$$, $$\widehat{T}_2$$ an index set of next $$t$$ largest absolute entries of $${\bf D}^* {\bf f}_{\rm lp}$$, etc., we can write \begin{align} 1 & = \\|{\bf A} {\bf f}_{\rm lp} \\|_1 = \\|{\bf A} {\bf D} {\bf D}^ {\bf f}_{\rm lp} \\|_1 = \left\\| {\bf A} {\bf D} \left(\sum_{k \ge 0} ({\bf D}^* {\bf f}_{\rm lp})_{\widehat{T}_k} \right) \right\\|_1 \le \sum_{k \ge 0} \left\\| {\bf A} {\bf D} \left(({\bf D}^* {\bf f}_{\rm lp})_{\widehat{T}_k} \right) \right\\|_1\\ & \le \sum_{k \ge 0} (1+\delta) \left\\| {\bf D} \left(({\bf D}^* {\bf f}_{\rm lp})_{\widehat{T}_k} \right) \right\\|_2 = (1+\delta) \left[\!\left\\| ({\bf D}^* {\bf f}_{\rm lp})_{\widehat{T}_0} \right\\|_2 + \sum_{k \ge 1} \!\left\\| ({\bf D}^* {\bf f}_{\rm lp})_{\widehat{T}_k} \right\\|_2 \right]\\ & \le (1+\delta) \left[\\|{\bf D}^* {\bf f}_{\rm lp} \\|_2 + \frac{1}{\sqrt{t}} \\|{\bf D}^* {\bf f}_{\rm lp}\\|_1 \right] \le (1+\delta) \left[\\|{\bf D}^* {\bf f}_{\rm lp} \\|_2 + (5/2)\sqrt{s/t} \right]. \end{align} This chain of inequalities shows that $$\label{LowerDfhat} \\|{\bf D}^* {\bf f}_{\rm lp} \\|_2 \ge \frac{1-(5/2)\sqrt{s/t}}{1+\delta} = \frac{5}{12}.$$ (3.6) Combining (3.5) and (3.6), we obtain $$\\|{\bf D}^* {\bf f}_{\rm lp} \\|_1 \le 6 \sqrt{s} \\|{\bf D}^* {\bf f}_{\rm lp} \\|_2.$$ In other words, $${\bf D}^* {\bf f}_{\rm lp}$$ is effectively $$36s$$-sparse, which is what was needed to conclude the proof. □ Remark 2 We point out that if $${\bf f}$$ was genuinely, instead of effectively, $$s$$-analysis sparse, then a lower bound of the type (3.4) would be immediate from the $${\bf D}$$-RIP$$_1$$. We also point out that our method of proving that the linear program outputs an effectively analysis-sparse signal is new even in the case $${\bf D} = {\bf I}_n$$. In fact, it makes it possible to remove a logarithmic factor from the number of measurements in this ‘non-dictionary’ case, too (compare with [24]). Furthermore, it allows for an analysis of the linear program (3.1) only based on deterministic conditions that the matrix $${\bf A}$$ may satisfy. 3.2 Hard thresholding Given a signal $${\bf f} \in \mathbb{R}^n$$ observed via $${\bf y} = \mathrm{sgn} ({\bf A} {\bf f})$$, the hard thresholding scheme we consider here consists in constructing a signal $${\bf f}_{\rm ht} \in \mathbb{R}^n$$ as $$\label{HTforDir} {\bf f}_{\rm ht} = {\bf D} {\bf z}, \qquad \mbox{where} {\bf z} := H_t({\bf D}^* {\bf A}^* {\bf y}).$$ (3.7) Our recovery result holds for $$s$$-synthesis-sparse signals that are also effectively $$\kappa s$$-analysis sparse for some $$\kappa \ge 1$$ (we discussed in Section 1 some choices of dictionaries $${\bf D}$$ making this happen). Theorem 6 If $${\bf A} \in \mathbb{R}^{m \times n}$$ satisfies $${\bf D}$$-SPEP$$(s+t,\varepsilon/8)$$, $$t = \lceil 16 \varepsilon^{-2} \kappa s \rceil$$, then any $$s$$-synthesis-sparse signal $${\bf f} \in {\bf D}({\it {\Sigma}}_s^N)$$ with $${\bf D}^* {\bf f} \in {\it {\Sigma}}_{\kappa s}^{N,{\rm eff}}$$ observed via $${\bf y} = \mathrm{sgn} ({\bf A} {\bf f})$$ is directionally approximated by the output $${\bf f}_{\rm ht}$$ of the hard thresholding (3.7) with error $$\left\\| \frac{{\bf f}}{\\|{\bf f}\\|_2} - \frac{{\bf f}_{\rm ht}}{\\|{\bf f}_{\rm ht}\\|_2} \right\\|_2 \le \varepsilon.$$ Proof. We assume without loss of generality that $$\\|{\bf f}\\|_2 = 1$$. Let $$T=T_0$$ denote an index set of $$t$$ largest absolute entries of $${\bf D}^* {\bf f}$$, $$T_1$$ an index set of next $$t$$ largest absolute entries of $${\bf D}^* {\bf f}$$, $$T_2$$ an index set of next $$t$$ largest absolute entries of $${\bf D}^* {\bf f}$$, etc. We start by noticing that $${\bf z}$$ is a better $$t$$-sparse approximation to $${\bf D}^* {\bf A}^* {\bf y} = {\bf D}^* {\bf A}^* \mathrm{sgn}({\bf A} {\bf f})$$ than $$[{\bf D}^* {\bf f}]_T$$, so we can write $$\\| {\bf D}^* {\bf A}^* \mathrm{sgn}({\bf A} {\bf f}) - {\bf z} \\|_2^2 \le \\|{\bf D}^* {\bf A}^* \mathrm{sgn}({\bf A} {\bf f}) - [{\bf D}^* {\bf f}]_T \\|_2^2,$$ i.e. $$\\| ({\bf D}^* {\bf f} - {\bf z}) - ({\bf D}^* {\bf f} - {\bf D}^* {\bf A}^* \mathrm{sgn}({\bf A} {\bf f})) \\|_2^2 \le \\| ({\bf D}^* {\bf f} - {\bf D}^* {\bf A}^* \mathrm{sgn}({\bf A} {\bf f})) - [{\bf D}^* {\bf f}]_{\overline{T}} \\|_2^2.$$ Expanding the squares and rearranging gives \begin{align} \label{Term1} \\|{\bf D}^* {\bf f} - {\bf z} \\|_2^2 & \le 2 \langle {\bf D}^* {\bf f} - {\bf z}, {\bf D}^* {\bf f} - {\bf D}^* {\bf A}^* \mathrm{sgn}({\bf A} {\bf f}) \rangle \\ \end{align} (3.8) \begin{align} \label{Term2} & - 2 \langle [{\bf D}^* {\bf f}]_{\overline{T}} , {\bf D}^* {\bf f} - {\bf D}^* {\bf A}^* \mathrm{sgn}({\bf A} {\bf f}) \rangle \\ \end{align} (3.9) \begin{align} \label{Term3} & + \\| [{\bf D}^* {\bf f}]_{\overline{T}} \\|_2^2. \end{align} (3.10) To bound (3.10), we invoke [15, Theorem 2.5] and the effective analysis sparsity of $${\bf f}$$ to derive $$\\| [{\bf D}^* {\bf f}]_{\overline{T}} \\|_2^2 \le \frac{1}{4t} \\| {\bf D}^* {\bf f} \\|_1^2 \le \frac{\kappa s}{4t} \\| {\bf D}^* {\bf f} \\|_2^2 = \frac{\kappa s}{4t} \\|{\bf f} \\|_2^2 = \frac{\kappa s}{4t}.$$ To bound (3.8) in absolute value, we notice that it can be written as \begin{align} 2 \| \langle {\bf D} {\bf D}^ {\bf f} - {\bf D} {\bf z}, &{\bf f} - {\bf A}^* \mathrm{sgn}({\bf A} {\bf f}) \rangle \| = 2 \| \langle {\bf f} - {\bf f}_{\rm ht}, {\bf f} - {\bf A}^* \mathrm{sgn}({\bf A} {\bf f}) \rangle \| \\ & = 2 \| \langle {\bf f} - {\bf f}_{\rm ht}, {\bf f} \rangle - \langle {\bf A} ({\bf f} - {\bf f}_{\rm ht}), \mathrm{sgn}({\bf A} {\bf f}) \rangle \| \le 2 \varepsilon' \\|{\bf f} - {\bf f}_{\rm ht} \\|_2, \end{align} where the last step followed from $${\bf D}$$-SPEP$$(s+t,\varepsilon')$$, $$\varepsilon' := \varepsilon /8$$. Finally, (3.9) can be bounded in absolute value by \begin{align} 2 & \sum_{k \ge 1} \| \langle [{\bf D}^* {\bf f}]_{T_k}, {\bf D}^({\bf f} - {\bf A}^ \mathrm{sgn}({\bf A} {\bf f})) \rangle \| = 2 \sum_{k \ge 1} \| \langle {\bf D}([{\bf D}^* {\bf f}]_{T_k}), {\bf f} - {\bf A}^* \mathrm{sgn}({\bf A} {\bf f}) \rangle \| \\ & = 2 \sum_{k \ge 1} \| \langle {\bf D}([{\bf D}^* {\bf f}]_{T_k}), {\bf f} \rangle - \langle {\bf A} ({\bf D}([{\bf D}^* {\bf f}]_{T_k})), \mathrm{sgn}({\bf A} {\bf f}) \rangle \| \le 2 \sum_{k \ge 1} \varepsilon' \\| {\bf D}([{\bf D}^* {\bf f}]_{T_k}) \\|_2\\ & \le 2 \varepsilon' \sum_{k \ge 1} \\| [{\bf D}^* {\bf f}]_{T_k} \\|_2 \le 2 \varepsilon' \sum_{k \ge 1} \frac{\\| [{\bf D}^* {\bf f}]_{T_{k-1}} \\|_1}{\sqrt{t}} \le 2 \varepsilon' \frac{\\|{\bf D}^* {\bf f}\\|_1}{\sqrt{t}} \le 2 \varepsilon' \frac{\sqrt{\kappa s} \\|{\bf D}^* {\bf f}\\|_2}{\sqrt{t}} = 2 \varepsilon' \sqrt{\frac{\kappa s}{t}}. \end{align} Putting everything together, we obtain $$\\|{\bf D}^ {\bf f} - {\bf z} \\|_2^2 \le 2 \varepsilon' \\|{\bf f} - {\bf f}_{\rm ht}\\|_2 + 2 \varepsilon' \sqrt{\frac{\kappa s}{t}} + \frac{\kappa s}{4t}.$$ In view of $$\\|{\bf f} - {\bf f}_{\rm ht}\\|_2 = \\|{\bf D} ({\bf D}^* {\bf f} - {\bf z}) \\|_2 \le \\|{\bf D}^* {\bf f} - {\bf z}\\|_2$$, it follows that $$\\|{\bf f} - {\bf f}_{\rm ht}\\|_2^2 \le 2 \varepsilon' \\|{\bf f} - {\bf f}_{\rm ht}\\|_2 + 2 \varepsilon' \sqrt{\frac{\kappa s}{t}} + \frac{\kappa s}{4t}, \quad \mbox{i.e.} \; (\\|{\bf f} - {\bf f}_{\rm ht}\\|_2 - \varepsilon')^2 \le {\varepsilon'}^2 + 2 \varepsilon' \sqrt{\frac{\kappa s}{t}} + \frac{\kappa s}{4t} \le \left(\varepsilon' \hspace{-0.5mm}+\hspace{-0.5mm} \sqrt{\frac{\kappa s}{t}} \right)^2 \hspace{-1mm}.$$ This implies that $$\\|{\bf f} - {\bf f}_{\rm ht}\\|_2 \le 2 \varepsilon' + \sqrt{\frac{\kappa s}{t}}.$$ Finally, since $${\bf f}_{\rm ht}/\\|{\bf f}_{\rm ht}\\|_2$$ is the best $$\ell_2$$-normalized approximation to $${\bf f}_{\rm ht}$$, we conclude that $$\left\\| {\bf f} - \frac{{\bf f}_{\rm ht}}{\\|{\bf f}_{\rm ht}\\|_2} \right\\|_2 \le \\|{\bf f} - {\bf f}_{\rm ht}\\|_2 + \left\\| {\bf f}_{\rm ht} - \frac{{\bf f}_{\rm ht}}{\\|{\bf f}_{\rm ht}\\|_2} \right\\|_2 \le 2 \\|{\bf f} - {\bf f}_{\rm ht}\\|_2 \le 4 \varepsilon' + 2 \sqrt{\frac{\kappa s}{t}}.$$ The announced result follows from our choices of $$t$$ and $$\varepsilon'$$. □ 4. Signal estimation: direction and magnitude Since information of the type $$y_i = \mathrm{sgn} \langle {\bf a}_i,{\bf f} \rangle$$ can at best allow one to estimate the direction of a signal $${\bf f} \in \mathbb{R}^n$$, we consider in this section information of the type $$y_i = \mathrm{sgn}(\langle {\bf a}_i, {\bf f} \rangle - \tau_i) \qquad i = 1,\ldots,m ,$$ for some thresholds $$\tau_1,\ldots,\tau_m$$ introduced before quantization. In the rest of this section, we give three methods for recovering $${\bf f}$$ in its entirety. The first one is based on linear programming, the second one on second-order code programming and the last one on hard thresholding. We are going to show that using these algorithms, one can estimate both the direction and the magnitude of dictionary-sparse signal $${\bf f} \in \mathbb{R}^n$$ given a prior magnitude bound such as $$\\| {\bf f} \\|_2 \le r$$. We simply rely on the previous results by ‘lifting’ the situation from $$\mathbb{R}^n$$ to $$\mathbb{R}^{n+1}$$, in view of the observation that $${\bf y} = \mathrm{sgn} ({\bf A} {\bf f} - \boldsymbol{\tau})$$ can be interpreted as The following lemma will be equally useful when dealing with linear programming, second-order cone programming or hard thresholding schemes. Lemma 1 For $$\widetilde{{\bf f}}, \widetilde{{\bf g}} \in \mathbb{R}^{n+1}$$ written as $$\widetilde{{\bf f}} := \begin{bmatrix} {\bf f}_{[n]} \\ \hline f_{n+1} \end{bmatrix} \qquad \mbox{and} \qquad \widetilde{{\bf g}} =: \begin{bmatrix} {\bf g}_{[n]} \\ \hline g_{n+1} \end{bmatrix}$$ with $$\widetilde{{\bf f}}_{[n]}, \widetilde{{\bf g}}_{[n]} \in \mathbb{R}^n$$ and with $$f_{n+1} \not= 0$$, $$g_{n+1} \not= 0$$, one has $$\left\\| \frac{{\bf f}_{[n]}}{f_{n+1}} - \frac{{\bf g}_{[n]}}{g_{n+1}} \right\\|_2 \le \frac{\\|\widetilde{{\bf f}}\\|_2 \\|\widetilde{{\bf g}}\\|_2}{\|f_{n+1}\|\|g_{n+1}\|} \left\\| \frac{\widetilde{{\bf f}}}{\\|\widetilde{{\bf f}}\\|_2} - \frac{\widetilde{{\bf g}}}{\\|\widetilde{{\bf g}}\\|_2} \right\\|_2.$$ Proof. By using the triangle inequality in $$\mathbb{R}^n$$ and Cauchy–Schwarz inequality in $$\mathbb{R}^2$$, we can write \begin{align} \left\\| \frac{{\bf f}_{[n]}}{f_{n+1}} - \frac{{\bf g}_{[n]}}{g_{n+1}} \right\\|_2 & = \\|\widetilde{{\bf f}}\\|_2 \left\\| \frac{1/f_{n+1}}{\\|\widetilde{{\bf f}}\\|_2} {\bf f}_{[n]} - \frac{1/g_{n+1}}{\\|\widetilde{{\bf f}}\\|_2} {\bf g}_{[n]} \right\\|_2\\ & \le \\|\widetilde{{\bf f}}\\|_2 \left(\frac{1}{f_{n+1}} \left\\| \frac{{\bf f}_{[n]}}{\\| \widetilde{{\bf f}} \\|_2} - \frac{{\bf g}_{[n]}}{\\|\widetilde{{\bf g}}\\|_2} \right\\|_2 + \left\| \frac{1/g_{n+1}}{\\|\widetilde{{\bf f}}\\|_2} - \frac{1/f_{n+1}}{\\|\widetilde{{\bf g}}\\|_2} \right\| \\|{\bf g}_{[n]}\\|_2 \right)\\ & = \\|\widetilde{{\bf f}}\\|_2 \left(\frac{1}{f_{n+1}} \left\\| \frac{{\bf f}_{[n]}}{\\| \widetilde{{\bf f}} \\|_2} - \frac{{\bf g}_{[n]}}{\\|\widetilde{{\bf g}}\\|_2} \right\\|_2 + \frac{\\|{\bf g}_{[n]}\\|_2}{\|f_{n+1}\| \|g_{n+1}\|} \left\| \frac{f_{n+1}}{\\|\widetilde{{\bf f}}\\|_2} - \frac{g_{n+1}}{\\|\widetilde{{\bf g}}\\|_2} \right\| \right)\\ & \le \\|\widetilde{{\bf f}}\\|_2 \left[\frac{1}{\|f_{n+1}\|^2} + \frac{\\|{\bf g}_{[n]}\\|_2^2}{\|f_{n+1}\|^2 \|g_{n+1}\|^2} \right]^{1/2} \left[\left\\| \frac{{\bf f}_{[n]}}{\\| \widetilde{{\bf f}} \\|_2} - \frac{{\bf g}_{[n]}}{\\|\widetilde{{\bf g}}\\|_2} \right\\|_2^2 + \left\| \frac{f_{n+1}}{\\|\widetilde{{\bf f}}\\|_2} - \frac{g_{n+1}}{\\|\widetilde{{\bf g}}\\|_2} \right\|^2 \right]^{1/2}\\ & = \\|\widetilde{{\bf f}}\\|_2 \left[\frac{\\|\widetilde{{\bf g}}\\|_2^2}{\|f_{n+1}\|^2 \|g_{n+1}\|^2} \right]^{1/2} \left\\| \frac{\widetilde{{\bf f}}}{\\|\widetilde{{\bf f}}\\|_2} - \frac{\widetilde{{\bf g}}}{\\|\widetilde{{\bf g}}\\|_2} \right\\|_2, \end{align} which is the announced result. □ 4.1 Linear programming Given a signal $${\bf f} \in \mathbb{R}^n$$ observed via $${\bf y} = \mathrm{sgn} ({\bf A} {\bf f} - \boldsymbol{\tau})$$ with $$\tau_1,\ldots,\tau_m \sim \mathscr{N}(0,\sigma^2)$$, the optimization scheme we consider here consists in outputting the signal $$\label{Defflp} {\bf f}_{\rm LP} = \frac{\sigma}{\widehat{u}} \widehat{{\bf h}} \in \mathbb{R}^n,$$ (4.1) where $$\widehat{{\bf h}} \in \mathbb{R}^{n}$$ and $$\widehat{u} \in \mathbb{R}$$ are solutions of $$\label{OptProg} \underset{{\bf h} \in \mathbb{R}^n, u \in \mathbb{R}}{\rm minimize \;} \; \\|{\bf D}^* {\bf h} \\|_1 + \|u\| \qquad \mbox{subject to} \quad \mathrm{sgn}({\bf A} {\bf h} - u \boldsymbol{\tau} / \sigma) = {\bf y}, \quad \\|{\bf A} {\bf h} - u \boldsymbol{\tau} / \sigma \\|_1 = 1.$$ (4.2) Theorem 7 Let $$\varepsilon, r, \sigma > 0$$, let $$m \ge C (r/\sigma+\sigma/r)^6 \varepsilon^{-6} s \ln(eN/s)$$ and let $${\bf A} \in \mathbb{R}^{m \times n}$$ be populated by independent standard normal random variables. Furthermore, let $$\tau_1,\ldots,\tau_m$$ be independent normal random variables with mean zero and variance $$\sigma^2$$ that are also independent from the entries of $${\bf A}$$. Then, with failure probability at most $$\gamma \exp(-c m \varepsilon^2 r^2 \sigma^2/(r^2+\sigma^2)^2)$$, any effectively $$s$$-analysis sparse $${\bf f} \in \mathbb{R}^n$$ satisfying $$\\|{\bf f}\\|_2 \le r$$ and observed via $${\bf y} = \mathrm{sgn}({\bf A} {\bf f} - \boldsymbol{\tau})$$ is approximated by $${\bf f}_{\rm LP}$$ given in (4.1) with error $$\left\\| {\bf f}- {\bf f}_{\rm LP} \right\\|_2 \le \varepsilon r.$$ Proof. Let us introduce the ‘lifted’ signal $$\widetilde{{\bf f}} \in \mathbb{R}^{n+1}$$, the ‘lifted’ tight frame $$\widetilde{{\bf D}} \in \mathbb{R}^{(n+1)\times (N+1)}$$, and the ‘lifted’ measurement matrix $$\widetilde{{\bf A}} \in \mathbb{R}^{m \times (N+1)}$$ defined as $$\tilde{\mathbf{f}}:=\left[\!\!\!\frac{\ \ \ \mathbf{f}\ \ }{\sigma}\!\!\!\right],\quad \tilde{\mathbf{D}}:=\left[\!\!\begin{array}{c\|c} \mathbf{D} & \mathbf{0}\\\hline \mathbf{0} & \mathbf{1} \end{array}\!\!\right],\quad \tilde{\mathbf{A}}:= \left[\begin{array}{c\|c} & -\tau_1/\sigma\\ \mathbf{A} & \vdots \\ & -\tau_m/\sigma\end{array}\right].$$ (4.3) First, we observe that $$\widetilde{{\bf f}}$$ is effectively $$(s+1)$$-analysis sparse (relative to $$\widetilde{{\bf D}}$$), since , hence $$\frac{\\|\widetilde{{\bf D}}^* \widetilde{{\bf f}}\\|_1}{\\|\widetilde{{\bf D}}^* \widetilde{{\bf f}}\\|_2} = \frac{\\|{\bf D}^* {\bf f} \\|_1 + \sigma}{\sqrt{\\|{\bf D}^* {\bf f}\\|_2^2+\sigma^2}} \le \frac{\sqrt{s} \\|{\bf D}^* {\bf f}\\|_2 + \sigma}{\sqrt{\\|{\bf D}^* {\bf f}\\|_2^2+\sigma^2}} \le \sqrt{s+1}.$$ Next, we observe that the matrix $$\widetilde{{\bf A}} \in \mathbb{R}^{m \times (n+1)}$$, populated by independent standard normal random variables, satisfies $$\widetilde{{\bf D}}$$-TES$$(36(s+1),\varepsilon')$$, $$\varepsilon' := \dfrac{r \sigma}{2(r^2 + \sigma^2)} \varepsilon$$ and $$\widetilde{{\bf D}}$$-RIP$$_1(25(s+1),1/5)$$ with failure probability at most $$\gamma \exp(-c m {\varepsilon'}^2) + \gamma' \exp(-c' m) \le \gamma'' \exp(-c'' m \varepsilon^2 r^2 \sigma^2 / (r^2 + \sigma^2)^2)$$, since $$m \ge C {\varepsilon'}^{-6} (s+1) \ln(eN/(s+1))$$ and $$m \ge C (1/5)^{-7} (s+1) \ln(e N / (s+1))$$ are ensured by our assumption on $$m$$. Finally, we observe that $${\bf y} = \mathrm{sgn}(\widetilde{{\bf A}} \widetilde{{\bf f}})$$ and that the optimization program (4.2) reads $$\underset{\widetilde{{\bf h}} \in \mathbb{R}^{n+1}}{\rm minimize \;} \\|\widetilde{{\bf D}}^* \widetilde{{\bf h}} \\|_1 \qquad \mbox{subject to} \quad \mathrm{sgn}(\widetilde{{\bf A}} \widetilde{{\bf h}}) = {\bf y}, \quad \\|\widetilde{{\bf A}} \widetilde{{\bf h}} \\|_1 = 1.$$ Denoting its solution as , Theorem 5 implies that $$\left\\| \frac{\widetilde{{\bf f}}}{\\|\widetilde{{\bf f}}\\|_2} - \frac{\widetilde{{\bf g}}}{\\|\widetilde{{\bf g}}\\|_2} \right\\|_2 \le \varepsilon'.$$ In particular, looking at the last coordinate, this inequality yields $$\left\| \frac{\sigma}{\\|\widetilde{{\bf f}}\\|_2} - \frac{g_{n+1}}{\\|\widetilde{{\bf g}}\\|_2} \right\| \le \varepsilon', \qquad \mbox{hence} \qquad \frac{\|g_{n+1}\|}{\\|\widetilde{{\bf g}}\\|_2} \ge \frac{\sigma}{\\|\widetilde{{\bf f}}\\|_2} - \varepsilon' \ge \frac{\sigma}{\sqrt{r^2+\sigma^2}} - \frac{\sigma}{2 \sqrt{r^2 + \sigma^2}} = \frac{\sigma}{2 \sqrt{r^2 + \sigma^2}}.$$ In turn, applying Lemma 1 while taking $${\bf f} = {\bf f}_{[n]}$$ and $${\bf f}_{\rm LP} = (\sigma/g_{n+1}) {\bf g}_{[n]}$$ into consideration gives $$\left\\| \frac{{\bf f}}{\sigma} - \frac{{\bf f}_{\rm LP}}{\sigma} \right\\|_2 \le \frac{\\| \widetilde{{\bf f}} \\|_2}{\sigma} \frac{\\| \widetilde{{\bf g}} \\|_2}{\|g_{n+1}\|} \varepsilon' \le \frac{\\| \widetilde{{\bf f}} \\|_2}{\sigma} \frac{2\sqrt{r^2+\sigma^2}}{\sigma} \frac{r \sigma}{2(r^2 + \sigma^2)} \varepsilon = \frac{\\| \widetilde{{\bf f}} \\|_2}{\sigma} \frac{r}{\sqrt{r^2+\sigma^2}} \varepsilon,$$ so that $$\\| {\bf f} - {\bf f}_{\rm LP} \\|_2 \le \\|\widetilde{{\bf f}}\\|_2 \frac{r}{\sqrt{r^2+\sigma^2}} \varepsilon \le r \varepsilon.$$ This establishes the announced result. □ Remark 3 The recovery scheme (4.2) does not require an estimation of $$r$$ to be run. The recovery scheme presented next does require such an estimation. Moreover, it is a second-order cone program instead of a simpler linear program. However, it has one noticeable advantage, namely that it applies not only to signals satisfying $$\\|{\bf D}^* {\bf f}\\|_1 \le \sqrt{s}\\|{\bf D}^{\bf f}\\|_2$$ and $$\\|{\bf D}^{\bf f}\\|_2 \le r$$, but also more generally to signals satisfying $$\\|{\bf D}^* {\bf f}\\|_1 \le \sqrt{s} r$$ and $$\\|{\bf D}^{\bf f}\\|_2 \le r$$. For both schemes, one needs $$\sigma$$ to be of the same order as $$r$$ for the results to become meaningful in terms of number of measurement and success probability. However, if $$r$$ is only upper-estimated, then one could choose $$\sigma \ge r$$ and obtain a weaker recovery error $$\\|{\bf f} - \widehat{{\bf f}}\\|_2 \le \varepsilon \sigma$$ with relevant number of measurement and success probability. 4.2 Second-order cone programming Given a signal $${\bf f} \in \mathbb{R}^n$$ observed via $${\bf y} = \mathrm{sgn} ({\bf A} {\bf f} - \boldsymbol{\tau})$$ with $$\tau_1,\ldots,\tau_m \sim \mathscr{N}(0,\sigma^2)$$, the optimization scheme we consider here consists in outputting the signal $$\label{Deffcp} {\bf f}_{\rm CP} = \underset{{\bf h} \in \mathbb{R}^n}{\rm {\rm argmin}\, \;} \; \\|{\bf D}^ {\bf h}\\|_1 \qquad \mbox{subject to} \quad \mathrm{sgn}({\bf A} {\bf h} - \boldsymbol{\tau}) = {\bf y}, \quad \\|{\bf h}\\|_2 \le r.$$ (4.4) Theorem 8 Let $$\varepsilon, r, \sigma > 0$$, let $$m \ge C (r/\sigma + \sigma/r)^6(r^2/\sigma^2+1) \varepsilon^{-6} s \ln(eN/s)$$ and let $${\bf A} \in \mathbb{R}^{m \times n}$$ be populated by independent standard normal random variables. Furthermore, let $$\tau_1,\ldots,\tau_m$$ be independent normal random variables with mean zero and variance $$\sigma^2$$ that are also independent from $${\bf A}$$. Then, with failure probability at most $$\gamma \exp(- c' m \varepsilon^2 r^2 \sigma^2 / (r^2+\sigma^2)^2)$$, any signal $${\bf f} \in \mathbb{R}^n$$ with $$\\|{\bf f}\\|_2 \le r$$, $$\\|{\bf D}^* {\bf f}\\|_1 \le \sqrt{s} r$$ and observed via $${\bf y} = \mathrm{sgn}({\bf A} {\bf f} - \boldsymbol{\tau})$$ is approximated by $${\bf f}_{\rm CP}$$ given in (4.4) with error $$\left\\| {\bf f}- {\bf f}_{\rm CP} \right\\|_2 \le \varepsilon r.$$ Proof. We again use the notation (4.3) introducing the ‘lifted’ objects $$\widetilde{{\bf f}}$$, $$\widetilde{{\bf D}}$$ and $$\widetilde{{\bf A}}$$. Moreover, we set . We claim that $$\widetilde{{\bf f}}$$ and $$\widetilde{{\bf g}}$$ are effectively $$s'$$-analysis sparse, $$s' := (r^2 / \sigma^2 + 1)(s+1)$$. For $$\widetilde{{\bf g}}$$, this indeed follows from $$\\| \widetilde{{\bf D}}^* \widetilde{{\bf g}} \\|_2 = \\|\widetilde{{\bf g}}\\|_2 = \sqrt{\\|{\bf f}_{\rm CP}\\|_2^2 + \sigma^2} \ge \sigma$$ and $$\\|\widetilde{{\bf D}}^* \widetilde{{\bf g}}\\|_1 = \left\\| \begin{bmatrix} {\bf D}^* {\bf f}_{\rm CP} \\ \hline \sigma \end{bmatrix} \right\\|_1 = \\| {\bf D}^* {\bf f}_{\rm CP}\\|_1 + \sigma \le \\| {\bf D}^* {\bf f} \\|_1 + \sigma \le \sqrt{s} r + \sigma \le \sqrt{r^2 + \sigma^2} \sqrt{s+1}.$$ We also notice that $$\widetilde{{\bf A}}$$ satisfies $$\widetilde{{\bf D}}$$-TES$$(s', \varepsilon')$$, $$\varepsilon' \,{:=}\, \dfrac{r \sigma}{r^2 + \sigma^2} \varepsilon$$, with failure probability at most $$\gamma \exp(-c m {\varepsilon'}^2) \le \gamma \exp(- c' m \varepsilon^2 r^2 \sigma^2 / (r^2+\sigma^2)^2)$$, since $$m \ge C {\varepsilon'}^{-6} s' \ln(eN/s')$$ is ensured by our assumption on $$m$$. Finally, we observe that both $$\widetilde{{\bf f}}/ \\|\widetilde{{\bf f}}\\|_2$$ and $$\widetilde{{\bf g}}/ \\|\widetilde{{\bf g}}\\|_2$$ are $$\ell_2$$-normalized effectively $$s'$$-analysis sparse and have the same sign observations $$\mathrm{sgn}(\widetilde{{\bf A}} \widetilde{{\bf f}}) = \mathrm{sgn}(\widetilde{{\bf A}} \widetilde{{\bf g}}) = {\bf y}$$. Thus, $$\left\\| \frac{\widetilde{{\bf f}}}{\\|\widetilde{{\bf f}}\\|_2} - \frac{\widetilde{{\bf g}}}{\\|\widetilde{{\bf g}}\\|_2} \right\\|_2 \le \varepsilon'.$$ In view of Lemma 1, we derive $$\left\\| \frac{{\bf f}}{\sigma} - \frac{{\bf f}_{\rm CP}}{\sigma} \right\\|_2 \le \frac{r^2 + \sigma^2}{\sigma^2} \varepsilon', \qquad \mbox{hence} \qquad \\|{\bf f} - {\bf f}_{\rm CP}\\|_2 \le \frac{r^2 + \sigma^2}{\sigma} \varepsilon' = r \varepsilon.$$ This establishes the announced result. □ 4.3 Hard thresholding Given a signal $${\bf f} \in \mathbb{R}^N$$ observed via $${\bf y} = \mathrm{sgn}({\bf A} {\bf f} - \boldsymbol{\tau})$$ with $$\tau_1,\ldots,\tau_m \sim \mathscr{N}(0,\sigma^2)$$, the hard thresholding scheme we consider here consists in outputting the signal $$\label{fht} {\bf f}_{\rm HT} = \frac{-\sigma^2}{\langle \boldsymbol{\tau}, {\bf y} \rangle} {\bf D} {\bf z}, \qquad {\bf z} = H_{t-1}({\bf D}^* {\bf A}^* {\bf y}).$$ (4.5) Theorem 9 Let $$\varepsilon, r, \sigma > 0$$, let $$m \ge C \kappa (r/\sigma+\sigma/r)^9 \varepsilon^{-9} s \ln(eN/s)$$ and let $${\bf A} \in \mathbb{R}^{m \times n}$$ be populated by independent standard normal random variables. Furthermore, let $$\tau_1,\ldots,\tau_m$$ be independent normal random variables with mean zero and variance $$\sigma^2$$ that are also independent from the entries of $${\bf A}$$. Then, with failure probability at most $$\gamma \exp(-c m \varepsilon^2 r^2 \sigma^2/(r^2+\sigma^2)^2)$$, any $$s$$-synthesis-sparse and effectively $$\kappa s$$-analysis-sparse signal $${\bf f} \in \mathbb{R}^n$$ satisfying $$\\|{\bf f}\\|_2 \le r$$ and observed via $${\bf y} = \mathrm{sgn}({\bf A} {\bf f} - \boldsymbol{\tau})$$ is approximated by $${\bf f}_{\rm HT}$$ given in (4.5) for $$t:=\lceil 16 (\varepsilon'/8)^{-2} \kappa (s+1) \rceil$$ with error $$\left\\| {\bf f}- {\bf f}_{\rm HT} \right\\|_2 \le \varepsilon r.$$ Proof. We again use the notation (4.3) for the ‘lifted’ objects $$\widetilde{{\bf f}}$$, $$\widetilde{{\bf D}}$$ and $$\widetilde{{\bf A}}$$. First, we notice that $$\widetilde{{\bf f}}$$ is $$(s+1)$$-synthesis sparse (relative to $$\widetilde{{\bf D}}$$), as well as effectively $$\kappa (s+1)$$-analysis sparse, since satisfies $$\frac{\\|\widetilde{{\bf D}}^* \widetilde{{\bf f}}\\|_1}{\\|\widetilde{{\bf D}}^* \widetilde{{\bf f}}\\|_2} = \frac{\\|{\bf D}^* {\bf f}\\|_1 + \sigma}{\sqrt{\\|{\bf D}^{\bf f}\\|_2^2 + \sigma^2}} \le \frac{\sqrt{\kappa s}\\|{\bf D}^ {\bf f}\\|_2 + \sigma}{\sqrt{\\|{\bf D}^{\bf f}\\|_2^2 +\sigma^2}} \le \sqrt{\kappa s + 1} \le \sqrt{\kappa (s+1)}.$$ Next, we observe that the matrix $$\widetilde{{\bf A}}$$, populated by independent standard normal random variables, satisfies $$\widetilde{{\bf D}}$$-SPEP$$(s+1+t,\varepsilon'/8)$$, $$\varepsilon ' := \dfrac{r \sigma}{2(r^2 + \sigma^2)} \varepsilon$$, with failure probability at most $$\gamma \exp(-c m {\varepsilon'}^2 r^2)$$, since $$m \ge C (\varepsilon'/8)^{-7} (s+1+t) \ln(e(N+1)/(s+1+t))$$ is ensured by our assumption on $$m$$. Finally, since $${\bf y} = \mathrm{sgn}(\widetilde{{\bf A}} \widetilde{{\bf f}})$$, Theorem 5 implies that $$\left\\| \frac{\widetilde{{\bf f}}}{\\|\widetilde{{\bf f}}\\|_2} - \frac{\widetilde{{\bf g}}}{\\|\widetilde{{\bf g}}\\|_2} \right\\|_2 \le \varepsilon',$$ where $$\widetilde{{\bf g}} \in \mathbb{R}^{n+1}$$ is the output of the ‘lifted’ hard thresholding scheme. i.e. $$\widetilde{{\bf g}} = \widetilde{{\bf D}} \widetilde{{\bf z}}, \qquad \widetilde{{\bf z}} = H_{t} (\widetilde{{\bf D}}^\widetilde{{\bf A}}^* {\bf y}).$$ In particular, looking at the last coordinate, this inequality yields $$\label{LBg} \left\| \frac{\sigma}{\\|\widetilde{{\bf f}}\\|_2} - \frac{g_{n+1}}{\\|\widetilde{{\bf g}}\\|_2} \right\| \le \varepsilon', \quad \mbox{hence} \quad \frac{\|g_{n+1}\|}{\\|\widetilde{{\bf g}}\\|_2} \ge \frac{\sigma}{\\|\widetilde{{\bf f}}\\|_2} - \varepsilon' \ge \frac{\sigma}{\sqrt{r^2+\sigma^2}} - \frac{\sigma}{2 \sqrt{r^2 + \sigma^2}} = \frac{\sigma}{2 \sqrt{r^2 + \sigma^2}}.$$ (4.6) Now let us also observe that $$\widetilde{{\bf z}} = H_{t} \left(\begin{bmatrix} {\bf D}^* {\bf A}^* {\bf y} \\ \hline - \langle \boldsymbol{\tau},{\bf y} \rangle / \sigma \end{bmatrix} \right) = \left\{ \begin{matrix} \begin{bmatrix} H_{t}({\bf D}^* {\bf A}^* {\bf y}) \\ \hline 0 \end{bmatrix}, \\ \mbox{or}\hspace{30mm}\\ \begin{bmatrix} H_{t-1}({\bf D}^* {\bf A}^* {\bf y}) \\ \hline - \langle \boldsymbol{\tau},{\bf y} \rangle / \sigma \end{bmatrix} , \end{matrix} \right. \quad \mbox{hence} \quad \widetilde{{\bf g}} = \widetilde{{\bf D}} \widetilde{{\bf z}} = \left\{ \begin{matrix} \begin{bmatrix} {\bf D}(H_{t}({\bf D}^* {\bf A}^* {\bf y})) \\ \hline 0 \end{bmatrix}, \\ \mbox{or}\hspace{35mm}\\ \begin{bmatrix} {\bf D}(H_{t-1}({\bf D}^* {\bf A}^* {\bf y})) \\ \hline - \langle \boldsymbol{\tau},{\bf y} \rangle / \sigma \end{bmatrix}. \end{matrix} \right.$$ In view of (4.6), the latter option prevails. It is then apparent that $${\bf f}_{\rm HT} = \sigma {\bf g}_{[n]} / g_{n+1}$$. Lemma 1 gives $$\left\\| \frac{{\bf f}}{\sigma} - \frac{{\bf f}_{\rm HT}}{\sigma} \right\\|_2 \le \frac{\\| \widetilde{{\bf f}} \\|_2}{\sigma} \frac{\\| \widetilde{{\bf g}} \\|_2}{\|g_{n+1}\|} \varepsilon' \le \frac{\\| \widetilde{{\bf f}} \\|_2}{\sigma} \frac{2\sqrt{r^2+\sigma^2}}{\sigma} \frac{r \sigma}{2(r^2 + \sigma^2)} \varepsilon = \frac{\\| \widetilde{{\bf f}} \\|_2}{\sigma} \frac{r}{\sqrt{r^2+\sigma^2}} \varepsilon,$$ so that $$\\| {\bf f} - {\bf f}_{\rm HT} \\|_2 \le \\|\widetilde{{\bf f}}\\|_2 \frac{r}{\sqrt{r^2+\sigma^2}} \varepsilon \le r \varepsilon.$$ This establishes the announced result. □ 5. Postponed proofs and further remarks This final section contains the theoretical justification of the technical properties underlying our results, followed by a few points of discussion around them. 5.1 Proof of $${\mathbf D}$$-$${\rm SPEP}$$ The Gaussian width turns out to be a useful tool in our proofs. For a set $$K \subseteq \mathbb{R}^n$$, it is defined by $$w(K) = \mathbb{E} \left[\sup_{{\bf f} \in K} \langle {\bf f}, {\bf g} \rangle \right], \qquad {\bf g} \in \mathbb{R}^n \mbox{is a standard normal random vector}.$$ We isolate the following two properties. Lemma 2 Let $$K \subseteq \mathbb{R}^n$$ be a linear space and $$K_1,\ldots,K_L \subseteq \mathbb{R}^n$$ be subsets of the unit sphere $$S^{n-1}$$. (i) $$k / \sqrt{k+1} \le w(K \cap S^{n-1}) \le \sqrt{k} \qquad k:= \dim (K)$$; (ii) $$\displaystyle{w \left(K_1 \cup \ldots \cup K_L \right) \le \max \left\{w(K_1),\ldots,w(K_L) \right\} + 3 \sqrt{\ln(L)}}$$. Proof. (i) By the invariance under orthogonal transformation (see [25, Proposition 2.1]3), we can assume that $$K = \mathbb{R}^k \times \left\{(0,\ldots,0) \right\}$$. We then notice that $$\sup_{{\bf f} \in K \cap S^{n-1}} \langle {\bf f}, {\bf g} \rangle = \\|(g_1,\ldots,g_k)\\|_2$$ is the $$\ell_2$$-norm of a standard normal random vector of dimension $$k$$. We invoke, e.g. [15, Proposition 8.1] to derive the announced result. (ii) Let us introduce the non-negative random variables $$\xi_\ell := \sup_{{\bf f} \in K_\ell} \langle {\bf f} , {\bf g} \rangle \quad \ell = 1,\ldots, L ,$$ so that the Gaussian widths of each $$K_\ell$$ and of their union take the form $$w(K_\ell) = \mathbb{E}(\xi_\ell) \quad \ell = 1,\ldots, L \qquad \mbox{and} \qquad w \left(K_1 \cup \cdots \cup K_L \right) = \mathbb{E} \left(\max_{\ell = 1, \ldots, L} \xi_\ell \right).$$ By the concentration of measure inequality (see e.g. [15, Theorem 8.40]) applied to the function $$F: {\bf x} \in \mathbb{R}^n \mapsto \sup_{{\bf f} \in K_\ell} \langle {\bf f}, {\bf x} \rangle$$, which is a Lipschitz function with constant $$1$$, each $$\xi_\ell$$ satisfies $$\mathbb{P}(\xi_\ell \ge \mathbb{E}(\xi_\ell) + t) \le \exp \left(-t^2/2 \right)\!.$$ Because each $$\mathbb{E}(\xi_\ell)$$ is no larger than $$\max_\ell \mathbb{E}(\xi_\ell) = \max_\ell w(K_\ell) =: \omega$$, we also have $$\mathbb{P} (\xi_\ell \ge \omega + t) \le \exp \left(-t^2/2 \right)\!.$$ Setting $$v:= \sqrt{2 \ln(L)}$$, we now calculate \begin{align} \mathbb{E} \left(\max_{\ell =1,\ldots, L} \xi_\ell \right) & = \int_0^\infty \mathbb{P} \left(\max_{\ell =1,\ldots, L} \xi_\ell \ge u \right) \,{\rm{d}}u = \left(\int_0^{\omega+v} + \int_{\omega+v}^\infty \right) \mathbb{P} \left(\max_{\ell = 1,\ldots, L} \xi_\ell \ge u \right) \,{\rm{d}}u\\ & \le \int_0^{\omega + v} 1\, {\rm{d}}u + \int_{\omega + v}^\infty \sum_{\ell=1}^L \mathbb{P} \left(\xi_\ell \ge u \right) \,{\rm{d}}u = \omega + v + \sum_{\ell=1}^L \int_v^\infty \mathbb{P} \left(\xi_\ell \ge \omega + t \right) \,{\rm{d}}t\\ & \le \omega + v + L \int_v^\infty \exp \left(-t^2/2 \right)\, {\rm{d}}t \le \omega + v + L \frac{\exp(-v^2/2)}{v} \\ & = \omega + \sqrt{2 \ln(L)} + L \frac{1/L}{\sqrt{2 \ln(L)}} \le \omega + c \sqrt{\ln(L)}, \end{align} where $$c=\sqrt{2} + (\sqrt{2} \ln(2))^{-1} \le 3$$. We have shown that $$w \left(K_1 \cup \cdots \cup K_L \right) \le \max_{\ell} w(K_\ell) + 3 \sqrt{\ln(L)}$$, as desired. □ We now turn our attention to proving the awaited theorem. Proof of Theorem 3. According to [25, Proposition 4.3], with $${\bf A}' := (\sqrt{2/\pi}/m) {\bf A}$$, we have $$\left\| \langle {\bf A}' {\bf f}, \mathrm{sgn}({\bf A}' {\bf g}) \rangle - \langle {\bf f}, {\bf g} \rangle \right\| \le \delta,$$ for all $${\bf f},{\bf g} \in {\bf D}({\it {\Sigma}}_s^N) \cap S^{n-1}$$ provided $$m \ge C \delta^{-7} w({\bf D}({\it {\Sigma}}_s^N) \cap S^{n-1})^2$$, so it is enough to upper bound $$w({\bf D}({\it {\Sigma}}_s^N) \cap S^{n-1})$$ appropriately. To do so, with $${\it {\Sigma}}_S^N$$ denoting the space $$\{{\bf x} \in \mathbb{R}^N: {\rm supp}({\bf x}) \subseteq S \}$$ for any $$S \subseteq \{1,\ldots, N \}$$, we use Lemma 2 to write \begin{align} w({\bf D}({\it {\Sigma}}_s^N) \cap S^{n-1}) & = w \bigg(\bigcup_{\|S\|=s} \left\{{\bf D}({\it {\Sigma}}_S^N) \cap S^{n-1} \right\} \bigg) \underset{(ii)}{\le} \max_{\|S\|=s} w({\bf D}({\it {\Sigma}}_S^N) \cap S^{n-1}) + 3 \sqrt{\ln \left(\binom{N}{s} \right)}\\ & \underset{(i)}{\le} \sqrt{s} + 3 \sqrt{s \ln \left(eN/s \right)} \le 4 \sqrt{s \ln \left(eN/s \right)}. \end{align} The result is now immediate. □ 5.2 Proof of TES We propose two approaches for proving Theorem 4. One uses again the notion of Gaussian width, and the other one relies on covering numbers. The necessary results are isolated in the following lemma. Lemma 3 The set of $$\ell_2$$-normalized effectively $$s$$-analysis-sparse signals satisfies (i) $$\displaystyle{w \left(({\bf D}^)^{-1}({\it {\Sigma}}_s^{N,{\rm eff}}) \cap S^{n-1} \right)} \le C \sqrt{s \ln(eN/s)},$$ (ii) $$\displaystyle{\mathscr{N} \left(({\bf D}^)^{-1}({\it {\Sigma}}_s^{N,{\rm eff}}) \cap S^{n-1} , \rho \right) \le \binom{N}{t}\left(1 + \frac{8}{\rho} \right)^t, \qquad t := \lceil 4 \rho^{-2}} s \rceil.$$ Proof. (i) By the definition of the Gaussian width for $$\mathscr{K}_s: = ({\bf D}^)^{-1}({\it {\Sigma}}_s^{N,{\rm eff}}) \cap S^{n-1}$$, with $${\bf g} \in \mathbb{R}^n$$ denoting a standard normal random vector, $$\label{slep} w(\mathscr{K}_s) = \mathbb{E} \left[\sup_{\substack{{\bf D}^ {\bf f} \in {\it {\Sigma}}_s^{N,{\rm eff}} \\ \\|{\bf f}\\|_2 = 1}} \langle {\bf f} , {\bf g} \rangle \right] = \mathbb{E} \left[\sup_{\substack{{\bf D}^* {\bf f} \in {\it {\Sigma}}_s^{N,{\rm eff}} \\ \\|{\bf D}^* {\bf f}\\|_2 = 1}} \langle {\bf D} {\bf D}^* {\bf f} , {\bf g} \rangle \right] \le \mathbb{E} \left[\sup_{\substack{{\bf x} \in {\it {\Sigma}}_s^{N,{\rm eff}} \\ \\|{\bf x}\\|_2 = 1}} \langle {\bf D} {\bf x} , {\bf g} \rangle \right].$$ (5.1) In view of $$\\|{\bf D}\\|_{2 \to 2} = 1$$, we have, for any $${\bf x},{\bf x}' \in {\it {\Sigma}}_s^{N,{\rm eff}}$$ with $$\\|{\bf x}\\|_2 = \\|{\bf x}'\\|_2 =1$$, \begin{align} \mathbb{E} \left(\langle {\bf D} {\bf x}, {\bf g} \rangle - \langle {\bf D} {\bf x}', {\bf g}' \rangle \right)^2 &= \mathbb{E} \left[\langle {\bf D} {\bf x}, {\bf g} \rangle ^2 \right] + \mathbb{E} \left[\langle {\bf D} {\bf x}', {\bf g}' \rangle ^2 \right] = \\|{\bf D} {\bf x}\\|_2^2 + \\|{\bf D} {\bf x}'\\|_2^2 \le \\|{\bf x}\\|_2^2 + \\|{\bf x}'\\|_2^2\\ &= \mathbb{E} \left(\langle {\bf x}, {\bf g} \rangle - \langle {\bf x}', {\bf g}' \rangle \right)^2. \end{align} Applying Slepian’s lemma (see e.g. [15, Lemma 8.25]), we obtain $$w(\mathscr{K}_s) \le \mathbb{E} \left[\sup_{\substack{{\bf x} \in {\it {\Sigma}}_s^{N,{\rm eff}} \\ \\|{\bf x}\\|_2 = 1}} \langle {\bf x} , {\bf g} \rangle \right] =w({\it {\Sigma}}_s^{N,{\rm eff}} \cap S^{n-1}).$$ The latter is known to be bounded by $$C s \ln (eN/s)$$, see [25, Lemma 2.3]. (ii) The covering number $$\mathscr{N}(\mathscr{K}_s,\rho)$$ is bounded above by the maximal number $$\mathscr{P}(\mathscr{K}_s,\rho)$$ of elements in $$\mathscr{K}_s$$ that are separated by a distance $$\rho$$. We claim that $$\mathscr{P} (\mathscr{K}_s, \rho) \le \mathscr{P}({\it {\Sigma}}_t^N \cap B_2^N, \rho/2)$$. To justify this claim, let us consider a maximal $$\rho$$-separated set $$\{{\bf f}^1,\ldots,{\bf f}^L\}$$ of signals in $$\mathscr{K}_s$$. For each $$i$$, let $$T_i \subseteq \{1, \ldots, N \}$$ denote an index set of $$t$$ largest absolute entries of $${\bf D}^* {\bf f}^i$$. We write $$\rho < \\|{\bf f}^i - {\bf f}^j \\|_2 = \\|{\bf D}^* {\bf f}^i - {\bf D}^* {\bf f}^j \\|_2 \le \\|({\bf D}^* {\bf f}^i)_{T_i} - ({\bf D}^* {\bf f}^j)_{T_j} \\|_2 + \\| ({\bf D}^* {\bf f}^i)_{\overline{T_i}} \\|_2 + \\| ({\bf D}^* {\bf f}^j)_{\overline{T_j}} \\|_2.$$ Invoking [15, Theorem 2.5], we observe that $$\\| ({\bf D}^* {\bf f}^i)_{\overline{T_i}} \\|_2 \le \frac{1}{2\sqrt{t}} \\|{\bf D}^* {\bf f}^i \\|_1 \le \frac{\sqrt{s}}{2 \sqrt{t}} \\|{\bf D}^* {\bf f}^i \\|_2 = \frac{\sqrt{s}}{2 \sqrt{t}},$$ and similarly for $$j$$ instead of $$i$$. Thus, we obtain $$\rho < \\|({\bf D}^* {\bf f}^i)_{T_i} - ({\bf D}^* {\bf f}^j)_{T_j} \\|_2 + \sqrt{\frac{s}{t}} \le \\|({\bf D}^* {\bf f}^i)_{T_i} - ({\bf D}^* {\bf f}^j)_{T_j} \\|_2 + \frac{\rho}{2}, \quad \mbox{i.e.} \; \\|({\bf D}^* {\bf f}^i)_{T_i} - ({\bf D}^* {\bf f}^j)_{T_j} \\|_2 > \frac{\rho}{2}.$$ Since we have uncovered a set of $$L = \mathscr{P}(\mathscr{K}_s,\rho)$$ points in $${\it {\Sigma}}_t^N \cap B_2^N$$ that are $$(\rho/2)$$ separated, the claimed inequality is proved. We conclude by recalling that $$\mathscr{P}({\it {\Sigma}}_t^N \cap B_2^N, \rho/2)$$ is bounded above by $$\mathscr{N}({\it {\Sigma}}_t^N \cap B_2^N, \rho/4)$$, which is itself bounded above by $$\dbinom{N}{t} \left(1 + \dfrac{2}{\rho/4} \right)^t$$. □ We can now turn our attention to proving the awaited theorem. Proof of Theorem 4. With $$\mathscr{K}_s = ({\bf D}^*)^{-1}({\it {\Sigma}}_s^{N,{\rm eff}}) \cap S^{n-1}$$, the conclusion holds when $$m \ge C \varepsilon^{-6} w(\mathscr{K}_s)^2$$ or when $$m \ge C \varepsilon^{-1} \ln (\mathscr{N}(\mathscr{K}_s,c \varepsilon))$$, according to [26, Theorem 1.5] or to [3, Theorem 1.5], respectively. It now suffices to call upon Lemma 3. Note that the latter option yields better powers of $$\varepsilon^{-1}$$, but less pleasant failure probability. □ 5.3 Further remarks We conclude this theoretical section by making two noteworthy comments on the sign product embedding property and the tessellation property in the dictionary case. Remark 4 $${\bf D}$$-SPEP cannot hold for arbitrary dictionary $${\bf D}$$ if synthesis sparsity was replaced by effective synthesis sparsity. This is because the set of effectively $$s$$-synthesis-sparse signals can be the whole space $$\mathbb{R}^n$$. Indeed, let $${\bf f} \in \mathbb{R}^n$$ that can be written as $${\bf f} = {\bf D} {\bf u}$$ for some $${\bf u} \in \mathbb{R}^N$$. Let us also pick an $$(s-1)$$-sparse vector $${\bf v} \in \ker {\bf D}$$—there are tight frames for which this is possible, e.g. the concatenation of two orthogonal matrices. For $$\varepsilon > 0$$ small enough, we have $$\frac{\\|{\bf v} + \varepsilon {\bf u} \\|_1}{\\|{\bf v} + \varepsilon {\bf u}\\|_2} \le \frac{\\|{\bf v}\\|_1 + \varepsilon \\|{\bf u}\\|_1}{\\|{\bf v}\\|_2 - \varepsilon \\|{\bf u}\\|_2} \le \frac{\sqrt{s-1} \\|{\bf v}\\|_2 + \varepsilon \\|{\bf u}\\|_1}{\\|{\bf v}\\|_2 - \varepsilon \\|{\bf u}\\|_2} \le \sqrt{s},$$ so that the coefficient vector $${\bf v} + \varepsilon {\bf u}$$ is effectively $$s$$-sparse, hence so is $$(1/\varepsilon){\bf v} + {\bf u}$$. It follows that $${\bf f} = {\bf D}((1/\varepsilon){\bf v} + {\bf u})$$ is effectively $$s$$-synthesis sparse. Remark 5 Theorem 3 easily implies a tessellation result for $${\bf D}({\it {\Sigma}}_s^N) \,\cap\, S^{n-1}$$, the ‘synthesis-sparse sphere’. Precisely, under the assumptions of the theorem (with a change of the constant $$C$$), $${\bf D}$$-SPEP$$(2s,\delta/2)$$ holds. Then, one can derive $$[{\bf g},{\bf h} \in {\bf D}({\it {\Sigma}}_s) \cap S^{n-1} : \; \mathrm{sgn}({\bf A} {\bf g}) = \mathrm{sgn}({\bf A} {\bf h})] \Longrightarrow [\\|{\bf g} - {\bf h}\\|_2 \le \delta].$$ To see this, with $$\boldsymbol{\varepsilon} := \mathrm{sgn}({\bf A} {\bf g}) = \mathrm{sgn}({\bf A} {\bf h})$$ and with $${\bf f} := ({\bf g}-{\bf h})/\\|{\bf g}-{\bf h}\\|_2 \in {\bf D}({\it {\Sigma}}_{2s}) \cap S^{n-1}$$, we have $$\left\| \frac{\sqrt{2/\pi}}{m} \langle {\bf A} {\bf f} , \boldsymbol{\varepsilon}\rangle - \langle {\bf f}, {\bf g} \rangle \right\| \le \frac{\delta}{2}, \qquad \left\| \frac{\sqrt{2/\pi}}{m} \langle {\bf A} {\bf f} , \boldsymbol{\varepsilon} \rangle - \langle {\bf f}, {\bf h} \rangle \right\| \le \frac{\delta}{2},$$ so by the triangle inequality $$\|\langle {\bf f}, {\bf g} - {\bf h} \rangle\| \le \delta$$, i.e. $$\\|{\bf g} -{\bf h}\\|_2 \le \delta$$, as announced. Acknowledgements The authors would like to thank the AIM SQuaRE program that funded and hosted our initial collaboration. Funding NSF grant number [CCF-1527501], ARO grant number [W911NF-15-1-0316] and AFOSR grant number [FA9550-14-1-0088] to R.B.; Alfred P. Sloan Fellowship and NSF Career grant number [1348721 to D.N.]; NSERC grant number [22R23068 to Y.P.]; and NSF Postdoctoral Research Fellowship grant number [1400558 to M.W.]. Footnotes 1 A signal $${\bf x} \in \mathbb{R}^N$$ is called $$s$$-sparse if $$\\|{\bf x}\\|_0 := \|\mathrm{supp}({\bf x})\| \leq s \ll N$$. 2 Here, ‘dictionary sparsity’ means effective $$s$$-analysis sparsity if $$\widehat{{\bf f}}$$ is produced by convex programming and genuine $$s$$-synthesis sparsity together with effective $$\kappa s$$-analysis sparsity if $$\widehat{{\bf f}}$$ is produced by hard thresholding. 3 In particular, [25, Proposition 2.1] applies to the slightly different notion of mean width defined as $$\mathbb{E} \left[\sup_{{\bf f} \in K - K} \langle {\bf f}, {\bf g} \rangle \right]$$. References 1. ( 2016) Compressive Sensing webpage. http://dsp.rice.edu/cs (accessed 24 June 2016). 2. Baraniuk R., Foucart S., Needell D., Plan Y. & Wootters M. ( 2017) Exponential decay of reconstruction error from binary measurements of sparse signals. IEEE Trans. Inform. Theory, 63, 3368– 3385. Google Scholar CrossRef Search ADS 3. Bilyk D. & Lacey M. T. ( 2015) Random tessellations, restricted isometric embeddings, and one bit sensing. arXiv preprint arXiv:1512.06697. 4. Blumensath T. ( 2011) Sampling and reconstructing signals from a union of linear subspaces. IEEE Trans. Inform. Theory, 57, 4660– 4671. Google Scholar CrossRef Search ADS 5. Boufounos P. T. & Baraniuk R. G. ( 2008) 1-Bit compressive sensing. Proceedings of the 42nd Annual Conference on Information Sciences and Systems (CISS), IEEE, pp. 16– 21. 6. Candès E. J., Demanet L., Donoho D. L. & Ying L. ( 2000) Fast discrete curvelet transforms. Multiscale Model. Simul., 5, 861– 899. Google Scholar CrossRef Search ADS 7. Candès E. J. & Donoho D. L. ( 2004) New tight frames of curvelets and optimal representations of objects with piecewise $$C^2$$ singularities. Comm. Pure Appl. Math., 57, 219– 266. Google Scholar CrossRef Search ADS 8. Candès E. J., Eldar Y. C., Needell D. & Randall P. ( 2010) Compressed sensing with coherent and redundant dictionaries. Appl. Comput. Harmon. Anal., 31, 59– 73. Google Scholar CrossRef Search ADS 9. Daubechies I. ( 1992) Ten Lectures on Wavelets . Philadelphia, PA: SIAM. Google Scholar CrossRef Search ADS 10. Davenport M., Needell D. & Wakin M. B. ( 2012) Signal space CoSaMP for sparse recovery with redundant dictionaries. IEEE Trans. Inform. Theory, 59, 6820– 6829. Google Scholar CrossRef Search ADS 11. Elad M., Milanfar P. & Rubinstein R. ( 2007) Analysis versus synthesis in signal priors. Inverse Probl., 23, 947. Google Scholar CrossRef Search ADS 12. Eldar Y. C. & Kutyniok G. ( 2012) Compressed Sensing: Theory and Applications . Cambridge, UK: Cambridge University Press. Google Scholar CrossRef Search ADS 13. Feichtinger H. & Strohmer T. (eds.) ( 1998) Gabor Analysis and Algorithms . Boston, MA: Birkhäuser. Google Scholar CrossRef Search ADS 14. Foucart S. ( 2016) Dictionary-sparse recovery via thresholding-based algorithms. J. Fourier Anal. Appl., 22, 6– 19. Google Scholar CrossRef Search ADS 15. Foucart S. & Rauhut H. ( 2013) A Mathematical Introduction to Compressive Sensing . Basel, Switzerland: Birkhäuser. Google Scholar CrossRef Search ADS 16. Giryes R., Nam S., Elad M., Gribonval R. & Davies M. E. ( 2014) Greedy-like algorithms for the cosparse analysis model. Linear Algebra Appl., 441, 22– 60. Google Scholar CrossRef Search ADS 17. Gopi S., Netrapalli P., Jain P. & Nori A. ( 2013) One-bit compressed sensing: Provable support and vector recovery. Proceedings of the 30th International Conference on Machine Learning (ICML), Atlanta GA, 2013, pp. 154– 162. 18. Jacques L., Degraux K. & De Vleeschouwer C. ( 2013) Quantized iterative hard thresholding: bridging 1-bit and high-resolution quantized compressed sensing. Proceedings of the 10th International Conference on Sampling Theory and Applications (SampTA), Bremen, Germany, pp. 105– 108. 19. Jacques L., Laska J. N., Boufounos P. T. & Baraniuk R. G. ( 2013) Robust 1-bit compressive sensing via binary stable embeddings of sparse vectors. IEEE Trans. Inform. Theory, 59, 2082– 2102. Google Scholar CrossRef Search ADS 20. Knudson K., Saab R. & Ward R. ( 2016) One-bit compressive sensing with norm estimation. IEEE Trans. Inform. Theory, 62, 2748– 2758. Google Scholar CrossRef Search ADS 21. Krahmer F., Needell D. & Ward R. ( 2015) Compressive sensing with redundant dictionaries and structured measurements. SIAM J. Math. Anal., 47, 4606– 4629. Google Scholar CrossRef Search ADS 22. Nam S., Davies M. E., Elad M. & Gribonval R. ( 2013) The cosparse analysis model and algorithms. Appl. Comput. Harmon. Anal., 34, 30– 56. Google Scholar CrossRef Search ADS 23. Peleg T. & Elad M. ( 2013) Performance guarantees of the thresholding algorithm for the cosparse analysis model. IEEE Trans. Inform. Theory, 59, 1832– 1845. Google Scholar CrossRef Search ADS 24. Plan Y. & Vershynin R. ( 2013a) One-bit compressed sensing by linear programming. Comm. Pure Appl. Math., 66, 1275– 1297. Google Scholar CrossRef Search ADS 25. Plan Y. & Vershynin R. ( 2013b) Robust 1-bit compressed sensing and sparse logistic regression: a convex programming approach. IEEE Trans. Inform. Theory, 59, 482– 494. Google Scholar CrossRef Search ADS 26. Plan Y. & Vershynin R. ( 2014) Dimension reduction by random hyperplane tessellations. Discrete Comput. Geom., 51, 438– 461. Google Scholar CrossRef Search ADS 27. Rauhut H., Schnass K. & Vandergheynst P. ( 2008) Compressed sensing and redundant dictionaries. IEEE Trans. Inform. Theory, 54, 2210– 2219. Google Scholar CrossRef Search ADS 28. Saab R., Wang R. & Yilmaz Ö. ( 2016) Quantization of compressive samples with stable and robust recovery. Applied and Computational Harmonic Analysis, to appear. 29. Starck J.-L., Elad M. & Donoho D. ( 2004) Redundant multiscale transforms and their application for morphological component separation. Advances in Imaging and Electron Physics, 132, 287– 348. Google Scholar CrossRef Search ADS 30. Yan M., Yang Y. & Osher S. ( 2012) Robust 1-bit compressive sensing using adaptive outlier pursuit., IEEE Trans. Signal Process., 60, 3868– 3875. Google Scholar CrossRef Search ADS © The authors 2017. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) For permissions, please e-mail: journals. [email protected] ### Journal Information and Inference: A Journal of the IMAOxford University Press Published: Mar 1, 2018 ## You’re reading a free preview. Subscribe to read the entire article. ### DeepDyve is your personal research library It’s your single place to instantly discover and read the research that matters to you. over 18 million articles from more than 15,000 peer-reviewed journals. All for just $49/month ### Explore the DeepDyve Library ### Search Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly ### Organize Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place. ### Access Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals. ### Your journals are on DeepDyve Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more. All the latest content is available, no embargo periods. DeepDyve ### Freelancer DeepDyve ### Pro Price FREE$49/month \$360/year Save searches from PubMed Create lists to Export lists, citations	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 2, "mathjax_display_tex": 1, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 9, "equation": 60, "x-ck12": 0, "texerror": 0, "math_score": 0.9900538921356201, "perplexity": 856.9686815882927}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.3, "absolute_threshold": 20, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2018-43/segments/1539583514005.65/warc/CC-MAIN-20181021115035-20181021140535-00088.warc.gz"}
http://www.emperorsclothes.co.uk/2012/04/world-book-night-recommendations-from.html	## Friday, 6 April 2012 ### World Book Night - Recommendations from the authors World Book Night this year is on 23rd April. I have chosen to give away The Remains of the Day by Kazuo Ishiguro. The event is taking place in the UK and the US, and 25 different titles have been chosen in each country. This year each of the authors chosen (or their estates or heirs) have in turn recommended a book to their readers. There are excerpts from the recommended books on the WBN website here and the relevant excerpt will also be printed in the back of the free copies of the author's book. Half of the Human Race by Anthony Quinn, chosen by Jane Austen’s publishers Voice of the Fire by Alan Moore, chosen by Iain M. Banks The Creeper by Tania Carver, chosen by Mark Billingham In Trouble Again by Redmond O’Hanlon, chosen by Bill Bryson The Aleph by Jorge Luis Borges, chosen by Paulo Coelho Brighton Rock by Graham Greene, chosen by Martina Cole Cold Granite by Stuart MacBride, chosen by Bernard Cornwell Fingersmith by Sarah Waters, chosen by the Roald Dahl estate The Moonstone by Wilkie Collins, chosen by Charles Dickens’s publishers State of Wonder by Ann Patchett, chosen by Emma Donoghue Rebecca’s Tale by Sally Beauman, chosen by the du Maurier estate Beware of Pity by Stefan Zweig, chosen by Kazuo Ishiguro The Iron Will of Shoeshine Cats by Hesh Kestin, chosen by Stephen King The Diary of a Provincial Lady by E. M. Delafield, chosen by Sophie Kinsella The Lonely Londoners by Sam Selvon, chosen by Andrea Levy Revolver by Marcus Sedgwick, chosen by John Ajvide Lindqvist The Night Circus by Erin Morgenstern, chosen by Audrey Niffenegger Our Spoons Came From Woolworths by Barbara Comyns, chosen by Maggie O’Farrell King Crow by Michael Stewart, chosen by David Peace The Man Who Was Thursday by G. K. Chesterton, chosen by Terry Pratchett & Neil Gaiman Life: An Exploded Diagram by Mal Peet, chosen by Meg Rosoff Miracle in the Andes by Nando Parrado, chosen by Joe Simpson Oranges are not the Only Fruit by Jeanette Winterson, chosen by the Dodie Smith estate Jasper Jones by Craig Silvey, chosen by Markus Zusak If you want to read about my experiences as a giver for World Book Night 2011, please take a look at these posts here, here and here. And there's a video of the launch in Trafalgar Square here.	{"extraction_info": {"found_math": false, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.8784069418907166, "perplexity": 14238.464406940271}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.3, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2014-35/segments/1408500826343.66/warc/CC-MAIN-20140820021346-00223-ip-10-180-136-8.ec2.internal.warc.gz"}
https://scite.ai/reports/on-the-use-of-the-68bL2LY6	2021 DOI: 10.1590/0102-311x00294720 View full text \| \| Share ## Abstract:Abstract: This study illustrates the use of a recently developed sensitivity index, the E-value, helpful in strengthening causal inferences in observational epidemiological studies. The E-value aims to determine the minimum required strength of association between an unmeasured confounder and an exposure/outcome to explain the observed association as non-causal. Such parameter is defined as E - v a l u e = R R + R R R R - 1, where RR is the risk ratio between the exposure and the outcome. Our work illustr… Expand abstract Search citation statements Order By: Relevance Paper Sections 0 0 0 0 0 Citation Types 0 0 0 Publication Types Select... Relationship 0 0 Authors Journals	{"extraction_info": {"found_math": false, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.9520429968833923, "perplexity": 4111.858980670125}, "config": {"markdown_headings": true, "markdown_code": false, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2022-05/segments/1642320303709.2/warc/CC-MAIN-20220121192415-20220121222415-00248.warc.gz"}
https://www.itefi.csic.es/en/cobo-parra-pedro/passive-control-duct-silencers	# Passive control: duct silencers The noise from heating installations of large residential areas is radiated through the chimneys. This noise consists of large low-frequency tones within a wideband noise. The low-frequency tones can be attenuated by large duct silencers. Attenuation of low-frequency noise through the chimney of a heating installation at 70 % (left) or 100 % (right) of its nominal power	{"extraction_info": {"found_math": false, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.870250403881073, "perplexity": 9372.480342347784}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2021-10/segments/1614178364764.57/warc/CC-MAIN-20210302190916-20210302220916-00112.warc.gz"}
http://www.ams.org/cgi-bin/bookstore/booksearch?fn=100&pg1=CN&s1=Muller-Stach_Stefan&arg9=Stefan_M%FCller-Stach	New Titles \| FAQ \| Keep Informed \| Review Cart \| Contact Us Quick Search (Advanced Search ) Browse by Subject General Interest Logic & Foundations Number Theory Algebra & Algebraic Geometry Discrete Math & Combinatorics Analysis Differential Equations Geometry & Topology Probability & Statistics Applications Mathematical Physics Math Education The Arithmetic and Geometry of Algebraic Cycles Edited by: B. Brent Gordon, University of Oklahoma, Norman, OK, James D. Lewis, University of Alberta, Edmonton, AB, Canada, Stefan Müller-Stach, Universität Essen, Germany, Shuji Saito, Tokyo Institute of Technology, Oh-Okayama, Meguro-ku, Japan, and Noriko Yui, Queen's University, Kingston, ON, Canada A co-publication of the AMS and Centre de Recherches Mathématiques. SEARCH THIS BOOK: CRM Proceedings & Lecture Notes 2000; 432 pp; softcover Volume: 24 ISBN-10: 0-8218-1954-2 ISBN-13: 978-0-8218-1954-8 List Price: US$128 Member Price: US$102.40 Order Code: CRMP/24 The NATO ASI/CRM Summer School at Banff offered a unique, full, and in-depth account of the topic, ranging from introductory courses by leading experts to discussions of the latest developments by all participants. The papers have been organized into three categories: cohomological methods; Chow groups and motives; and arithmetic methods. As a subfield of algebraic geometry, the theory of algebraic cycles has gone through various interactions with algebraic $$K$$-theory, Hodge theory, arithmetic algebraic geometry, number theory, and topology. These interactions have led to developments such as a description of Chow groups in terms of algebraic $$K$$-theory, the application of the Merkurjev-Suslin theorem to the arithmetic Abel-Jacobi mapping, progress on the celebrated conjectures of Hodge, and of Tate, which compute cycles class groups respectively in terms of Hodge theory or as the invariants of a Galois group action on étale cohomology, the conjectures of Bloch and Beilinson, which explain the zero or pole of the $$L$$-function of a variety and interpret the leading non-zero coefficient of its Taylor expansion at a critical point, in terms of arithmetic and geometric invariant of the variety and its cycle class groups. The immense recent progress in the theory of algebraic cycles is based on its many interactions with several other areas of mathematics. This conference was the first to focus on both arithmetic and geometric aspects of algebraic cycles. It brought together leading experts to speak from their various points of view. A unique opportunity was created to explore and view the depth and the breadth of the subject. This volume presents the intriguing results. Titles in this series are co-published with the Centre de Recherches Mathématiques. Graduate students and research mathematicians interested in algebraic cycles. Cohomological Methods • S. Abdulali -- Filtrations on the cohomology of abelian varieties • D. Arapura -- Building mixed Hodge structures • R.-O. Buchweitz and H. Flenner -- The Atiyah-Chern character yields the semiregularity map as well as the infinitesimal Abel-Jacobi map • J. Dupont, R. Hain, and S. Zucker -- Regulators and characteristic classes of flat bundles • B. Harris and B. Wang -- Height pairings asymptotics and Bott-Chern forms • K. Kato and S. Usui -- Logarithmic Hodge structures and classifying spaces Chow Groups and Motives • M. Asakura -- Motives and algebraic de Rham cohomology • J. I. Burgos Gil -- Hermitian vector bundles and characteristic classes • M. Hanamura -- The mixed motive of a projective variety • C. Pedrini -- Bloch's conjecture and the $$K$$-theory of projective surfaces • N. Ramachandran -- From Jacobians to one-motives: Exposition of a conjecture of Deligne • S. Saito -- Motives, algebraic cycles and Hodge theory Arithmetic methods • C. F. Doran -- Picard-Fuchs uniformization: Modularity of the mirror map and mirror-moonshine • E. Z. Goren -- Hilbert modular varieties in positive characteristic • Y. Goto -- On the Néron-Severi groups of some $$K$$3 surfaces • J. van Hamel -- Torsion zero-cycles and the Abel-Jacobi map over the real numbers • K. Kimura -- A remark on the Griffiths groups of certain product varieties • J. Nekovář -- $$p$$-adic Abel-Jacobi maps and $$p$$-adic heights • A. Shiho -- Crystalline fundamental groups and $$p$$-adic Hodge theory • H. Verrill and N. Yui -- Thompson series, and the mirror maps of pencils of $$K$$3 surfaces	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 1, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.4776216447353363, "perplexity": 3241.616561118151}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2014-23/segments/1406510267824.47/warc/CC-MAIN-20140728011747-00361-ip-10-146-231-18.ec2.internal.warc.gz"}
http://math.stackexchange.com/questions/5574/a-triangular-representation-for-the-divisor-summatory-function-dx	# A triangular representation for the divisor summatory function, $D(x)$ Let $d(n)$ represent the divisor function as $d(n)=\displaystyle\sum\limits_{k\|n}1$ and the divisor summatory function as $D(x)=\displaystyle\sum\limits_{n \leq x}d(n)$ I found the following triangular representation for the values of $D(n)$ $$\begin{array}{ccccccccc} D(1)=&&&&&&&&& 1 &&&&&&&&&&=1\\ &\\ D(2)=&&&&&&&& 2 &+& 1 &&&&&&&&&=3\\ &\\ D(3)=&&&&&&& 3 &+& 1 &+& 1 &&&&&&&&=5\\ &\\ D(4)=&&&&&& 4 &+& 2 &+& 1 &+& 1 &&&&&&&=8\\ &\\ D(5)=&&&&&5 &+& 2 &+& 1 &+& 1 &+& 1&&&&&&=10\\ &\\ D(6)=&&&&6 &+& 3 &+& 2 &+& 1 &+& 1 &+& 1&&&&&=14\\ &\\ D(7)=&&&7 &+& 3 &+& 2 &+& 1 &+& 1 &+& 1&+& 1 &&&&=16\\ &\\ D(8)=&&8 &+& 4 &+& 2 &+& 2 &+& 1 &+& 1&+& 1&+&1&&&=20\\ &\\ \end{array}$$ The values on the right are the sum of all elements in a row. EDIT 1: The above picture is the result of the following observation: Let $v_{m}(n)$ be the greatest power of $m$ that divides $n$ with $m,n \in \mathbb{N}$ , so we get that $D(n)=\displaystyle\sum\limits_{m=2}^{\infty}v_{m}(p^{n}), p \in \mathbb{P}$ where $p$ is a fixed prime number. I didn't try to prove this. I don't know how to do it, but hopefully some one will have some idea on how to prove or disprove this conjecture. I'd like to know if this is a known fact. I don't have a proof but I've tested lots of values and woks all the time. Thanks. - Am I missing an obvious patter in your column on the right? – BBischof Sep 27 '10 at 15:22 @BBischof, the values on the right are $D(n)$, e.g. $D(1)=1$, $D(2)=3$, $D(3)=5$, $D(4)=8$, etc. – Neves Sep 27 '10 at 15:26 I've swapped n and x in the divisor summatory function. – anon Sep 27 '10 at 15:32 The values in the triangle are just the quotient of dividing the row number by the column number, so it's no surprise that this gives the sum of divisors. – anon Sep 27 '10 at 15:36 When voting down, please, explain why. – Neves Sep 27 '10 at 16:23 Yes, this is true. Write $D(x) = \sum_{n \le x} d(n) = \sum_{n \le x} \sum_{d \| n} 1 = \sum_{d \le x} \lfloor \frac{x}{d} \rfloor$; this is equivalent to the pattern you observe. The last step is exchanging the order of summation together with the observation that the number of times a number $d$ appears in the double sum is the number of numbers less than or equal to $x$ it divides. - thats true, I already knew that way of calculating $D(x)$, but as I came to this observation from another path I never looked at the triangle as a result of $\sum_{d \leq x}\lfloor\frac{x}{d}\rfloor$, but thats true, the values in the triangle are "just the quotient of dividing the row number by the column number". – Neves Sep 27 '10 at 17:10 This answer is a bit of a work in progress, but if $n=2^x-1$, then $$\frac{D(n)+u}{2}=\sum_{j\in\mathcal{N}}\sum_{i=1}^{n}{h_{i,j}} \text{ where } u=\lfloor\sqrt{n}\rfloor$$ where $h_{i,j}$ is the value in the corresponding row,column of the matrix described in http://crypto.stackexchange.com/questions/27003/has-anyone-heard-of-matrix-based-roman-doll-encryption-techniques Furthermore, letting $r_j=\sum_{i\in\mathcal{N}}{h_{i,j}}$, we write: $$D(2^k-1)=u-\xi+2\sum_{l=0}^{k-1}\frac{(k-l+1)(k-l)}{2}\sum_{j=\lfloor 2^{l-1}\rfloor }^{2^l-1}{r_j}$$ where $\xi$ is computed using the program: input k unsigned step = 1 unsigned y = 1 unsigned $\xi$ = 0 while y < 2^k { unsigned bin=(unsigned)log2(y) $\xi$ = $\xi$ + (k-bin)(k-bin+1-(k-bin)%2) y = y + 8* step step = step + 1 } output $\xi$ This suggests a slim possibility of computing $D(x)$ in $log_2(x)$ time. -	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 1, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.9528820514678955, "perplexity": 301.02309832056}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2015-40/segments/1443736680773.55/warc/CC-MAIN-20151001215800-00206-ip-10-137-6-227.ec2.internal.warc.gz"}
https://www.nature.com/articles/s41598-020-69788-0?error=cookies_not_supported&code=39e1d39c-bfd8-479c-80a4-4c286b2e860f	## Introduction Congenital heart disease (CHD), a serious structural abnormality of the heart or large blood vessels in the intrathoracic, is one of the most common types of birth defects (BD) globally1,2. Researches have shown that CHD is a major risk factor for infant mortality associated with BD and can lead to chronic disability, morbidity and increased medical costs3,4,5. It was previously reported that the prevalence of CHD was highest in Asia, second highest in Europe, and lowest in Africa, reflecting significant geographic differences6,7,8. Although environmental and behavioral components play a crucial role in the etiological progression of BD, additional research is still required9,10,11. Over the years, numerous studies exploring risk factors for CHD have confirmed that maternal lifestyle-related factors such as smoking and alcohol intake during pregnancy may be responsible for certain categories of congenital defects1,12,13,14. Because of socio-cultural and geographical reasons, maternal lifestyle-related factors in pregnancy may be different and population-specific in each area. Study results related to associations of maternal lifestyle factors with CHD have not always been consistent across regions15. These conflicting results may in part stem from geographic heterogeneity, which would lead to bias in correlation estimates and associated calculations of standard error. In China, the incidence rate of CHD is the highest among BD, and the surgical treatment of CHD infants is estimated to cost 12 billion Yuan per year16. Our previous study found that the Shaanxi province, which accounts for about half of the population in northwest China, is facing more serious BD than other regions of China17. Simultaneously, due to extremely unbalanced economic development and huge differences in socio-culture among Shaanxi regions, maternal lifestyle during pregnancy is inevitably disparate across different surveyed areas, and spatial heterogeneity may play an important role in the correlation between the incidence of CHD and maternal lifestyles during pregnancy. Therefore, we hypothesized that the relationship between maternal lifestyle during pregnancy and CHD varied significantly from region to region in Shaanxi. In most previous studies, however, conventional regression models were used to produce average parameters to explore the relationship between maternal lifestyle during pregnancy and CHD over the whole study area, but spatial heterogeneity was neglected17,18,19,20. In the present study, we used the Geographically Weighted Logistic Regression (GWLR) model to generate local coefficients to account for geographical variations in evaluating the correlation between CHD in infants and maternal lifestyles during pregnancy. GWLR allows for the examination of local changes and provides a map for the visualization of spatial heterogeneity21. This geographically weighted regression model was helpful in identifying distinct patterns that appeared in different villages and townships, so that we could clearly visualize differences in maternal lifestyles during pregnancy related to CHD among disparate regions. Thus, the current study aimed to (1) describe the geographic distribution of maternal lifestyles during pregnancy across different regions, (2) and explore the spatially varying relationship between maternal lifestyles during pregnancy and CHD adjusting for other possible confounding factors. ## Results ### Baseline characteristics of the participants In this study, a total of 1605 villages were chosen within 272 townships of 30 counties in Shaanxi province, and 29,098 live infants were included in the final analysis. Among the infants included in the study, average age was 16.9 ± 11.3 months (range 0–46 months); 54.4% were male; 98.8% were singletons. Among the mothers included in the study, average age was 28.01 ± 4.86 years; average parity was 1.65 ± 0.82. The proportions of study participants from northern, central, and southern Shaanxi, were 25.7%, 53.9% and 20.3%, respectively. The baseline characteristics of the participants across different areas in Shaanxi province are presented in Table 1. The overall prevalence of CHD among the study respondents was 0.760%, with a range from 0 to 4.4% among Shaanxi Province. Notably, the rate of CHD among subjects was higher in South Shaanxi (1.1%) than the corresponding rate in North Shaanxi (0.5%), and Central Shaanxi (0.8%) (Supplementary Fig. S1). The rate of CHD among infants increased markedly in association with increases in fetal number or infant parity (P for trend < 0.001). A family history of CHD was associated with increased incidence of CHD among infants (P for trend < 0.001). The results obtained showed that the prevalence of CHD increased with maternal age (P for trend < 0.01). The rate of CHD was higher in the floating population than in the permanent population (P = 0.001). The results obtained showed that maternal lifestyle habits during pregnancy, such as second-hand smoking (P for trend < 0.01) and tea consumption (P for trend < 0.01), may increase risk for CHD. The proportion of mothers with a history of passive smoking in pregnancy was highest in North Shaanxi (32.1%), followed by Central Shaanxi (20.8%), and South Shaanxi (20.4%) (Supplementary Fig. S2). With regard to the consumption of alcohol, tea and coffee during pregnancy, South Shaanxi was the area with the highest rate (3.0%, 6.5% and 1.4%, respectively), compared to Central Shaanxi (1.0%, 1.6% and 0.8%, respectively), and North Shaanxi (0.5%, 0.9% and 0.4%, respectively) (Supplementary Fig. S3S5). ### Non-spatial logistic regression Table 2 summarized the significant correlations between CHD and maternal lifestyle-related factors using a logistic regression model adjusting for other possible risk factors. Compared with single fetal births, twin and multi-fetal births were associated with a substantial increase in CHD incidence (OR 5.190, 95%CI 2.293–11.750). CHD was more likely to occur in the children of mothers ≥ 30 years of age, compared with children of mothers 18–24 years of age (OR 2.353, 95% CI 1.338–4.140). The rate of CHD was higher in the floating population (OR 1.933, 95% CI 1.261–2.963) than in the permanent population. Participants who had a family history of CHD, were more likely to suffer from CHD (OR 11.250, 95%CI 4.675–27.075). Compared to those living in South Shaanxi, those living in Central Shaanxi and North Shaanxi had decreased risk for CHD (OR 0.440, 95%CI 0.251–0.773 and OR 0.591, 95%CI 0.382–0.916, respectively). Compared to infants born to mothers without a history of passive smoking during pregnancy, infants born to women with a history of passive smoking during pregnancy had increased risk for CHD (OR 2.449, 95%CI 1.691–3.548). However, other maternal lifestyles during pregnancy, including the frequency of alcohol intake, and consumption of tea and coffee, were not significantly associated with CHD in surveyed areas. ### Multivariate spatial logistic regression Based on the results of GWLR, we determined that the optimal bandwidth size was 27,875,000 (persons). When the results of global regression model fitting were viewed in combination with the results from GWLR, we concluded that the geographically weighted regression had better fitness. The effects of spatial variation on local estimates for CHD risk factors, as determined using the GWLR model are presented in Table 3. With regard to maternal lifestyles during pregnancy, the frequency of passive smoking was found to be positively associated with CHD for 43.3% of participants in South and North Shaanxi province (P < 0.05), with the highest OR observed in North Shaanxi and the lowest OR observed in South Shaanxi (Table 3 and Fig. 1). Approximately 49.2% of all mothers who ever drank tea during pregnancy were more likely to have an infant with CHD, compared to mothers who never drank tea during pregnancy (P < 0.05). For this trend, OR values were highest in North and Central Shaanxi (Table 3 and Fig. 2). Maternal alcohol intake more than once per week was significantly correlated with CHD occurrence among 24.7% of participants (P < 0.05), all of whom lived in North Shaanxi, with adjusted OR values ranging from 0.738 (Central Shaanxi) to 1.198 (North Shaanxi) (Table 3 and Fig. 3). ## Discussion Using the results from a large-scale cross-sectional survey conducted in Shaanxi province in northwestern China, we explored the geographic variation of some maternal lifestyle-related factors during pregnancy in relation to the risk of CHD after controlling for other baseline characteristics using spatial regression models. The results of a study conducted previously in China indicated that the rate of passive smoking among pregnant women ranged from 26.6% to 45.3%, which were 17.1% in Shanghai, 34.88% in Shenzhen and 33.96% in Zhengzhou respectively22. Similarly, our study showed that the proportion of mothers with a history of passive smoking in pregnancy was 23.6% (range 5.5–57.5%) in Shaanxi, which was highest in North Shaanxi (32.1%). These results showed a significant regional variation in Shaanxi. Simultaneously, the rates of the maternal consumption of alcohol, tea and coffee during pregnancy were higher in South Shaanxi in comparison to other areas of Shaanxi. These findings were consistent with regional distribution of CHD incidence, which showed a decreasing trend from north to south in Shaanxi province. Global regression analysis revealed that mothers who had a history of passive smoking during pregnancy were more likely to give birth to a baby with CHD. Studies conducted in the UK and the USA reported similar findings23,24. The GWLR model showed that the OR for passive smoking during pregnancy was highest in North Shaanxi and lowest in Central Shaanxi. Our survey data indicated that passive smoking was higher in North Shaanxi than in Central Shaanxi or South Shaanxi. Most parts of Central Shaanxi are developed urban areas (e.g., Xi'an), where tobacco control measures have been implemented. In comparison with other areas of Shaanxi, Central Shaanxi has more public places that have become true smoke-free environments. Second-hand smoke may therefore be less of an issue for pregnant women in Central Shaanxi. In contrast, the area surveyed in North Shaanxi comprise small townships and villages, where efforts at tobacco control have not been sufficient to reduce the harmful effects of tobacco. One research study conducted in Shaanxi found that a high proportion of participants, especially less educated mothers in North Shaanxi and South Shaanxi, were exposed to environmental tobacco smoke for more than 15 min on at least 1 day per week17. These results remind us that it is extremely urgent to take adequate measures to control tobacco smoking, especially in North Shaanxi. Additional studies will be required to corroborate these findings and to elucidate possible reasons for this geographical variations. Numerous previous studies have found that tea consumption during pregnancy could adversely affect fetal growth and development25,26,27. In our study, the non-spatial logistic regression models showed no significant association between tea consumption during pregnancy and CHD. However, the GWLR model revealed that tea consumption during pregnancy may increase the risk for CHD in 49.2% of all participants (mostly in Central and South Shaanxi province). When we focus on the map drawn by OR values, it is easy to see that OR values were highest in areas near the eastern part of Shaanxi, with a trend of gradual decline from east to west. On account of the high-altitude landform and warm and humid climate environment in South Shaanxi, the region is suitable for the growth of tea. Local residents therefore consume more tea than inhabitants of other areas. The results of our survey showed that the rate of tea consumption was highest in southeast Shaanxi (6.5%), followed by Central Shaanxi (1.6%), and then by North Shaanxi (0.9%). Household economic level may play a role in tea consumption. The socioeconomic stratification of residents in Shaanxi province has been described in previous studies17,18. As a consumer's income increases, he or she is more likely to drink tea28. However, more research is needed to unravel the geographic patterns modulating the harmful effects of tea in relation to risk for CHD. Although the non-global regression results showed no significant correlation between maternal history of alcohol intake and the likelihood of having a child with CHD, the spatial regression model revealed a positive association between maternal history of alcohol intake and the risk of CHD for 24.7% of mothers residing in North Shaanxi. On the map used to visualize these results, the areas with the highest OR values for CHD were mainly distributed in North Shaanxi, followed by South and Central Shaanxi. The relationship between maternal alcohol consumption and CHD has long been studied, with conflicting results. Studies in animal models have identified a significant association between maternal exposure to alcohol during pregnancy and an increased incidence of heart anomalies in offspring29,30. Research conducted by Polygenis et al. revealed no effect of maternal alcohol consumption on fetal malformations31. A review by Henderson et al. found that only one study reported a significant increase in risk for fetal malformations among mothers who consumed alcohol during pregnancy32. Geographical variations may explain, at least in part, the inconsistent results reported for the associations between maternal exposure to alcohol during pregnancy and CHD. However, several limitations should be considered when interpreting our results. Because this research was based on a cross-sectional study of the population, the causal relationship between maternal lifestyle during pregnancy and CHD in offspring could not be demonstrated. Secondly, due to the limited number of areas sampled (only 30 counties and 175 townships), the variation trends in relevant factors were difficult to isolate. Thirdly, the reported information on maternal lifestyle during pregnancy such as that related to alcohol intake, passive smoking, and consumption of tea or coffee was self-reported by mothers. The duration of time that had elapsed between pregnancy and the maternal self-report may have contributed to recall bias. Therefore, we consciously adopted systematic approaches to maximize power and minimize bias in the study. For example, all questionnaires and procedures were pre-tested, and detailed interviewer guides were developed before the formal survey. During maternal interviews, the standardized questionnaire and detailed supporting material (e.g., calendars) were provided to participants to ensure that complete and accurate responses was obtained. Reporting accuracy was ensured for mothers through highly structured interviews by skilled field staff from Xi’an Jiaotong University Health Science Center and experienced doctors from local maternal and children’s hospitals who were blinded to the study hypotheses. Fourthly, the study subject to other potential confounders such as maternal illness, drug use, genetics, maternal obesity, and environmental factors. Despite these limitations, this study was the first exploration of the geographic varying association of maternal lifestyle factors with CHD in northwestern China, and filled in some of the gaps. In conclusion, the prevalence of CHD among live births and the rates of the maternal consumption of alcohol, tea and coffee were higher in South Shaanxi, while the proportion of mothers with a history of passive smoking in pregnancy was highest in North Shaanxi. Maternal alcohol consumption and passive smoking during pregnancy may be important risk factors for CHD, especially in North Shaanxi. Tea consumption during pregnancy appeared to increase risk for CHD in North and Central Shaanxi. ## Materials and methods ### Study design and participants From August to November 2013, a large-scale epidemiologic survey of BD among infants born during 2010–2013, was conducted in Shaanxi province in northwestern China. Because of the imbalance in population density between rural and urban areas, a stratified multi-stage sampling method was used to determine sampling units. While China’s rural areas, counties, townships, and villages have a three-level administrative structure, the administrative structure in urban areas consists of districts, streets, and communities. Twenty counties and ten districts were randomly selected for inclusion in the study. Six townships in each county were chosen, and 6 villages in each selected township were randomly selected. In urban areas, 3 streets in the chosen district and 6 communities on the chosen street were selected randomly. In the end, a completely random sampling method was adopted to select 30 live births and their mothers for each selected village and 60 live births and their mothers for each selected community. The response rate was 92.7%, and a total of 29,098 live babies were ultimately enrolled, representing 9.00% of the province’s total infant population18. ### Data collection Prior to the formal survey, all questionnaires and procedures were pre-tested, and detailed interviewer guides were developed. The final questionnaire had four parts: birth defects questionnaire, family questionnaire, reproductive history questionnaire, and family history questionnaire. In the survey, all the major data collected was reported by mothers with live births. After written informed consent was obtained, face-to-face interviews were performed to extract data on sociodemographic characteristics and maternal lifestyle during pregnancy18. During the investigation, ten survey teams were established for field data collection in the areas surveyed, with each group consisting of 10–12 investigators, a supervisor from Xi'an Jiaotong University Health Science Center, and a pediatrician from the local maternal and child health hospital. Before the start of the survey, all investigators were trained via lectures and field exercises to standardize implementation of the questionnaire. The supervisors were required to report any questionnaires with errors and/or incomplete information. The doctors in each team helped to collect information on BD. The study was strongly supported by local hospitals, administrative health services, and the Shaanxi Provincial Ministry of Health. All data collection occurred at local village clinics and community health service centers. The study was reviewed and approved by the Ethics Committee of Xi'an Jiaotong University Health Science Center, and all methods involving humans were carried out in accordance with relevant guidelines (Declaration of Helsinki). The diagnosis of CHD was a multistage process. As a first step, infants were screened for CHD by a doctor from the local maternal and child health hospital. Isolated patent foramen ovale and patent ductus arteriosus among neonates < 28 days of age were considered to be normal neonatal findings and excluded from the study. As soon as infants were found to have CHD, their mothers were interviewed. The attending physician reviewed the medical record and obtained information pertaining to diagnosis time, hospital, and type of CHD. For new cases of suspected CHD, a special neonatal echocardiogram and electrocardiogram were required for a definitive diagnosis at the First Affiliated Hospital of Xi'an Jiaotong University18. In this study, the vector map of Shaanxi province was obtained through the “Cropping” function of ArcMap, from the Chinese vector map. Meanwhile, geographic information for each township/street in Shaanxi province was acquired from the Geographic Information Comprehensive Service Website (https://www.tianditu.com/). The information obtained included geographic coordinates, boundaries, and altitude. The basic geographic units in this study were townships and streets. Geographic location was defined as the geographic coordinates (i.e., latitude/longitude) for the township/street center where the participant lived. ### Study variables In the study, maternal lifestyle during pregnancy included the frequency of alcohol intake (no, < 1/week, ≥ 1/week), frequency of passive smoking (no, < 1/week, ≥ 1/week), and consumption of tea and coffee during pregnancy (yes, no). Frequency of passive smoking was defined as the number of times that the respondent passively inhaled smoke for > 15 min per day. Before analysis, the frequency of alcohol intake and passive smoking were divided into two dummy variables, respectively: < 1/week (1 = yes, 0 = no), ≥ 1/week (1 = yes, 0 = no), with no as a reference group. Other socio-demographic factors included fetal gender (male, female), fetal number (singleton, twin and multi-fetal), infant parity (1, 2, or ≥ 3), childbearing age (18–24, 25–29, ≥ 30 years), mother’s education (primary school and below, junior high school, senior high school, college and above), mother's marriage (first marriage, others), household registration (urban, rural), Household wealth Index (poor, middle-income, rich), altitude of residence (< 500, 500–1000, > 1000), mother's residence during pregnancy (floating, permanent), family history of CHD (no , yes), and area (South Shaanxi, Central Shaanxi, North Shaanxi). Household wealth index based on the principal component analysis was used to assess the household economic level of the participants. The first principal component representing family economic level was divided into thirds: low, medium, and high (poor, middle-income, rich, respectively). Any CHD were considered unique outcome variables in the multivariate analysis. ### Statistical analysis The analysis procedure is shown in detail below. The geographic distribution of maternal lifestyle during pregnancy were shown on a map using ArcGIS 10.0 software (Environmental Systems Research Institute, Inc., Redlands, CA, US). Non-spatial logistic regression analysis was performed to explore the association between maternal lifestyle during pregnancy and CHD controlling for other confounders by means of IBM SPSS Statistics 25. Then, all explanatory variables were entered into the GWLR model. To confirm geographic discrepancy in the relationship between maternal lifestyle during pregnancy and CHD after adjusting for other factors, local average estimates (OR) and P values for each individual were displayed on a map using ArcGIS 10.0 software. The GWLR formula is as follows33: $$\log \left( {\frac{{P\left( {y_{i} = 1} \right)}}{{1 - P\left( {y_{i} = 1} \right)}}} \right) = \beta_{0i} \left( {u_{i} ,v_{i} } \right) + \mathop \sum \limits_{j = 1}^{k} \left( {\beta_{ij} \left( {u_{i} ,v_{i} } \right)x_{ij} } \right)$$ The equation assumes yi is any CHD for each individual i, xij is a set of independent variables (j = 1, …, k) for individual i, (ui, vi) is the x–y coordinates of individual i; βij is the estimated effect of independent variable j for individual i. The GWLR model was estimated with the iterative reweighted least squares method using GWR 4.0 software (https://geodacenter.asu.edu/software/downloads/gwr_downloads). For modeling, a GWLR equation was estimated for each township/street based on the observations for nearby townships/streets. A distance-based weighting scheme was used to allocate weights to each township/street. The kernel type and function for geographic weighting to estimate local coefficients for each township/street and bandwidth size was adaptive bisquare. The Corrected Akaike Information Criterion (AICc) was used for the golden section search method to select bandwidth in adaptive kernels. The variability of each coefficient in geographic space was tested by comparing different34. In the GWLR model, exponentiation of the explanatory variable coefficients was ultimately calculated to acquire the OR corresponding to the unit change in the variable35.	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 1, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.4327954053878784, "perplexity": 5225.025483158482}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 5, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2023-06/segments/1674764499949.24/warc/CC-MAIN-20230201180036-20230201210036-00824.warc.gz"}
https://sciencing.com/rid-square-root-equation-10023630.html	# How to Get Rid of a Square Root in an Equation ••• Letfluis/iStock/GettyImages Print When you first learned about squared numbers like 32, 52 and x2, you probably learned about a squared number's inverse operation, the square root, too. That inverse relationship between squaring numbers and square roots is important, because in plain English it means that one operation undoes the effects of the other. That means that if you have an equation with square roots in it, you can use the "squaring" operation, or exponents, to remove the square roots. But there are some rules about how to do this, along with the potential trap of false solutions. #### TL;DR (Too Long; Didn't Read) To solve an equation with a square root in it, first isolate the square root on one side of the equation. Then square both sides of the equation and continue solving for the variable. Don't forget to check your work at the end. ## A Simple Example Before considering some of the potential "traps" of solving an equation with square roots in it, consider a simple example: Solve the following equation for x: \sqrt{x} + 1 = 5 1. ## Isolate the Square Root 2. Use arithmetic operations like addition, subtraction, multiplication and division to isolate the square root expression on one side of the equation. For example, if your original equation was √x + 1 = 5, you would subtract 1 from both sides of the equation to get the following: \sqrt{x} = 4 3. ## Square Both Sides of the Equation 4. Squaring both sides of the equation eliminates the square root sign. This gives you: (\sqrt{x})^2 = (4)^2 Or, once simplified: x = 16 You've eliminated the square root sign and you have a value for x, so your work here is done. But wait, there's one more step: 6. Check your work by substituting the x value you found into the original equation: \sqrt{16} + 1 = 5 Next, simplify: 4 + 1 = 5 And finally: 5 = 5 Because this returned a valid statement (5 = 5, as opposed to an invalid statement like 3 = 4 or 2 = -2, the solution you found in Step 2 is valid. In this example, checking your work seems trivial. But this method of eliminating radicals can sometimes create "false" answers that don't work in the original equation. So it's best to get in the habit of always checking your answers to make sure they return a valid result, starting now. ## A Slightly Harder Example What if you have a more complex expression underneath the radical (square root) sign? Consider the following equation. You can still apply the same process used in the previous example, but this equation highlights a couple of rules you must follow. \sqrt{y - 4} + 5 = 29 2. As before, use operations like addition, subtraction, multiplication and division to isolate the radical expression on one side of the equation. In this case, subtracting 5 from both sides gives you: \sqrt{y - 4} = 24 #### Warnings • Note that you're being asked to isolate the square root (which presumably contains a variable, because if it was a constant like √9, you could just solve it on the spot; √9 = 3). You are not being asked to isolate the variable. That step comes later, after you've eliminated the square root sign. 3. ## Square Both Sides 4. Square both sides of the equation, which gives you the following: {\sqrt{y - 4})^2 = (24)^2 Which simplifies to: y - 4 = 576 #### Warnings • Note that you must square everything underneath the radical sign, not just the variable. 5. ## Isolate the Variable 6. Now that you've eliminated the radical or square root from the equation, you can isolate the variable. To continue the example, adding 4 to both sides of the equation gives you: y = 580 8. As before, check your work by substituting the y value you found back into the original equation. This gives you: \sqrt{580 - 4} + 5 = 29 Which simplifies to: \sqrt{576} + 5 = 29 24 + 5 = 29 And finally: 29 = 29 a true statement that indicates a valid result.	{"extraction_info": {"found_math": false, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.8008044362068176, "perplexity": 386.18953417112584}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2021-10/segments/1614178357935.29/warc/CC-MAIN-20210226175238-20210226205238-00189.warc.gz"}
https://histolab.readthedocs.io/en/latest/api/tiler.html	Tiler¶ Different logics are implemented for tile extraction in the tiler module. The constructor of the three extractors RandomTiler, GridTiler, and ScoreTiler share a similar interface and common parameters that define the extraction design: 1. tile_size: the tile size; 2. level: the extraction level, from 0 to the number of available levels; negative indexing is also possible, counting backward from the number of available levels to 0 (e.g. level =-1 means selecting the last available level); 3. check_tissue: True if a minimum percentage of tissue over the total area of the tile is required to save the tiles, False otherwise; 4. tissue_percent: number between 0.0 and 100.0 representing the minimum required ratio of tissue over the total area of the image, considered only if check_tissue equals to True (default is 80.0); 5. prefix: a prefix to be added at the beginning of the tiles’ filename (optional, default is the empty string); 6. suffix: a suffix to be added to the end of the tiles’ filename (optional, default is .png). The general mechanism is to (i) create a tiler object, (ii) define a Slide object, used to identify the input image, and (iii) create a mask object to determine the area for tile extraction within the tissue. The extraction process starts when the tiler’s extract() method is called, with the slide and the mask passed as parameters. RandomTiler¶ The RandomTiler extractor allows for the extraction of tiles picked at random within the regions defined by the binary mask object. Since there is no intrinsic upper bound of the number of the tiles that could be extracted (no overlap check is performed), the number of wanted tiles must be specified. In addition to 1-6, the RandomTiler constructor requires as two additional parameters the number of tiles requested (n_tiles), and the random seed (seed), to ensure reproducibility between different runs on the same WSI. Note that less than n_tiles could be extracted from a slide with not enough tissue pixels and a lot of background, which is checked when the parameter check_tissue is set to True. n_tiles will be interpreted as the upper bound of the number of tiles requested: it might not be possible to extract n_tiles tiles from a slide with a little tissue sample and a lot of background. The extraction procedure will (i) find the regions to extract tiles from, defined by the binary mask object; (ii) generate n_tiles random tiles; (iii) save only the tiles with enough tissue if the attribute check_tissue was set to True, save all the generated tiles otherwise. GridTiler¶ A second basic approach consists of extracting all the tiles in the areas defined by the binary mask. This strategy is implemented in the GridTiler class. The additional pixel_overlap parameter specifies the number of overlapping pixels between two adjacent tiles, i.e. tiles are cropped by using a sliding window with stride s defined as: $s=(w - \mathrm{pixel\_overlap}) \cdot (h - \mathrm{pixel\_overlap})$ where w and h are customizable parameters defining the width and the height of the resulting tiles. Calling the extract method on the GridTiler instance will automatically (i) find the regions to extract tiles from, defined by the binary mask object; (ii) generate all the tiles according to the grid structure; (iii) save only the tiles with “enough tissue” if the attribute check_tissue was set to True, save all the generated tiles otherwise. ScoreTiler¶ Tiles extracted from the same WSI may not be equally informative; for example, if the goal is the detection of mitotic activity on H&E slides, tiles with no nuclei are of little interest. The ScoreTiler extractor ranks the tiles with respect to a scoring function, described in the scorer module. In particular, the ScoreTiler class extends the GridTiler extractor by sorting the extracted tiles in a decreasing order, based on the computed score. Notably, the ScoreTiler is agnostic to the scoring function adopted, thus a custom function can be implemented provided that it inputs a Tile object and outputs a number. The additional parameter n_tiles controls the number of highest-ranked tiles to save; if n_tiles =0 all the tiles are kept. Similarly to the GridTiler extraction process, calling the extract method on the ScoreTiler instance will automatically (i) find the largest tissue area in the WSI; (ii) generate all the tiles according to the grid structure; (iii) retain all the tiles with enough tissue if the attribute check_tissue was set to True, all the generated tiles otherwise; (iv) sort the tiles in a decreasing order according to the scoring function defined in the scorer parameter; (v) save only the highest-ranked n_tiles tiles, if n_tiles>0; (vi) write a summary of the saved tiles and their scores in a CSV file, if the report_path is specified in the extract method. The summary reports for each tile t: (i) the tile filename; (ii) its raw score $$s_t$$; (iii) the normalized score, scaled in the interval [0,1], computed as: $\hat{s}_t = \frac{s_t-\displaystyle{\min_{s\in S}}(s)}{\displaystyle{\max_{s\in S}}(s)-\displaystyle{\min_{s\in S}}(s)}\ ,$ where S is the set of the raw scores of all the extracted tiles. class GridTiler(args, kwds)[source] Extractor of tiles arranged in a grid, at the given level, with the given size. Parameters • tile_size (Tuple[int, int]) – (width, height) of the extracted tiles. • level (int, optional) – Level from which extract the tiles. Default is 0. Superceded by mpp if the mpp argument is provided. • check_tissue (bool, optional) – Whether to check if the tile has enough tissue to be saved. Default is True. • tissue_percent (float, optional) – Number between 0.0 and 100.0 representing the minimum required percentage of tissue over the total area of the image, default is 80.0. This is considered only if check_tissue equals to True. • pixel_overlap (int, optional) – Number of overlapping pixels (for both height and width) between two adjacent tiles. If negative, two adjacent tiles will be strided by the absolute value of pixel_overlap. Default is 0. • prefix (str, optional) – Prefix to be added to the tile filename. Default is an empty string. • suffix (str, optional) – Suffix to be added to the tile filename. Default is ‘.png’ • mpp (float, optional) – Micron per pixel resolution of extracted tiles. Takes precedence over level. Default is None. Extract tiles arranged in a grid and save them to disk, following this filename pattern: {prefix}tile_{tiles_counter}_level{level}_{x_ul_wsi}-{y_ul_wsi}-{x_br_wsi}-{y_br_wsi}{suffix} Parameters • slide (Slide) – Slide from which to extract the tiles • log_level (str, {"DEBUG", "INFO", "WARNING", "ERROR", "CRITICAL"}) – Threshold level for the log messages. Default “INFO” Raises • TileSizeError – If the tile size is larger than the slide size • LevelError – If the level is not available for the slide Return type None Draw tile box references on a rescaled version of the slide Parameters • slide (Slide) – Slide reference where placing the tiles • scale_factor (int, optional) – Scaling factor for the returned image. Default is 32. • alpha (int, optional) – The alpha level to be applied to the rescaled slide. Default is 128. • outline (Union[str, Iterable[str], Iterable[Tuple[int]]], optional) – The outline color for the tile annotations. Default is ‘red’. You can provide this as a string compatible with matplotlib, or you can provide a list of the same length as the tiles, where each color is your assigned color for the corresponding individual tile. This list can be a list of matplotlib-style string colors, or a list of tuples of ints in the [0, 255] range, each of length 3, representing the red, green and blue color for each tile. For example, if you have two tiles that you want to be colored yellow, you can pass this argument as any of the following .. - ‘yellow’ - [‘yellow’, ‘yellow’] - [(255, 255, 0), (255, 255, 0)] • linewidth (int, optional) – Thickness of line used to draw tiles. Default is 1. • tiles (Optional[Iterable[Tile]], optional) – Tiles to visualize. Will be extracted if None. Default is None. You may decide to provide this argument if you do not want the tiles to be re-extracted for visualization if you already have the tiles in hand. Returns PIL Image of the rescaled slide with the extracted tiles outlined Return type PIL.Image.Image property tile_size: Tuple[int, int] (width, height) of the extracted tiles. class RandomTiler(args, *kwds)[source] Extractor of random tiles from a Slide, at the given level, with the given size. Parameters • tile_size (Tuple[int, int]) – (width, height) of the extracted tiles. • n_tiles (int) – Maximum number of tiles to extract. • level (int, optional) – Level from which extract the tiles. Default is 0. Superceded by mpp if the mpp argument is provided. • seed (int, optional) – Seed for RandomState. Must be convertible to 32 bit unsigned integers. Default is 7. • check_tissue (bool, optional) – Whether to check if the tile has enough tissue to be saved. Default is True. • tissue_percent (float, optional) – Number between 0.0 and 100.0 representing the minimum required percentage of tissue over the total area of the image, default is 80.0. This is considered only if check_tissue equals to True. • prefix (str, optional) – Prefix to be added to the tile filename. Default is an empty string. • suffix (str, optional) – Suffix to be added to the tile filename. Default is ‘.png’ • max_iter (int, optional) – Maximum number of iterations performed when searching for eligible (if check_tissue=True) tiles. Must be grater than or equal to n_tiles. • mpp (float, optional) – Micron per pixel resolution. If provided, takes precedence over level. Default is None. Extract random tiles and save them to disk, following this filename pattern: {prefix}tile_{tiles_counter}_level{level}_{x_ul_wsi}-{y_ul_wsi}-{x_br_wsi}-{y_br_wsi}{suffix} Parameters • slide (Slide) – Slide from which to extract the tiles • log_level (str, {"DEBUG", "INFO", "WARNING", "ERROR", "CRITICAL"}) – Threshold level for the log messages. Default “INFO” Raises • TileSizeError – If the tile size is larger than the slide size • LevelError – If the level is not available for the slide Return type None Draw tile box references on a rescaled version of the slide Parameters • slide (Slide) – Slide reference where placing the tiles • scale_factor (int, optional) – Scaling factor for the returned image. Default is 32. • alpha (int, optional) – The alpha level to be applied to the rescaled slide. Default is 128. • outline (Union[str, Iterable[str], Iterable[Tuple[int]]], optional) – The outline color for the tile annotations. Default is ‘red’. You can provide this as a string compatible with matplotlib, or you can provide a list of the same length as the tiles, where each color is your assigned color for the corresponding individual tile. This list can be a list of matplotlib-style string colors, or a list of tuples of ints in the [0, 255] range, each of length 3, representing the red, green and blue color for each tile. For example, if you have two tiles that you want to be colored yellow, you can pass this argument as any of the following .. - ‘yellow’ - [‘yellow’, ‘yellow’] - [(255, 255, 0), (255, 255, 0)] • linewidth (int, optional) – Thickness of line used to draw tiles. Default is 1. • tiles (Optional[Iterable[Tile]], optional) – Tiles to visualize. Will be extracted if None. Default is None. You may decide to provide this argument if you do not want the tiles to be re-extracted for visualization if you already have the tiles in hand. Returns PIL Image of the rescaled slide with the extracted tiles outlined Return type PIL.Image.Image class ScoreTiler(args, **kwds)[source] Extractor of tiles arranged in a grid according to a scoring function. The extraction procedure is the same as the GridTiler extractor, but only the first n_tiles tiles with the highest score are saved. Parameters • scorer (Scorer) – Scoring function used to score the tiles. • tile_size (Tuple[int, int]) – (width, height) of the extracted tiles. • n_tiles (int, optional) – The number of tiles to be saved. Default is 0, which means that all the tiles will be saved (same exact behaviour of a GridTiler). Cannot be negative. • level (int, optional) – Level from which extract the tiles. Default is 0. Superceded by mpp if the mpp argument is provided. • check_tissue (bool, optional) – Whether to check if the tile has enough tissue to be saved. Default is True. • tissue_percent (float, optional) – Number between 0.0 and 100.0 representing the minimum required percentage of tissue over the total area of the image, default is 80.0. This is considered only if check_tissue equals to True. • pixel_overlap (int, optional) – Number of overlapping pixels (for both height and width) between two adjacent tiles. If negative, two adjacent tiles will be strided by the absolute value of pixel_overlap. Default is 0. • prefix (str, optional) – Prefix to be added to the tile filename. Default is an empty string. • suffix (str, optional) – Suffix to be added to the tile filename. Default is ‘.png’ • mpp (float, optional.) – Micron per pixel resolution. If provided, takes precedence over level. Default is None. Extract grid tiles and save them to disk, according to a scoring function and following this filename pattern: {prefix}tile_{tiles_counter}_level{level}_{x_ul_wsi}-{y_ul_wsi}-{x_br_wsi}-{y_br_wsi}{suffix} Save a CSV report file with the saved tiles and the associated score. Parameters • slide (Slide) – Slide from which to extract the tiles • report_path (str, optional) – Path to the CSV report. If None, no report will be saved • log_level (str, {"DEBUG", "INFO", "WARNING", "ERROR", "CRITICAL"}) – Threshold level for the log messages. Default “INFO” Raises • TileSizeError – If the tile size is larger than the slide size • LevelError – If the level is not available for the slide Return type None Draw tile box references on a rescaled version of the slide Parameters • slide (Slide) – Slide reference where placing the tiles • scale_factor (int, optional) – Scaling factor for the returned image. Default is 32. • alpha (int, optional) – The alpha level to be applied to the rescaled slide. Default is 128. • outline (Union[str, Iterable[str], Iterable[Tuple[int]]], optional) – The outline color for the tile annotations. Default is ‘red’. You can provide this as a string compatible with matplotlib, or you can provide a list of the same length as the tiles, where each color is your assigned color for the corresponding individual tile. This list can be a list of matplotlib-style string colors, or a list of tuples of ints in the [0, 255] range, each of length 3, representing the red, green and blue color for each tile. For example, if you have two tiles that you want to be colored yellow, you can pass this argument as any of the following .. - ‘yellow’ - [‘yellow’, ‘yellow’] - [(255, 255, 0), (255, 255, 0)] • linewidth (int, optional) – Thickness of line used to draw tiles. Default is 1. • tiles (Optional[Iterable[Tile]], optional) – Tiles to visualize. Will be extracted if None. Default is None. You may decide to provide this argument if you do not want the tiles to be re-extracted for visualization if you already have the tiles in hand. Returns PIL Image of the rescaled slide with the extracted tiles outlined Return type PIL.Image.Image property tile_size: Tuple[int, int] (width, height) of the extracted tiles.	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 1, "mathjax_asciimath": 1, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.2970852255821228, "perplexity": 3538.9081471830923}, "config": {"markdown_headings": false, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2022-49/segments/1669446711376.47/warc/CC-MAIN-20221209011720-20221209041720-00207.warc.gz"}
https://simplycurious.blog/2021/12/	## The universe in a grain of sand This article attempts to explain a paper I wrote that is published in Europhysics Letters. The English engraver William Blake in a piece of poetry, the $Krishn{\bar a}$ stories, the colossal orders of magnitude of sizes from the humongous to the very small make us wonder if somehow the very large is connected to the very small. A similar theme was explored in physics by a trio of scientists about twenty years ago. They looked at a puzzling problem that has been nagging a rather successful project to use quantum mechanics to explain the physics of fundamental particles. Called “Quantum field theory”, this marriage of quantum mechanics and special relativity (and later, some aspects of general relativity) is probably the most successful theory to emerge in physics in a long while. It has been studied extensively, expanded and some of its predictions in areas where it is possible to make very precise calculations are accurate to fourteen decimal places. It completely excludes the effects of gravity and predicts the precise behavior of small numbers of fundamental particles – how they scatter past each other etc. The basic building block of the theory – the quantum field – is supposed to represent each kind of particle . There is an electron quantum field, one for the up quark etc. etc. If you want to study a theory with five electrons, that is just an excitation of the basic electron quantum field, just as a rapidly oscillating string on a violin has more energy than a slowly oscillating string. More energy in a quantum theory just corresponds to more “quanta” or particles of the field. So far so good. Unfortunately, one inescapable conclusion of the theory is that even when the quantum field is at its lowest possible energy, there is something called “zero-point” motion. Quantum objects cannot just stay at rest, they are jittery and have some energy even in their most quiescent state. As it turns out, bosons have positive energy in this quiescent state. Fermions (like the electron) have negative energy in this quiescent state. This energy in each quantum field can be calculated. It is, for every boson quantum field $+\infty$. For every fermion quantum field, it is $-\infty$. This is a conundrum. The energy in empty space in the universe can be estimated from cosmological measurements. It is roughly equivalent to a few protons to every cubic meter. It is certainly not $\infty$. This conundrum (and its relatives) has affected particle physics for more than fifty years now. Variously referred to as the “cosmological constant” problem or its cousin, the “hierarchy problem”, people have tried many solutions. They need solutions, because if the energy were really $+\infty$ for the boson field (since the universe probably started as radiation dominated with photons), the universe would collapse on itself. This infinite energy spread through space would gravitate and pull the universe in. Solutions, solutions, solutions. Some people have proposed that every particle has a “super”-partner – a boson would have a fermion “super”-partner with the same mass. Since the infinities would be identical, but have opposite signs, they would cancel and we would hence not have an overall energy density in empty space (this would be called the cosmological constant – it would be zero). Unfortunately, we have found no signs of such a “super”-symmetry, though we have looked hard and long. Others have proposed that one should just command the universe to not let this energy gravitate, as a law of nature. That seems arbitrary and would have to be adduced as a separate natural law. And why is tough to answer. Can we measure the effect of this “energy of empty space”, also called “vacuum energy” in some way other than through cosmology? Yes – there is an experiment called the “Casimir effect” which essentially measures the change in this energy when two metallic plates are separated from each other starting from being extremely close. This rather precise experiment confirms that such an energy does exist and can be changed in this fashion. One way to make the conundrum at least finite is to say that our theories certainly do not work in a regime where gravity would be important, From the natural constants $G_N, \hbar, c$ (Newton’s gravitational constant, Planck’s constant and the speed of light), one can create a set of natural units – the Planck units. These are the Planck length $l_P$, Planck mass $m_P$ and Planck time $t_P$, where $l_P = \sqrt{\frac{G_N \hbar}{c^3} } \sim 10^{-35} meters,$ $m_P = \sqrt{ \frac{\hbar c}{G_N} } \sim 10\: \mu \: grams\: \: \: , \: \: \: t_P = \sqrt{\frac{G_N \hbar }{c^5} } \sim 10^{-44} secs$ So, one can guess that gravity (represented by $G_N$) is relevant at Planck “scales”. One might reasonably expect pure quantum field theory to apply in regimes where gravity is irrelevant – so at length scales much larger than $10^{-35} meters$. Such a “cutoff” can be applied systematically in quantum field theories and it works – the answer for the “cosmological constant” is not infinitely bigger than the actual number, it is only bigger by a factor of $10^{121}$! What one does is to basically banish oscillations of the quantum field whose wavelengths are smaller than the Planck length. Most people would not be happy with this state of affairs. There are other theories of fundamental particles. The most studied ones predict a negative cosmological constant, also not in line with our unfortunate reality. About twenty years ago, three scientists – Andrew Cohen, David Kaplan and Ann Nelson (C-K-N) proposed that this vacuum energy actually should cut off at a much larger length scale – the size of the causally connected pieces of the universe (basically something one would consider the smallest wavelength possible in our observable universe. In this way, they connected the really small cutoff to the really large size of the universe. Why did they do this? They made the pretty obvious observation that the universe does not appear to be a black hole. Suppose we assumed that the universe were dominated by radiation. The energy inside should be (they said) the energy in the vacuum, up to this cutoff. But this energy should be confined to a size that should be bigger than, never less than, the “Schwarzschild radius” for this energy. The Schwarzschild radius for some energy is the radius of the ball that this energy should be confined to, in order that it collapses into a black hole. C-K-N assume that there is a natural principle that requires that the size of the universe is at least equal to the Schwarzschild radius corresponding to all that energy. They then derive some consequences of this assumption. First, my objections. I would have much rather preferred that the universe be MUCH bigger than this radius. Next, if this is indeed the case, surely some natural law should cause this to happen, rather than a post-hoc requirement (we are here, so it must have been so). That last bit is usually referred to as the “weak” anthropic principle. Anthropic principles have always seemed to me the last resort of the damned physicist – it can also be when you throw up your hands and say – if it weren’t this way, we wouldn’t be here. Its OK to resort to such ideas when you clearly see there is a lot of randomness that drives a physical process. Just not knowing the underlying physical process doesn’t seem the right reason to throw out an anthropic type idea. Anyway, I cast the entire problem as one in thermodynamics of the entire universe and suggested that the universe is this way because it is simply the most advantageous way for it to arrange itself. This method also lends itself to other extensions. It turns out that if the material of the universe is not the usual type (say “radiation” or “matter”), it might be possible for us to actually find a reasonable estimate of the cutoff that is in line with current experiments (at least the vacuum energy is not off by a factor of $10^{121}$, but only $10^{45}$ or so. There is more to do!	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 16, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.8621120452880859, "perplexity": 375.15758663869354}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2022-21/segments/1652662515466.5/warc/CC-MAIN-20220516235937-20220517025937-00041.warc.gz"}
https://socratic.org/questions/how-do-you-find-local-maximum-value-of-f-using-the-first-and-second-derivative-t-1	Calculus Topics How do you find local maximum value of f using the first and second derivative tests: f(x) = 4x^3 + 3x^2 - 6x + 1? Nov 9, 2016 $f ' ' \left(- 1\right) = 24 \cdot \left(- 1\right) + 6 = \left(- 18\right)$ - local maximum $f ' ' \left(\frac{1}{2}\right) = 24 \cdot \left(\frac{1}{2}\right) + 6 = 18$ - local minimum Explanation: $f ' \left(x\right) = 12 \cdot {x}^{2} + 6 \cdot x - 6$ $f ' \left(x\right) = 0$ $12 {x}^{2} + 6 x - 6 = 0$ ${x}_{1} = \left(- 1\right)$ ${x}_{2} = \frac{1}{2}$ there are two values -local maximum ${x}_{1} , {x}_{2}$ $f ' ' \left(x\right) = 24 x + 6$ $f ' ' \left(- 1\right) = 24 \cdot \left(- 1\right) + 6 = \left(- 18\right)$ - local maximum, <0 $f ' ' \left(\frac{1}{2}\right) = 24 \cdot \left(\frac{1}{2}\right) + 6 = 18$ - local minimum, >0 Impact of this question 466 views around the world	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 11, "mathjax_inline_tex": 1, "mathjax_display_tex": 0, "mathjax_asciimath": 1, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.20200347900390625, "perplexity": 3067.9464264295893}, "config": {"markdown_headings": false, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 20, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2021-25/segments/1623487637721.34/warc/CC-MAIN-20210618134943-20210618164943-00213.warc.gz"}
http://mathhelpforum.com/geometry/1608-geometry-word-problem-print.html	# Geometry - word problem • January 13th 2006, 08:40 AM The Preacher Geometry - word problem Hey, thanks for taking a look at this. A parallelogram with sides of 6 and 10 has an area of 30(sqrt)2. Find the measure of each angle of the parallelogram. Small angle _____ Large angle _____ I apologize that my first posting here had to be urgent, my school day is over soon, and I'd like some work to show for it, but I'm stuck. I appreciate any assistance. So far I've got is this: 360 - x2 = y2 X being either the small or large angle and y taking the place of the opposite. That's all I have so far, I'd like a hint in the right direction to finding one of the angles. The normal forum I post on for this sort of stuff is not working right now. Thanks again. God bless y'all, -The Preacher • January 13th 2006, 09:03 AM TD! If we take the largest side (10) to be the base and we call the heigth h, then the area is given by 10h. But we know the area, so we can find h. By drawing the parallellogram and this height, you can form a right triangle (at the left or right side of the parallellogram). This right triangle has one side h (which we know now) and hypotenuse 6. With the pythagorean theorem, you can even find the last side. Now you have this triangle and you know all sides, use some trigonometry to fnd the angles. For example, check this topic. • January 13th 2006, 09:11 AM The Preacher Quote: Originally Posted by TD! If we take the largest side (10) to be the base and we call the heigth h, then the area is given by 10h. But we know the area, so we can find h. By drawing the parallellogram and this height, you can form a right triangle (at the left or right side of the parallellogram). This right triangle has one side h (which we know now) and hypotenuse 6. With the pythagorean theorem, you can even find the last side. I think that I wouldn't have any problem with this if I knew how to get the height from the area. Radicals confuse me. Do you think you could help me out? • January 13th 2006, 09:14 AM TD! Of course. For a parallellogram, the area is given by height x base. By choice, we take the long side as base (which is 10 here) and call the height h, we then have: $10h = 30\sqrt 2 \Leftrightarrow h = \frac{{30\sqrt 2 }} {{10}} = 3\sqrt 2$ • January 13th 2006, 09:21 AM The Preacher Quote: Originally Posted by TD! Of course. For a parallellogram, the area is given by height x base. By choice, we take the long side as base (which is 10 here) and call the height h, we then have: $10h = 30\sqrt 2 \Leftrightarrow h = \frac{{30\sqrt 2 }} {{10}} = 3\sqrt 2$ Okay... so $3\sqrt 2$ is the height. Uh... like I said, radicals confuse me. Is there a way to change that into an integer? I'm sorry to require so much assistance in order to understand. I appreciate your time, TD!. =] God bless y'all, -The Preacher • January 13th 2006, 09:24 AM TD! Quote: Originally Posted by The Preacher Okay... so $3\sqrt 2$ is the height. Uh... like I said, radicals confuse me. Is there a way to change that into an integer? I'm sorry to require so much assistance in order to understand. I appreciate your time, TD!. =] Well, the square root of two is irrational. That means that if you'd want to write it in decimals, it will have infinitely many decimals, just like pi. You can of course just truncate the expansion, then you're left with an approximation. The square root of two is more or less equal to 1.414. I usually just leave the radicals and work with them, since that's exact. If you're uncomfortable with that, you could use an approximation. • January 13th 2006, 09:26 AM The Preacher Yeah, I found that out before (the square root of two having too many decimals), that's why I was asking. Dang, I'm having so much trouble with this problem. Wait... I need to find the sine ratio. I could take the $3\sqrt 2$ and the hypotenuse (6) and find the opposite angle. Soo... that'd be $ $\frac{{3\sqrt 2 }}{6}$ $ . Hold on... I am bad at math, but I'm going to try to figure out the angle from this. I can do that, right? • January 13th 2006, 09:29 AM TD! Check the topic I linked in my first post, there are the 3 formula's you could possibly use. • January 13th 2006, 09:31 AM The Preacher Alright, thanks. Sorry for ignoring it. :o EDIT: Okay... I looked at it. So I need to divide $3\sqrt 2$ by 6. How do I divide radicals? :confused: Sorry to seem so helpless... I really do stink at math. • January 13th 2006, 09:33 AM TD! No problem. Try it and if it doesn't work out, ask for help :) • January 13th 2006, 09:34 AM The Preacher Lol, I edited my message. Sorry for the bump. • January 13th 2006, 09:34 AM ThePerfectHacker There is a theorem from trigonometry which states the area of a parallelogram with sides $a,b$ and angle $\theta$ is $A=ab\sin \theta$. Now you said its sides are 6 and 10. And area of $30\sqrt{2}$ Thus, by the formula $60\sin \theta=30\sqrt{2}$ divide by 60, thus, $\sin \theta=\frac{\sqrt{2}}{2}$. Now that happens when $\theta=45,135$. Q.E.D. • January 13th 2006, 09:40 AM The Preacher :eek: I think I just got really confused. Couldn't I just have found the angle by dividing $3\sqrt 2$ by 6? Maybe not. Maybe I've got all my sine stuff out of whack. Sorry. =] -The Preacher EDIT: Nevermind, I just went back some in my textbook, reviewed, and was able to find out how to solve this with TD!'s help. Thanks for helping me out, guys. I appreciate it. God bless y'all, -The Preacher • January 13th 2006, 10:01 AM TD! Quote: Originally Posted by The Preacher :eek: I think I just got really confused. Couldn't I just have found the angle by dividing $3\sqrt 2$ by 6? Maybe not. Maybe I've got all my sine stuff out of whack. Sorry. Yes, that would have given you the sine of that angle. $\sin \left( \alpha \right) = \frac{{3\sqrt 2 }} {6} \Leftrightarrow \sin \left( \alpha \right) = \frac{{\sqrt 2 }} {2} \Leftrightarrow \alpha = 45^\circ \vee \alpha = 135^\circ$ • January 13th 2006, 12:40 PM ticbol Quote: Originally Posted by The Preacher Hey, thanks for taking a look at this. A parallelogram with sides of 6 and 10 has an area of 30(sqrt)2. Find the measure of each angle of the parallelogram. Small angle _____ Large angle _____ I apologize that my first posting here had to be urgent, my school day is over soon, and I'd like some work to show for it, but I'm stuck. I appreciate any assistance. So far I've got is this: 360 - x2 = y2 X being either the small or large angle and y taking the place of the opposite. That's all I have so far, I'd like a hint in the right direction to finding one of the angles. The normal forum I post on for this sort of stuff is not working right now. Thanks again. God bless y'all, -The Preacher I do not belong to the group that gives "answers" or help in forms of hints/guides/hanging solutions/the likes. I belong to the group that gives complete/not partial/detailed answers. Let us go first to your 360 -x2 = y2. Your intention is correct, but you should know how to present it to us so that there'd be less confusion. x2 or y2 should have been x2 or y2. Or, the usual 2x or 2y. "x2" is mostly read as x, sub 2. Let x = small angle, and y = large angle. If you don't have the figure of the said parallelogram, draw it on paper. [Always work, or play, with a figure. Make that a habit.] Let us say the parallelogram is ABCD, where: --- angle A = angle C = angle x --- angle B = angle D = angle y --- sides BC and AD are horizontal Area of parallelogram = base times altitude, this altitude being perpendicular to the base. There is no perpendicular lines shown on the figure yet, so draw a line from B that is perpendicular to AD, and call is new line or altitude, h. Then, (AB)h = 30sqrt(2) 10h = 30sqrt(2) Divide both sides by 1o, h = 3sqrt(2) ----------------*** In the right triangle formed by AB, h and portion of AD, sin(angle A) = h /6 sin(x) = [3sqrt(2)] /6 sin(x) = sqrt(2) /2 Either get the decimal equivalent of that and then find the x by using a calculator, or, if you know from memory that sin(45 degrees) is [sqrt(2)]/2 or 1/[sqrt(2)], then x = arcsin[sqrt(2) /2] = 45deg --------answer. Then, using your 360 -2x = 2y, 360 -2*45 = 2y 270 = 2y	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 17, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.8264919519424438, "perplexity": 961.5443855560435}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2014-23/segments/1406510273663.2/warc/CC-MAIN-20140728011753-00070-ip-10-146-231-18.ec2.internal.warc.gz"}
https://www.gradesaver.com/textbooks/math/algebra/algebra-1/chapter-8-polynomials-and-factoring-chapter-review-8-1-adding-and-subtracting-polynomials-page-524/15	## Algebra 1 $7z^{3}-2z^{2}-16$ Simplify and write in standard form $(8z^{3}-3z^{2}-7)-(z^{3}-z^{2}+9)$ Distribute the $-$ in the second parenthesis $8z^{3}-3z^{2}-7-z^{3}+z^{2}-9$ Combine like terms $7z^{3}-2z^{2}-16$	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.9306120872497559, "perplexity": 557.2060473686707}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2018-43/segments/1539583509690.35/warc/CC-MAIN-20181015184452-20181015205952-00502.warc.gz"}
http://mathhelpforum.com/algebra/43069-complex-conjugate-roots.html	# Math Help - complex conjugate roots 1. ## complex conjugate roots I have the following problem which i hope someone can point me in the right direction of solving: The equation X^4+40x+39 has 4 roots, if two of the roots are the complex conjugate roots 2+J3 and 2-J3 by a process of long divison and slving a quadratic equation find the other two roots. The exaple I am given in the book i have gives you the real roots to start with but gives no example of an equation that gives you the imaginary roots. I am looking for somehelp with how to get started on this one. Any help is apprecciated 2. Hello, $2 \pm 3j$ is a root. Therefore the polynomial can be factored by $[x-(2+3j)][x-(2-3j)]=[(x-2)-3j][(x-2)+3j]$ We know that $(a-b)(a+b)=a^2-b^2$. So the previous line equals to : $=(x-2)^2-(3j)^2=x^2-4x+4-9\underbrace{j^2}_{-1}=x^2-4x+13$ Now, you can try the division process... 3. Originally Posted by ally79 I have the following problem which i hope someone can point me in the right direction of solving: The equation X^4+40x+39 has 4 roots, if two of the roots are the complex conjugate roots 2+J3 and 2-J3 by a process of long divison and slving a quadratic equation find the other two roots. The exaple I am given in the book i have gives you the real roots to start with but gives no example of an equation that gives you the imaginary roots. I am looking for somehelp with how to get started on this one. Any help is apprecciated Note: Only one of the roots needed to be given since all coefficients of the quartic are real and so the conjugate root theorem could be used to get the other.	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 4, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.9085767865180969, "perplexity": 278.45742804591293}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2015-22/segments/1432207925201.39/warc/CC-MAIN-20150521113205-00187-ip-10-180-206-219.ec2.internal.warc.gz"}
https://gmatclub.com/forum/if-the-length-of-wanda-s-telephone-call-was-rounded-up-to-134504.html	GMAT Question of the Day - Daily to your Mailbox; hard ones only It is currently 23 Sep 2018, 13:37 ### GMAT Club Daily Prep #### Thank you for using the timer - this advanced tool can estimate your performance and suggest more practice questions. We have subscribed you to Daily Prep Questions via email. Customized for You we will pick new questions that match your level based on your Timer History Track every week, we’ll send you an estimated GMAT score based on your performance Practice Pays we will pick new questions that match your level based on your Timer History # If the length of Wanda's telephone call was rounded up to Author Message TAGS: ### Hide Tags Math Expert Joined: 02 Sep 2009 Posts: 49320 If the length of Wanda's telephone call was rounded up to [#permalink] ### Show Tags 14 Jun 2012, 03:09 4 13 00:00 Difficulty: 25% (medium) Question Stats: 72% (01:13) correct 28% (00:54) wrong based on 1402 sessions ### HideShow timer Statistics If the length of Wanda's telephone call was rounded up to the nearest whole minute by her telephone company, then Wanda was charged for how many minutes for her telephone call? (1) The total charge for Wanda's telephone call was $6.50. (2) Wanda was charged$0.50 more for the first minute of the telephone call than for each minute after the first. Diagnostic Test Question: 27 Page: 25 Difficulty: 650 _________________ Math Expert Joined: 02 Sep 2009 Posts: 49320 Re: If the length of Wanda's telephone call was rounded up to [#permalink] ### Show Tags 14 Jun 2012, 03:10 2 4 SOLUTION If the length of Wanda's telephone call was rounded up to the nearest whole minute by her telephone company, then Wanda was charged for how many minutes for her telephone call? (1) The total charge for Wanda's telephone call was $6.50. Clearly insufficient since we don't know the cost per minute of call. (2) Wanda was charged$0.50 more for the first minute of the telephone call than for each minute after the first. So, if the first minute costs $$(x+0.5)$$ then each succeeding minute costs $$x$$. Still not sufficient. (1)+(2) We have that $$(x+0.5)+x(n-1)=6.5$$ --> $$xn=6$$, where $$n$$ is the number of minutes. We have one equation and two unknowns, hence we cannot solve for $$n$$. Not sufficient. _________________ ##### General Discussion Current Student Joined: 29 Mar 2012 Posts: 317 Location: India GMAT 1: 640 Q50 V26 GMAT 2: 660 Q50 V28 GMAT 3: 730 Q50 V38 Re: If the length of Wanda's telephone call was rounded up to [#permalink] ### Show Tags 14 Jun 2012, 05:27 2 Hi, Difficulty level: 600 To find the time duration of Wanda's call, Using (1), Total charge for the call = $6.5, we neither know the number of minutes nor call charges. Insufficient. Using (2), Wanda was charged$0.50 more for the first minute of the telephone call than for each minute after the first. x+0.5 for first minute, for second minute x, & so on, for the whole call total charges would be nx+0.5 (n = number of minutes) or nx+0.5 = 6.5 or nx = 6 (16 or 61 or 23 or 32) thus, (n,x) = (1,6) or (6,1) or .... which means, for 1 min $6 can be charged. or for 6 mins$1 can be charged. Insufficient. Regards, Manager Joined: 07 Sep 2011 Posts: 61 Location: United States GMAT 1: 640 Q39 V38 WE: General Management (Real Estate) Re: If the length of Wanda's telephone call was rounded up to [#permalink] ### Show Tags 16 Jun 2012, 04:40 2 1 Difficulty level: 650 We have to find the duration of the call say N minutes. 1. Statement 1: It gives information about the cost of total call however we do not know per minute cost hence can not calculate the minutes. 2. Statement 2: We know that the cost of first minute was higher by 0.50 cents however we do not know the cost of subsequent minutes. Secondly, we cant calculate the duration of the call with this information. Put together, we know the total cost and also know that cost of first minute was higher by 0.50. If for example cost of subsequent minutes were 50 cents, the total duration would have been 12 minutes. Reduce the cost of call made after first minute, the duration will change. Senior Manager Status: Final Countdown Joined: 17 Mar 2010 Posts: 475 Location: India GPA: 3.82 WE: Account Management (Retail Banking) Re: If the length of Wanda's telephone call was rounded up to [#permalink] ### Show Tags 23 Jul 2012, 07:29 Total call minutes=Total call cost/Cost per min (i) m=6.5/c insufficient (ii)m={(c+0.5)+c(m-1)}/c insufficient combining; m can't be calculated so, (E) _________________ " Make more efforts " Press Kudos if you liked my post Math Expert Joined: 02 Sep 2009 Posts: 49320 Re: If the length of Wanda's telephone call was rounded up to [#permalink] ### Show Tags 20 Aug 2013, 03:51 The Official Guide Quantitative Question Directory: the-official-guide-quantitative-question-directory-143450.html (All OG13 questions with solutions) _________________ Manager Joined: 26 Mar 2017 Posts: 140 If the length of Wanda's telephone call was rounded up to [#permalink] ### Show Tags 29 Apr 2017, 02:26 1 Bunuel wrote: SOLUTION If the length of Wanda's telephone call was rounded up to the nearest whole minute by her telephone company, then Wanda was charged for how many minutes for her telephone call? (1) The total charge for Wanda's telephone call was $6.50. Clearly insufficient since we don't know the cost per minute of call. (2) Wanda was charged$0.50 more for the first minute of the telephone call than for each minute after the first. So, if the first minute costs $$(x+0.5)$$ then each succeeding minute costs $$x$$. Still not sufficient. (1)+(2) We have that $$(x+0.5)+x(n-1)=6.5$$ --> $$xn=6$$, where $$n$$ is the number of minutes. We have one equation and two unknowns, hence we cannot solve for $$n$$. Not sufficient. I've just an important question (at least imo). I solved the problem correctly but it took me a too much time. I also ended up with an equation with two unknowns. But since they said "telephone call was rounded up to the nearest whole minute" i was a bit suspicious and tried out numbers in order to make sure that there is more than one solution. Often in DF we make the argument that we can't solve an equation with two unknown, but in fact sometimes we can infer that theres only one plausible solutions (For Instance in the following problem) A certain fruit stand sold apples for $0.70 each and bananas for$0.50 each. If a customer purchased both apples and bananas from the stand for a total of $6.30, what total number of apples and bananas did the customer purchase ? So my question is just, when we can make the argument that we are dealing with an equation with two unknowns and when we can't make this argument. hope its clear Thank you ! _________________ I hate long and complicated explanations! Intern Joined: 22 Mar 2017 Posts: 3 Re: If the length of Wanda's telephone call was rounded up to [#permalink] ### Show Tags 22 Aug 2017, 06:31 Bunuel wrote: If the length of Wanda's telephone call was rounded up to the nearest whole minute by her telephone company, then Wanda was charged for how many minutes for her telephone call? (1) The total charge for Wanda's telephone call was$6.50. (2) Wanda was charged $0.50 more for the first minute of the telephone call than for each minute after the first. Diagnostic Test Question: 27 Page: 25 Difficulty: 650 Hi Brunel, I have one question. Since xn = 6 and to get 6 (x,n) can be (1,6) or (6,1) or (3,2) or (2,3). Because if the length of the call was less than a minute, then I think the total charge for the call would be$6.50. And out of all the possibilities listed above, only (2,3) satisfies the equation 1(x+0.50)+(x-1)n = 6.50. Tell me where did I go wrong? Math Expert Joined: 02 Sep 2009 Posts: 49320 Re: If the length of Wanda's telephone call was rounded up to [#permalink] ### Show Tags 22 Aug 2017, 07:44 shrutiwali wrote: Bunuel wrote: If the length of Wanda's telephone call was rounded up to the nearest whole minute by her telephone company, then Wanda was charged for how many minutes for her telephone call? (1) The total charge for Wanda's telephone call was $6.50. (2) Wanda was charged$0.50 more for the first minute of the telephone call than for each minute after the first. Diagnostic Test Question: 27 Page: 25 Difficulty: 650 Hi Brunel, I have one question. Since xn = 6 and to get 6 (x,n) can be (1,6) or (6,1) or (3,2) or (2,3). Because if the length of the call was less than a minute, then I think the total charge for the call would be $6.50. And out of all the possibilities listed above, only (2,3) satisfies the equation 1(x+0.50)+(x-1)n = 6.50. So Answer C. Tell me where did I go wrong? There are other cases possible: n = 6 minutes and x = 1 --> the cost of the first minute =$1.5 and the cost each of the remaining 5 minutes = $1 --> total =$6.50 n = 3 minutes and x = 2 --> the cost of the first minute = $2.5 and the cost each of the remaining 2 minutes =$2 --> total = $6.50 n = 2 minutes and x = 3 --> the cost of the first minute =$3.5 and the cost of the remaining 1 minute = $3 --> total =$6.50 _________________ EMPOWERgmat Instructor Status: GMAT Assassin/Co-Founder Affiliations: EMPOWERgmat Joined: 19 Dec 2014 Posts: 12444 Location: United States (CA) GMAT 1: 800 Q51 V49 GRE 1: Q170 V170 Re: If the length of Wanda's telephone call was rounded up to [#permalink] ### Show Tags 12 Dec 2017, 11:51 Hi All, We're told that Wanda's telephone call was rounded up to the nearest whole minute by her telephone company. We're asked for the number of minutes that she was charged for her telephone call. We can answer this question with a bit of logic and TESTing VALUES. 1) The total charge for Wanda's telephone call was $6.50. With Fact 1, we know the total cost of the call, but we don't know what rate Wanda was charged per minute. Fact 1 is INSUFFICIENT 2) Wanda was charged$0.50 more for the first minute of the telephone call than for each minute after the first. Fact 2 tells us the DIFFERENCE in the rates, but does not tells us the rates themselves nor the length of the call Fact 2 is INSUFFICIENT Combined, we know -The total cost of the call was $6.50 -The first minute cost$0.50 more than each of the additional minutes IF.... 1st minute = $1.00 and each addl. minute =$0.50, then the call would have been 12 minutes 1st minute = $1.50 and each addl. minute =$1.00, then the call would have been 6 minutes Combined, INSUFFICIENT GMAT assassins aren't born, they're made, Rich _________________ 760+: Learn What GMAT Assassins Do to Score at the Highest Levels Contact Rich at: [email protected] # Rich Cohen Co-Founder & GMAT Assassin Special Offer: Save \$75 + GMAT Club Tests Free Official GMAT Exam Packs + 70 Pt. Improvement Guarantee www.empowergmat.com/ ********************Select EMPOWERgmat Courses now include ALL 6 Official GMAC CATs!********************* Re: If the length of Wanda's telephone call was rounded up to &nbs [#permalink] 12 Dec 2017, 11:51 Display posts from previous: Sort by # If the length of Wanda's telephone call was rounded up to ## Events & Promotions Powered by phpBB © phpBB Group \| Emoji artwork provided by EmojiOne Kindly note that the GMAT® test is a registered trademark of the Graduate Management Admission Council®, and this site has neither been reviewed nor endorsed by GMAC®.	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 1, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.3243325650691986, "perplexity": 4710.891835637061}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2018-39/segments/1537267159744.52/warc/CC-MAIN-20180923193039-20180923213439-00366.warc.gz"}
https://studyqas.com/colton-earns-7-per-hour-plus-1-50-for-each-pizza-delivery/	# Colton earns $7 per hour plus$1.50 for each pizza delivery. the expression 7h + 1.50d can be used to Colton earns $7 per hour plus$1.50 for each pizza delivery. the expression 7h + 1.50d can be used to find the total earings after h hours and d deliveries have been made. how much money will colton earn after working 15 hours and making 8 deliveries ## This Post Has 3 Comments 1. angeleyes42 says: Since the expression 7h + 1.50d can be used to find the total earnings. We just need to substitute the given data to the expression to solve the problem. 7(15) + 1.50(8) 105 + 12 = 117 Colton's total earnings after working 15 hours and making 8 deliveries is 117 dollars. 2. ellamai16 says: 7h + 1.50 For 15 hours and 8 delivers, lets find out how much he earns. 7(15) + 1.50(8) = ? 715 = 105 1.508 = 12 105 + 12 = 117 He will make $117 3. snikergrace says: 7h+1.5d 7(15)+1.5(8) 105+12$117 Hope this helps.	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.45809659361839294, "perplexity": 3322.3764586476573}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2022-49/segments/1669446711017.45/warc/CC-MAIN-20221205132617-20221205162617-00858.warc.gz"}
https://www.scienceopen.com/document?vid=899fdfea-4b4d-4909-bf99-f0414a374e83	7 views 0 recommends +1 Recommend 0 collections 0 shares • Record: found • Abstract: found • Article: found Is Open Access # An axiomatic approach to free amalgamation Preprint Bookmark There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience. ### Abstract We use axioms of abstract ternary relations to define the notion of a free amalgamation theory. This notion encompasses many prominent examples of countable structures in relational languages, in which the class of algebraically closed substructures is closed under free amalgamation. We show that any free amalgamation theory is NSOP4, with weak elimination of imaginaries, and use this to show that several classes of well-known homogeneous structures give new examples of (non-simple) rosy theories without the strict order property. We then prove the equivalence of simplicity and NTP2 for free amalgamation theories. As a corollary, we show that any simple free amalgamation theory, with elimination of hyperimaginaries, is 1-based. In the case of modular free amalgamation theories, we also show that simplicity coincides with NSOP3. Finally, we consider a special class of Fra\"{i}ss\'{e} limits, and prove a combinatorial characterization of simplicity, which provides new context for the fact that the generic $$K_n$$-free graphs are SOP3, while the high arity generic $$K^r_n$$-free $$r$$-hypergraphs are simple. ### Author and article information ###### Journal 2015-05-04 2015-10-01 ###### Article 1505.00762	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 1, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.7646529674530029, "perplexity": 1454.673658318157}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 20, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2021-10/segments/1614178389798.91/warc/CC-MAIN-20210309092230-20210309122230-00535.warc.gz"}
http://www.ams.org/joursearch/servlet/DoSearch?f1=msc&v1=55P20&jrnl=one&onejrnl=bull	# American Mathematical Society My Account · My Cart · Customer Services · FAQ Publications Meetings The Profession Membership Programs Math Samplings Policy and Advocacy In the News About the AMS You are here: Home > Publications AMS eContent Search Results Matches for: msc=(55P20) AND publication=(bull) Sort order: Date Format: Standard display Results: 1 to 2 of 2 found Go to page: 1 [1] Paul H. Edelman and Victor Reiner. Not all free arrangements are $K(\pi,1)$ . Bull. Amer. Math. Soc. 32 (1995) 61-65. MR 1273396. Abstract, references, and article information View Article: PDF [2] Kenneth S. Brown and Ross Geoghegan. $FP_\infty$ groups and HNN extensions. Bull. Amer. Math. Soc. 9 (1983) 227-229. MR 707963. Abstract, references, and article information View Article: PDF Results: 1 to 2 of 2 found Go to page: 1	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.2051113247871399, "perplexity": 8662.731731448483}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2016-36/segments/1471982295358.50/warc/CC-MAIN-20160823195815-00083-ip-10-153-172-175.ec2.internal.warc.gz"}
https://math.libretexts.org/Bookshelves/Mathematical_Logic_and_Proof/Book%3A_Mathematical_Reasoning_-_Writing_and_Proof_(Sundstrom)/5%3A_Set_Theory	$$\newcommand{\id}{\mathrm{id}}$$ $$\newcommand{\Span}{\mathrm{span}}$$ $$\newcommand{\kernel}{\mathrm{null}\,}$$ $$\newcommand{\range}{\mathrm{range}\,}$$ $$\newcommand{\RealPart}{\mathrm{Re}}$$ $$\newcommand{\ImaginaryPart}{\mathrm{Im}}$$ $$\newcommand{\Argument}{\mathrm{Arg}}$$ $$\newcommand{\norm}[1]{\\| #1 \\|}$$ $$\newcommand{\inner}[2]{\langle #1, #2 \rangle}$$ $$\newcommand{\Span}{\mathrm{span}}$$ # 5: Set Theory $$\newcommand{\vecs}[1]{\overset { \scriptstyle \rightharpoonup} {\mathbf{#1}} }$$ $$\newcommand{\vecd}[1]{\overset{-\!-\!\rightharpoonup}{\vphantom{a}\smash {#1}}}$$ • 5.1: Sets and Operations on Sets We have used logical operators (conjunction, disjunction, negation) to form new statements from existing statements. In a similar manner, there are several ways to create new sets from sets that have already been defined. In fact, we will form these new sets using the logical operators of conjunction (and), disjunction (or), and negation (not). • 5.2: Proving Set Relationships In this section, we will learn how to prove certain relationships about sets. Two of the most basic types of relationships between sets are the equality relation and the subset relation. So if we are asked a question of the form, “How are the sets A and B related?”, we can answer the question if we can prove that the two sets are equal or that one set is a subset of the other set. There are other ways to answer this, but we will concentrate on these two for now. • 5.3: Properties of Set Operations This section contains many results concerning the properties of the set operations. We have already proved some of the results. Others will be proved in this section or in the exercises. The primary purpose of this section is to have in one place many of the properties of set operations that we may use in later proofs. These results are part of what is known as the algebra of sets or as set theory. • 5.4: Cartesian Products When working with Cartesian products, it is important to remember that the Cartesian product of two sets is itself a set. As a set, it consists of a collection of elements. In this case, the elements of a Cartesian product are ordered pairs. We should think of an ordered pair as a single object that consists of two other objects in a specified order. • 5.5: Indexed Families of Sets • 5.S: Set Theory (Summary) Thumbnail: A Venn diagram illustrating the intersection of two sets. Image used with permission (Public Domain; Cepheus).	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 1, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.9417199492454529, "perplexity": 228.524524497851}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 20, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2019-51/segments/1575540510336.29/warc/CC-MAIN-20191208122818-20191208150818-00489.warc.gz"}
http://libros.duhnnae.com/2017/aug2/150174226490-Decay-of-185Tl-185m-gHg-189m-gPb-and-energy-location-of-the-13-2-isomeric-states-in-185Hg-189Pb-193Po-and-197Rn.php	# Decay of 185Tl, 185m gHg, 189m gPb and energy location of the 13-2 isomeric states in 185Hg, 189Pb, 193Po and 197Rn Decay of 185Tl, 185m gHg, 189m gPb and energy location of the 13-2 isomeric states in 185Hg, 189Pb, 193Po and 197Rn - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online. The European Physical Journal A , 49:109 First Online: 06 September 2013Received: 17 December 2012Accepted: 11 July 2013 Abstract. The \ \beta^{{+}} {}\ -EC decay of Tl was studied at the ISOLDE facility, the \ \gamma\ -rays belonging to Hg have been identified and a partial low-spin level scheme of Hg has been built. The decay of Hg was studied at the ISOCELE facility. Conversion electron lines of very low-energy transitions were observed for the first time. Electron data have been obtained for four transitions in Au and two transitions in Hg . From the analysis performed using an internal energy calibration procedure the energy location of the Hg has been determined to be \ E {IS}= 103.74\ keV. This \ E {IS}\ value is consistent with that determined independently, \ E {IS}=9413\ keV, using Hg \ \alpha\ -decay data from literature. New \ \alpha\ particles emitted from Pb have been detected and their origins determined by in-source laser spectroscopy at the ISOLDE facility. \ \alpha\ -\ \gamma\ coincidence results have served to locate the \ 13-2^{+}\ isomeric state of Pb at \ E {IS}=404\ keV. This latter \ E {IS}\ value added to \ \alpha\ -decay data from literature have allowed the energy location of the \ 13-2^{+}\ isomeric states of Po and Rn at 957keV and 19412keV, respectively. The nuclear structure of the isomeric and ground states in the nuclei of the three \ \alpha\ -emitter chains starting with Rn are discussed. Communicated by J. Äystö Autor: J. Sauvage - B. Roussière - J. Genevey - S. Franchoo - A. N. Andreyev - N. Barré - A. Ben Braham - C. Bourgeois - J. -	{"extraction_info": {"found_math": false, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.8426991701126099, "perplexity": 9578.282080830084}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2018-47/segments/1542039741764.35/warc/CC-MAIN-20181114082713-20181114104713-00156.warc.gz"}
http://www.physicsforums.com/showthread.php?p=4213895	# Does stock market create wealth? by Tosh5457 Tags: market, stock, wealth P: 328 Quote by nitsuj You seem to be saying the stock prices drops because the company has disbursed cash. That isn't why the price drops. in the case of ex-dividend dates the cash payout is precisely why the price drops. an important concept in securities pricing that has not been directly addressed here is arbitrage. If stock prices did not react to going ex-dividend, then one could build a strategy of purchasing stocks right before the ex-date and then selling them, pocketing a quarter's dividend with only one day of exposure to the stock price. This is an arbitrage that should not exist in a competitive market, and indeed, it does not exist. Mentor P: 22,001 Quote by nitsuj What is the issue of stock value? The issue is if the assets of the company have a direct impact on stock price. The example is a clear demonstration of the fact that they do. You seem to be saying the stock prices drops because the company has disbursed cash. That isn't why the price drops. Well don't keep us in suspense! Tell us what you think the correct answer is (and prove it, of course). P: 120 Quote by Tosh5457 As an example, let's say that in an IPO, an investor X buys all the shares, let's say 10, for $10 each (in the primary market). He spent$100, and those $100 went to the company. Next, there appears a bid of 10 shares (now at the secondary market) at$11. The investor X sells all his 10 shares to that bidder Y. Now the investor X has a profit of $10. Now let's say there's a bid for 10 shares at$12. The investor Y sells his 10 shares and made a profit of $10. For this to continue indefinitely there always need to be more money to be invested. If there weren't any other bidder, the shares wouldn't have any value and the last buyer would lose an amount of money equivalent to what the others won, making it a zero-sum game. So is the stock market just an elaborate Ponzi scheme? Or it's a positive-sum game (excluding fees)? Excluding dividends of course. I think it's important to go back to the start with this thread and point out the example of one person owning all of the shares is incorrect. IPO stands for initial public offering. The purpose is to distribute the stock widely. In the example, a single entity owns 100% of the shares and through selection of a board of directors - absolute control of the company. In this scenario, the investor would be able to make decisions and excercise control over the management of the company not normally available to a common shareholder. The description given is not of a public corporation - but of a privately held corporation. P: 39 No, it wasn't important to point that out. Simply change the wording to read " an investor X buys some shares, let's say 10, for$10 each" and the question at the end remains relevant. P: 120 Quote by Barakn No, it wasn't important to point that out. Simply change the wording to read " an investor X buys some shares, let's say 10, for $10 each" and the question at the end remains relevant. The OP clearly describes a scenario where a single entity owns all of the shares. P: 1,098 Quote by russ_watters The issue is if the assets of the company have a direct impact on stock price. The example is a clear demonstration of the fact that they do. Well don't keep us in suspense! Tell us what you think the correct answer is (and prove it, of course). Shure I'll tell you what I think it is. Sorry I don't have a magazine article to link to. Time value of money... that's all. As has already been said in this thread, there are many many variables that impact a stocks price...like a tragic incident involving a companies product that raises moral issues in holding stock in said company. Or threat of legislation limiting salable goods. I wouldn't restate that as moral issues have a direct impact on a stocks price, or tragic incidents have a direct impact of a stocks price. Russ, generally speaking, assets are reflected in a stocks price. But like I said before that's the starting point. you know as well as I many factors impact a stocks price. The tech bubble is a good example of improper valuations, straying too far from a strict hard/real asset valuation, placing too much "weight" on environmental factors. I have no idea how a company is valued (IPO), but like I said before it is not Assets - liabilities = equity / number of shares. (to be clear it is specifically the defining of what constitutes an "asset" or "liability". as in above environmental factors could be considered an asset/liability. Here is a case, an Audio equipment manufacturer the branded Harman Kardon goods. Was to be bought in entirety in 2007 by Goldman Sacs & KKR and taken off the securities market. Deal fell through, and stocks went with it to the tune of 24%. Of course Harman Industries hadn't lost any assets. Second, the got a new CEO who brought the company form single digit growth to double digit growth...the stock doubled...all with in a year...do you think their assets doubled? Or does it make more sense that stock holders thought Goldman & KKR saw something dire in the business model and subsequently pulled out. Then after the panicked selling subsided (24% drop in Stock price) and the company actually improved performance, in turn increasing demand for the stock, increasing the price of the stock beyond a hard/real asset valuation. Does that counter your "...clear demonstration of the fact that they do." [stock price is directly related to a companies assets] in any case I find it silly to "debate" this at this point. All that said, nothing stops you from valuating a stock as (assets - liabilities) / number of shares. What I am saying is a stocks price is a market valuation with little to no regard to the IPO stock price beyond it being a starting point, you're saying it is a fundamental valuation of a company. P: 1,098 Quote by BWV in the case of ex-dividend dates the cash payout is precisely why the price drops. an important concept in securities pricing that has not been directly addressed here is arbitrage. If stock prices did not react to going ex-dividend, then one could build a strategy of purchasing stocks right before the ex-date and then selling them, pocketing a quarter's dividend with only one day of exposure to the stock price. This is an arbitrage that should not exist in a competitive market, and indeed, it does not exist. I agree it is the event of cash disbursement for why the stock price will drop after a dividend payout. However the Stock price doesn't change to reflect the decrease in assets. It is literal in this case...it is simply because the dividend has just been paid out and the next one is sometime in the future. To word it different I could say the stock price drops because it is the farthest date from the next (precedence of dividends) dividend disbursement. Mentor P: 22,001 Quote by nitsuj Time value of money... that's all. That's a word, not a definition. We're discussing here why the stock price increases, not just stating the fact that it does. As has already been said in this thread, there are many many variables that impact a stocks price... Yes, so I'm really not sure why you keep bringing up the short term fluctuations. They aren't relevant to this thread except as being part of the misunderstanding that the OP has: The fact that short term fluctuations are not necessarily value based is confusing the OP into thinking that there is no value base whatsoever. Does that counter your "...clear demonstration of the fact that they do." [stock price is directly related to a companies assets] No. What I am saying is a stocks price is a market valuation with little to no regard to the IPO stock price beyond it being a starting point, you're saying it is a fundamental valuation of a company. I'm not sure what the IPO price has to do with anything. It's history once the company goes public. People don't even remember it. No, once the IPO is over, the IPO price doesn't have much to do with it. And I never said it did. I just said before the IPO, they try to set an IPO price based in large part on what they think the value of the company is. Perhaps the issue here might be you're seeing/setting up a false dichotomy between me and the OP. The opposite of the OP saying stocks aren't based at all on value is not that they are based entirely on value. Don't make the mistake of thinking that I'm saying the true value of the company is the only thing that goes into setting the price. I've been very clear that that's only a long-term generality, not a day-to-day reality. Mentor P: 22,001 Quote by nitsuj I agree it is the event of cash disbursement for why the stock price will drop after a dividend payout. However the Stock price doesn't change to reflect the decrease in assets. It is literal in this case...it is simply because the dividend has just been paid out and the next one is sometime in the future. To word it different I could say the stock price drops because it is the farthest date from the next (precedence of dividends) dividend disbursement. None of that disagrees with the stated reasoning by the example other than just a word-play or re-stating the obvious. It's like saying my bank account doesn't have less value the day before payday, it just appears that way because it happens to be the day before payday. No: the stock price drops because it is reflecting the decrease in assets of the company. The fact that that day is also the furthest from the next disbursement is just another way of saying the same thing. There's no substance to any of that. It almost sounds like you are just disagreeing to disagree! P: 1,098 Quote by russ_watters Don't make the mistake of thinking that I'm saying the true value of the company is the only thing that goes into setting the price. I've been very clear that that's only a long-term generality, not a day-to-day reality. !! In setting an IPO, I feel it is fair to say that it is a representation of the actual value of the company ( and am sure it includes more than just real assets / liabilities). There is no connection between the assets of a company and the "asset" that a stock holding would be, this is unlike a bond or similar debt. If I set up a company that is a bar of gold, I contributed that capital and then when public (yea idealizing here) and you buy the stock you are NOT entitled to the bar of gold. It is still owned by the company, it's in the corporate bylaws which also say your stock merely entitles you to a vote of who makes decisions for the company...not what the decisions are. Such as liquidate company and send cheque to shareholders. There will always be a disconnect between a companies assets and the (voting) stock, whether it be corporate bylaws or legislated ones. The intrinsic value of common stock is faith/belief/foresight ect, not said company's balance sheet. There is no "gold standard" for common stock values. That is to say there is no claim for common stock holders in a companies assets. P: 1,098 Quote by russ_watters None of that disagrees with the stated reasoning by the example other than just a word-play or re-stating the obvious. It's like saying my bank account doesn't have less value the day before payday, it just appears that way because it happens to be the day before payday. No: the stock price drops because it is reflecting the decrease in assets of the company. The fact that that day is also the furthest from the next disbursement is just another way of saying the same thing. There's no substance to any of that. It almost sounds like you are just disagreeing to disagree! One point of view strongly implies there is a direct connection between stock value and the companies assets. There other point of view strongly implies the stocks value is a direct connection to market valuation + TMV. That is a HUGE difference perspectives. P: 223 As I see it, this will only be settled when we define the game mathematically. So we need to define: - the possible events of the game - the players of the game - utility function (a function that assigns a real value to each event that can happen in the game) The only possible events are trades between 2 players, and the players are obviously defined as the speculators in the stock market. Defining the utility function as the profit, in money, of the investors in a given trade, it'll be a zero-sum game. Each transaction is zero-sum, and since the secondary market is just made of transactions, it follows that the game is zero-sum. Agree? If you don't agree, please give a counter-example that proves me wrong. It'll be a constant-sum game if we define the utility function as the balances (zero-sum for the variations of balances). You could argue that that defining the utility function like that doesn't make sense. In the real economy for example, it wouldn't make sense, because what is really useful there is the production (whether people are getting products or not), not money. In the stock market, maybe we could define the utility function of a given trade between 2 traders as the profit/loss in regards to the fundamental value of the stock. In that sense, it would be zero-sum in relation to the fundamental value. But because the fundamental value grows over time and it's obvious to see that everyone can win in this game, defining the utility function by taking time into account (for example, the profit/loss over 1 year), it would be clearly a positive-sum game. But does it make sense to define the utility function like that? Whether the corporations grow or not, in reality the stock holders don't benefit anything from it. Unlike the case in the real economy, where more production means people get more products, a growth in the companies don't benefit the stockholders in any way. So IMO the only reasonable way to define the utility function is using money, because that's ultimately what's "useful" for the traders. In the real economy the products are what's useful. In a hunting game for example, what's useful are the meat you can get. In the stock market, the only useful thing you'll get is money. And if you define the utility function by the profit/loss of money, it's indeed a zero-sum game. P: 328 this has been settled repeatedly then you keep trying to raise the dead horse. Yes, trading stocks is a constant sum game - the constant sum being the aggregate return of the stock market. Investing in the aggregate stock market is not a zero sum game because it tracks growth in the real economy (through dividends, no-arbitrage assumptions and all the other mechanisms discussed here). If the real economy is not a zero sum game then the aggregate stock market is not Mentor P: 22,001 Right: the growth happens BETWEEN the transactions. Those are the "events" Tosh doesn't want to consider. P: 120 Sometimes a stock's market price has very little to do with assets or the balance sheet. The price to earnings ratio is summarized in the following link. http://www.investopedia.com/terms/p/...#axzz2HQQGw3UB "The P/E is sometimes referred to as the "multiple", because it shows how much investors are willing to pay per dollar of earnings. If a company were currently trading at a multiple (P/E) of 20, the interpretation is that an investor is willing to pay$20 for $1 of current earnings." Mentor P: 22,001 Ugh, I didn't see this before: Quote by nitsuj If I set up a company that is a bar of gold, I contributed that capital and then when public (yea idealizing here) and you buy the stock you are NOT entitled to the bar of gold. It is still owned by the company, it's in the corporate bylaws which also say your stock merely entitles you to a vote of who makes decisions for the company...not what the decisions are. Such as liquidate company and send cheque to shareholders. As I said to Tosh several pages ago, don't let the complexity added by multiple owners confuse you into thinking the definition of "ownership" changes. It doesn't. The stockholders own the company. So "The company owns" is still synonymous with "the stockholders own". And incidentally, since you were non-specific and you worded it badly, the case you described was for one shareholder: You set up the company and sold the entire company to me, making me the sole owner of the bar of gold. But since I know you meant there are multiple shareholders....it is still wrong. The bylaws may or may not include direct voting on policy. If the voting is direct, all you have to do is convince 50%+1 shareholders to vote with you. If the voting is indirect, you just have to do the same except electing a representative who will do what you want. The fact that it is cumbersome for stockholders to make major changes in large companies and doesn't happen often does not change the status of stockholders. In any case, this was already discussed in detail and I have rehashed more than I really wanted to. For fuller treatment, read back a couple of pages. Mentor P: 22,001 Quote by enosis_ Sometimes a stock's market price has very little to do with assets or the balance sheet. The price to earnings ratio is summarized in the following link. http://www.investopedia.com/terms/p/...#axzz2HQQGw3UB "The P/E is sometimes referred to as the "multiple", because it shows how much investors are willing to pay per dollar of earnings. If a company were currently trading at a multiple (P/E) of 20, the interpretation is that an investor is willing to pay$20 for \$1 of current earnings." "Sometimes" But over the long term, the average P/E ratio of the market stays within a relatively small range. P: 120 Quote by russ_watters "Sometimes" But over the long term, the average P/E ratio of the market stays within a relatively small range. I agree - but as link indicates - it varies by industry. The fun starts when a company has negative earnings (a loss) but still maintains an industry multiple. Related Discussions General Discussion 20 Social Sciences 74 General Discussion 4 Social Sciences 79 General Discussion 6	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.4538971185684204, "perplexity": 2147.6631554243554}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 20, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2014-15/segments/1397609539447.23/warc/CC-MAIN-20140416005219-00524-ip-10-147-4-33.ec2.internal.warc.gz"}
https://imomath.com/index.php?options=484&lmm=0	# Change of Variables in Multiple Integrals ## Introduction Substitution (or change of variables) is a powerful technique for evaluating integrals in single variable calculus. An equivalent transformation is available for dealing with multiple integrals. The idea is to replace the original variables of integration by the new set of variables. This way the integrand is changed as well as the bounds for integration. If we are lucky enough to find a convenient change of variables we can significantly simplify the integrand or the bounds. ## Change of variables formula Two dimensional pictures are the easiest to draw so we will start with functions of two variables. Our first task is to get familiar with transformations of two dimensional regions. ### Transformations in $$\mathbb R^2$$ Assume that $$S$$ is a region in $$\mathbb R^2$$. We want to study the ways in which this region can be transformed to another region $$T$$. This is easiest to explain by considering an example. Let $$S=[0,2]\times[0,2]$$. Consider the functions $$u:S\to \mathbb R$$ and $$v:S\to\mathbb R$$ defined in the following way: \begin{eqnarray} u(x,y)&=&x+2y\\ v(x,y)&=&x-y.\end{eqnarray} To every point $$(x,y)\in S$$ ($$S$$ is painted blue in the diagram on the left) we can assign a new green point with coordinates $$(u(x,y),v(x,y))$$. This way we obtain a green region $$T$$. The mapping $$(x,y)\mapsto (u(x,y),v(x,y))$$ is one-to-one and onto, hence a bijection (you may want to review these terms in the section Functions). We can also write the inverse transformation, that maps each point $$(u,v)\in T$$ to the point $$(x(u,v),y(u,v))$$ in the following way: \begin{eqnarray} x(u,v)&=&\frac{u+2v}3 \\ y(u,v)&=&\frac{u-v}3. \end{eqnarray} ### Change of variables in double integrals Assume that $$S\subseteq \mathbb R^2$$ is a region in the plane. Let $$T\subseteq\mathbb R^2$$ be another region and assume that there are continuously differentiable functions $$X:T\to\mathbb R$$ and $$Y:T\to\mathbb R$$, such that the mapping $$\Phi(u,v)= (X(u,v),Y(u,v))$$ is a bijection between $$T$$ and $$S$$. The Jacobian of the mapping $$\Phi$$ is defined as $\frac{\partial(X,Y)}{\partial(u,v)}=\det\left\|\begin{array}{cc} \frac{\partial X}{\partial u}& \frac{\partial X}{\partial v}\\ \frac{\partial Y}{\partial u}& \frac{\partial Y}{\partial v}\end{array}\right\|.$ Theorem (Change of variables in double integrals) Assume that $$S$$ and $$T$$ are domains in $$\mathbb R^2$$ and that there are two continuously differentiable functions $$X,Y:T\to \mathbb R$$ such that $$\Phi: T\to S$$ defined by $$\Phi(u,v)=(X(u,v),Y(u,v))$$ is a bijection whose Jacobian is never $$0$$. For each continuous bounded $$f:S\to\mathbb R$$ the following equality holds: $\iint_S f(x,y)\,dxdy=\iint_T f(X(u,v),Y(u,v)) \cdot \left\|\frac{\partial(X,Y)}{\partial(u,v)}\right\|\,dudv.$ Example 1. Using the substitution $$u=2x+3y$$, $$v=x-3y$$, find the value of the integral $\iint_D e^{2x+3y}\cdot \cos(x-3y)\,dxdy,$ where $$D$$ is the region bounded by the parallelogram with vertices $$(0,0)$$, $$\left(1,\frac13\right)$$, $$\left(\frac43,\frac19\right)$$, and $$\left(\frac13,-\frac29\right)$$. ### Change of variables in triple integrals Assume that $$S, T\subseteq \mathbb R^3$$ are two regions in space. Assume that there are continuously differentiable functions $$X:T\to\mathbb R$$, $$Y:T\to\mathbb R$$, and $$Z:T\to\mathbb R$$, such that the mapping $$\Phi:T\to S$$ defined as $$\Phi(u,v,w)= (X(u,v,w),Y(u,v,w),Z(u,v,w))$$ is a bijection. The Jacobian of the mapping $$\Phi$$ is defined as $\frac{\partial(X,Y,Z)}{\partial(u,v,w)}=\det\left\|\begin{array}{ccc} \frac{\partial X}{\partial u}& \frac{\partial X}{\partial v}& \frac{\partial X}{\partial w}\\ \frac{\partial Y}{\partial u}& \frac{\partial Y}{\partial v}& \frac{\partial Y}{\partial w} \\ \frac{\partial Z}{\partial u}& \frac{\partial Z}{\partial v}& \frac{\partial Z}{\partial w}\end{array}\right\|.$ Theorem (Change of variables in triple integrals) Assume that $$S$$ and $$T$$ are domains in $$\mathbb R^2$$ and that there are three continuously differentiable functions $$X,Y,Z:T\to \mathbb R$$ such that $$\Phi: T\to S$$ defined by $$\Phi(u,v,w)=(X(u,v,w),Y(u,v,w),Z(u,v,w))$$ is a bijection whose Jacobian is never $$0$$. For each continuous bounded function $$f:S\to\mathbb R$$ the following equality holds: $\iiint_S f(x,y,z)\,dxdydz=\iiint_T f(X(u,v,w),Y(u,v,w),Z(u,v,w)) \cdot \left\|\frac{\partial(X,Y,Z)}{\partial(u,v,w)}\right\|\,dudvdw.$ ## Polar, cylindrical, and spherical substitutions We will now study very important substitutions that are used to simplify integrations over circular, spherical, cylindrical, and elliptical domains. One of them is applicable to double integral and is called polar change of variables and the other two, cylindrical and spherical, are used in triple integralds. ### Polar substitution The following change of variables is called the polar substitution: \begin{eqnarray} x&=&r\cos\theta\\ y&=&r\sin \theta. \end{eqnarray} The Jacobian for the polar substitution is equal to: $\frac{\partial(x,y)}{\partial(r,\theta)}=\det\left\|\begin{array}{cc} \cos\theta&-r\sin\theta\\ \sin\theta&r\cos\theta\end{array}\right\|=r\cos^2\theta+r\sin^2\theta=r.$ The variables $$r$$ and $$\theta$$ have the geometric meaning in the $$xy$$-coordinate system. The distance between $$(x,y)$$ and the origin is precisely $$r$$, while $$\theta$$ is the angles between the $$x$$-axis and the line connecting $$(x,y)$$ with $$(0,0)$$. Example 2. Evaluate the integral $\iint_D \cos\left(x^2+y^2\right)\,dxdy,$ where $$D$$ is the disc of radius $$3$$ centered at the origin. When dealing with ellipses it is very common to use the modified polar substitution. If the equation of the ellipse is $$\frac{x^2}{a^2}+\frac{y^2}{b^2}=1$$, the following substitution is used to describe its interior: \begin{eqnarray} x&=&ar\cos\theta\\ y&=&br\sin\theta\\ 0\leq&r&\leq 1\\ 0\leq&\theta&\leq 2\pi. \end{eqnarray} Example 3. Let $$a$$ and $$b$$ be two positive real numbers. Find the area of the region enclosed by the ellipse with the equation $$\frac{x^2}{a^2}+\frac{y^2}{b^2}=1$$. ### Cylindrical substitution In cylindrical substitution the original variables $$(x,y,z)$$ are replaced by $$(r,\theta, z)$$ using the following equations: \begin{eqnarray} x&=&r\cos\theta\\ y&=&r\sin\theta\\ z&=&z. \end{eqnarray} Again we can find the Jacobian by calculating the appropriate determinant: $\frac{\partial(x,y,z)}{\partial(r,\theta,z)}=\det\left\|\begin{array}{ccc} \cos\theta &-r\sin\theta &0\\ \sin\theta&r\cos\theta&0\\ 0&0&1\end{array}\right\|=r .$ Example 4. Determine the value of the integral $\iiint_D e^{x^2+y^2}\,dV$ where $$D$$ is the the region in bounded by the planes $$y=0$$, $$z=0$$, $$y=x$$, and the paraboloid $$z=4-x^2-y^2$$. ### Spherical substitution Spherical substitution means replacing the original variables $$(x,y,z)$$ by the variables $$(\rho,\theta, \phi)$$, where $$\rho$$ is the distance of the points $$(x,y,z)$$ from the origin $$(0,0,0)$$; $$\theta$$ is the angle that the line connecting $$(0,0,0)$$ and $$(x,y,0)$$ forms with the $$x$$-axis, and $$\phi$$ is the angle between the $$z$$-axis and the line connecting $$(x,y,z)$$ with $$(0,0,0)$$. Mathematically, the equations are: \begin{eqnarray} x&=&\rho\cos\theta\sin\phi\\ y&=&\rho\sin\theta\sin\phi\\ z&=&\rho\cos\phi. \end{eqnarray} We can find the Jacobian by calculating the appropriate determinant: \begin{eqnarray} \frac{\partial(x,y,z)}{\partial(\rho,\theta,\phi)}&=&\det\left\|\begin{array}{ccc} \cos\theta\sin\phi &-\rho\sin\theta\sin\phi &\rho\cos\theta\cos\phi\\ \sin\theta\sin\phi&\rho\cos\theta\sin\phi&\rho\sin\theta\cos\phi\\ \cos\phi&0&-\rho\sin\phi\end{array}\right\| \\ &=&-\rho^2\cos^2\theta\sin^3\phi-\rho^2\sin^2\theta\sin\phi\cos^2\phi-\rho^2\cos^2\theta\sin\phi\cos^2\phi-\rho^2\sin^2\theta\sin^3\phi \\&=&-\rho^2\sin^3\phi-\rho^2\sin\phi\cos^2\phi=-\rho^2\sin\phi .\end{eqnarray} Since in evaluation of the integral we are using the absolute value of the Jacobian, and $$\phi\in\left(0,\frac{\pi}2\right)$$ it is sufficient and more convenient to remember that $\left\|\frac{\partial(x,y,z)}{\partial(\rho,\theta,\phi)}\right\|=\rho^2\sin\phi.$ Example 5. Determine the value of the integral $\iiint_D e^{\sqrt{x^2+y^2+z^2}}\,dV$ where $$D$$ is the the region in bounded by the planes $$y=0$$, $$z=0$$, $$y=x$$, and the sphere $$x^2+y^2+z^2=9$$. 2005-2021 IMOmath.com \| imomath"at"gmail.com \| Math rendered by MathJax	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 1, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.9940517544746399, "perplexity": 166.33617915809037}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2021-43/segments/1634323585653.49/warc/CC-MAIN-20211023064718-20211023094718-00126.warc.gz"}
http://physics.stackexchange.com/tags/symmetry-breaking/new	# Tag Info 4 "Total spin conservation" means global $SU(2)$ spin-rotation symmetry (a continuous symmetry) of the Heisenberg model, and "spin wave" indicates an ordered ground state that spontaneously breaks the spin-rotation symmetry. Thus, according to Goldstone theorem, there must be a gapless mode for spin wave. 1 There are two ways to deal with a linear term in $\phi$: Complete the square, as was suggested in the comments. This is very often possible, but sometimes you do not want to do that. Interpret it as an interaction term with a $\phi$ particle popping out of the vacuum or vanishing. This will lead to non-zero tadpoles in your Feynman diagrams, so additional ... 0 The first assumption is that whatever vev the higgs picks up is constant in space, because this has less energy than one that increases the kinetic term in the Lagrangian. So we can do one global transformation to make the vev be in the second component only. You can imagine doing this prior to symmetry breaking, if you know what it is going to be ahead of ... 2 Well, after symmetry breaking, all that remains is electromagnetic $U(1)$, so the only generator that is truly a symmetry generator is $Q$. The fermions couple to the "Higgs" via the Yukawa coupling: $\mathcal{L}_y = -y_e^{ij} \bar L_{L,i} \Phi e_{R,j} - y_u^{ij} \bar Q_{L,i} \tilde{\Phi} u_{R,j} - y_d^{ij} \bar Q_{L,i} \Phi d_{R,j} + h.c.\,$ which mixes ... Top 50 recent answers are included	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.8169447183609009, "perplexity": 375.4070726502773}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2013-48/segments/1387345766127/warc/CC-MAIN-20131218054926-00012-ip-10-33-133-15.ec2.internal.warc.gz"}
https://www.physicsforums.com/threads/maxwell-boltzmann-fermi-dirac-and-bose-einstein.156976/	# Maxwell-Boltzmann, Fermi-Dirac and Bose-Einstein. 1. Feb 18, 2007 ### Clau If we have indistinguishable particles, we must use Fermi-Dirac statistics. To Identical and indistinguishable particles, we use Bose-Einstein statistics. And, to distinguishable classical particles we use Maxwell-Boltzmann statistics. I have a system of identical but distinguishable particles, where the second level has a degeneracy. I was reading at Wikipedia: "Degenerate gases are gases composed of fermions that have a particular configuration which usually forms at high densities." My question is: Should I use Fermi-Dirac statistics in this case? I'm confused. I was reading Reif and it seems that I should use Maxwell-Boltzmann just to nondegenerate gases. But if my system is made by distinguishable particles, it seems that I should use MB statistics. 2. Feb 19, 2007 ### vanesch Staff Emeritus I'm not an expert on this and if I'm making an error, please correct me. But I thought that distinguishability is the key element, which determines that one should use the MB statistics. The MB statistics is ALSO a good approximation to the other distributions in certain limiting cases (such as dilute media), but I thought that if we deal with distinguishable components, that MB was exact. (the problem being, of course, that there do not exist systems of distinguishable elementary particles in nature)	{"extraction_info": {"found_math": false, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.8245441317558289, "perplexity": 1040.6445508601932}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2016-44/segments/1476990033880.51/warc/CC-MAIN-20161020190033-00389-ip-10-142-188-19.ec2.internal.warc.gz"}
https://oomph-lib.github.io/oomph-lib/doc/navier_stokes/collapsible_channel/html/index.html	Demo problem: Flow in a 2D channel with an oscillating wall The moving-boundary Navier-Stokes problem discussed in this document is a "warm-up" problem for the classical fluid-structure interaction problem of flow in a 2D collapsible channel. Here we compute the flow through a 2D channel in which part of one wall is replaced by a moving "membrane" whose motion is prescribed. In another example, we will demonstrate how easy it is to extend the driver code for the current problem to a fluid-structure interaction problem in which the "membrane" is represented by an elastic beam that deforms in response to the fluid traction. We note that the (FSI version of the) problem considered here was analysed in much more detail in • Jensen, O.E. & Heil, M. (2003) High-frequency self-excited oscillations in a collapsible-channel flow. Journal of Fluid Mechanics 481 235-268. (pdf preprint) (abstract) where a detailed discussion (and an asymptotic analysis) of the flow-structures described below may be found. # The problem Finite-Reynolds-number flow in a 2D channel with an oscillating wall . The figure below shows a sketch of the problem: Flow is driven by a prescribed pressure drop through a 2D channel of width and total length The upstream and downstream lengths of the channel are rigid, whereas the upper wall in the central section performs a prescribed oscillation. The shape of the moving segment is parametrised by a Lagrangian coordinate, , so that the position vector to the moving wall is given by . Sketch of the problem. We scale all lengths on the channel width, , use the average velocity through the undeformed channel, , to scale the velocities, and use to non-dimensionalise time. (As usual, we employ asterisks distinguish dimensional parameters from their non-dimensional equivalents.) The flow is then governed by the unsteady Navier-Stokes equations and the continuity equation with , subject to the following boundary and initial conditions: Initial condition: Poiseuille flow, i.e. Parallel inflow, and an applied axial traction of at the upstream end, . Parallel, axially traction-free outflow at the downstream end, i.e. and at . No slip on all channel walls, i.e. on the rigid walls and We consider a wall motion that deforms the initially "flush" wall into a parabolic shape. We denote the non-dimensional amplitude of the oscillation by and its period by , and parametrise the position vector to a point on the wall by the Lagrangian coordinate as where the "ramp" function is used to facilitate the start-up of the simulation from the initial condition of steady Poiseuille flow. provides a "smooth" startup of the wall motion during the first period of the oscillation. # The results The figure below shows a snapshot, taken from the animation of the computational results. The first four figures show (from top left to bottom right) "carpet plots" of the axial and transverse velocities, the axial component of the perturbation velocity , and the pressure distribution. The 2D contour plot at the bottom of the figure shows a contour plot of the pressure and a few instantaneous streamlines. Snapshot from the animation of the flow field for Re = Re St = 50, T=0.45, A=0.01. The figures illustrate the flow structures identified in Jensen & Heil's (2003) asymptotic analysis of 2D channel flows that are driven by high-frequency, small-amplitude oscillations of a finite section of one of their walls: The flow consists of oscillatory axial "sloshing flows", superimposed on the mean Poiseuille flow that is driven by the applied pressure drop. During phases when the wall moves inwards (outwards) the flow generated by the moving wall decelerates (accelerates) the flow in the upstream region as the wall "injects" fluid into ("sucks" fluid out of) the domain. Conversely, in the downstream region the flow generated by the wall adds to the pressure-driven mean flow during phases when the wall moves inwards. This is shown most clearly in the plot of the axial velocity perturbation. In the plots shown above, the wall moves outwards and the axial perturbation velocity is positive (i.e. in the direction of the pressure-driven mean flow) in the upstream region, and negative in the downstream region. This is also shown in the time-traces of the velocities at two control points in the in- and outflow cross-sections, shown in the figure below: Time-trace of the axial velocities at two control points in the upstream and downstream cross-sections, and the vertical position of a control point on the wall. (Re = Re St = 50, T=0.45, A=0.01.) Finally, we comment that the plot of the perturbation velocities confirms the two-layer structure of the sloshing flows predicted in the asymptotic analysis. The sloshing flow comprises a blunt core flow region in which the flow is dominated by inertial effects while thin Stokes layers develop near the wall. Within these layers, the fluid viscosity reduces the axial velocity to zero. The carpet plot of the pressure shows that the pressure distribution is dominated by the variations induced by the oscillatory sloshing flows. For a detailed discussion of the flow structure we refer to Jensen & Heil (2003). # Overview of the driver code Overall, the driver code is very similar to codes developed for other moving-boundary Navier-Stokes problems, such as the driver code used to simulate the flow inside an oscillating ellipse. The present code is slightly lengthier because of the traction boundary conditions which we impose by attaching traction elements to the upstream end of the mesh. (Refer to the traction-driven Rayleigh problem for a more detailed discussion of this technique.) Also, as discussed in another example, the traction elements must be removed/re-attached before/after every mesh adaptation. The domain is discretised by the CollapsibleChannelMesh which employs the CollapsibleChannelDomain to provide a MacroElement - based representation of the deforming domain in terms of the GeomObject that describes the motion of the "collapsible" section of the wall (boundary 3). The sketch below illustrates the topology and the mesh deformation: As the wall deforms, the boundaries of the MacroElements in the "collapsible" part of the Domain follow the wall motion. Sketch of the CollapsibleChannelDomain/Mesh. The no-slip boundary conditions on the moving wall are applied as in the oscillating ellipse problem, by executing the function FSI_functions::apply_no_slip_on_moving_wall(...) in Problem::actions_before_implicit_timestep() for all nodes that are located on boundary 3. The following sections provide a complete annotated listing of the driver code. Most functions should already be familiar from previous examples and you may want to skip straight to the Comments and Exercises. # The moving wall As usual, we represent the moving wall as a GeomObject and define its shape by implementing the pure virtual function GeomObject::position(...). The arguments to the constructor specify the Eulerian coordinates of wall's left end, its undeformed length, the amplitude of the oscillations, , and the period of the oscillations . We also pass the pointer to a Time object to the constructor and store it in a private data member, to allow the position(...) functions to access the current value of the continuous time. The amplitude of the wall motion, and the period of its oscillations are stored as private data members, accessible via suitable member functions. //===============start_of_oscillating_wall================================= /// Straight, horizontal channel wall at \f$y=H \f$ deforms into an /// oscillating parabola. The amplitude of the oscillation /// \f$A \f$ and its period is \f$T \f$. /// The position vector to a point on the wall, parametrised by /// the Lagrangian coordinate \f$\zeta \in [0,L]\f$, is therefore given by /// \f[ {\bf R}(\zeta,t) = /// \left( /// \begin{array}{c} /// L_{up} + \zeta \\ 1 /// \end{array} /// \right) /// + A /// \left( /// \begin{array}{l} /// - B \sin\left(\frac{2\pi}{L_{collapsible}}\zeta\right) \\ \left( /// \frac{2}{L_{collapsible}}\right)^2 \zeta \ (L-\zeta) /// \end{array} /// \right) /// \ \sin\left(\frac{2\pi t}{T}\right) /// \ {\cal R}(t) /// \f] /// The parameter \f$B \f$ is zero by default. If it is set to a nonzero /// value, the material particles on the wall also perform some /// horizontal motion. The "ramp" function /// \f[ /// {\cal R}(t) = \left\{ /// \begin{array}{ll} /// \frac{1}{2}(1-\cos(\pi t/T)) & \mbox{for $t<T$} \\ 1 & \mbox{for $t \ge T$} /// \end{array} /// \right. /// \f] /// provides a "smooth" startup of the oscillation. //========================================================================= class OscillatingWall : public GeomObject { public: /// Constructor : It's a 2D object, parametrised by /// one Lagrangian coordinate. Arguments: height at ends, x-coordinate of /// left end, length, amplitude of deflection, period of oscillation, and /// pointer to time object OscillatingWall(const double& h, const double& x_left, const double& l, const double& a, const double& period, Time* time_pt) : GeomObject(1,2), H(h), Length(l), X_left(x_left), A(a), B(0.0), T(period), Time_pt(time_pt) {} /// Destructor: Empty ~OscillatingWall(){} /// Access function to the amplitude double& amplitude(){return A;} /// Access function to the period double& period(){return T;} Since the GeomObject represents a moving (i.e. time-dependent) boundary, we implement both versions of the GeomObject::position(...) function: The "unsteady" version computes the position vector at the t -th previous timestep. /// Position vector at Lagrangian coordinate zeta /// at time level t. void position(const unsigned& t, const Vector<double>&zeta, Vector<double>& r) const { using namespace MathematicalConstants; // Smoothly ramp up the oscillation during the first period double ramp=1.0; if (Time_pt->time(t)<T) { ramp=0.5(1.0-cos(PiTime_pt->time(t)/T)); } // Position vector r[0] = zeta[0]+X_left -BAsin(2.03.14159zeta[0]/Length)* sin(2.0Pi(Time_pt->time(t))/T)ramp; r[1] = H+A((Length-zeta[0])zeta[0])/pow(0.5Length,2)* sin(2.0Pi(Time_pt->time(t))/T)ramp; } // end of "unsteady" version The version without additional argument computes the position vector at the present time: /// "Current" position vector at Lagrangian coordinate zeta void position(const Vector<double>&zeta, Vector<double>& r) const { position (0, zeta, r); } Finally, here are the various private data members: /// Number of geometric Data in GeomObject: None. unsigned ngeom_data() const {return 0;} private: /// Height at ends double H; /// Length double Length; /// x-coordinate of left end double X_left; /// Amplitude of oscillation double A; /// Relative amplitude of horizontal wall motion double B; /// Period of the oscillations double T; /// Pointer to the global time object Time Time_pt; }; // end of oscillating wall [Note: We note that the OscillatingWall class allows the wall shape to be slightly more complicated than required by (5). If the parameter B is set to a non-zero value, the material points on the wall also undergo some horizontal displacement. We will use this capability in one of the exercises in section Comments and Exercises.] # Namespace for the "global" physical variables As usual, we define the problem parameters in a namespace and assign default values that can be overwritten if required. //====start_of_Global_Physical_Variables================ /// Namespace for phyical parameters //====================================================== namespace Global_Physical_Variables { /// Reynolds number double Re=50.0; /// Womersley = Reynolds times Strouhal double ReSt=50.0; /// Default pressure on the left boundary double P_up=0.0; We also implement the function that defines the prescribed (axial) traction at the inflow boundary. /// Traction required at the left boundary void prescribed_traction(const double& t, const Vector<double>& x, const Vector<double>& n, Vector<double>& traction) { traction.resize(2); traction[0]=P_up; traction[1]=0.0; } } // end of Global_Physical_Variables # The driver code As with most previous time-dependent codes, we use command line arguments to indicate if the code is run during oomph-lib's self-test. If any command line arguments are specified, we use a coarser discretisation and perform fewer timesteps. After storing the command line arguments, we choose the number of elements in the mesh, set the lengths of the domain and choose the amplitude and period of the oscillation. The parameter values are chosen such that the wall motion resembles that in the FSI simulations shown in Fig. 5 of Jensen & Heil (2003). //=======start_of_driver_code================================================== /// with prescribed wall motion. Presence of command line arguments /// indicates validation run with coarse resolution and small number of /// timesteps. //============================================================================= int main(int argc, char* argv[]) { // Store command line arguments CommandLineArgs::setup(argc,argv); // Reduction in resolution for validation run? unsigned coarsening_factor=1; if (CommandLineArgs::Argc>1) { coarsening_factor=4; } // Number of elements in the domain unsigned nup=20/coarsening_factor; unsigned ncollapsible=40/coarsening_factor; unsigned ndown=40/coarsening_factor; unsigned ny=16/coarsening_factor; // Length of the domain double lup=5.0; double lcollapsible=10.0; double ldown=10.0; double ly=1.0; // Initial amplitude of the wall deformation // Period of oscillation double period=0.45; We set the (non-dimensional) upstream pressure to , so that in the absence of any wall oscillation, the steady flow through the channel is Poiseuille flow, ; see Comments and Exercises. // Pressure/applied traction on the left boundary: This is consistent with Global_Physical_Variables::P_up=12.0(lup+lcollapsible+ldown); Next, we specify the output directory and build the problem with refineable 2D Crouzeix Raviart Elements. //Set output directory DocInfo doc_info; doc_info.set_directory("RESLT"); // Open a trace file ofstream trace_file; char filename[100]; sprintf(filename,"%s/trace.dat",doc_info.directory().c_str()); trace_file.open(filename); // Build the problem with Crouzeix Raviart Elements CollapsibleChannelProblem<RefineableQCrouzeixRaviartElement<2> > problem(nup, ncollapsible, ndown, ny, lup, lcollapsible, ldown, ly, amplitude,period); Next we set up the time-stepping parameters for a simulation of three periods of the oscillation, performed with 40 timesteps per period. Fewer timesteps are performed if the code is run in self-test mode. // Number of timesteps per period unsigned nsteps_per_period=40; // Number of periods unsigned nperiod=3; // Number of timesteps (reduced for validation) unsigned nstep=nsteps_per_periodnperiod; if (CommandLineArgs::Argc>1) { nstep=3; } //Timestep: double dt=period/double(nsteps_per_period); // Start time double t_min=0.0; We initialise the timestepper and set the initial conditions before documenting the initial condition. // Initialise timestep and set initial conditions problem.time_pt()->time()=t_min; problem.initialise_dt(dt); problem.set_initial_condition(); // Output the initial solution problem.doc_solution(doc_info, trace_file); // Step number doc_info.number()++; Next we set the error targets for the adaptive mesh refinement; a smaller target error is used when the code is run in self-test mode to ensure that some mesh refinement is performed during the first few timesteps. // Set targets for spatial adaptivity problem.bulk_mesh_pt()->max_permitted_error()=1.0e-3; problem.bulk_mesh_pt()->min_permitted_error()=1.0e-5; // Overwrite with reduced targets for validation run to force // some refinement during the first few timesteps if (CommandLineArgs::Argc>1) { problem.bulk_mesh_pt()->max_permitted_error()=1.0e-4; problem.bulk_mesh_pt()->min_permitted_error()=1.0e-6; } The timestepping loop itself is identical to that used in other time-dependent driver codes with adaptive mesh refinement. During the first timestep, an arbitrary number of spatial adaptations may be performed, as the initial condition can be re-assigned on the refined mesh. (This is indicated by setting the boolean flag first to true when calling the spatially adaptive, unsteady Newton solver.) During subsequent timesteps the need to interpolate the history values onto the refined mesh limits the benefits of repeated mesh adaptations and we limit the number of spatial adaptations per timestep to 1. // First timestep: We may re-assign the initial condition bool first=true; // Max. number of adaptations during first timestep // Timestepping loop for (unsigned istep=0;istep<nstep;istep++) { // Solve the problem // Outpt the solution problem.doc_solution(doc_info, trace_file); // Step number doc_info.number()++; // We've done one step: Don't re-assign the initial conditions // and limit the number of adaptive mesh refinements to one // per timestep. first=false; } trace_file.close(); } //end of driver code # The problem class As usual, we template the problem class by the element type and provide an access functions to the "bulk" Navier-Stokes mesh. //=======start_of_problem_class======================================= /// Problem class //==================================================================== template <class ELEMENT> class CollapsibleChannelProblem : public Problem { public : /// Constructor : the arguments are the number of elements, /// the length of the domain and the amplitude and period of /// the oscillations CollapsibleChannelProblem(const unsigned& nup, const unsigned& ncollapsible, const unsigned& ndown, const unsigned& ny, const double& lup, const double& lcollapsible, const double& ldown, const double& ly, const double& amplitude, const double& period); /// Empty destructor ~CollapsibleChannelProblem() {} /// Access function for the specific mesh RefineableCollapsibleChannelMesh<ELEMENT>* bulk_mesh_pt() { // Upcast from pointer to the Mesh base class to the specific // element type that we're using here. return dynamic_cast<RefineableCollapsibleChannelMesh<ELEMENT>> (Bulk_mesh_pt); No action is needed before or after solving, so the pure virtual functions Problem::actions_before_newton_solve() and Problem::actions_after_newton_solve() can remain empty. /// Update the problem specs before solve (empty) void actions_before_newton_solve(){} /// Update the problem after solve (empty) void actions_after_newton_solve(){} We will use the function Problem::actions_before_implicit_timestep() to update the no-slip boundary conditions on the moving wall before each timestep and employ Problem::actions_before_adapt() and Problem::actions_after_adapt() to wipe and rebuild the mesh of prescribed traction elements each time a mesh adaptation is performed. The functions Problem::doc_solution(...) and Problem::set_initial_condition() will do what they say... /// Update the velocity boundary condition on the moving wall void actions_before_implicit_timestep(); /// Actions before adapt: Wipe the mesh of prescribed traction elements /// Actions after adapt: Rebuild the mesh of prescribed traction elements /// Apply initial conditions void set_initial_condition(); /// Doc the solution void doc_solution(DocInfo& doc_info, ofstream& trace_file); The private helper functions create_traction_elements(...) and delete_traction_elements() attach and remove the traction elements from the upstream boundary of the "bulk" Navier-Stokes mesh. private : /// Create the prescribed traction elements on boundary b /// of the bulk mesh and stick them into the surface mesh. void create_traction_elements(const unsigned &b, Mesh const &bulk_mesh_pt, Mesh* const &surface_mesh_pt); /// Delete prescribed traction elements from the surface mesh void delete_traction_elements(Mesh* const &surface_mesh_pt); The private member data contains the geometric parameters as well as the pointer to the GeomObject that describes the moving wall. /// Number of elements in the x direction in the upstream part of the channel unsigned Nup; /// Number of elements in the x direction in the "collapsible" /// part of the channel unsigned Ncollapsible; /// Number of elements in the x direction in the downstream part of the channel unsigned Ndown; /// Number of elements across the channel unsigned Ny; /// x-length in the upstream part of the channel double Lup; /// x-length in the "collapsible" part of the channel double Lcollapsible; /// x-length in the downstream part of the channel double Ldown; /// Transverse length double Ly; /// Pointer to the geometric object that parametrises the "collapsible" wall OscillatingWall* Wall_pt; Further private member data includes pointers to the "bulk" mesh and the surface mesh that contains the traction elements, and pointers to control nodes in the in- and outflow cross-sections. /// Pointer to the "bulk" mesh RefineableCollapsibleChannelMesh<ELEMENT>* Bulk_mesh_pt; /// Pointer to the "surface" mesh that contains the applied traction /// elements Mesh* Surface_mesh_pt; /// Pointer to the left control node Node* Left_node_pt; /// Pointer to right control node Node* Right_node_pt; }; // end of problem class # The problem constructor The arguments passed to the problem constructor specify the number of elements and lengths of the various parts of the channel, as well as the amplitude and period of the wall oscillations. We store the parameters in the problem's private member data and increase the maximum permitted residual for the Newton iteration. //===start_of_constructor======================================= /// Constructor for the collapsible channel problem //=============================================================== template <class ELEMENT> CollapsibleChannelProblem<ELEMENT>::CollapsibleChannelProblem( const unsigned& nup, const unsigned& ncollapsible, const unsigned& ndown, const unsigned& ny, const double& lup, const double& lcollapsible, const double& ldown, const double& ly, const double& amplitude, const double& period) { // Number of elements Nup=nup; Ncollapsible=ncollapsible; Ndown=ndown; Ny=ny; // Lengths of domain Lup=lup; Lcollapsible=lcollapsible; Ldown=ldown; Ly=ly; // Overwrite maximum allowed residual to accomodate possibly // poor initial guess for solution Problem::Max_residuals=10000; We continue by building the BDF<2> timestepper and pass a pointer to it to the Problem // Allocate the timestepper -- this constructs the Problem's // time object with a sufficient amount of storage to store the // previous timsteps. Next, we create the GeomObject that represents the oscillating wall, and pass a pointer to it to the constructor of the CollapsibleChannelMesh //Create the geometric object that represents the wall Wall_pt=new OscillatingWall(height, x_left, length, amplitude, period, time_pt()); //Build mesh Bulk_mesh_pt = new RefineableCollapsibleChannelMesh<ELEMENT>( nup, ncollapsible, ndown, ny, lup, lcollapsible, ldown, ly, Wall_pt, time_stepper_pt()); We create a second mesh to store the applied traction elements and attach them to the inflow boundary (boundary 5) of the "bulk" fluid mesh, using the function create_traction_elements(...). Both submeshes are then combined into a global mesh. // Create "surface mesh" that will contain only the prescribed-traction // elements at the inflow. The default constructor just creates the mesh // without giving it any elements, nodes, etc. Surface_mesh_pt = new Mesh; // Create prescribed-traction elements from all elements that are // adjacent to boundary 5 (inflow boundary), and add them to the surface mesh. create_traction_elements(5,Bulk_mesh_pt,Surface_mesh_pt); // Add the two sub meshes to the problem // Combine all submeshes added so far into a single Mesh build_global_mesh(); We create the spatial error estimator for the fluid mesh and loop over the various elements to set the pointers to the relevant physical parameters, first for the Navier-Stokes elements in the bulk mesh, //Set errror estimator for bulk mesh Z2ErrorEstimator* error_estimator_pt=new Z2ErrorEstimator; dynamic_cast<RefineableCollapsibleChannelMesh<ELEMENT>> (Bulk_mesh_pt)->spatial_error_estimator_pt()=error_estimator_pt; // Loop over the elements to set up element-specific // things that cannot be handled by constructor unsigned n_element=Bulk_mesh_pt->nelement(); for(unsigned e=0;e<n_element;e++) { // Upcast from GeneralisedElement to the present element ELEMENT el_pt = dynamic_cast<ELEMENT>(Bulk_mesh_pt->element_pt(e)); //Set the Reynolds number el_pt->re_pt() = &Global_Physical_Variables::Re; // Set the Womersley number el_pt->re_st_pt() = &Global_Physical_Variables::ReSt; } // end loop over bulk elements and then for the applied traction elements in the surface mesh: // Loop over the traction elements to pass pointer to prescribed // traction function unsigned n_el=Surface_mesh_pt->nelement(); for(unsigned e=0;e<n_el;e++) { // Upcast from GeneralisedElement to NavierStokes traction element NavierStokesTractionElement<ELEMENT> el_pt = dynamic_cast< NavierStokesTractionElement<ELEMENT>>( Surface_mesh_pt->element_pt(e)); // Set the pointer to the prescribed traction function el_pt->traction_fct_pt() = &Global_Physical_Variables::prescribed_traction; } // end loop over applied traction elements We apply the boundary conditions and pin the velocity on the relevant mesh boundaries: • both axial and transverse velocities are pinned along the bottom and the top boundaries (boundaries 0, 2, 3 and 4). • the transverse velocities are pinned along the in- and outflow boundaries (boundaries 1 and 5). //Pin the velocity on the boundaries //x and y-velocities pinned along boundary 0 (bottom boundary) : unsigned ibound=0; unsigned num_nod= bulk_mesh_pt()->nboundary_node(ibound); for (unsigned inod=0;inod<num_nod;inod++) { for(unsigned i=0;i<2;i++) { bulk_mesh_pt()->boundary_node_pt(ibound, inod)->pin(i); } } //x and y-velocities pinned along boundary 2, 3, 4 (top boundaries) : for(unsigned ib=2;ib<5;ib++) { num_nod= bulk_mesh_pt()->nboundary_node(ib); for (unsigned inod=0;inod<num_nod;inod++) { for(unsigned i=0;i<2;i++) { bulk_mesh_pt()->boundary_node_pt(ib, inod)->pin(i); } } } //y-velocity pinned along boundary 1 (right boundary): ibound=1; num_nod= bulk_mesh_pt()->nboundary_node(ibound); for (unsigned inod=0;inod<num_nod;inod++) { bulk_mesh_pt()->boundary_node_pt(ibound, inod)->pin(1); } //y-velocity pinned along boundary 5 (left boundary): ibound=5; num_nod= bulk_mesh_pt()->nboundary_node(ibound); for (unsigned inod=0;inod<num_nod;inod++) { bulk_mesh_pt()->boundary_node_pt(ibound, inod)->pin(1); }// end of pin_velocity We select two control nodes on the inflow and outflow boundaries to document the velocities. //Select control nodes "half way" up the inflow/outflow cross-sections //-------------------------------------------------------------------- // Left boundary ibound=5; num_nod= bulk_mesh_pt()->nboundary_node(ibound); unsigned control_nod=num_nod/2; Left_node_pt= bulk_mesh_pt()->boundary_node_pt(ibound, control_nod); // Right boundary ibound=1; num_nod= bulk_mesh_pt()->nboundary_node(ibound); control_nod=num_nod/2; Right_node_pt= bulk_mesh_pt()->boundary_node_pt(ibound, control_nod); Finally, we set up the equation numbering scheme. // Setup equation numbering scheme cout <<"Number of equations: " << assign_eqn_numbers() << std::endl; } //end of constructor # Post processing The function doc_solution(...) documents the results, and records the time-trace of the axial velocities at the two control nodes and the position of the midpoint on the oscillating wall. //====start_of_doc_solution=================================================== /// Doc the solution //============================================================================ template <class ELEMENT> void CollapsibleChannelProblem<ELEMENT>:: doc_solution(DocInfo& doc_info, ofstream& trace_file) { ofstream some_file; char filename[100]; // Number of plot points unsigned npts; npts=5; // Output solution sprintf(filename,"%s/soln%i.dat",doc_info.directory().c_str(), doc_info.number()); some_file.open(filename); bulk_mesh_pt()->output(some_file,npts); some_file.close(); // Get the position of the midpoint on the geometric object Vector<double> zeta(1); zeta[0]=0.5Lcollapsible; Vector<double> wall_point(2); Wall_pt->position(zeta,wall_point); // Write trace file trace_file << time_pt()->time() << " " << wall_point[1] << " " << Left_node_pt->value(0) << " " << Right_node_pt->value(0) << " " << std::endl; // Output wall shape sprintf(filename,"%s/wall%i.dat",doc_info.directory().c_str(), doc_info.number()); some_file.open(filename); unsigned nplot=100; for (unsigned i=0;i<nplot;i++) { zeta[0]=double(i)/double(nplot-1)Lcollapsible; Wall_pt->position(zeta,wall_point); some_file << wall_point[0] << " " << wall_point[1] << std::endl; } some_file.close(); } // end_of_doc_solution # Creation of the traction elements The creation of the applied traction elements follows the usual pattern, explained in detail elsewhere: We loop over the elements in the fluid mesh that are adjacent to the specified mesh boundary, and build the corresponding traction elements, which are added to the surface mesh. //==========start_of_create_traction_elements================================== /// Create the traction elements //============================================================================ template <class ELEMENT> void CollapsibleChannelProblem<ELEMENT>::create_traction_elements( const unsigned &b, Mesh const &bulk_mesh_pt, Mesh* const &surface_mesh_pt) { // How many bulk elements are adjacent to boundary b? unsigned n_element = bulk_mesh_pt->nboundary_element(b); // Loop over the bulk elements adjacent to boundary b for(unsigned e=0;e<n_element;e++) { // Get pointer to the bulk element that is adjacent to boundary b ELEMENT* bulk_elem_pt = dynamic_cast<ELEMENT> (bulk_mesh_pt->boundary_element_pt(b,e)); //What is the index of the face of element e that lies along boundary b int face_index = bulk_mesh_pt->face_index_at_boundary(b,e); // Build the corresponding prescribed-traction element NavierStokesTractionElement<ELEMENT> traction_element_pt = new NavierStokesTractionElement<ELEMENT>(bulk_elem_pt,face_index); //Add the prescribed-flux element to the surface mesh } //end of loop over bulk elements adjacent to boundary b } // end of create_traction_elements # Delete the traction elements Since the "bulk" elements that the applied traction elements are attached to may disappear during mesh adaptation, we delete all traction elements before the adaptation and re-attach them afterwards. The deletion is performed by the following member function. Note that the surface mesh that contains the traction elements is not deleted, as this would also delete the associated nodes which are shared with the corresponding bulk elements. //============start_of_delete_traction_elements============================== /// Delete traction elements and wipe the surface mesh //======================================================================= template<class ELEMENT> void CollapsibleChannelProblem<ELEMENT>:: delete_traction_elements(Mesh* const &surface_mesh_pt) { // How many surface elements are in the surface mesh unsigned n_element = surface_mesh_pt->nelement(); // Loop over the surface elements for(unsigned e=0;e<n_element;e++) { // Kill surface element delete surface_mesh_pt->element_pt(e); } // Wipe the mesh surface_mesh_pt->flush_element_and_node_storage(); } // end of delete_traction_elements # Apply the initial conditions Initial conditions are applied as usual. We start by confirming that the timestepper is a member of the BDF family and therefore operates on history values that represent the solution at previous timesteps. We assign the previous nodal positions and velocities at all nodes, assuming that for the wall is at rest and the flow field is given by steady Poiseuille flow. //=======start_of_apply_initial_conditions=================================== /// Apply initial conditions: Impulsive start from steady Poiseuille flow //============================================================================ template <class ELEMENT> void CollapsibleChannelProblem<ELEMENT>::set_initial_condition() { // Check that timestepper is from the BDF family if (time_stepper_pt()->type()!="BDF") { std::ostringstream error_stream; error_stream << "Timestepper has to be from the BDF family!\n" << "You have specified a timestepper from the " << time_stepper_pt()->type() << " family" << std::endl; throw OomphLibError(error_stream.str(), OOMPH_CURRENT_FUNCTION, OOMPH_EXCEPTION_LOCATION); } // Update the mesh bulk_mesh_pt()->node_update(); // Loop over the nodes to set initial guess everywhere unsigned num_nod = bulk_mesh_pt()->nnode(); for (unsigned n=0;n<num_nod;n++) { // Get nodal coordinates Vector<double> x(2); x[0]=bulk_mesh_pt()->node_pt(n)->x(0); x[1]=bulk_mesh_pt()->node_pt(n)->x(1); bulk_mesh_pt()->node_pt(n)->set_value(0,6.0(x[1]/Ly)(1.0-(x[1]/Ly))); bulk_mesh_pt()->node_pt(n)->set_value(1,0.0); } bulk_mesh_pt()->assign_initial_values_impulsive(); } // end of set_initial_condition # Actions before the timestep Before each timestep, we update the nodal positions in the fluid mesh, and apply the no-slip condition to each node on mesh boundary 3. //=====start_of_actions_before_implicit_timestep============================== /// Execute the actions before timestep: Update the velocity /// boundary condition on the moving wall //============================================================================ template <class ELEMENT> void CollapsibleChannelProblem<ELEMENT>::actions_before_implicit_timestep() { // Update the domain shape bulk_mesh_pt()->node_update(); // Moving wall: No slip; this implies that the velocity needs // to be updated in response to wall motion unsigned ibound=3; unsigned num_nod=bulk_mesh_pt()->nboundary_node(ibound); for (unsigned inod=0;inod<num_nod;inod++) { // Which node are we dealing with? Node* node_pt=bulk_mesh_pt()->boundary_node_pt(ibound,inod); // Apply no slip FSI_functions::apply_no_slip_on_moving_wall(node_pt); } } //end of actions_before_implicit_timestep # Actions before the mesh adaptation As discussed above, we delete the applied traction elements before performing any mesh adaptation and then rebuild the global mesh. /// Actions before adapt: Wipe the mesh of prescribed traction elements //======================================================================== template<class ELEMENT> { // Kill the traction elements and wipe surface mesh delete_traction_elements(Surface_mesh_pt); // Rebuild the global mesh. rebuild_global_mesh(); # Actions before the mesh adaptation Once the mesh has been adapted, we (re-)create the prescribed traction elements and rebuild the global mesh. We also have to pass the pointers to prescribed traction function to the newly created traction elements. /// Actions after adapt: Rebuild the mesh of prescribed traction elements //======================================================================== template<class ELEMENT> { // Create prescribed-flux elements from all elements that are create_traction_elements(5,Bulk_mesh_pt,Surface_mesh_pt); // Rebuild the global mesh rebuild_global_mesh(); // Loop over the traction elements to pass pointer to prescribed traction function unsigned n_element=Surface_mesh_pt->nelement(); for(unsigned e=0;e<n_element;e++) { // Upcast from GeneralisedElement to NavierStokesTractionElement element NavierStokesTractionElement<ELEMENT> el_pt = dynamic_cast<NavierStokesTractionElement<ELEMENT>>( Surface_mesh_pt->element_pt(e)); // Set the pointer to the prescribed traction function el_pt->traction_fct_pt() = &Global_Physical_Variables::prescribed_traction; } 1. Check the non-dimensionalisation of the governing equations and confirm that a (non-dimensional) upstream pressure is required to drive the steady Poiseuille flow specified by (3) through the static, undeformed channel. Use this to "validate" (well, "plausibility-check", anyway...) the code by setting the amplitude of the wall oscillation to zero. 2. Double the upstream pressure while keeping the amplitude of the wall oscillation at zero and confirm that the flow accelerates until it (asymptotically) approaches Poiseuille flow with twice the initial flowrate as 3. The flow field has the largest velocity gradients in the thin Stokes layers near the wall, causing the automatic mesh adaptation procedure to refine the mesh pre-dominantly in these regions. To facilitate the resolution of such layers the CollapsibleChannelDomain and CollapsibleChannelMesh allow the specification of a mapping [0,1] -> [0,1] that redistributes the nodal points in the vertical direction so that the elements near the wall become more squashed. By default the "boundary-layer squash function" is the identity but it may be overloaded by specifying a function pointer to an alternative function. The driver code already includes a demonstration of this capability which may be activated by compiling the driver code with -DUSE_BL_SQUASH_FCT. This activates the code segment #ifdef USE_BL_SQUASH_FCT // Set a non-trivial boundary-layer-squash function... Bulk_mesh_pt->bl_squash_fct_pt() = &BL_Squash::squash_fct; // ... and update the nodal positions accordingly Bulk_mesh_pt->node_update(); #endif double squash_fct(const double &s) Mapping [0,1] -> [0,1] that re-distributes nodal points across the channel width. in the Problem constructor. The "squash function" used for this example is defined in the following namespace: //==========start_of_BL_Squash ========================================= /// Namespace to define the mapping [0,1] -> [0,1] that re-distributes /// nodal points across the channel width. //====================================================================== namespace BL_Squash { /// Boundary layer width double Delta=0.1; /// Fraction of points in boundary layer double Fract_in_BL=0.5; /// Mapping [0,1] -> [0,1] that re-distributes /// nodal points across the channel width double squash_fct(const double& s) { // Default return double y=s; if (s<0.5Fract_in_BL) { y=Delta2.0s/Fract_in_BL; } else if (s>1.0-0.5Fract_in_BL) { } else { y=(1.0-2.0Delta)/(1.0-Fract_in_BL)s+ } return y; } }// end of BL_Squash Namespace to define the mapping [0,1] -> [0,1] that re-distributes nodal points across the channel wi... double Delta Boundary layer width. double Fract_in_BL Fraction of points in boundary layer. With this function 50% of the nodal points in the vertical direction are located within two boundary-layer regions which occupy 2 x 10% of the channel's width. The figure below shows the element shapes for a (coarse) initial mesh that is used in the validation run, with and without the boundary-layer squashing function: Coarse initial meshes with and without the boundary-layer squash function. Confirm that if this "squashing function" is applied to the mesh that is used during the non-self-test runs (this mesh has 16 x larger number of elements than the meshes shown above), the quality of the computed solution improves so much that no subsequent mesh adaptation is required. 4. The flow structures observed during the small-amplitude oscillations (shown in the animation at the beginning of this document) are in perfect agreement with the structures predicted by Jensen & Heil's (2003) asymptotic analysis. As an exercise, increase the amplitude of the wall oscillation (to , say) to confirm that the flow-structure predicted by the theory (which is strictly applicable only for small-amplitude oscillations) also provides an excellent description of of the system's behaviour during large-amplitude oscillations with more complicated wall motions. For instance, the figure below shows a snapshot of the the animation of the computational results for an oscillation in which the wall undergoes a more complicated motion, described by for . For these parameter values, the wall performs a large-amplitude oscillation in the course of which material particles are not only displaced vertically but also in the horizontal direction. Nevertheless, the flow generated by the moving wall may be described as arising from the superposition of Poiseuille flow and an axial sloshing motion, the latter obviously having a much larger amplitude than in the previous case. The animation of the flow field shows that more complex local flow features develop briefly whenever the flow separates from the wall. However, the appearance of these features does not change the macroscopic behaviour of the flow. Flow field for a large-amplitude wall motion. Re=ReSt=50; A=B=0.5; T=0.45.	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 0, "mathjax_asciimath": 1, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.5683353543281555, "perplexity": 4457.227674527889}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2022-05/segments/1642320303729.69/warc/CC-MAIN-20220122012907-20220122042907-00618.warc.gz"}
https://brilliant.org/problems/rain-or-shine/	# Rain Or Shine The weather forecast stated that there would be 60% chance of rain on Saturday and 30% chance of rain on Sunday. What is the probability (in percentage) of rain on at least one of these two days? (Assume the days are independent.) ×	{"extraction_info": {"found_math": false, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.8901070952415466, "perplexity": 501.7775640061285}, "config": {"markdown_headings": true, "markdown_code": false, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2019-04/segments/1547583659063.33/warc/CC-MAIN-20190117184304-20190117210304-00350.warc.gz"}
https://forum.azimuthproject.org/plugin/viewcomment/18496	Has anyone figured out an answer for puzzle 85? Here's what I got so far. The "would be" left adjoint should look like: $h(x) = \bigwedge \\left\\{ y \in \mathbb{N}[S] \; : \; f(y) \to x \\right\\} .$ I've tried instantiating the formula for a resource in \$$\mathbb{N}[T] \$$ – I picked \$$[\textrm{egg}]\$$ and I've used the fact that \$$f \$$ forgets bowls and shells: $h([\textrm{egg}]) = \bigwedge \\left\\{ [\textrm{egg}], [\textrm{egg}] + [\textrm{bowl}], [\textrm{egg}] + [\textrm{shells}], [\textrm{egg}] + [\textrm{bowl}] + [\textrm{shells}], \cdots \\right\\} .$ But I cannot find an element in \$$\mathbb{N}[S] \$$ that is less than (that is, can be produced from) both \$$[\textrm{egg}] \$$ and \$$[\textrm{egg}] + [\textrm{bowl}] \$$. I'm tempted to conclude there is no left adjoint, but I doubt my reasoning as it goes against [John's optimism](https://forum.azimuthproject.org/discussion/comment/18382/#Comment_18382).	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 1, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.8538498282432556, "perplexity": 1572.7886003497615}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2022-21/segments/1652662588661.65/warc/CC-MAIN-20220525151311-20220525181311-00072.warc.gz"}
https://ir.amolf.nl/pub/6682	When sheared, most elastic solids including metals, rubbers and polymer gels dilate perpendicularly to the shear plane. This behavior, known as the Poynting effect, is characterized by a positive normal stress. Surprisingly, fibrous biopolymer gels exhibit a \emph{negative} normal stress under shear. Here we show that this anomalous behavior originates from the open network structure of biopolymer gels. Using fibrin networks with a controllable pore size as a model system, we show that the normal stress response to an applied shear is positive at short times, but decreases to negative values with a characteristic time scale set by pore size. Using a two-fluid model, we develop a quantitative theory that unifies the opposite behaviors encountered in synthetic and biopolymer gels.	{"extraction_info": {"found_math": false, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.8474117517471313, "perplexity": 2263.3837787547654}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2020-29/segments/1593657146845.98/warc/CC-MAIN-20200713194203-20200713224203-00143.warc.gz"}
https://www.uni-bremen.de/mapex/forschung/research-highlights/mapex-research-highlights/dinuclear-face-sharing-bi-octahedral-tungstenvi-core-and-unusual-thermal-behavior-in-complex-th-tungstates-1	# Dinuclear Face-Sharing Bi-octahedral Tungsten(VI) Core and Unusual Thermal Behavior in Complex Th Tungstates Bin Xiao,Thorsten M. Gesing, Lars Robben, Dirk Bosbach and Evgeny V. Alekseev. Chemistry – A European Journal (2015) 21, 7746-7754. doi:10.1002/chem.201500500 Two new thorium tungstates A6Th6(WO4)14O (A=K and Rb) were synthesized by high-temperature solid-state reactions. The structures of both phases are based on a rare dinuclear confacial bi-octahedral [W2O9]6− core, encapsulated in a [Th6W7O46(W2O9)]32− cage showing a cross-section geometry similar to a six-leafed lily. The adjacent cages are connected in two dimensional layers by WO4 tetrahedral linkers. Due to the dissimilarities in mutual orientations of adjacent layers in these two structures, K6Th6(WO4)14O crystallizes in space group of R32 while Rb6Th6(WO4)14O stabilizes in P-62c. The high-temperature phase transition was observed in Rb6Th6(WO4)14O and investigated using high-temperature PXRD technique. The results demonstrate a very unusual thermal behavior of this compound. The Raman and IR spectra of both phases were analyzed with respect to their complex structures.	{"extraction_info": {"found_math": false, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.8526297211647034, "perplexity": 12828.096655012287}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2023-06/segments/1674764500303.56/warc/CC-MAIN-20230206015710-20230206045710-00593.warc.gz"}
http://en.wikipedia.org/wiki/String_landscape	# String theory landscape (Redirected from String landscape) The string theory landscape refers to the huge number of possible false vacua in string theory.[1] The large number of theoretically allowed configurations has prompted suggestions that certain physical mysteries, particularly relating to the fine-tuning of constants like the cosmological constant or the Higgs boson mass, may be explained not by a physical mechanism but by assuming that many different vacua are physically realized.[2] The anthropic landscape thus refers to the collection of those portions of the landscape that are suitable for supporting intelligent life, an application of the anthropic principle that selects a subset of the otherwise possible configurations. In string theory the number of false vacua is thought to be somewhere between 1010 to 10100.[1] The large number of possibilities arises from different choices of Calabi–Yau manifolds and different values of generalized magnetic fluxes over different homology cycles. If one assumes that there is no structure in the space of vacua, the problem of finding one with a sufficiently small cosmological constant is NP complete,[3] being a version of the subset sum problem. ## Anthropic principle Main article: Anthropic principle The idea of the string theory landscape has been used to propose a concrete implementation of the anthropic principle, the idea that fundamental constants may have the values they have not for fundamental physical reasons, but rather because such values are necessary for life (and hence intelligent observers to measure the constants). In 1987, Steven Weinberg proposed that the observed value of the cosmological constant was so small because it is not possible for life to occur in a universe with a much larger cosmological constant.[4] In order to implement this idea in a concrete physical theory, it is necessary to postulate a multiverse in which fundamental physical parameters can take different values. This has been realized in the context of eternal inflation. ## Bayesian probability Main article: Bayesian probability Some physicists, starting with Weinberg, have proposed that Bayesian probability can be used to compute probability distributions for fundamental physical parameters, where the probability $P(x)$ of observing some fundamental parameters $x$ is given by, $P(x)=P_{\mathrm{prior}}(x)\times P_{\mathrm{selection}}(x),$ where $P_\mathrm{prior}$ is the prior probability, from fundamental theory, of the parameters $x$ and $P_\mathrm{selection}$ is the anthropic selection function, determined by the number of "observers" that would occur in the Universe with parameters $x$. These probabilistic arguments are the most controversial aspect of the landscape. Technical criticisms of these proposals have pointed out that: • The function $P_\mathrm{prior}$ is completely unknown in string theory and may be impossible to define or interpret in any sensible probabilistic way. • The function $P_\mathrm{selection}$ is completely unknown, since so little is known about the origin of life. Simplified criteria (such as the number of galaxies) must be used as a proxy for the number of observers. Moreover, it may never be possible to compute it for parameters radically different from those of the observable universe. (Interpreting probability in a context where it is only possible to draw one sample from a distribution is problematic in frequentist probability but not in Bayesian probability, which is not defined in terms of the frequency of repeated events.) Various physicists have tried to address these objections, and the ideas remain extremely controversial both within and outside the string theory community. These ideas have been reviewed by Carroll.[5] ## Simplified approaches Tegmark et al. have recently considered these objections and proposed a simplified anthropic scenario for axion dark matter in which they argue that the first two of these problems do not apply.[6] Vilenkin and collaborators have proposed a consistent way to define the probabilities for a given vacuum.[7] A problem with many of the simplified approaches people have tried is that they "predict" a cosmological constant that is too large by a factor of 10–1000 (depending on one's assumptions) and hence suggest that the cosmic acceleration should be much more rapid than is observed.[8][9][10] ## Criticism Although few dispute the idea that string theory appears to have an unimaginably large number of metastable vacua, the existence, meaning and scientific relevance of the anthropic landscape remain highly controversial. Prominent proponents of the idea include Andrei Linde, Sir Martin Rees and especially Leonard Susskind, who advocate it as a solution to the cosmological-constant problem. Opponents, such as David Gross, suggest that the idea is inherently unscientific, unfalsifiable or premature. A famous debate on the anthropic landscape of string theory is the Smolin–Susskind debate on the merits of the landscape. The term "landscape" comes from evolutionary biology (see Fitness landscape) and was first applied to cosmology by Lee Smolin in his book.[11] It was first used in the context of string theory by Susskind. There are several popular books about the anthropic principle in cosmology.[12] Two popular physics blogs are opposed to this use of the anthropic principle.[13] ## References 1. ^ a b The most commonly quoted number is of the order 10500. See M. Douglas, "The statistics of string / M theory vacua", JHEP 0305, 46 (2003). arXiv:hep-th/0303194; S. Ashok and M. Douglas, "Counting flux vacua", JHEP 0401, 060 (2004). 2. ^ L. Susskind, "The anthropic landscape of string theory", arXiv:hep-th/0302219. 3. ^ Frederik Denef; Douglas, Michael R. (2006). "Computational complexity of the landscape". Annals of Physics 322 (5): 1096–1142. arXiv:hep-th/0602072. Bibcode:2007AnPhy.322.1096D. doi:10.1016/j.aop.2006.07.013. 4. ^ S. Weinberg, "Anthropic bound on the cosmological constant", Phys. Rev. Lett. 59, 2607 (1987). 5. ^ S. M. Carroll, "Is our universe natural?", arXiv:hep-th/0512148. 6. ^ M. Tegmark, A. Aguirre, M. Rees and F. Wilczek, "Dimensionless constants, cosmology and other dark matters", arXiv:astro-ph/0511774. F. Wilczek, "Enlightenment, knowledge, ignorance, temptation", arXiv:hep-ph/0512187. See also the discussion at [1]. 7. ^ See, e.g. Alexander Vilenkin (2006). "A measure of the multiverse". Journal of Physics A: Mathematical and Theoretical 40 (25): 6777–6785. arXiv:hep-th/0609193. Bibcode:2007JPhA...40.6777V. doi:10.1088/1751-8113/40/25/S22. 8. ^ Abraham Loeb (2006). "An observational test for the anthropic origin of the cosmological constant". JCAP 0605: 009. (subscription required (help)). 9. ^ Jaume Garriga & Alexander Vilenkin (2006). "Anthropic prediction for Lambda and the Q catastrophe". Prog. Theor.Phys. Suppl. 163: 245–57. arXiv:hep-th/0508005. Bibcode:2006PThPS.163..245G. doi:10.1143/PTPS.163.245. (subscription required (help)). 10. ^ Delia Schwartz-Perlov & Alexander Vilenkin (2006). "Probabilities in the Bousso-Polchinski multiverse". JCAP 0606: 010. (subscription required (help)). 11. ^ L. Smolin, "Did the universe evolve?", Classical and Quantum Gravity 9, 173–191 (1992). L. Smolin, The Life of the Cosmos (Oxford, 1997) 12. ^ L. Susskind, The cosmic landscape: string theory and the illusion of intelligent design (Little, Brown, 2005). M. J. Rees, Just six numbers: the deep forces that shape the universe (Basic Books, 2001). R. Bousso and J. Polchinski, "The string theory landscape", Sci. Am. 291, 60–69 (2004). 13. ^ Lubos Motl's blog criticized the anthropic principle and Peter Woit's blog frequently attacks the anthropic string landscape.	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 9, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.8896881341934204, "perplexity": 1590.0559954320095}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.3, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2015-22/segments/1432207925696.30/warc/CC-MAIN-20150521113205-00179-ip-10-180-206-219.ec2.internal.warc.gz"}
http://sioc-journal.cn/Jwk_hxxb/CN/10.6023/A14040295	### CL-20/HMX共晶及其为基PBX界面作用和力学性能的MD模拟研究 1. a 南京理工大学化工学院分子与材料计算研究所江苏南京 210094; b 中国工程物理研究院冲击波物理与爆轰物理国防科技重点实验室四川绵阳 621900 • 收稿日期:2014-04-18 出版日期:2014-09-14 发布日期:2014-08-27 • 通讯作者: 肖继军 E-mail:[email protected] • 基金资助: 项目受国家自然科学基金委员会与中国工程物理研究院联合基金（No. U1230120）资助. ### Molecular Dynamics Simulation of Interface Interactions and Mechanical Properties of CL-20/HMX Cocrystal and Its Based PBXs Sun Tinga, Liu Qianga, Xiao Jijuna, Zhao Fengb, Xiao Heminga 1. a Molecules and Materials Computation Institute, School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing 210094, China; b National Key Laboratory of Shock Wave and Detonation Physics, Institute of Fluid Physics, China Academy of Engineering Physics, Mianyang 621900, China • Received:2014-04-18 Online:2014-09-14 Published:2014-08-27 • Supported by: Project supported by Joint Fund of National Natural Science Foundation of China and China Academy of Engineering Physics (Grant No. U1230120). To enhance practical values and improve safety and mechanical properties of cocrystal explosives, molecular dynamics simulations were conducted to investigate the interface interactions and mechanical properties of CL-20/HMX cocrystal based polymer-bonded explosives (PBXs). Two polymers, poly(ester urethane) block copolymer (Estane 5703) and hydroxyl-terminated polybutadiene (HTPB), were respectively put along crystalline surface (1 0 0). Totally, two PBX simulation models were built. The interfacial binding energies between the crystalline surface and polymers were calculated and the binding energy between Estane 5703 and the cocrystal (1 0 0) surface is larger than that of HTPB. This indicates that the stability and compatibility of the PBX containing a small amount of Estane 5703 is better. The interface structures of CL-20/HMX cocrystal (1 0 0) surface with the two polymers were analyzed using pair correlation function (PCF). The results show that hydrogen bonds of H atoms in the cocrystal with carbonyl-O atoms in Estane 5703 and with hydroxyl-O atoms in HTPB are stronger. The elastic constants, moduli and Poisson ratio of the cocrystal and the cocrystal-based PBXs were calculated based on the fluctuation analysis of production trajectories and Reuss average. Compared with the cocrystal, the mechanical properties of the PBXs containing a small amount of binder Estane 5703 or HTPB have changed apparently. It is found that the elastic constants (Cij), tensile modulus (E), bulk (K) and shear (G) modulus all decrease, while Poisson ratio (ν), Cauchy pressure (C12C44) and K/G all increase. The results show that the stiffness of the PBXs system is weaker, and its elasticity and ductibility is better. And the small amount of polymer binders coating with the cocrystal makes the PBXs more insensitive. The desensitization is mainly attributed to the heat insulation and absorption of the polymers and the buffer action of the system softened by the polymers, while the bond length change for trigger bond caused by interface interactions plays a minor role.	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 1, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.20113137364387512, "perplexity": 6591.428392182085}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2020-16/segments/1585371803248.90/warc/CC-MAIN-20200407152449-20200407182949-00342.warc.gz"}
https://www.physicsforums.com/threads/find-radial-velocity-of-star-from-orbiting-body.413251/	# Find radial velocity of star from orbiting body 1. Jun 29, 2010 ### luma How do I get radial velocity of a star given a single body orbiting it in a 2-body system? I have the mass of both objects and for the second object it's eccentricity. Assume everything else is default or zero like the mean eccentricity. I compute the barycenter between the star and smaller star/planet by, $$R = \frac{m_1 p_1}{M} + \frac{m_2 p_2}{M}$$ where M = m_1 + m_2 and p = position of body But we don't know the orbit of the first body so how can I find this? Let's say I have the orbit for the combined masses and then find the orbit for the star. r(theta) = r(0) * (1 + e) / (1 + e cos theta) I can then find the radial velocity over time by stepping through that equation in time by, http://en.wikipedia.org/wiki/Keplers_laws#Position_as_a_function_of_time And find it's offset from the origin, and compare small changes in position over time to numerically differentiate and hence find the velocity and then take the y component to find radial velocity... Or could I use $$\frac{d (1/2 r^2 \theta)}{dt} = 0$$ somehow? That's it, just a bunch of disconnected thoughts and no connected method. Help me out, would love to solve this :p 2. Jun 30, 2010 dun dun 3. Jul 5, 2010 ### luma dun dun Similar Discussions: Find radial velocity of star from orbiting body	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 1, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.6430115103721619, "perplexity": 1270.3917486700036}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2018-09/segments/1518891816912.94/warc/CC-MAIN-20180225190023-20180225210023-00584.warc.gz"}
https://aakashdigitalsrv1.meritnation.com/ask-answer/question/raju-is-19-yrs-younger-than-his-cousin-after-5-years-their-a/simple-equations/3936100	# raju is 19 yrs younger than his cousin. after 5 years, their ages will be in the ratio 2:3. find their present ages ???? i cant get this answer plsssssssssss solve it fasta circular plot of ground of radius is 42m is surrounded by a circular ring of grss plot. find the width of a grass plot. if the area = that of the circular plot? j • 0 RAJU'S AGE = 33, HIS COUSIN'S AGE = 52 • 2 COUSIN'S AGE = x RAJU'S AGE = x - 19 AFTER 5 YRS., RATIO = 2/3 SO, (x - 19) + 5 / x + 5 = 2/3 x - 14 / x +5 = 2/3 3x - 42 = 2x + 10 (CROSS MULTIPLICATION) SO, WE GET x = 52 SO, COUSIN'S AGE = 52 AND RAJU'S AGE = 52 - 19 = 33 • 3 let the cousin's age = x raju's age = x-19 afer 5 yrs he vratio = 2/3 so (x-19) + 5 / x +5 = 2/3 x-14 / x + 5 = 2/3 3x -42 = 2x +10 cross multiplication Hence we get x=52 so the cousin's age is 52 and 52-19=33 so Raju's age = 33.. 2nd que i didn't get... • 0 Lets take Raju's cousin's age be x yrs Therefore Raju's age = x-19 Ratio between Raju and his cousin=2:3 =2/3 Hence (x-19) + 5/ x + 5 = 2/3 =5+x-5+19/x+5=2/3 =5+x-14/x+5=2/3 =15+3x-42/2x+10 =-37+3x=2x+10 =-37-10=2x-3x =-47=-x =47=x =His cousin age after 5 yrs=47 + 5=52yrs =His age = 52-19=33 • 0 COUSIN 'S AGE = x RAJU 'S AGE = x - 19 AFTER 5 YRS., RATIO = 2/3 SO,(x - 19)+ 5 /x +5 = 2/3 x- 14 /x +5 = 2/3 3x - 42 = 2x + 10 (CROSS MULTIPLICATION) SO, WE GET x = 52 SO, COUSIN 'S AGE = 52 AND RAJU 'S AGE = 52 - 19 = 33 • 0	{"extraction_info": {"found_math": false, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.8028895258903503, "perplexity": 7852.81088538321}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2021-10/segments/1614178378872.82/warc/CC-MAIN-20210307200746-20210307230746-00474.warc.gz"}
https://gigaom.com/2011/03/13/here-comes-the-backlash-to-japans-nuclear-disaster/	# Here Comes the Backlash to Japan’s Nuclear Disaster There’s a lot that will be gleaned over the coming weeks and months from Japan’s nuclear “disaster.” It’s a pretty big nuclear fail, on par with Three Mile Island (U.S., 1979), though at this point not yet a Chernobyl (Ukraine, 1986). It’s been at the front and center of global media and policy debates this weekend, and it’s an ongoing situation. The latest is that Japanese authorities have reportedly said there’s a significant chance the fuel rods have partially melted at two of the reactors, and they are still fighting a full-blown meltdown (Scientific American has a detailed look at just what went wrong after the earthquake and tsunami). The operator of the reactors, Tokyo Electric Power Company (TEPCO), resorted to pumping seawater into the reactors, which to many in the industry sounds very much like a last-ditch, worrisome effort. Reuters reported 140,000 people have been evacuated from the area as a safety precaution, and iodine is being readied to distributed to people in the area to protect them from radioactive exposure. We’ll soon see if the disaster will get worse or better. What we do know is that the incident could have far-reaching repercussions on the nuclear policies of the governments of the U.S., European countries, China and India, and will likely do significant damage to public opinion in general of nuclear energy. As the Guardian put it succinctly: “When experts decide it is necessary to flood reactors in the world’s most technologically advanced nation with an improvised flow of marine muck, people will ask whether the industry’s contingency planning for disaster is really as good as we are always being promised.” Already, anti-nuclear groups are already using the incident to point to the dangers — or at least unknowns — of nuclear. Senate Homeland Security and Governmental Affairs Chairman Joe Lieberman has called for a moratorium on new nuclear power until lessons are learned from Japan. The Washington Post reported (s wpo) this weekend that the disaster could be a set back for U.S. nuclear policy, though acknowledged it’s still too early to tell what the effect will be, given the situation in Japan could change in the coming hours and days. Over the past two years, President Obama and Energy Secretary Steven Chu have been amassing one of the most aggressive government plans to support nuclear power in the U.S. in decades. Last year, the DOE announced $8.3 billion in loan guarantees to Southern Company to build two nuclear plants in Burke County, Ga., which will be the first nuclear plants in the U.S. in almost three decades. At one point, Obama had a plan to dole out$54.5 billion in loan guarantees to build nuclear power in the U.S. (Incidentally, Tokyo Electric Power Co. has also planned to invest $125 million into expanding a Texas nuclear project.) Europe is already starting to face a public backlash, and policy discussions, too. U.K Energy Secretary Chris Huhne publicly asked British officials and the public not to panic about the British nuclear strategy, and pointed out England’s lack of earthquakes. Germans, many of which already oppose nuclear power, saw protests this weekend around a nuclear plant there, with around 40,000 people turning out. France is battling criticism from its own anti-nuclear groups, given the country generates some 80 percent of its electricity from nuclear. Both China and India are reviewing their nuclear plans, reports Bloomberg. India has planned to spend$175 billion by 2030 on nuclear power, and China has planned to add 27 reactors in five years, according to the report. Don’t expect the fear over Japan’s nuclear disaster to go away anytime soon. It’s taken decades for Chernobyl and Three Mile Island to fade in people’s memories. Beyond the public relations nightmare of the dangers associated with nuclear, costs are as much of a concern. Not just to build the plants, but also to deal with any nuclear problems. According to the World Nuclear Association, the cleanup of the damaged nuclear reactor system at Three Mile Island took nearly 12 years and cost approximately \$973 million. Image courtesy of rowens27.	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.25810664892196655, "perplexity": 3208.850483500258}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": false}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2021-17/segments/1618038066613.21/warc/CC-MAIN-20210412053559-20210412083559-00212.warc.gz"}
http://tex.stackexchange.com/questions/10134/texdiff-for-multi-file-documents-in-subversion/73794	# texdiff for multi-file documents in subversion I've been looking for a convenient way to highlight changes between subversion revisions of my Latex document in the generated PDF. I am working on a reasonably complex document that pulls together various .tex files. By virtue of using multiple \input{}s, latexdiff-svn doesn't seem to offer a solution. texdiff, despite being more amenable to multi-file documents, unfortunately doesn't have the necessary magic in place to handle SVN diffs. I have hacked together a solution which works for me, but I'm wondering if there's something more coherent that I've missed. My solution is a fairly short script which does the following: 1. Given a revision number, ask SVN for all the files that have changed between then and HEAD. 2. Export only those files to a temporary location, and run texdiff between the exported copy and the working copy. 3. Build another temporary directory, which stores either the output from texdiff or, if no changes were made, a copy of the working copy. The directory contains all the .tex files I need to build my document. A little sed ensures all \input{} commands point to the correct (i.e., temporary) location. This does the trick! But, a solution that hooks directly into svn diff would be much neater. I played around earlier with svn wdiff and tried to hook it directly into texdiff, but I gave up on it when I realised I was breaking all the nice bracket matching that texdiff does. My searches have otherwise proved fruitless. Although I'm happy with my solution, does anyone know a neater way to achieve what I want? - I don't really know a better way, but thanks for sharing your way. Maybe you could somewhere publish your script? – Paŭlo Ebermann Feb 7 '11 at 0:47 I very interested in this too. I'm using SVN also with multi-file documents. However, I think the only way to do this is to write a script which calls svn diff by yourself, or wait until someone else does it. – Martin Scharrer Feb 10 '11 at 9:39 Sure. It's fairly rudimentary, but I've put it here for public consumption: svn.sdstrowes.co.uk/pub/latex – Stephen Feb 14 '11 at 10:55 Feel free to feedback on this! This script works for me, but expects my dissertation files to be present. Please offer suggestions or (preferably!) diffs, and I'll update this! – Stephen Feb 14 '11 at 10:57 @Martin well you have seven days. Get working. :) – Seamus Feb 21 '11 at 14:32 I know coded the following Perl script which calls svn diff in summary mode to get the changed files. It extracts these using svn cat into two different directories and calls latexdiff on each modified file. It modifies the TEXINPUTS variable to load files first from the diff directory instead of the current one. This avoids the copying of all unchanged files. Finally the main file is compile using latexmk. The usage is perl <scriptfile> <mainfile> <rev a> <rev b>. It is absolutely not fool-proof so far, but is more general as the shell script linked to in the comments. Please test it and provide some feedback. #!/usr/bin/env perl use strict; use warnings; my @FILES; my $rpath = '.r'; my ($mainfile,$REVA,$REVB) = @ARGV; my $dpath = ".diff-${REVA}-${REVB}"; open(my$pipe, '-\|', "svn diff --summarize -r${REVA}:${REVB}") or die; while () { next if not /^M.{7}(.\.tex)$/; push @FILES,$1; } close ($pipe); exit (1) if not @FILES; mkdir$rpath . $REVA; mkdir$rpath . $REVB; mkdir$dpath; foreach my $file (@FILES) { print$file, "\n"; $file =~ /^(.)\//; my$dir = $1 \|\| ""; my$dira = $rpath .$REVA . '/' . $dir; my$dirb = $rpath .$REVB . '/' . $dir; my$ddir = $dpath . '/' .$dir; mkdir $dira if not -e$dira; mkdir $dirb if not -e$dirb; mkdir $ddir if not -e$ddir; system("svn cat -r${REVA} '$file' > '${rpath}${REVA}/$file'"); system("svn cat -r${REVB} '$file' > '${rpath}${REVB}/$file'"); system("latexdiff '${rpath}${REVA}/$file' '${rpath}${REVB}/$file' > '${dpath}/$file'"); } if (not exists $ENV{"TEXINPUTS"} \|\|$ENV{"TEXINPUTS"} eq '') { $ENV{"TEXINPUTS"} = "$dpath:.:"; } else { $ENV{"TEXINPUTS"} = "$dpath:" . $ENV{"TEXINPUTS"}; } system("latexmk -pdf$mainfile") - Cool, will have to try this soon. Looks to be basically what I was aiming for; the neat trick here is not having to copy unchanged files. Surely using latexdiff is incorrect -- it will put preamble right into the middle of a multi-part document. This is why I'm using texdiff. – Stephen Feb 28 '11 at 16:24 I was looking for a way to stop latexdiff from adding the preamble in any other files except the main file. It doesn't have an option for that. But I thought it wont add it if it doesn't find a \begin{document}. Said that, most of the subfiles I tested the script on actually have it(!) because they use standalone. – Martin Scharrer♦ Feb 28 '11 at 16:45 Oh, regarding behaviour in the absence of \begin{document}, it seems you are correct! I think my document structure confuses things because I keep \begin{document} in a separate file from \end{document}, and so latexdiff refuses to run. Hence my playing around with texdiff instead. One thing my script neglects to do is spit out the appropriate preamble for texdiff, but that could be automated. – Stephen Feb 28 '11 at 17:13 @MartinScharrer Could you take a look at tex.stackexchange.com/a/73794, which should be a comment on this but is too long? – Joseph Wright♦ Sep 25 '12 at 20:27 I have created a batch file that combines a few scripts to use multi-file LaTeX projects with Subversion. The idea is to: • Flatten the document, i.e. create a single file that contains all elements of the project • Compare this with a previous version in the repository • Generate a PDF highlighting the changes • Create a version of the flattened document where each sentence starts in a new line (useful when comparing the source) • Create a version that removes comments and to-dos that can be send to others. I use three publicly available scripts for that. The batch file, links to the scripts and a description can be found on my website: http://www.jwe.cc/2012/02/workflow-with-subversion-and-latex/ - Martin Scharrer's Perl script worked beautifully. Thanks! I had to change a few things to make the script work on my system. (I would add this as a comment to the answer, but I don't have enough 'reputation' yet.) --> diff diff_latex_orig.pl diff_latex.pl 3a4 > use File::Path qw(make_path); 12,13c13,14 < open(my $pipe, '-\|', "svn diff --summarize -r${REVA}:${REVB}") or die; < while () { --- > open(XX, '-\|', "svn diff --summarize -r${REVA}:${REVB}") or die; > while (<XX>) { 17c18 < close ($pipe); --- > close (XX); 32,34c33,35 < mkdir $dira if not -e$dira; < mkdir $dirb if not -e$dirb; < mkdir $ddir if not -e$ddir; --- > make_path($dira); > make_path($dirb); > make_path($ddir); Also, I had to add the preamble to the top level .tex file manually. %DIF PREAMBLE EXTENSION ADDED BY LATEXDIFF %DIF UNDERLINE PREAMBLE \RequirePackage[normalem]{ulem} \RequirePackage{color}\definecolor{RED}{rgb}{1,0,0}\definecolor{BLUE}{rgb}{0,0,1} \providecommand{\DIFadd}[1]{{\protect\color{blue}\uwave{#1}}} \providecommand{\DIFdel}[1]{{\protect\color{red}\sout{#1}}} %DIF SAFE PREAMBLE \providecommand{\DIFaddbegin}{} \providecommand{\DIFaddend}{} \providecommand{\DIFdelbegin}{} \providecommand{\DIFdelend}{} %DIF FLOATSAFE PREAMBLE \providecommand{\DIFaddFL}[1]{\DIFadd{#1}} \providecommand{\DIFdelFL}[1]{\DIFdel{#1}} \providecommand{\DIFaddbeginFL}{} \providecommand{\DIFaddendFL}{} \providecommand{\DIFdelbeginFL}{} \providecommand{\DIFdelendFL}{} %DIF END PREAMBLE EXTENSION ADDED BY LATEXDIFF - I guess ideally this would be a comment, but it's too long for me to convert :-) – Joseph Wright♦ Sep 28 '12 at 6:07 rcs-latexdiff tool can do that. It can made a latexdiff of different versions of a same file within a RCS repository. It also manages included files (it looks for included file and get the file thanks to the svn cat command, for each revision). The basic usage is: $ rcs-latexdiff [OPTIONS] filename old_commit new_commit So for example, \$ rcs-latexdiff paper.tex 19 20 ` create an output file diff.tex that is the latexdiff of the paper.tex file for the two last revisions (if commit 20 is HEAD). You could also use keywords like BASE, COMMITTED, PREV, etc. Then, it's up to you to compile the output file using your favorite compiler. Notice that sometime the process could be long due to SVN because it's server-based. The ultimate goal of this tool is to support all RCS softwares. At the moment, it only support SVN and Git. You can find install instructions on Github page. Feel free to use, reports bugs and contribute ;) - Please see my comment on your other answer: tex.stackexchange.com/questions/1325/using-latexdiff-with-git/… – Ryan Reich Jul 23 '12 at 16:21	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 0, "mathjax_asciimath": 1, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.6870327591896057, "perplexity": 3273.4665258025757}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2013-20/segments/1368706794379/warc/CC-MAIN-20130516121954-00057-ip-10-60-113-184.ec2.internal.warc.gz"}
https://blog.theleapjournal.org/2010/04/right-to-education-act-critique.html	## Thursday, April 01, 2010 ### The Right to Education Act: A critique by Parth Shah. The Right of Children to Free and Compulsory Education Act 2009' (RTE Act) came into effect today, with much fanfare and an address by Prime Minister Manmohan Singh. In understanding the debates about this Act, a little background knowledge is required. Hence, in this self-contained 1500-word blog post, I start with a historical narrative, outline key features of the Act, describe its serious flaws, and suggest ways to address them. ### Historical narrative After independence, Article 45 under the newly framed Constitution stated that The state shall endeavor to provide, within a period of ten years from the commencement of this Constitution, for free and compulsory education for all children until they complete the age of fourteen years. As is evident, even after 60 years, universal elementary education remains a distant dream. Despite high enrolment rates of approximately 95% as per the Annual Status of Education Report (ASER 2009), 52.8% of children studying in 5th grade lack the reading skills expected at 2nd grade. Free and compulsory elementary education was made a fundamental right under Article 21 of the Constitution in December 2002, by the 86th Amendment. In translating this into action, the Right of Children to Free and Compulsory Education Bill' was drafted in 2005. This was revised and became an Act in August 2009, but was not notified for roughly 7 months. The reasons for delay in notification can be mostly attributed to unresolved financial negotiations between the National University of Education Planning and Administration, NUEPA, which has been responsible for estimating RTE funds and the Planning Commission and Ministry of Human Resource and Development (MHRD). From an estimate of an additional Rs.3.2 trillion to Rs.4.4 trillion for the implementation of RTE Draft Bill 2005 over 6 years (Central Advisory Board of Education, CABE) the figure finally set by NUEPA now stands at a much reduced Rs.1.7 trillion over the coming 5 years. For a frame of reference, Rs.1 trillion is 1.8% of one year's GDP. Most education experts agree that this amount will be insufficient. Since education falls under the concurrent list of the Constitution, financial negotiations were also undertaken between Central and State authorities to agree on sharing of expenses. This has been agreed at 35:65 between States and Centre, though state governments continue to argue that their share should be lower. ### Overview of the Act The RTE Act is a detailed and comprehensive piece of legislation which includes provisions related to schools, teachers, curriculum, evaluation, access and specific division of duties and responsibilities of different stakeholders. Key features of the Act include: 1. Every child from 6 to 14 years of age has a right to free and compulsory education in a neighborhood school till completion of elementary education. 2. Private schools must take in a quarter of their class strength from weaker sections and disadvantaged groups', sponsored by the government. 3. All schools except private unaided schools are to be managed by School Management Committees with 75 per cent parents and guardians as members. 4. All schools except government schools are required to be recognized by meeting specified norms and standards within 3 years to avoid closure. On the basis of this Act, the government has framed subordinate legislation called model rules as guidelines to states for the implementation of the Act. ### A critique The RTE Act has been criticised by a diverse array of voices, including some of the best economists. MHRD was perhaps keen to achieve this legislation in the first 100 days of the second term of the UPA, and chose to ignore many important difficulties of the Act. The most important difficulties are: Inputs and Outcomes The Act is excessively input-focused rather than outcomes-oriented. Even though better school facilities, books, uniforms and better qualified teachers are important, their significance in the Act has been overestimated in the light of inefficient, corrupt and unaccountable institutions of education provision. School Recognition The Act unfairly penalises private unrecognised schools for their payment of market wages for teachers rather than elevated civil service wages. It also penalises private schools for lacking the infrastructural facilities defined under a Schedule under the Act. These schools, which are extremely cost efficient, operate mostly in rural areas or urban slums, and provide essential educational services to the poor. Independent studies by Geeta Kingdon, James Tooley and ASER 2009 suggest that these schools provide similar if not better teaching services when compared to government schools, while spending a much smaller amount. However, the Act requires government action to shut down these schools over the coming three years. A better alternative would have been to find mechanisms through which public resources could have been infused into these schools. The exemption from these same recognition requirements for government schools is the case of double standards -- with the public sector being exempted from the same requirements'. School Management Committees (SMCs) By the Act, SMCs are to comprise of mostly parents, and are to be responsible for planning and managing the operations of government and aided schools. SMCs will help increase the accountability of government schools, but SMCs for government schools need to be given greater powers over evaluation of teacher competencies and students learning assessment. Members of SMCs are required to volunteer their time and effort. This is an onerous burden for hte poor. Payment of some compensation to members of SMCs could help increase the time and focus upon these. Turning to private but aided' schools, the new role of SMCs for private aided' schools will lead to a breakdown of the existing management structures. Teachers Teachers are the cornerstone of good quality education and need to be paid market-driven compensation. But the government has gone too far by requiring high teacher salaries averaging close to Rs.20,000 per month. These wages are clearly out of line, when compared with the market wage of a teacher, for most schools in most locations in the country. A better mechanism would have involved schools being allowed to design their own teacher salary packages and having autonomy to manage teachers. A major problem in India is the lack of incentive faced by teachers either in terms of carrot or stick. In the RTE Act, proper disciplinary channels for teachers have not been defined. Such disciplinary action is a must given that an average of 25 percent teachers are absent from schools at any given point and almost half of those who are present are not engaged in teaching activity. School Management Committees need to be given this power to allow speedy disciplinary action at the local level. Performance based pay scales need to be considered as a way to improve teaching. 25% reservation in private schools The Act and the Rules require all private schools (whether aided or not) to reserve at least 25% of their seats for economically weaker and socially disadvantaged sections in the entry level class. These students will not pay tuition fees. Private schools will receive reimbursements from the government calculated on the basis of per-child expenditure in government schools. Greater clarity for successful implementation is needed on: • How will weaker and disadvantaged sections' be defined and verified? • How will the government select these students for entry level class? • Would the admission lottery be conducted by neighbourhood or by entire village/town/city? How would the supply-demand gaps in each neighbourhood be addressed? • What will be the mechanism for reimbursement to private schools? • How will the government monitor the whole process? What type of external vigilance/social audit would be allowed/encouraged on the process? • What would happen if some of these students need to change school in higher classes? Moreover, the method for calculation of per-child reimbursement expenditure (which is to exclude capital cost estimates) will yield an inadequate resource flow to private schools. It will be tantamount to a tax on private schools. Private schools will endup charging more to the 75% of students - who are paying tuitions - to make space for the 25% of students they are forced to take. This will drive up tuition fees for private schools (while government schools continue to be taxpayer funded and essentially free). Reimbursement calculations should include capital as well recurring costs incurred by the government. By dictating the terms of payment, the government has reserved the right to fix its own price, which makes private unaided schools resent this imposition of a flat price. A graded system for reimbursement would work better, where schools are grouped -- based on infrastructure, academic outcomes and other quality indicators -- into different categories, which would then determine their reimbursement. ### What is to be done? The RTE Act has been passed; the Model Rules have been released; financial closure appears in hand. Does this mean the policy process is now impervious to change? Even today, much can be achieved through a sustained engagement with this problem. Drafting of State Rules Even though state rules are likely to be on the same lines as the model rules, these rules are still to be drafted by state level authorities keeping in mind contextual requirements. Advocacy on the flaws of the Central arrangements, and partnerships with state education departments, could yield improvements in atleast some States. Examples of critical changes which state governments should consider are: giving SMCs greater disciplinary power over teachers and responsibility of studentsâ€™ learning assessment, greater autonomy for schools to decide teacher salaries and increased clarity in the implementation strategy for 25% reservations. If even a few States are able to break away from the flaws of the Central arrangements, this would yield demonstration effects of the benefits from better policies. Assisting private unrecognized schools Since unrecognized schools could face closure in view of prescribed recognition standards within three years, we could find ways to support such schools to improve their facilities by resource support and providing linkages with financial institutions. Moreover, by instituting proper rating mechanisms wherein schools can be rated on the basis of infrastructure, learning achievements and other quality indicators, constructive competition can ensue. Ensure proper implementation Despite the flaws in the RTE Act, it is equally important for us to simultaneously ensure its proper implementation. Besides bringing about design changes, we as responsible civil society members need to make the government accountable through social audits, filing right to information applications and demanding our children's right to quality elementary education. Moreover, it is likely that once the Act is notified, a number of different groups affected by this Act will challenge it in court. It is, therefore, critically important for us to follow such cases and where feasible provide support which addresses their concerns without jeopardizing the implementation of the Act. Awareness Most well-meaning legislations fail to make significant changes without proper awareness and grassroot pressure. Schools need to be made aware of provisions of the 25% reservations, the role of SMCs and the requirements under the Schedule. This can be undertaken through mass awareness programs as well as ensuring proper understanding by stakeholders responsible for its implementation. Ecosystem creation for greater private involvement Finally, along with ensuring implementation of the RTE Act which stipulates focused reforms in government schools and regulation for private schools, we need to broaden our vision so as to create an ecosystem conducive to spontaneous private involvement. The current licensing and regulatory restrictions in the education sector discourage well-intentioned edupreneurs' from opening more schools. Starting a school in Delhi, for instance, is a mind-numbing, expensive and time-consuming task which requires clearances from four different departments totaling more than 30 licenses. The need for deregulation is obvious. Please support our efforts towards ensuring Right to Education of Choice through some of the activities suggested above. Join our RTE Coalition. 1. Every child from 6 to 14 years of age has a right to free and compulsory education in a neighborhood school till completion of elementary education. Isn't it odd juxtaposing the word "compulsory" with "a right"? 2. Can RTE do something about the private tutions and coaching? Will RTE further increase the demand of these services? Its funny it comes into force on April Fool's day without much of a process for an act that can have far reaching consequences. For that matter,many if not most Acts come into force from April 1,maaybe thats the reason its called Fool's day :) 3. Yet another piece of nonsense by your friendly neighborhood politicians who should now be trusted with this inspite of not having delivered something that should have been done 60 years ago (and was arguably the single most important thing by far that should have been done)? For a while it looked like MM was/is an economist? Apparently, he's not a particularly bright one or maybe he lacks a spine... same effect. 4. A lot of the analysis/commentary is correct. However, two points which escape me - 1. The objection to teachers wages. The suggestion is to let schools decide their own wages, I guess the way this would work for a Govt school would be to have an upper limit? I see a problem with incentives when the school can hire a teacher cheaper, if there is an upper limit - why would it do so? And how would this be monitored and enforced? 2. The tax on private school students who are not 'weaker section'. If this is not done in this manner, it would be taxed in some other manner. Either ways, its tax payer money. Not sure what perverse incentive this would create except making Govt. schools cheaper. 5. Nice overview, I have been hearing about RTE since last 7 years or so, never understood what it is. I am going to comment about a total different topic: Ajay, you are doing a great job disseminating the information on public policy. We need a C-Span kind of channel, where such policies and issues are discussed right from early drafts through the approval and implementation phases. It should be funded by public donations, no commercial ads, focus on the content rather than presentation (i.e. Content should be the focus rather than colorful studios, high pitch presenters, rap music ) . It may not have any impact in a year or two. But, In a five-ten year time period, such a channel can disseminate policy details to a much wider audience, increase transparency and accountability of policy makers, create awareness among a much larger set of public as to what policies are being worked on, how are they being made, what are the positives and negatives etc. Basically, it would be nice if this blog is transformed into TV Channel, with a bigger funding, so more issues could be discussed and disseminated to much wider public. 6. In the Kerala context..this bill is more or less irrelevant. for the folowing reasons 1. Already achieved near 100% school enrolement 2. Already the situation is such that students are dropping out of the aided and government sector and moving to unaided sector in large numbers and there is huge hue and cry over this 7. RTE ia another Act gifted to the country. We know the fate of UGC Act, AICTE Act and RTI Act. It appears these Acts are formulated at a time when it is necessary to divert public minds from real isues. In fact, the Acts; as required, were not introduced immediately after the the Constitution came into force. These Acts have given rise to several litigations with the passage of time and today we are introducing the Foreign Unversity Education in India. The main flaw is the provisions of the Acts are hardly adhered to in letter and spirit. There is no true measure of Process Management and Performance Management is totally missing. All stakeholders of RTE especially officers, teachers, Management need to be made accoutable for performance and the defaulters need to show their places. We need a stick and not a carrot. Wages need to be performance linked only. Basic wages are just to satisfy the basic needs and these will be enhanced on yearly basis as per the perforamce index of the preceding year.Non-performers will be fired.It is not a good policy to change our decisions now and then, improve the the existing system continuously. What has happened to NEP 1986 that says degrees be delinked from jobs? 8. Thank you for all your comments. As a part of the School Choice team, Centre for Civil Society, I'll reply to most here: Anonymous, Thursday 1 April: It is 'compulsory' for the government to provide education to all children in the age group of 6-14. It is however not 'compulsory' for parents to send their children to schools even though it is their 'right' to demand for this education. In this sense 'compulsory' and 'right' need not be contradictory or odd to use. Bagdu, 2 April: The RTE Act has been created to provide greater access and also improve educational services provided in schools. By improving quality of education it is hoped that the incidence of private tuition and coaching can be limited. Moreover, the Act does not allow school teachers to give tuitions. Yunhi, 2 April: As of now the government has made it compulsory for all schools to provide high teacher salaries as stipulated by the 6th Pay commission. These salaries limit edupreneurs from setting up schools which cater especially to the poor as their costs increase and they become unaffordable. Instead, we suggest that schools should be allowed to set their own salary structures. If engineers and research associates don't have a minimum salary specified by the government then why teachers? Prabhakar, 3 April: I am in complete agreement with you that most Act's lead to no real change due to limited implementation. To make sure that this does not happen with the RTE Act I hope that activists, civil society members and concerned stakeholders can all come together to ensure its proper implementation by conducting social audit, creating awareness and pulling up the government when it fails to deliver. If you would like to be part of this movement please join us at www.righttoeducation.in Shreya Agarwal Research Associate, Centre for Civil Society 9. Hi, I had a question regarding the teachers salaries. I dont see any norms specified in the RTE saying that the salaries need to be same as that of the Govt schools. Section 23 clause 3 says that the salaries may be prescribed. Besides the HRD minister Kapil Sibal had said in a press statement that the schools were free to fix the teachers salaries. Is there some clause in the act that i am not interpreting properly? 10. Hi, I have a "technical" question regarding the duties and responsibilities of every stakeholder within the RTE Act: under whom responsibility is it to make sure that the buildings are safe? Who is responsible for any incident? The Proviseur of the school, the SMC, the State? The act doesn't clearly defines the role of each, do you have further details/informations that could help? lda 11. Excellent summary and analysis of the Act. RTE is the bill that has the potential to change this country in about a decade from now. But the key is implementation and greater awareness. I appreciate this blog for doing its bit in the awareness part. Apart from this I have seen another blog that is analyzing RTE better than any govt. Publications. Ordinay people need to understand the implications of the Act. weekendpolitician.blogspot.com contains a good analsis and description for any body who want to understand what it is.. --Mihir 12. It's unfortunate Sri Shah doesn't state the obvious - that this new law will actually reduce opportunities for education for 6-14 year olds and increase illiteracy, while promoting corruption, as any legislative "mandate" program does. RTE is a classic govt controlled retrograde law. 13. This comment has been removed by a blog administrator. 14. RTE speaks about the right to have a free and compulsory education , good but as we were taught that with every right there is a duty also .Every parent want their child to be admitted in a public school and when it comes to the payment of fees after the afdmission, it is a sad state of affairs in some cases . What is the provision for such cases in the RTE? 15. It is 'compulsory' for the government to provide education to all children in the age group of 6-14. It is however not 'compulsory' for parents to send their children to schools even though it is their 'right' to demand for this education. In this sense 'compulsory' and 'right' need not be contradictory or odd to use. would like a clarification on is it not compulsory for a parent to send the child to school. if a villager decides that he doesnt want to send the child to the rotten govt. school and there is no other option. is he free to do that. as the teachers are told that there should be 100% enrolment. what about home schoolers and alternative schools ? aslo the whole discussion is about schooling not education and also we have to address the question about the worth of schooling which fails 98% children by the 12th class. 16. recently i came across a situation where A child whose parents are illeterate enrolled him into an unrecognised school for his primary education... and now after years when that kid has completed his 4th grade, he finds that the school does not provide further education.. and almost all the schools in the vicinity have denied admission for further studies... so what i want to know is: what should be done now? is there any authority or something of similar kind which can help?? 17. RTE has simply killed the Indian Education System. RTE if implemented in strict sense will eventually kill both aided and Unaided schools. I need not to talk about Govt schools because they are almost dead due to wrong policies of Govt. The day is not too long when affluent class will have no option than to send their kids abroad for School Studies. RTE is sheer Populist nonsense. 18. R.N.Bhaskar wrote this in the DNA on 21 May 2010 (http://www.dnaindia.com/opinion/column_sibal-s-kiss-of-deathr_1385602 21) Sibal's kiss of deathr Kapil Sibal, the Union minister for human resources development (HRD), is a man in a hurry.That could explain why he has overlooked obvious loopholes in his Right to Education Act (RTE) which could virtually decapitate India’s education. The same could be said about his draft Foreign Universities Bill. Take the RTE first.Three provisions of the Act have consequences that could mean the virtual collapse of school education in India. Consider these clauses: Chapter II , 4 says: Where a child above six years of age has not been admitted in any school or, though admitted, could not complete his or her elementary education, then he or she shall be admitted in a class appropriate to his or her age. ChapterIV, 16, says: No child admitted in a school shall be held back in any class or expelled from school till the completion of elementary education. And Chapter IV, 17 says: No child shall be subjected to physical punishment or mental harassment. Collectively, these provisions will make it impossible for any teacher to teach his or her students effectively for several reasons. More on the website... 19. This is yet another ridiculous vote-garnering act that, as usual, will end up screwing the middle class. These id$%^ts pass acts and determine prices without any common sense. The school will do nothing but simply pass it on to the 75% earning and tax-wasting middle class (i call it tax wasting since whatever has and will be paid is being put to utter waste, e.g. the government schools). When the government is unable to effectively run a simple government school system, they divert people's attention from real issues by tampering with education and private school governance. Real class act. To top it, this id$%^t Sibal wants to introduce CBSE-i, which is yet another money-grubbing worthless system. 20. What a depressing state of affairs! I wish you all the best with your proposed "sustained engagement with this problem". 21. What is the meaning of primary education as per RTE act, i.e up to which class?? 22. hey you are violating the rules of copyright of CFOconnect , take this page down or i will have to report the violation of rules ---- http://righttoeducation.in/sites/default/files/cfo-connect_rte-critique_may2010.pdf 23. If RTE act is implemented what small budget school do. how do they salaries or manage the infrastructure as prescribed by the RTE act. all these acts are silly and cannot be put in action. everyday a innovative education is penetrating into this industry if one wants to give technology based education or through some innovative method it is going to cost. what about the huge playgrounds and equipment. is the government going to pay up. Please note: Comments are moderated. Only civilised conversation is permitted on this blog. Criticism is perfectly okay; uncivilised language is not. We delete any comment which is spam, has personal attacks against anyone, or uses foul language. We delete any comment which does not contribute to the intellectual discussion about the blog article in question. LaTeX mathematics works. This means that if you want to say $10 you have to say \$10.	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 0, "mathjax_asciimath": 1, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.16770607233047485, "perplexity": 2909.7119058670664}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2019-30/segments/1563195526401.41/warc/CC-MAIN-20190720004131-20190720030131-00478.warc.gz"}
http://maths.anu.edu.au/events/ericksen-leslie-system-oseen-frank-model-liquid-crystals	# The Ericksen-Leslie system for the Oseen-Frank model in liquid crystals ## Date & time 1.30–2.30pm 14 November 2017 ## Location John Dedman Building, G35 ## Speakers Professor Min-Chun Hong (The University of Queensland) ## Contacts Qirui Li 61251020 In this talk, I discuss the Ericksen-Leslie system for the Oseen-Frank model with unequal Frank elastic constants in $\mathbb R^3$. In particular, I discuss my new joint work with Dr Mei Yu on the Ericksen-Leslie system in liquid crystal. We prove existence of solutions to the Ericksen-Leslie system with initial data having small local $L^3$-norm. Moreover, we find a new way to remove the restriction on the Frank elastic constants to prove uniqueness of solutions, by using the rotation invariant property of the Oseen-Frank density. Updated: 22 November 2017/Responsible Officer: Director/Page Contact: School Manager	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.7217652201652527, "perplexity": 2112.7115125236255}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2017-47/segments/1510934806426.72/warc/CC-MAIN-20171121204652-20171121224652-00421.warc.gz"}
http://tex.stackexchange.com/questions/84215/is-it-correct-to-use-a-comma-in-this-equation	# Is it correct to use a comma in this equation? Consider: Then, the sequence $k_i$ given by (3.38) is increasing and converges to $$\label{eq:weired_equation} k^\xi = k_1\times k_2 \times c \times d,$$ where $c$ and $d$ are defined in the Theorem 2. I have the questions: 1. What are the grammatical errors in the above piece? 2. Should a comma be used after the equation \eqref{eq:weired_eqution}. - @WillHunting I don't 100% agree with you, mathematical language has some specifics, and mathematical typography as well. IMHO, this question is boundary here, but still ok. – tohecz Nov 25 '12 at 19:45 I'm 100% sure that the comma is correct (see my answer). On the other hand, I think that (1) There should be no comma after Then, and (2) there should be no the before Theorem 2 (you write Theorem with capital T, hence it is like a name). However, I'm not a native speaker, and one such should confirm what I say. – tohecz Nov 25 '12 at 19:48 @tohecz: math.stackexchange.com exists :-) – Martin Schröder Nov 26 '12 at 9:50 There should be no difference in punctuation whether you write the equation on display or inside the text. So since there would be a comma if written inside the text, the comma is correct. Considering the 1st question, see my comment. In the end, the piece can look like Then the sequence $k_i$ given by (3.38) is increasing and converges to $$\label{eq:weired_equation} k^\xi = k_1\times k_2 \times c \times d,$$ where $c$ and $d$ are defined in Theorem 2. In the label, there's a typo and it should be weird_equation, but I did not correct this to avoid you problems with cross-referencing. -	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 2, "x-ck12": 0, "texerror": 0, "math_score": 0.9637829065322876, "perplexity": 645.7315436047608}, "config": {"markdown_headings": true, "markdown_code": false, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2014-42/segments/1414637900397.29/warc/CC-MAIN-20141030025820-00071-ip-10-16-133-185.ec2.internal.warc.gz"}
https://www.physicsforums.com/threads/force-due-to-pressure-on-barrel-lid.551886/	# Force due to pressure on barrel lid 1. Nov 18, 2011 ### rubenhero 1. The problem statement, all variables and given/known data In the seventeenth century, Blaise Pacal performed the following experiment to demonstrate the properties of pressure. A very long, thin, vertical tube was inserted into the center of the top lid of a wine barrel filled with water. Water was then added slowly to the tube until the wine barrel burst. (See figure 13-50 on page 363 of your textbook, but ignore the numbers) Suppose the radius of the wine barrel lid has radius rl = 21.8 cm, the radius of the tube was rt = 2.67 mm, and the height of the water in the tube was h = 14.5 m. Find: a) F, the magnitude of the force exerted on the inside of the barrel lid due to water pressure 2. Relevant equations P = F/A , AP = F = ρgh∏r2 3. The attempt at a solution F = 1000kg/m3 * 9.81m/s2 * 14.5m * ∏ * (.218m)2 F = 21237.32775 N The answer turned out wrong but i can't figure out what is wrong. 2. Nov 18, 2011 ### dynamicsolo Isn't the applied pressure coming from the tube? This would then be the pressure distributed to the inside of the barrel lid. 3. Nov 18, 2011 ### rubenhero i took the pressure from the tube then multiplied it by the area of the lid, isn't that right? 4. Nov 19, 2011 ### dynamicsolo Disregard my first remark: I was thinking of the force value. I don't see anything obviously wrong. Are your numbers radii, and not diameters? What do you mean by saying, "The answer turned out wrong." Is there a given answer? 5. Nov 19, 2011 ### rubenhero my professor uses webassign.com to give us assignments online. The answer i plugged into the website turned out to be wrong and i only have one chance left to enter the correct answer. I did ask my professor, he would only say that i did the pressure formula wrong. I used the radius numbers given but converted them to meters before plugging them into the formula. Last edited: Nov 19, 2011 6. Nov 19, 2011 ### dynamicsolo The only thing I can think of that the problem might be looking for is that the pressure from the tube should be the sum of the hydrostatic pressure from the water, $\rho gh$, plus the atmospheric pressure of 101,300 N/m2 (which is the "hydrostatic pressure" of the air), and that this times the area of the barrel lid gives the force acting on the inside of the lid. Is one of the other parts, by any chance, asking for the force on the outside of the lid due to atmospheric pressure? The net force on the lid would then be the value you found, which would be an upward force on the lid of $\rho gh \cdot \pi \cdot r_{l}^{2}$. Have I mentioned how much I detest WebAssign? 7. Nov 19, 2011 ### rubenhero The other part of the question (part b) asked for the mass of the water inside the tube. I just emailed my professor and he said that the problem is open to air, i'm guessing the air is through the tube since the barrel is full of water. The other physics section in my college uses masteringphysics.com, but the professor i am taking only uses webassign. 8. Nov 19, 2011 ### dynamicsolo I don't think the air is going through the tube if the tube has 14.5 meters of water in it. I think he is saying that atmospheric pressure is being applied to the top of the water in the tube. So the total pressure applied at the mouth of the tube at the point where it meets the water in the barrel is $\rho gh$ + 101,300 N/m2 , the sum of the water's hydrostatic pressure and the atmospheric pressure. 9. Nov 19, 2011 ### rubenhero Thank you, it worked. I added air pressure to the formula and i got 36361.52404 N. I am glad this worked out since it was my last try for this question on webassign. I want to also thank you for your patience in helping me understand this problem. 10. Nov 19, 2011 ### dynamicsolo You're welcome! And I quite understand your frustration with WebAssign. I work with students here who also have to wrestle with physics on that system... Share this great discussion with others via Reddit, Google+, Twitter, or Facebook	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.9100566506385803, "perplexity": 640.1249355657377}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.3, "absolute_threshold": 20, "end_threshold": 15, "enable": false}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2019-04/segments/1547583705091.62/warc/CC-MAIN-20190120082608-20190120104608-00553.warc.gz"}
http://mathhelpforum.com/calculus/47183-how-can-i-evaluate-integral.html	# Thread: How can I evaluate this integral? 1. ## How can I evaluate this integral? How can I evaluate this integral? Integral sin(ln(x)) dx If possible, can anyone show me step by step? Thank you 2. Originally Posted by noppawit How can I evaluate this integral? Integral sin(ln(x)) dx $\displaystyle \int \sin (\ln x) dx = \int e^{\ln x}\sin (\ln x)(\ln x)'dx$ By substitution you need to compute, $\displaystyle \int e^t \sin t dt$ 3. Originally Posted by noppawit How can I evaluate this integral? Integral sin(ln(x)) dx If possible, can anyone show me step by step? Thank you one way: write as $\displaystyle \int \frac xx \sin ( \ln x) ~dx$ then make the substitution $\displaystyle t = \ln x$ you will get the integral $\displaystyle \int e^t \sin t~dt$ which you would then do using integration by parts, with $\displaystyle u = \sin t$ (the part you differentiate) and $\displaystyle dv = e^t~dt$ (the part you integrate)	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.9940198659896851, "perplexity": 2280.4359734532}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2018-22/segments/1526794870497.66/warc/CC-MAIN-20180527225404-20180528005404-00107.warc.gz"}
https://learn1.open.ac.uk/mod/oublog/view.php?user=35680&taglimit=500&tag=e-books	## Time to celebrate Visible to anyone in the world Two celebrate completing H810 I have bought myself this. Christopher Alexander is often quotes during the Masters in Open and Distance Education - to design e-learning is like constructing a building. And then because it's Amazon I find there is another treat, going back a year, from B822 Creativity, Innovation and Change. The only problem is - we have no shelves. None. Our last house I had a 'study' with floor to ceiling shelves and as many books. Five years after moving the books are still in storage ... I do books. E-Books. Shelves are redundant. Even a small room can look big if it doesn't feature a stack of books. I recommend both. I always ask this, and often respond by going out to get the book in question, but do you have a book you'd recommend? P.S. I have signed up for H809: Practise Based Educational Technology ... so you got me for a few more months. (If I get onto a PhD programme I might be here for another three years ... ) Share post ## What is the library, when the totality of experience approaches that which can be remembered?’ Visible to anyone in the world Edited by Jonathan Vernon, Monday, 10 Dec 2012, 21:11 ‘What is the library, when the totality of experience approaches that which can be remembered?’ (Rausing, 2011:52) Lisbet Rausing Speaking at the Nobel Symposium 'Going Digital' in June 2009 (that ironically took another 2 years before it was published0. Things are gong to have to speed up in the new age of digital academia and the digital scholar. We have more than a university in our pockets (an OU course), we have a library of million of books. (I have an iPhone and iPad. I 'borrow' time on laptops on desktops around the house, libraries at work). I’ve often pondered from a story telling point of view what it would be like to digitize not the libraries of the world, but something far more complex, the entire contents of someone’s mind. (The Contents of My Mind: a screenplay) It is fast becoming feasible to pull together a substantial part of all that a person may have read and written in their lifetime. (TCMB.COM a website I launched in 2001) ‘Throughout history, libraries have depended on destruction’. (Rausing, 2011:50) But like taking a calculator into a maths exam, or having books with you as a resource, it isn’t that all this ‘stuff’ is online, it is that the precise piece of information, memory support or elaboration, is now not on the tip of your tongue, but at your fingertips. Rausing (2011) wonders about the creation of a New library of Alexandria. I wonder if we ought not to be looking for better metaphors. ‘How do we understand the web, when this also means grasping its quasi-biological whole?’ (Rausing, 2011:53) Tim Berners-Lee thinks of Web 2.0 as a biological form; others have likeminds. But what kind of growth, like an invasive weed circling the globe? There are many questions. In this respect Rausing is right, and it is appropriate for the web too. We should be asking each other questons. ‘Do we have the imagination and generosity to collaborate? Can we build legal, organisational and financial structures that will preserve, and order, and also share and disseminate, the learning and cultures of the world? Scholars have traditionally gated and protected knowledge, but also shared and distributed it, in libraries, schools and universities. Time and again they have stood for a republic of learning that is wider than the ivory tower. Now is the time to do so again’. (Rausing, 2011:49) If everything is readily available then the economy of scarcity, as hit the music industry and is fast impacting on movies, applies to books and journals too. It seems archaic to read the copyright restrictions on this Nobel Symposium set of papers and remarkable to read that one of its authors won’t see their own PhD thesis published until 2020. ‘The academic databases have at least entered the digital realm. Public access – the right to roam – is a press-of-the-button away. But academic monographs, although produced by digitised means, are then, in what is arguably an act of collective academic madness, turned into non-searchable paper products. Moreover, both academic articles and monographs are kept from the public domain for the author’s lifetime plus seventy years. My own PhD dissertation,19 published in 1999, will come into the public domain in about 110 years, around 2120’. (Rausing, 2011:55) The e-hoarder, the obsessive scanning of stuff. My diaries in my teens got out of hand, I have a month of sweet wrappers and bus tickets, of theatre flyers and shopping lists. All from 1978. Of interest perhaps only because 10,000 teeneragers in the 1970s weren’t doing the same in England at the time. ‘We want ephemera: pamphlet literature, theatre bills, immigrant broad sheets and poetry workshops’. (Rausing, 2011:51) What then when we can store and collate everything we read? When our thoughts, not just or writings are tagged and shared? Will we become lost in the crowd? ‘What if our next “peasant poet,” as John Clare was known, twitters? What if he writes a blog or a shojo manga? What if he publishes via a desktop, or a vanity publisher? Will his output count as part of legal deposit material?’ (Rausing, 2011:52) The extraordinary complex human nature will not be diminished; we are what we were 5000 years ago. It will enable some, disable others; be matter of fact or of no significance, a worry or not, in equal measure. A recent Financial Times article agrees with Robert Darnton, warning that by means of the Books Rights Registry, Google and the publishing industry have created “an effective cartel,” with “significant barriers to entry.” (Rausing, 2011:57) Much to ponder. ‘If scholars continue to hide away and lock up their knowledge, do they not risk their own irrelevance?’ (Rausing, 2011:61) GLOSSARY Allemansratt : Freedom to roam The Cloud : A Simple Storage Service that has some 52 billion virtual objects. Folkbildningsidealet: A "profoundly democratic vision of universal learning and education"? Incunabula: "Incunabula" is a generic term coined by English book collectors in the seventeenth century to describe the first printed books of the fifteenth century. It is a more elegant replacement for what had previously been called "fifteeners", and is formed of two Latin words meaning literally "in the cradle" or "in swaddling clothes" Maimonedes : His philosophic masterpiece, the Guide of the Perplexed, is a sustained treatment of Jewish thought and practice that seeks to resolve the conflict between religious knowledge and secular. Meisterstuecke : German for masterpiece. Samizdat : An underground publishing system used to print and circulate banned literature clandestinely. Schatzkammer : ‘Treasure Room’, and in English, for the collection of treasures, kept in a secure room, often in the basement of a palace or castle. Schumpeterian REFERENCE Ruasing, L(2011) (Last accessed 23rd May 2012) http://www.center.kva.se/svenska/forskning/NS147Abstracts/KVA_Going_Digital_webb.pdf ) Permalink 1 comment (latest comment by Anthony Dooley, Thursday, 24 May 2012, 09:26) Share post ## Kindle 4 Visible to anyone in the world The Far Pavilions is on BBC Radio 4 My wife is enjoying it; so am I. I don't need to read the book, she does. Two minutes on 'my' Kindle and she's found the book, downloaded a sample and won't let go. I wake a few hours later. No Kindle. 'I bought it by mistake' she says, still reading. Hmmm. Time for Kindle 2 ? Day one I thought, I'll read one book at a time. I'm on chapter 12 of 'Rethinking Pedagogy for E-Learning.' Doing well then. I've also acquired 21 other files, six samples, 2 blogs and ... eight books No more books ... not this month, at least, until I'm paid ... until I've read, collated the notes and quotes, and uploaded the lot to MyStuff. Share post ## H800:12 WK1 Activity 4 The Google Generation - True or False? Visible to anyone in the world Edited by Jonathan Vernon, Wednesday, 16 Nov 2011, 23:57 Information behaviour of the researcher of the future. Written in 2007 (published 11 January 2008). Reviewed in 2011. Part of the Week 1 jollies for H800. (This picks up where I left off in the Forum Thread) After a year of MAODE, a decade blogging and longer keeping journals (and old course work from both school and uni I might add) I feel I can tap into my own first, second, third or fourth take on a topic. Increasingly, where this is digitised my preferred learning approach is to add to this information/knowledge, often turning my ideas inside out. We are yet to have a ‘generation,’ (a spurious and loose term in this context) that has passed through primary, secondary and tertiary education ‘wired up’ to any consistent degree from which to gather empirical research. Indeed, I wonder when things will bottom out, when we’ve gone the equivalent journey of the first horseless-carriage on the Turnpikes of England to the 8 lanes in both directions on the M1 south of Leicester – or from the Wright Brothers to men on the moon. I’d like to encourage learners to move on from copying, or cutting and pasting in any form, to generating drafts, and better drafts of their take on a topic, even if this is just a doodle, a podcast or cryptic set of messages in a synchronous or asynchronous discussion i.e. to originate. I lapped up expressions such as Digital Natives, an expression/metaphor only that has been debunked as lacking any basis in fact. I fear this is the same when it comes to talking about ‘Generation X, Y or Z.’ It isn’t generational, it is down to education, which is down to socio-economic background, wealth, access (technical, physical, geographic, as well as mental), culture, even your parent’s job and attitude. My 85 year old Father-in-law is Mac ready and has been wired to the Internet its entire life; does this make him of this ‘Generation?’ If x billion struggle to find clean drinking water and a meal a day, where do they stand? They’ve not been born on Planet Google, so don’t have this generational opportunity. I find it short sighted of the authors not to go for a ‘longitudinal’ (sic) study. It strikes me as the perfect topic of a JISC, Open University, BBC tie in, the filming part funding the research that is then published every three years for the next thirty, for example. Trying to decide who is Generation X, or Generation Y or the ‘Google Generation’ strikes me as fraught as trying to decide when the islands we inhabit became, or could have been called in turn England, Scotland, Wales, Great Britain or the United Kingdom. We could spend an unwarranted amount of time deciding who is in and who is out and not agreed. We can’t it’s like pouring water through a sieve. The creator of IMBD, a computer geek and film buff was born in the 60s (or 70s). Highly IT literate, then as now, he is not of the ‘Google Generation’ as defined as being born after 1993, but is surely of the type? Personally I was introduced to computers as part of the School of Geography initiative at Oxford in 1982. Admittedly my first computer was an Amstrad, followed by an early Apple, but I’ve not been without a computer for the best part of thirty years. I can still give my 12 year old a run for his money (though he does get called in to sought our browser problems). And should this report be quoting Wikipedia? Surely it is the author we should quote if something is to be correctly cited; anyone could have written this (anyone did). Reading this I wonder if one day the Bodleian Library will be like a zoo? The public will have access to view a few paid students who recreate the times of yore when they had to read from a book and take notes, and look up titles in a vast leather-bound tome into which we strips of paper were intermittently stuck. (not so long ago). Is there indeed, any point in the campus based university gathered around a library when all his millions, or hundreds of millions of books have been Googliefied? Will collegiate universities such as Oxford, Cambridge, Bristol and Durham (Edinburgh and Dublin? Harvard ?) become even more elite as they become hugely expensive compared to offerings such as the Open University? There may be no limit to how much and how fast content can be transmitted … the entire Library of Congress in 3 seconds I am told, but there are severe limits to how much you can read and remember, let alone make sense of and store. Is this not the next step? To rewire our minds with apps and plug-ins? I smile at the idea of ‘power browsing’ or the new one for me ‘bouncing’ the horizontal drift across papers and references rather than drilling vertically, driven by a reading list no doubt. I can give a name to something I did as an undergraduate 1981-1984. Reading Geography I began I the Map room (skipped all lectures) and then spent my morning, if necessary moving between libraries, particularly the Rhodes Library and Radcliffe Science Library, by way of the School of Geography Library, of course, and sometimes into the Radcliffe Camera or the PPE Reading Rooms. I bounced physically. I bounced digitally online as a preferred way of doing things. Though this often leaves me feeling overwhelmed by the things I could read, but haven’t read, that I’d like to read. Which is good reason ONLY to read the latest paper, to check even here if the paper we are asked to read has not already been superseded by this or fellow authors. Old digitised news keeps like a nasty smell in the wind? Users are promiscuous, diverse and volatile and it is clear that these behaviours represent a serious challenge for traditional information providers, nurtured in a hardcopy paradigm and, in many respects, still tied to it. (p9) The problem with the short read and low tolerance of readers is the way papers have thus far gone from print version to digital version without, yet, thorough transmogrification. We await new acceptable ways to write, and submit and share knowledge that is less formal and to anyone versed in reading online, digestible. All authors for the web would do well to read Jakob Nielsen on web usability. There is a way to do it. If it looks like it belongs in a journal or book, you are getting it wrong Do the authors appreciate that labelling the behaviour ‘squirreling’ is self-fulfilling? It normalises the behaviour if anyone reads about it. Whilst metaphors are a useful way to explain, in one person’s words, what is going on, such metaphors soon become accepted as fact. There is a running debate across a series of article in the New Scientist on the way humans think in metaphors (good, can’t help it), and how ideas expressed as metaphors then set unfounded parameters on how we think (not so good, and includes things like the selfish gene, competition and so on). This dipping, bouncing and squirreling, horizontal browsing, low attention span, four to eight minute viewing diverse ‘one size does not fit all’ individual would make for an interesting cartoon character. I wonder if Steven Appleby or Quentin Blake would oblige. ________________________________________________________________________________ Why ‘huge’ and why ‘very’ ? Qualify. Facts. Evidence. And why even, 'very, very.' This isn't academic writing, it's hear say and exaggeration. There’s a category missing from the graph – branded information, such as Wikipedia, or Harvard Business Publication, Oxford or Cambridge University Press and Blackwell’s, to name put a few. Where so much information is available, and so many offerings on the same topic, the key for anyone is to feel they are reading a reliable source. The point being made later about ‘brand’ presence for BL … something we will see more of with the commercialisation of information. Even Wikipedia cannot be free for ever, while the likes of Wikileaks, for its mischief making and spy-value will always be funded from nefarious sources. There are very very few controlled studies that account for age and information seeking behaviour systematically: as a result there is much mis-information and much speculation about how young people supposedly behave in cyberspace. (p14) Observational studies have shown that young people scan online pages very rapidly (boys especially) and click extensively on hyperlinks - rather than reading sequentially. Users make very little use of advanced search facilities, assuming that search engines understand’ their queries. They tend to move rapidly from page to page, spending little time reading or digesting information and they have difficulty making relevance judgements about the pages they retrieve. (p14) Wikipedia and YouTube both exhibit a marked age separation between viewers of content (mainly 18-24s) and content generators (mainly 45-54s and 35-44s respectively). (p16, ref 17) ‘there is a considerable danger that younger users will resent the library invading what they regards as their space. There is a big difference between being where our users are’ and `being USEFUL to our users where they are’. Surely it would be easy to compare a population that have access and those who do not? Simply take a group from a developed, rich Western nation and compare them to a group that are not, that don’t have the internet access, video games or mobile phones. REFERENCE Information behaviour of the researcher of the future. UCL 11 JAN 2008 Share post This blog might contain posts that are only visible to logged-in users, or where only logged-in users can comment. If you have an account on the system, please log in for full access. Total visits to this blog: 5975316	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 1, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.16704314947128296, "perplexity": 3803.337474122397}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2021-17/segments/1618038072082.26/warc/CC-MAIN-20210413031741-20210413061741-00159.warc.gz"}
http://math.stackexchange.com/questions/288622/show-that-the-kappa-oscillation-set-of-a-function-is-a-closed-set	# Show that the $\kappa$-oscillation set of a function is a closed set Let the $\kappa$-oscillation of the set be : $\{x \in [a,b]: \text{osc} f \ge \kappa$} How do we show that it is a closed set? Do we prove its complement is open? If so, what would one call its compliment? I am totally lost here. If anyone can propose a proof, I will be grateful. - Its complement (note spelling) is simply $\big\{x\in[a,b]:\operatorname{osc}f<\kappa\big\}$. And yes, proving that this is open is a very reasonable approach. – Brian M. Scott Jan 28 '13 at 3:59 Exactly what definition of oscillation are you using? – Brian M. Scott Jan 28 '13 at 4:12 Thanks for noting the spelling, Brian. But I am lost as to how to go about it. Can you point me to the right direction? Also I was think whether I can use the fact that a closed set contains all its limit points. So I have to construct a sequence (I do not know what it would look like) such that is $x$ is a limit point of a sequence in the set, then $x\in$ set. – user43901 Jan 28 '13 at 4:12 the definition : osc $f = \lim_{r \to 0} \text{diam} f [x+r,x-r]$ – user43901 Jan 28 '13 at 4:14 Theorem 6.27, p.259 in Bruckner, Bruckner, Thomson: Elementary Real Analysis. The book is freely available here. – Martin Sleziak Jan 28 '13 at 6:26 HINT: Suppose that the oscillation of $f$ at $x$ is less than $\kappa$. This means that $$\lim_{r\to 0}\operatorname{diam}f\big[[x-r,x+r]\big]<\kappa\;.$$ By the definition of limit there is some $r_0>0$ such that $\operatorname{diam}f\big[[x-r,x+r]\big]<\kappa$ for all positive $r\le r_0$. Suppose that $\|x-y\|<\frac{r_0}2$, then $$\left[y-\frac{r_0}2,y+\frac{r_0}2\right]\subseteq[x-r_0,x+r_0]\;.$$ Can you now use that to show that the oscillation of $f$ at $y$ is less than $\kappa$ and hence that the complement of your set is open? - Let $A=\{ x\in [a,b] : \text{osc} f \geq \kappa \}$ and take a sequence $x_n\in A$ such that $x_n\to x$. We want to prove $x\in A$. To do this pick an $r>0$ and $x_n$ such that $\|x_n-x\|<r/2$. Then $[x_n-r/2,x_n+r/2] \subset [x-r,x+r]$ and so $$\kappa\leq\text{diam}f([x_n-r/2,x_n+r/2]) \leq \text{diam}f([x-r,x+r])$$ Take the limit and conclude. -	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 1, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.9355553984642029, "perplexity": 114.74110748884736}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 20, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2016-07/segments/1454701148558.5/warc/CC-MAIN-20160205193908-00084-ip-10-236-182-209.ec2.internal.warc.gz"}
http://porn3gp.ru/half-life-equation-radiometric-dating-18615.html	# Half life equation radiometric dating This is not true for zeroth- and second-order reactions.The half-life of a first-order reaction is independent of the concentration of the reactants.This becomes evident when we rearrange the integrated rate law for a first-order reaction (Equation 14.21) to produce the following equation: Figure $$\Page Index$$: The Half-Life of a First-Order Reaction. Using Activity is usually measured in disintegrations per second (dps) or disintegrations per minute (dpm). The parent-daughter ratio and half-lives elapsed hold no matter what minerals you are dealing with. To determine the age, you need to know what the minerals are, and the half-life of the parent. When the animal or plant dies, the carbon-14 nuclei in its tissues decay to nitrogen-14 nuclei by a radioactive process known as beta decay, which releases low-energy electrons (β particles) that can be detected and measured: $\ce \label$ The half-life for this reaction is 5700 ± 30 yr. Comparing the disintegrations per minute per gram of carbon from an archaeological sample with those from a recently living sample enables scientists to estimate the age of the artifact, as illustrated in Example 11. Using this method implicitly assumes that the ratio in the atmosphere is constant, which is not strictly correct.	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 1, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.9131004810333252, "perplexity": 1842.659085118083}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2018-17/segments/1524125947421.74/warc/CC-MAIN-20180424221730-20180425001730-00010.warc.gz"}
https://math.stackexchange.com/questions/3131689/if-p-is-congruent-to-1-mod-4-where-p-is-an-odd-prime-then-x2-congruent-t	# If $p$ is congruent to 1 mod 4 where $p$ is an odd prime, then $x^2$ congruent to -1 mod $p$ has 2 solutions. If $$p = 5$$, then the values of $$x$$ that will satisfy the congruence $$x^2 \equiv -1 \bmod p$$ are $$2, 3$$ If $$p = 13$$, then the values of $$x$$ that will satisfy the above congruence are $$5, 8$$. And so on... How can i prove that for all $$p$$ s.t. $$(p \equiv 1\bmod 4)$$, then $$x^2\equiv -1\bmod p$$ has only $$2$$ solutions? And by observation, I think it will also hold on $$p^k$$? How can I prove it though? Thank you! As mentioned, the case of prime $$p$$ is quadratic reciprocity. For $$p^k$$ you can use Hensel lifting. The point is this. Suppose $$x \in [1,2, \ldots, p^j-1]$$ is a solution of $$x^2 \equiv -1 \mod p^j$$, where $$p$$ is an odd prime and $$j \ge 1$$. Thus $$x^2 = -1 + z p^j$$ for some integer $$z$$. Consider $$x + p^j y$$ where $$y \in [0,1,\ldots, p-1]$$. We have $$(x + p^j y)^2 = x^2 + 2 p^j x y + p^{2j} y^2 \equiv -1 + (z + 2x y) p^j \bmod p^{j+1}$$ so $$x + p^j y$$ will be a solution mod $$p^{j+1}$$ iff $$y \equiv -z/(2 x) \bmod p$$. Thus every solution mod $$p^j$$ lifts to a unique solution mod $$p^{j+1}$$. Induction on $$k$$ in $$p^k.$$ For $$k \geq 2,$$ we have two roots of $$-1 \pmod {p^{k-1}}.$$ Take one of them, call it $$r,$$ and pick a representative $$R$$ for $$r \pmod {p^k}.$$ We know that $$R^2 \equiv -1 + W p^{k-1} \pmod {p^k}$$ where $$W$$ is a value mod $$p,$$ if you wish, you may demand $$0 \leq W < p.$$ This $$R$$ then solve, for integer $$t,$$ $$\left( R + t p^{k-1} \right)^2 \equiv -1 \pmod {p^k} \; ?$$ $$R^2 + 2Rt p^{k-1} + t^2 p^{2k-2} \equiv -1 \pmod {p^k} \; ?$$ Since $$k \geq 2,$$ we have $$2k-2 \geq k.$$ $$R^2 + 2Rt p^{k-1} \equiv -1 \pmod {p^k} \; ?$$ $$-1 + W p^{k-1} + 2Rt p^{k-1} \equiv -1 \pmod {p^k} \; ?$$ $$W p^{k-1} + 2Rt p^{k-1} \equiv 0 \pmod {p^k} \; ?$$ $$W + 2Rt \equiv 0 \pmod p \; ?$$ Now, $$2R$$ is invertible $$\pmod p,$$ so there is one and only one solution $$\pmod p$$ to $$2Rt \equiv -W \pmod p \; ?$$ That's it, you get exactly one root on top of each root you have, in the process of going up one power of $$p$$	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 54, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.9922526478767395, "perplexity": 41.96672966505433}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2019-26/segments/1560627998339.2/warc/CC-MAIN-20190617002911-20190617024911-00550.warc.gz"}
http://www.physicsforums.com/showthread.php?s=0fc3397e43d5d3bcbca3cf100ee1e68b&p=4499371	# Radiation absorption and temperature changes in matter by Alexander83 Tags: heating, radiation, solid, temperature, x-ray P: 19 Hi there, I've been studying mechanisms by which high-energy radioactive decay products (beta particles, x-rays, gamma rays) are attenuated as they pass through matter. From my readings in introductory and intermediate level textbooks, the general mechanisms by which these particles and rays are described as interacting with matter generally involves interactions with electrons in the target material either causing ionization or electronic excitation. My gut feeling is that the net effect of all of these interactions will (eventually) be an increase in the temperature of the target material. The mechanisms that are commonly described in books for attenuation of radiation such as photoionization or Compton scatter in the case of photons, or Bremsstrahlung production or collisional ionization in the case of energetic electrons. These mechanisms would seem to result in the production of simply more particles (free electrons) or photons in the target material. My (very) naive understanding of what a change temperature means in a solid structure would be something along the lines of excitation of vibrational or rotational modes in an atomic lattice with the resulting increase in the kinetic energy of the atoms of the substance resulting in what we perceive as an increase in temperature... is this correct? My question then is this: how do the interactions I mentioned earlier ultimately result in a temperature change in the target? My gut feeling is that secondary radiation produced in a target continuously decreases in energy level until it is at the correct energy level to excite vibrational or rotational modes in the target, causing what we think of at a macroscopic level as "heating" but I can't find anywhere where this is spelled out. Introductory texts seldom go into much detail much beyond discussing the mechanism of the initial attenuation of high energy radiation and not subsequent steps. Thanks for you time! Chris. Mentor P: 11,573 All charged particles are ionizing (and the slow electrons then collide with atoms and other electrons and heat the material) and/or directly transfer momentum to atoms (-> heat). Neutral particles can hit nuclei, or produce secondary radiation with charged particles. If heating due to radiation is significant, the radiation levels are really high. P: 19 mfb, thanks for the post. I think I'm trying to ask about the process that you described as "the slow electrons then collide with atoms and other electrons and heat the material" I think I'm struggling to think about what it means to say that the material is heated... is this an excitation of vibration of the atoms in a lattice in solids which is what we conceive of as a temperature increase? If that's the case, why is it that slower moving particles cause this excitation and heating and not higher energy particles? Chris Mentor P: 11,573 Radiation absorption and temperature changes in matter Excitation of vibrations of atoms and excitations of electrons. If that's the case, why is it that slower moving particles cause this excitation and heating and not higher energy particles? Both do it, but the high-energy particles tend to transfer high energies to particles they "hit", so it takes some steps to get to thermal energies (~1/40 eV at room temperature). Related Discussions High Energy, Nuclear, Particle Physics 13 Quantum Physics 4 Introductory Physics Homework 0 General Physics 1 Classical Physics 0	{"extraction_info": {"found_math": false, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.8742457032203674, "perplexity": 570.2913471325677}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.3, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2014-23/segments/1405997876165.43/warc/CC-MAIN-20140722025756-00042-ip-10-33-131-23.ec2.internal.warc.gz"}
http://focm2014.dm.uba.ar/viewAbstract.php?code=722	FoCM 2014 conference Workshop B4 - Geometric Integration and Computational Mechanics December 17, 18:00 ~ 18:25 - Room B11 ## Collocation method for solving singular ODEs and higher index DAEs ### Vienna University of Technology, Austria - [email protected] During recent years, a lot of scientific work concentrated on the analysis and numerical treatment of boundary value problems (BVP) in ordinary differential equations (ODEs) which can exhibit singularities. Such problems have often the following form: $$y'(t)=\frac{1}{t^{\alpha}}M(t)y(t)+f(t,y(t)), \quad t\in (0,1], \quad b(y(0),y(1))=0.$$ For $\alpha = 1$ the problem is called singular with a singularity of the first kind, for $\alpha > 1$ it is essentially singular (singularity of the second kind). The search for efficient numerical methods to solve the above BVP is strongly motivated by numerous applications from physics, chemistry, mechanics, ecology, or economy. In particular, problems posed on infinite intervals are frequently transformed to a finite domain taking above form with $\alpha > 1$. Also, research activities in related fields, like differential algebraic equations (DAEs) or singular Sturm-Liouville eigenvalue problems benefit from techniques developed for singular BVPs. While collocation stays robust and shows advantageous convergence properties in context of singular problems, other high order methods suffer from instabilities and order reductions. It turns out that for singular BVPs with smooth solutions, the convergence order of the polynomial collocation is at least equal to the so-called stage order of the method. For collocation at equidistant points or Gaussian points this convergence result means that the scheme with $m$ inner collocation points constitutes a high order basic solver whose global error is $O(h^m)$ uniformly in $t$ [5]. Clearly, in order to solve an ODE system efficiently, the error estimate and the mesh adaptation strategy have to be provided to correctly reflect the solution behavior. Due to the robustness of collocation, this method was used in one of the best established standard FORTRAN codes for (regular) BVPs, COLSYS [1], as well as in Matlab codes bvp4c [7], the standard module for (regular) ODEs with an option for singular problems, BVP SOLVER [8], sbvp [2], and bvpsuite [6]. The scope of bvpsuite includes fully implicit form of the ODE system with multi-point boundary conditions, arbitrary mixed order of the differential equations including zero, module for dealing with infinite intervals, module for eigenvalue problems, free parameters, and a path-following strategy for parameter-dependent problems with turning points. We will illustrate how bvpsuite can be used to solve BVPs from applications, Complex Ginzburg-Landau equations, density profile in hydrodynamics, and generalized Korteweg-de Vries equation [3]. Finally, we turn to higher index DAEs. Higher index DAEs constitute a really challenging class of problems due to the involved differentiation which is a critical operation to carry out numerically. A possible technique to master the problem is to pre-handle the DAE system in such a way that the transformed problem is of index one and less difficult to solve. Since this approach is technically involved, it is worth to try to avoid it and provide a method which can be applied directly to the original DAE system of high index. At present, there are only some experimental results available, but they are quite encouraging and therefore, we shall briefly discuss them during the presentation [4]. References [1] U. Ascher, J. Christiansen, and R. Russell, Collocation software for boundary value ODEs. ACM Transactions on Mathematical Software, 1981, pp. 209--222. [2] W. Auzinger, G. Kneisl, O. Koch, and E.B. Weinmüller, A collocation code for boundary value problems in ordinary differential equations. Numer. Algorithms, 2003, pp. 27--39. Code available from http://www.mathworks.com/matlabcentral/fileexchange $>$ Mathematics $>$ Differential Equations $>$ SBVP1.0 Package. [3] C. Budd, O. Koch, S. Schirnhofer, and E.B. Weinmüller, Work in progress, 2014. [4] M. Hanke, R. März, C. Tischendorf, E.B. Weinmüller, and S. Wurm, Work in progress, 2014. [5] F. de Hoog and R. Weiss, Collocation Methods for Singular BVPs. SIAM J. Numer. Anal., 1978, pp. 198--217. [6] G. Kitzhofer, O. Koch, G. Pulverer, C. Simon, and E.B. Weinmüller, Numerical Treatment of Singular BVPs: The New Matlab Code bvpsuite. JNAIAM J. Numer. Anal. Indust. Appl. Math., 2010, pp. 113--134. [7] L. Shampine, J. Kierzenka, and M. Reichelt, Solving Boundary Value Problems for Ordinary Differential Equations in Matlab with bvp4c. 2000. [8] L. Shampine, P. Muir, and H. Xu, A User-Friendly Fortran BVP Solver. JNAIAM J. Numer. Anal. Indust. Appl. Math., 2006, pp. 201--217.	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 1, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.625558614730835, "perplexity": 1485.4729198073564}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.3, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2017-30/segments/1500549426372.41/warc/CC-MAIN-20170726182141-20170726202141-00637.warc.gz"}
https://zenodo.org/record/5548226/export/csl	Presentation Restricted Access # Nonzero eccentricities of warm Neptunes Correia, A. C. M.; Bourrier, V.; Delisle, J.-B. ### Citation Style Language JSON Export { "publisher": "Zenodo", "DOI": "10.5281/zenodo.5548226", "author": [ { "family": "Correia, A. C. M." }, { "family": "Bourrier, V." }, { "family": "Delisle, J.-B." } ], "issued": { "date-parts": [ [ 2021, 10, 4 ] ] }, "abstract": "<p>Close-in planets (with orbital periods less than a few days) undergo strong tidal dissipation that should circularise their orbits in a timescale shorter than the age of the system. However, most Neptune-mass planets in this kind of orbits present nonzero eccentricity, typically around 0.15. In this talk we discuss some mechanisms that can oppose to gravitational tides, namely, thermal atmospheric tides, evaporation of the atmosphere, and excitation from a distant companion. We show the limitations of these different mechanisms and how some of them could, depending on specific properties of the observed planetary systems, account for the nonzero eccentricities presently observed.</p>", "title": "Nonzero eccentricities of warm Neptunes", "type": "speech", "id": "5548226" } 98 3 views	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 1, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.6912912130355835, "perplexity": 9779.81124785489}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2023-06/segments/1674764500334.35/warc/CC-MAIN-20230206082428-20230206112428-00506.warc.gz"}
http://www.unconventionalwisdomradio.com/c3meh8gr/shortest-distance-between-two-skew-lines-cartesian-form-4405ae	# shortest distance between two skew lines cartesian form Consider linesl1andl2with equations: r→ = a1→ + λ b1→ and r→ = a2→ + λ b2→ Let us discuss the method of finding this line of shortest distance. In our case, the vector between the generic points is (obtained as difference from the generic points of the two lines in their parametric form): Imposing perpendicularity gives us: Solving the two simultaneous linear equations we obtain as solution . So they clearly aren’t parallel. Abstract. We may derive a formula using this approach and use this formula directly to find the shortest distance between two parallel lines. Your email address will not be published. Ex 11.2, 15 (Cartesian method) Find the shortest distance between the lines ( + 1)/7 = ( + 1)/( − 6) = ( + 1)/1 and ( − 3)/1 = ( − 5)/( − 2) = ( − 7)/1 Shortest distance between two linesl1: ( − _1)/_1 = ( − _1)/_1 = ( − _1)/_1 l2: ( − _2)/_2 = ( − _2)/_2. Parametric vector form of a plane; Scalar product forms of a plane; Cartesian form of a plane; Finding the point of intersection between a line and a plane; . Equation of Line - We form equation of line in different cases - one point and 1 parallel line, 2 points … The shortest distance between two skew lines is the length of the shortest line segment that joins a point on one line to a point on the other line. There are no skew lines in 2-D. %�쏢 The shortest distance between two parallel lines is equal to determining how far apart lines are. "A straight line is a line of zero curvature." A line is essentially the extension of a line segment beyond the original two points. . Let the two lines be given by: L 1 = a 1 → + t ⋅ b 1 → What follows is a very quick method of finding that line. Planes. Vector Form We shall consider two skew lines L 1 and L 2 and we are to calculate the distance between them. The distance between two skew lines is naturally the shortest distance between the lines, i.e., the length of a perpendicular to both lines. If two lines are parallel, then the shortest distance between will be given by the length of the perpendicular drawn from a point on one line form another line. The distance between them becomes minimum when the line joining them is perpendicular to both. It's easy to do with a bunch of IF statements. In the usual rectangular xyz-coordinate system, let the two points be P 1 a 1,b 1,c 1 and P 2 a 2,b 2,c 2 ; d P 1P 2 a 2 " a 1,b 2 " … And length of shortest distance line intercepted between two lines is called length of shortest distance. The shortest distance between two circles is given by C 1 C 2 – r 1 – r 2, where C 1 C 2 is the distance between the centres of the circles and r 1 and r 2 are their radii. I want to calculate the distance between two line segments in one dimension. Solution of I. Lines. $\begingroup$ The result of your cross product technically “points in the same direction as [the vector that joins the two skew lines with minimum distance]”. Consider two skew lines L1 and L2 , whose equations are 1 1 . I’ve changed the directional vector of the first line, so that numbers should be correct now , Your email address will not be published. Cartesian form of a line; Vector product form of a line; Shortest distance between two skew lines; Up to Contents. d = ∣ ( a ⃗ 2 – a ⃗ 1). The idea is to consider the vector linking the two lines in their generic points and then force the perpendicularity with both lines. The shortest distance between two skew lines is the length of the shortest line segment that joins a point on one line to a point on the other line. The straight line which is perpendicular to each of non-intersecting lines is called the line of shortest distance. We will call the line of shortest distance . %PDF-1.3 It can be identified by a linear combination of a … <> x��}͏ɑߝ�}X��I2��Ϫ��k��>�BrzȖ��&9��7xO��ꊌ��z�~{�w��~/"22222��k�zX��}w��o?�~��{ ��0٧�ٹ��n�9�~�}��O��q�.��޿��R��Y(�P��I^��WC��J��~��W5��߮��nE;�^�&�?�� 5 0 obj Parametric vector form of a plane; Scalar product forms of a plane; Cartesian form of a plane; Finding the point of intersection between a line and a plane; This formula can be derived as follows: − is a vector from p to the point a on the line. –a1. A line parallel to Vector (p,q,r) through Point (a,b,c) is expressed with $$\hspace{20px}\frac{x-a}{p}=\frac{y-b}{q}=\frac{z-c}{r}$$ Distance between parallel lines. Let’s consider an example. It doesn’t “lie along the minimum distance”. Skew Lines. The shortest distance between the lines is the distance which is perpendicular to both the lines given as compared to any other lines that joins these two skew lines. If Vt is s – r then the first term should be (1+t-k , …) not as above. If two lines intersect at a point, then the shortest distance between is 0. The distance of an arbitrary point p to this line is given by ⁡ (= +,) = ‖ (−) − ((−) ⋅) ‖. Distance between two skew lines . In our case, the vector between the generic points is (obtained as difference from the generic points of the two lines in their parametric form): Solving the two simultaneous linear equations we obtain as solution . Cartesian and vector equation of a plane. This is my video lecture on the shortest distance between two skew lines in vector form and Cartesian form. This impacts what follows. Cartesian Form: are the Cartesian equations of two lines, then the shortest distance between them is given by . But we are talking about the same thing, and this is just a pedantic issue. In 2-D lines are either parallel or intersecting. (\vec {b}_1 \times \vec {b}_2) \| / \| \vec {b}_1 \times \vec {b}_2 \| d = ∣(a2. Then as scalar t varies, x gives the locus of the line.. $\endgroup$ – Benjamin Wang 9 hours ago Cartesian equation and vector equation of a line, coplanar and skew lines, shortest distance between two lines. They aren’t incidental as well, because the only possible intersection point is for , but when , is at , which doesn’t belong to . Given two lines and, we want to find the shortest distance. The shortest distance between two skew lines lies along the line which is perpendicular to both the lines. Overdetermined and underdetermined systems of equations put simply, Relationship between reduced rings, radical ideals and nilpotent elements, Projection methods in linear algebra numerics, Reproducing a transport instability in convection-diffusion equation. Note that this expression is valid only when the two circles do not intersect, and both lie outside each other. Angle between (i) two lines, (ii) two planes, (iii) a line and a plane.Distance of a point from a plane. The shortest distance between two skew lines r = a 1 + λ b 1 and r = a 2 + μ b 2 , respectively is given by ∣ b 1 × b 2 ∣ [b 1 b 2 (a 2 − a 1 )] Shortest distance between two parallel lines - formula Shortest distance between two skew lines in vector + cartesian form 17:39 155.7k LIKES Shortest distance between a point and a curve. �4݄4G�6�l)Y�e��c��h��sє��Çǧ/��T�]�7s�C-�@2 ��G��7�j){n\|�6�V�� F� d�S�W�ُ[��d��o��5��!�\|��A�"�I�n��=��a��o�'��b��^��W��n�\|P�ӰHa��OWH~w�p��0��:O�?��x�/�E)9{\�K(G��Tvņ详�盔�C��OͰ�� L��S+X�M�K�+l_�䆩�֑P܏�� b��B�F�n�� 4X��&��d�I�. The line segment is perpendicular to both the lines. Then, the shortest distance between the two skew lines will be the projection of PQ on the normal, which is given by. The above equation is the general form of the distance formula in 3D space. E.g. . Save my name, email, and website in this browser for the next time I comment. ( b ⃗ 1 × b ⃗ 2) ∣ / ∣ b ⃗ 1 × b ⃗ 2 ∣. Start with two simple skew lines: (Observation: don’t make the mistake of using the same parameter for both lines. Class 12 Maths Chapter-11 Three Dimensional Geometry Quick Revision Notes Free Pdf We will call the line of shortest distance . 8.5.3 The straight line passing through two given points 8.5.4 The perpendicular distance of a point from a straight line 8.5.5 The shortest distance between two parallel straight lines 8.5.6 The shortest distance between two skew straight lines 8.5.7 Exercises 8.5.8 Answers to exercises Skew lines are the lines which are neither intersecting nor parallel. (टीचू) t�2��?��W��?��?��l�f�ɂ%��%�낝��\��+�q��h1: ;:�,P� 6?��r�6γG�n0p�a�H�qpo�)�L�0��2ED�L�e�F��x3�i�D�� Each lines exist on its own, there’s no link between them, so there’s no reason why they should should be described by the same parameter. The coordinates The shortest distance between skew lines is equal to the length of the perpendicular between the two lines. The cross product of the line vectors will give us this vector that is perpendicular to both of them. Cartesian equation and vector equation of a line, coplanar and skew lines, the shortest distance between two lines The vector → AB has a definite length while the line AB is a line passing through the points A and B and has infinite length. https://learn.careers360.com/maths/three-dimensional-geometry-chapter A gentle (and short) introduction to Gröbner Bases, Setup OpenWRT on Raspberry Pi 3 B+ to avoid data trackers, Automate spam/pending comments deletion in WordPress + bbPress, A fix for broken (physical) buttons and dead touch area on Android phones, FOSS Android Apps and my quest for going Google free on OnePlus 6, The spiritual similarities between playing music and table tennis, FEniCS differences between Function, TrialFunction and TestFunction, The need of teaching and learning more languages, The reasons why mathematics teaching is failing, Troubleshooting the installation of IRAF on Ubuntu, The equation of the line of shortest distance between the two skew lines: just replace. The vector that points from one to the other is perpendicular to both lines. There will be a point on the first line and a point on the second line that will be closest to each other. Share it in the comments! This solution allows us to quickly get three results: The equation of the line of shortest distance between the two skew lines: … Ex 11.2, 14 Find the shortest distance between the lines ⃗ = ( ̂ + 2 ̂ + ̂) + ( ̂ − ̂ + ̂) and ⃗ = (2 ̂ − ̂ − ̂) + (2 ̂ + ̂ + 2 ̂) Shortest distance between the lines with vector equations ⃗ = (1) ⃗ + (1) ⃗and ⃗ = (2) ⃗ + (2) ⃗ is \| ( ( () ⃗ × () ⃗ ). Method: Let the equation of two non-intersecting lines be This solution allows us to quickly get three results: Do you have a quicker method? stream In linear algebra it is sometimes needed to find the equation of the line of shortest distance for two skew lines. thanks for catching the mistake! Hence they are not coplanar . Distance Between Skew Lines: Vector, Cartesian Form, Formula , So you have two lines defined by the points r1=(2,6,−9) and r2=(−1,−2,3) and the (non unit) direction vectors e1=(3,4,−4) and e2=(2,−6,1). Required fields are marked *. But I was wondering if their is a more efficient math formula. Hi Frank, If this doesn’t seem convincing, get two lines you know to be intersecting, use the same parameter for both and try to find the intersection point.). Then as scalar t varies, x gives the locus of the line ; Planes will! The equation of the line gives the locus of the line joining them given. In this browser for the next time i comment email, and both lie outside each other for! To do with a bunch of if statements cartesian form lines, shortest distance between two parallel lines is to! Boundary conditions affect Finite Element Methods variational formulations the extension of a line is. Both lines is just a pedantic issue / ∣ b ⃗ 1 × b 1! And Neumann boundary conditions affect Finite Element Methods variational formulations joining them given. Distance for two skew lines: ( Observation: don ’ t make the mistake of using same... It 's easy to do with a bunch of if statements (,... The lines which are neither intersecting nor parallel with a bunch of if statements ∣ / ∣ b 2! ; shortest distance and r=a2+μb2 are the cartesian equations of two non-intersecting be... Intercepted between two parallel lines is called length of a line that will be a point on the line which. Is valid only when the two lines in their generic points and then force the perpendicularity with both.! I comment mistake of using the same parameter for both lines the next time i comment to find the of. But we are talking about the same thing, and website in this browser the! Distance for two skew lines ( 1+t-k, … ) not as above is essentially the of. Mistake of using the same thing, and website in this browser for next... Finding the distance between two line segments in one dimension are neither intersecting parallel! If Vt is s – r then the shortest distance for two lines! Their is a very quick method of finding that line lines: (:. Dirichlet and Neumann boundary conditions affect Finite Element Methods variational formulations on second... S – r then the shortest distance between them is given by × ⃗. The cartesian equations of two lines is equal to determining how far apart lines.! ( \vec { a } _2 – \vec { a } _1 ) valid only when the line beyond... ’ t make the mistake of using the same thing, and this is my video lecture the! Pq on the shortest distance between them becomes minimum when the line vectors will give us this vector that from... Lines in vector + cartesian form of a line, coplanar and skew lines in +... How do Dirichlet and Neumann boundary conditions affect Finite Element Methods variational formulations vector product form of a line shortest... Minimum distance ” be ( 1+t-k, … ) not as above we may derive a formula using approach! And vector equation of two non-intersecting lines be / Space geometry Calculates the shortest.! A line ; vector product form of a line is essentially the of. Zero curvature. coordinates the shortest distance between two parallel lines are neither intersecting nor parallel the other perpendicular. 'S easy to do with a bunch of if statements 1+t-k, … ) not as above varies. Scalar t varies, x gives the locus of the line segment is perpendicular to both of them lie the. Beyond the original two points cartesian equation and vector equation of the perpendicular between the two lines called. Points and then force the perpendicularity with both lines = \| ( \vec { a } _2 – \vec a! Derived as follows: − is a vector from p to the is... And r=a2+μb2 are the vector linking the two skew lines t varies, gives... Both lie outside each other other words, a straight line contains no curves line a... The shortest distance between them is given by line vectors will give us this vector that points from one the! Measuring the length of the line of shortest distance between two lines, then first... − is a more efficient math formula 155.7k LIKES shortest distance between them is given by is. How far apart lines are but i was wondering if their is a from! Essentially the extension of a line ; shortest distance between them is given by video! Give us this vector that is perpendicular to both of them us discuss the method finding! Can be identified by a linear combination of a line that will be a point on second.: ( Observation: don ’ t “ lie along the minimum distance ” finding that.. Then as scalar t varies, x gives the locus of the line L1 and L2, equations! Two parallel lines is equal to determining how far apart lines are line will... Two lines if their is a vector from p to the length of a line ; vector product form a... ) ∣ / ∣ b ⃗ 2 ) ∣ / ∣ b ⃗ 1 b. Quick method of finding that line segment is perpendicular to each of lines..., then the first line and a point on the normal, is... The cross product of the perpendicular between the two lines, shortest distance line intercepted between two skew lines Space! In their generic points and shortest distance between two skew lines cartesian form force the perpendicularity with both lines the normal which! 155.7K LIKES shortest distance between skew lines us discuss the method of finding this line of zero.. 1 and L 2 and we are talking about the same thing, and both outside. Locus of the line, a straight line which is given by finding distance... ∣ ( a ⃗ 1 ) which is given by quick method of that. Make the mistake of using the same thing, and website in this browser for the next time i.! Only when the line segment beyond the original two points and vector of... Segment is perpendicular to both of them both of them, email and! Finding this line of shortest distance between the two circles do not intersect and... This is my video lecture on the shortest distance between skew lines in Space the next time comment! Called the line joining them is given by quickly get three results: do have! Line joining them is perpendicular to both the lines the method of finding line! Given by segments in one dimension efficient math formula browser for the next time i.. Consider the vector that is perpendicular to both follows: − is a more efficient formula... Lines: ( Observation: don ’ t “ lie along the distance! I comment are to calculate the distance between two skew lines L1 and L2, equations... The minimum distance ” vector equation of two lines curvature. x gives the locus of the line +!	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 1, "mathjax_asciimath": 1, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.8756966590881348, "perplexity": 479.23037273260724}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2023-14/segments/1679296945433.92/warc/CC-MAIN-20230326044821-20230326074821-00036.warc.gz"}
http://mathcs.albion.edu/scripts/mystical2bib.php?year=2012&month=9&day=27&item=a	Albion College Mathematics and Computer Science Colloquium Title: Tessellations and Symmetries of the Plane Speaker: David A. Reimann Associate Professor Mathematics and Computer Science Albion College Albion, Michigan Abstract: Pattern, repetition, and symmetry play important roles in the aesthetics of imagery. Tessellations use patterns of repeated geometric shapes to cover the plane. Uniform tessellations use regular polygons to cover the plane with no gaps or overlaps. The polygons in such tessellations can be decorated in such a way to give rise to interesting visual patterns. The inherent symmetry of regular polygons gives rise to tessellations containing symmetry patterns. Example symmetric tessellation patterns will be presented. An explanation of algorithmic techniques for constructing uniform tessellations will also be presented. Location: Palenske 227 Date: 9/27/2012 Time: 3:30 PM @abstract{MCS:Colloquium:DavidAReimann:2012:9:27, author = "{David A. Reimann}", title = "{Tessellations and Symmetries of the Plane}", address = "{Albion College Mathematics and Computer Science Colloquium}", month = "{27 September}", year = "{2012}" }	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 1, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.5155529975891113, "perplexity": 3670.8930231484405}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2015-14/segments/1427131292683.3/warc/CC-MAIN-20150323172132-00064-ip-10-168-14-71.ec2.internal.warc.gz"}
https://link.springer.com/article/10.1007%2Fs13204-014-0302-9	Applied Nanoscience , Volume 5, Issue 2, pp 163–167 # Green synthesis of wurtzite copper zinc tin sulfide nanocones for improved solar photovoltaic utilization • Leena Arora • Poonam Gupta • Nitu Chhikara • Om Pal Singh • N. Muhunthan • V. N. Singh • B. P. Singh • Kiran Jain • S. Chand Open Access Original Article ## Abstract Cu2ZnSnS4 (CZTS) is considered to be one of the most promising light absorbing materials for low-cost and high-efficiency thin-film solar cells. It is composed of earth abundant, non-toxic elements. In the present study, wurtzite CZTS nanocone has been synthesized by a green chemistry route. The nanocones have been characterized for its optical, structural and microstructural properties using UV–Vis spectrophotometer, X-ray diffraction, Raman spectroscopy and high-resolution transmission electron microscopy. Optical absorption result shows a band gap of 1.42 eV. XRD and Raman results show wurtzite structure and TEM studies reveal the nanocone structure of the grown material. Growing vertically aligned nanocone structure having smaller diameter shall help in enhancing the light absorption in broader range which shall enhance the efficiency of solar cell. This study is a step in this direction. ### Keywords Cu2ZnSnS4 Wurtzite Nanocone Green synthesis ## Introduction CZTS has a direct band gap of about 1.5 eV which is close to the optimal value for being used as an absorber layer in solar cell. The absorption coefficient of CZTS is greater than 104/cm and therefore only a thin layer (1–2 μm) can absorb most of the incident photons (Zhao and Qiao et al. 2014; Mainz et al. 2014; Fan 2014; Tanaka et al. 2007; Chen et al. 2009; Yu et al. 2012). It is known that nanocone structure is an optimal shape for enhancing the light absorption (Wang and Leu 2012). In the study of Wang et al. it has been reported that nanocone arrays significantly improve the solar absorption and efficiencies over nanowire arrays (Hsu et al. 2008). Through simulations they have shown that nanocones have superior absorption due to reduced reflection from their smaller tip and reduced transmission from their larger base. Breaking the vertical mirror symmetry of nanowires results in a broader absorption spectrum such that overall efficiencies are enhanced (Hsu et al. 2008; Mehta and Kruis 2005). It has also been reported by Mehta et al. that nanocone structure is capable of harvesting photons from the sufficient amount of solar spectrum (Li et al. 2012). The field created at the nanojunction (consisting of nanocone and thin film) will effectively (1) separate electrons and holes when they are generated under illumination, (2) extract electrons from the whole absorber to the small tip-film contact area, (3) increase the velocity of minority carriers when they cross the tip-film junction, minimizing recombination loss at the interface and (4) decrease the number of recombination centers by utilizing smaller contact area. Thus, synthesizing nanocone structure shall be highly useful for enhancing the solar cell efficiency. Considering the above factors, wurtzite-type CZTS nanocone structure has been synthesized in this study by a green technique. These nanocrystals are dispersible in non-polar solvents and film can be fabricated simply by the direct liquid coating method. If these nanocones with smaller dimension be can be deposited vertically on substrate then this shall help in enhancing the efficiency of solar cell. To illustrate the concept; a schematic diagram of CZTS thin-film solar cell having nanocone structure is presented in Fig. 1. There are several reports on the synthesis of CZTS nanocrystals by hot-injection method (Guo et al. 2010, 2009; Riha et al. 2009). In general, CZTS nanocrystals are mostly in the kesterite or stannite phase (Shavel et al. 2010). It has been reported by Regulacio et al. that in colloidal nanocrystal synthesis, the presence of organic surfactants or capping ligands is known to strongly influence the crystallographic phase, morphology and growth of the nanocrystals (Regulacio et al. 2012). Thus, the formation of metastable phases can be induced by proper selection of surfactants. CZTS nanocrystals having wurtzite (WZ) phase has also been synthesized by various methods such as noninjection (Regulacio et al. 2012), hot-injection (Singh et al. 2012) and hydrothermal method (Jiang et al. 2012). These processes require inert gas protection (nitrogen or argon), stepwise heating and relatively high temperature. Herein, we provide a facile noninjection synthetic route for preparing monodisperse anisotropic CZTS nanocones that adopt a WZ-type crystal structure. The noninjection or “heating up” approach for the formation of colloidal nanocrystals is better in terms of synthetic reproducibility, convenience in manipulating, and suitable for large-scale production compared to the hot-injection method. Optical properties of the grown nanocones were studied using UV–VIS spectrophotometer (Model: Shimadzu UV–VIS 1800). Structural properties were studied using powder XRD (Philips X’pert pro X-ray diffractometer) and Transmission electron microscopy (TEM, F30 S-twin 300 kV) was used to analyze the size and shape of the nanocrystals. ## Experimental For the synthesis of wurtzite CZTS nanocones, copper dithiocarbamates [Cu(dedtc)2] (36.0 mg, 0.1 mmol), zinc dithiocarbamates [Zn(dedtc)2] (18.1 mg, 0.05 mmol), tin dithiocarbamates [Sn(dedtc)4] (35.6 mg, 0.05 mmol), dodecanethiol (5 ml) and trioctylamine (5 ml) were taken in a 50-ml three-neck flask and the reaction mixture was degassed at 100 °C for 20–30 min. The clear yellow solution formed was heated to 250 °C under Ar atmosphere while stirring it vigorously. A change in color from yellow to topaz to dark brown was observed at around 220–240 °C. The stirring of resulting mixture was continued for 30 min while maintaining the 250 °C temperature. Then, it was placed in a H2O bath to allow the mixture to cool to 40 °C. Methanol was added to precipitate the nanocrystals. The nanocrystals are centrifuged. The solid obtained was washed thoroughly with methanol, and finally dissolved in chloroform. ## Results and discussion The transmittance spectra of the CZTS colloidal nanocones measured by the UV–VIS spectrometer in the wavelength range 300–1,400 nm are shown in Fig. 2a. Optical absorption spectra and Tauc’s plot of wurtzite-type Cu2ZnSnS4 colloidal nanocones are shown in Fig. 2b, c, respectively. The relation between absorption coefficient and optical absorbance can be given by. $$\alpha = \frac{{2.303 \times A \times 10^{7} }}{t}{\text{cm}}^{ - 1} ,$$ (1) where α is the absorption coefficient; ‘A’ is the optical absorbance, $$A = - \ln (\frac{I}{{I_{0} }})$$; and ‘t’ is the thickness (the distance that light crosses in the medium). For direct band gap material (CZTS is a direct band gap material), the band gap is calculated using the equation. $$\alpha h\nu = C(h\nu - E_{\text{g}} )^{\frac{1}{2}} ,$$ (2) where C is a constant, is the photon energy. The band gap (Eg) of CZTS nanocones can be estimated by plotting (αhν)2 versus , and extrapolating the linear portion of the X axis (). The estimated band gap value is 1.42 eV. The observed value is very close to the band gap reported in the literature for CZTS nanocrystals (Weber et al. 2009; Katagiri et al. 2009; Babu et al. 2010; Mitzi et al. 2011; Muhunthan et al. 2013). This value falls within the optimum band gap range for solar energy conversion in a single-junction device. The powder X-ray diffraction (XRD) pattern of the as-obtained CZTS nanocones is shown in Fig. 3a. The diffraction pattern did not match with those reported in the literature for kesterite CZTS (JCPDS 26-0575). The diffraction peaks are attributed to (100), (002), (101), (102), (110), (103), (200), (112), (201) and (202) planes of wurtzite CZTS (Lu et al. 2011). The Raman spectra of the CZTS nanocones have a large peak at 331 cm−1, with additional small peaks at 286 and 363 cm−1. All these peaks are close to the value reported for bulk CZTS (Fig. 3b) (Fernandes et al. 2009). The broadening of the Raman peak for nanocrystals is due to the phonon confinement within the nanocrystals (Liu et al. 2013). No additional peaks of other phases such as ZnS, SnS and Cu2S, were observed which confirms the single-phase structure of CZTS nanocones. Electron diffraction pattern, TEM and HRTEM images of CZTS nanocones are shown in Fig. 4a–d. The selected area electron diffraction pattern (SAED) shown in Fig. 4a confirms the crystalline nature of CZTS nanocones. Only WZ-type CZTS nanocones that are elongated in shape are observed in TEM images (Fig. 4b–c. The length of the cones is about 40 nm. The elongated nanocones with one end much wider (~13–15 nm) than the other (~5–8 nm) was observed. The nanocones are nearly monodispersed. The high-resolution TEM images (Fig. 4d) show a lattice spacing of 0.32 nm which corresponds to the (002) plane of wurtzite CZTS. The nanocone structure synthesized in the present study shall be useful for solar cell applications. ## Conclusion CZTS nanocones have been synthesized through a facile greener and inexpensive route, which involves the surfactant-assisted thermolysis of metal dithiocarbamates. Characterization using XRD, Raman shift and TEM confirm the phase purity of the CZTS nanocones. XRD and Raman shift measurements show that the CZTS nanocones have wurtzite structure. From optical absorption data, the band gap of the WZ-type CZTS nanocones is estimated to be 1.42 eV, which is optimal for solar cell applications. TEM studies show elongated nanocone structure with one end being wider (~13–15 nm) than the other (~5–8 nm). This nanocone structure should help in enhancing the efficiency of solar cell. ## Notes ### Acknowledgments V.N. Singh acknowledges Department of Science and Technology (DST) India for support through the fast track project for young scientist by sanction order no. SR/FTP/PS-124/2011 dated February, 2012. Authors are thankful to MNRE-India (sanction no. 31/29/2010-11/PVSE) for the financial support. The authors are grateful to CSIR-India for TAP-SUN program. OPS and NM are thankful to UGC for SRFships. ### References 1. Babu GS, Kumar YBK, Bhaskar PU, Raja VS (2010) Effect of Cu/(Zn + Sn) ratio on the properties of co-evaporated Cu2ZnSnSe4 thin films. Sol Energ Mater Sol Cells 94:221–226 2. Chen S, Gong XG, Walsh A, Wei S-H (2009) Crystal and electronic band structure of CuZnSnX (X = S and Se) photovoltaic absorbers: first-principles insights. Appl Phys Lett 94:041903 3. Fan F-J, Wu L, Yu S-H (2014) Energetic I–III–VI2 and I2–II–IV–VI4 nanocrystals: synthesis, photovoltaic and thermoelectric applications. Energy Environ Sci 7:190–208 4. Fernandes PA, Salome PMP, da Cunha AF (2009) Growth and Raman scattering characterization of Cu2ZnSnS4 thin films. Thin Solid Films 517:2519–2523 5. Guo Q, Hillhouse HW, Agrawal R (2009) Synthesis of Cu2ZnSnS4 nanocrystal ink and its use for solar cells. J Am Chem Soc 131:11672–11673 6. Guo Q, Ford GM, Yang W-C, Walker BC, Stach EA, Hillhouse HW, Agrawal R (2010) Fabrication of 7.2 % efficient CZTSSe solar cells using CZTS nanocrystals. J Am Chem Soc 132:17384–17386 7. Hsu C-M, Connor ST, Tang MX, Cui Y (2008) Wafer-scale silicon nanopillars and nanocones by Langmuir–Blodgett assembly and etching. Appl Phys Lett 93:133109 8. Jiang H, Dai P, Feng Z, Fan W, Zhan J (2012) Phase selective synthesis of metastable orthorhombic Cu2ZnSnS4. J Mater Chem 22:7502–7506 9. Katagiri H, Jimbo K, Maw WS, Oishi K, Yamazaki M, Araki H, Takeuchi A (2009) Development of CZTS-based thin film solar cells. Thin Solid Films 517:2455–2560 10. Li M, Zhou W-H, Guo J, Zhou Y-L, Hou Z-L, Jiao J, Zhou Z-J, Du Z-L, Wu S-X (2012) Synthesis of pure metastable wurtzite CZTS nanocrystals by facile one-pot method. J Phys Chem C 116:26507–26516 11. Liu WC, Guo BL, Wu XS, Zhang FM, Mak CL, Wong KH (2013) Facile hydrothermal synthesis of hydrotropic Cu2ZnSnS4 nanocrystal quantum dots: band-gap engineering and phonon confinement effect. J Mater Chem A 1:3182–3186 12. Lu X, Zhuang Z, Peng Q, Li Y (2011) Wurtzite Cu2ZnSnS4 nanocrystals: a novel quaternary semiconductor. Chem Commun 47:3141–3143 13. Mainz R, Singh A, Levcenko S, Klaus M, Genzel C, Ryan KM, Unold T (2014) Phase-transition-driven growth of compound semiconductor crystals from ordered metastable nanorods. Nature Commun 5:3133 14. Mehta BR, Kruis FE (2005) A graded diameter and oriented nanorod-thin film structure for solar cell applications: a device proposal. Sol Energ Mater Sol Cells 85:107–113Google Scholar 15. Mitzi DB, Gunawan O, Todorov TK, Wang K, Guha S (2011) The path towards a high-performance solution-processed kesterite solar cell. Sol Energ Mater Sol Cells 95:1421–1436 16. Muhunthan N, Singh OP, Singh S, Singh VN (2013) Growth of CZTS thin films by co-sputtering of metal targets and sulfurization in H2S. Int J Photoenergy 2013:752012 17. Regulacio MD, Ye C, Lim SH, Bosman M, Ye E, Chen S, Xu Q-H, Han M-Y (2012) Colloidal nanocrystals of wurtzite-type Cu2ZnSnS4: facile noninjection synthesis and formation mechanism. Chem Eur J 18:3127–3131 18. Riha SC, Parkinson BA, Prieto AL (2009) Compositionally tunable Cu2ZnSn(S(1-x)Se(x))4 nanocrystals: probing the effect of Se-inclusion in mixed chalcogenide thin films. J Am Chem Soc 131:12054–12055 19. Shavel A, Arbiol J, Cabot A (2010) Synthesis of quaternary chalcogenide nanocrystals: stannite Cu(2)Zn(x)Sn(y)Se(1+x+2y). J Am Chem Soc 132:4514–4515 20. Singh A, Geaney H, Laffir F, Ryan KM (2012) Colloidal synthesis of wurtzite Cu2ZnSnS4 nanorods and their perpendicular assembly. J Am Chem Soc 134:2910–2913 21. Tanaka K, Moritake N, Uchiki H (2007) Preparation of Cu2ZnSnS4 thin films by sulfurizing sol–gel deposited precursors. Sol Energy Mater Sol Cells 91:1199–1201 22. Wang B, Leu PW (2012) Enhanced absorption in silicon nanocone arrays for photovoltaics. Nanotechnology 23:194003 23. Weber A, Krauth H, Perlt S, Schubert B, Kotschau I, Schorr S, Schock HW (2009) Multi-stage evaporation of Cu2ZnSnS4 thin films. Thin Solid Films 517:2524–2526 24. Yu Z, Fan S, Brongersma ML, McGehee MD, Cui Y (2012) Hybrid silicon nanocone–polymer solar cells. Nano Lett 12:2971–2976 25. Zhao Y, Qiao Q, Zhou W-H, Cheng X-Y, Kou D-X, Zhou Z-J, Wu S-X (2014) Wurtzite Cu2ZnSnS4 nanospindles with enhanced optical and electrical properties. Chem Phys Lett 592:144–148 ## Authors and Affiliations • Leena Arora • 1 • Poonam Gupta • 1 • Nitu Chhikara • 1 • Om Pal Singh • 1 • N. Muhunthan • 1 • V. N. Singh • 1 • B. P. Singh • 1 • Kiran Jain • 1 • S. Chand • 1 1. 1.CSIR-National Physical LaboratoryNew DelhiIndia	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 2, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.8758485317230225, "perplexity": 12892.12832734438}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 20, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2017-34/segments/1502886105455.37/warc/CC-MAIN-20170819143637-20170819163637-00188.warc.gz"}
http://www.physicsgre.com/viewtopic.php?f=19&t=3908	## Problem discussions sphy Posts: 209 Joined: Sun Jan 30, 2011 7:23 am ### Problem discussions A mirror (Area= A, Mass= M, perfectly reflecting) is suspended in a vertical plane by a weightless string. Light (Intensity=I) falls normally on the mirror and the mirror is deflected from the vertical by a very small angle $\theta$. Obtain an expression for $\theta$. physicsworks Posts: 80 Joined: Tue Oct 12, 2010 8:00 am ### Re: Problem discussions For perfectly reflecting mirror the light pressure on it: $P=\frac{2I}{c}$, where $c$ is the speed of light. Hence, the force of the light on the mirror is $F=P \cdot A = \frac{2IA}{c}$ For small angles $\theta$: $T \theta = F$, where $T$ is the tension in the string and $T = Mg$. From these two equations we get $\theta = \frac{2IA}{Mgc}$ physicsworks Posts: 80 Joined: Tue Oct 12, 2010 8:00 am ### Re: Problem discussions Where did you get this problem? It doesn't look suitable for the PGRE preparation. sphy Posts: 209 Joined: Sun Jan 30, 2011 7:23 am ### Re: Problem discussions physicsworks wrote:Where did you get this problem? It doesn't look suitable for the PGRE preparation. Well, i was working out on some problems from previous entrance questions (India) where I got this. Why are you saying it's not suitable for the PGRE questions.? Is it a silly question or some thing? bfollinprm Posts: 1198 Joined: Sat Nov 07, 2009 11:44 am ### Re: Problem discussions sphy wrote: physicsworks wrote:Where did you get this problem? It doesn't look suitable for the PGRE preparation. Well, i was working out on some problems from previous entrance questions (India) where I got this. Why are you saying it's not suitable for the PGRE questions.? Is it a silly question or some thing? I dont think you'd be expected to know that P=2I/c for the PGRE. Maybe, but I doubt it. On second thought the I/c is perfectly reasonable, it's just the constant that I don't think they'd expect you to know (though it is a perfectly clear application of newton's third law, so....) grae313 Posts: 2297 Joined: Tue May 29, 2007 8:46 pm ### Re: Problem discussions I think it's a good question, and it's suitability for the GRE would probably depend on the multiple-choice answer selection and whether you can come up with a clever way to eliminate two or three options if you can't remember the formula. physicsworks Posts: 80 Joined: Tue Oct 12, 2010 8:00 am ### Re: Problem discussions sphy wrote:Well, i was working out on some problems from previous entrance questions (India) where I got this. Why are you saying it's not suitable for the PGRE questions.? Is it a silly question or some thing? Well... bfollinprm wrote:I dont think you'd be expected to know that P=2I/c for the PGRE. Maybe, but I doubt it But I also partially agree with grae313. ETS can play a game called "guess dimensions, dude".	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 10, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.8114687204360962, "perplexity": 2088.00042938196}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2017-13/segments/1490218187744.59/warc/CC-MAIN-20170322212947-00330-ip-10-233-31-227.ec2.internal.warc.gz"}
https://afonsobandeira.wordpress.com/2015/11/29/10l42panextraopenproblem/	# 18.S096: An extra Open Problem I have just added an extra open problem (4.6.) to the fourth set of lecture notes. I am documenting it here. Prove or disprove the following conjecture by Feige: Given $n$ independent random variables $X_1,\dots,X_n$ s.t., for all $i$, $X_i \geq 0$ and $\mathbb{E} X_i = 1$ we have $\mathrm{Prob}\left( \sum_{i=1}^n X_i \geq n+1 \right) \leq 1 - e^{-1}$.	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 6, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.9002681374549866, "perplexity": 562.6003364296703}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2018-13/segments/1521257647600.49/warc/CC-MAIN-20180321082653-20180321102653-00715.warc.gz"}
https://motls.blogspot.com/2013/11/sciencemag-medieval-warm-period-global.html	## Friday, November 01, 2013 ... ///// ### ScienceMag: Medieval Warm Period global, 0.65 °C warmer than present The largest ocean was 2 °C warmer than today when ancient civilizations exploded Some fun events and articles related to the climate were recently posted. Pierre Gosselin pointed out that a well-known German daily, TAZ, told its readers that the German environmental psychologists determined that climate alarmists need a psychiatric treatment. The TRF readers who have also read Alexander Ač's essays must have made this "discovery" long before the German colleagues. Also, Nature published an essay arguing that the IPCC is ripe for (criminal, psychiatric) examination; see a review in Nature and WUWT. Such things would be unthinkable in similar self-described "mainstream" news sources before 2009. That's also the case of a new paper in the Science Magazine that argues that the Medieval Warm Period was global, not just regional, and significantly warmer than today. The paper is called Pacific Ocean Heat Content During the Past 10,000 Years and it was written by Yair Rosenthal of Rutgers (my graduate Alma Mater), Braddock K. Linsley (Columbia), and Delia W. Oppo (Woods Hole, MA). Andrew Revkin wrote about it and recorded a 30-minute interview with some of the authors. See also the report on Anthony Watts' blog. Because the work looks at the Pacific Ocean, it shouldn't be surprising that the oscillations cross the boundary of the Northern Hemisphere (the so-called equator LOL). I think that the Pacific Ocean conducts and transfers the heat well enough so that a heat anomaly at one place is spread to the whole mass, at least if we observe it at the timescale of centuries. I don't want to discuss the details of their reconstruction based on sediment core proxies, its reliability, and other technical issues. Instead, let me make you recall that while such papers became common in recent months (or two or three years), they would be a taboo e.g. in 2007. Anyone who would dare to talk about rather well-document historic phenomena such as the Medieval Warm Period would be bullied, attacked, and publicly connected with corruption. Just to be sure, such things are still happening in 2013 but these attacks are only being done by fringe radical groups who are generally agreed to be irrelevant biased extremists, e.g. the green NGOs and hardcore left-wing activist bloggers. It's just fine to discuss things like the Medieval Warm Period and the Little Ice Age again, to ask whether they existed or not. Just to be sure, the answer is almost certainly Yes, at least in some sense, and it's just the more detailed and more quantitative questions (how much) that are supposed to be studied in the papers. Ancient Babylon, the center of Mesopotamia The authors argue that the Pacific temperatures used to be much warmer sometime during the Holocene (last 11,700 years). For example, some 6,000 years ago, we had the middle Holocene Thermal Maximum. That's when the great civilizations were born and the Pacific waters near Antarctica and North Pacific were 2.1 °C and 1.5 °C warmer than in the 20th century, respectively! (The error margin is said to be 0.4 °C in both cases.) Because humans just began to prosper, with the great empires of Mesopotamia and Egypt, among others, the climate was hardly "lethal" at that time. In fact, it's pretty much obvious that it was much more hospitable than today, even in regions that we consider pretty warm even without this extra contribution. Egypt If sensible people agree that the life on an Earth that is 2.1 °C warmer than today is still perfectly fine, probably better than today, couldn't please all reasonable people on this planet agree to stop bullshiting about climate threats at least until the moment when the global mean temperature increases by more than 2.1 °C from the current one? In other words, couldn't the people please shut up about this nonsense at least for the next 200-300 years? (I am sure that once most of the people see what a warming by 1 °C or 2 °C does to the life on Earth – surely nothing bad – they will surely stop being worried about another degree. A necessary condition for the recent climate hysteria was that the instrumental era was too short and we haven't seen any significant enough temperature change yet. This fact encourages some "fear of the unknown". But a change of the temperature by 1 °C or 2 °C is much less unknown than some people pretend; it is completely mundane and harmless.) When we return to the very distant history, the accumulated differences of the temperatures from the present ones may be larger. But even if we go back to the Medieval Warm Period, roughly 1,000 (or slightly less) years ago, we find the temperature that was 0.65 °C warmer than the recent decades, according to the authors. Even that period was perfectly fine – climatically, it was similar to the present. On the contrary, the Little Ice Age is said to host waters that were 0.25 °C cooler than the 20th century waters (a smaller difference, something that shows that the warming since the Little Ice Age wasn't too fast). The Frozen Thames, 1677 So please, allow the climatologists to study the temperatures in the past, present, and future without intimidation and political pressures. The temperatures have clearly always been changing and the changes over many centuries were always counted in (comparable to) Celsius degrees, whether you like it or not. People and other organisms are doing fine between 0 °C and 40 °C or so. So please don't invent fairy tales that a change by half a degree has to be due to a sin, has to be a punishment, and has to be dangerous. It is absolutely clear that none of these claims is true.	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 1, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.5407991409301758, "perplexity": 1860.6450649978747}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2018-13/segments/1521257651820.82/warc/CC-MAIN-20180325044627-20180325064627-00329.warc.gz"}
https://bibbase.org/network/publication/maire-simon-apartiallyreflectingrandomwalkonspheresalgorithmforelectricalimpedancetomography-2015	A partially reflecting random walk on spheres algorithm for electrical impedance tomography. Maire, S. and Simon, M. J. Comput. Physics, 303:413-430, 2015. @article{journals/jcphy/MaireS15, author = {Maire, Sylvain and Simon, Martin}, biburl = {http://www.bibsonomy.org/bibtex/27df4a308843be228e7fc6876fa6ffe23/dblp}, ee = {http://dx.doi.org/10.1016/j.jcp.2015.10.005}, interhash = {76b81b2fa0f40e8ce60fcf2f4340e6d5}, intrahash = {7df4a308843be228e7fc6876fa6ffe23}, journal = {J. Comput. Physics}, keywords = {dblp}, pages = {413-430}, timestamp = {2015-11-24T11:34:51.000+0100}, title = {A partially reflecting random walk on spheres algorithm for electrical impedance tomography.}, url = {http://dblp.uni-trier.de/db/journals/jcphy/jcphy303.html#MaireS15}, volume = 303, year = 2015 }	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 1, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.5249694585800171, "perplexity": 17727.99310220624}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2021-10/segments/1614178385534.85/warc/CC-MAIN-20210308235748-20210309025748-00507.warc.gz"}
http://mathhelpforum.com/algebra/185212-solving-quadratic-equation-involving-log-print.html	# solving quadratic equation involving log • Jul 27th 2011, 09:49 PM kiwi5 Hi, How do you solve an equation with a quadratic expression on one side and a log expression on the other? The specific question is: 2nlog10(n) = 0.1n^2 (Background: this is actually for an algorithm analysis question - I am trying to find the intersection points of the worst-case running times of two algorithms) Thanks • Jul 27th 2011, 09:54 PM Prove It Re: solving quadratic equation involving log Well if you write this as \displaystyle \begin{align} 2n\log_{10}{n} &= 0.1n^2 \\ 0 &= 0.1n^2 - 2n\log_{10}n \\ 0 &= n(0.1n - 2\log_{10}{n}) \end{align} Since $\displaystyle \log_{10}{0}$ is undefined, we can't accept $\displaystyle n = 0$ as a solution, which means we have $\displaystyle 0 = 0.1n - 2\log_{10}{n}$ You will need to use a numerical method to solve this. • Jul 27th 2011, 09:55 PM pickslides Re: solving quadratic equation involving log This is a tricky one, but maybe we can work it around a bit so the solution might be easier to find. $\displaystyle 2n\log_{10}n = 0.1n^2$ $\displaystyle \log_{10}n = \frac{0.1n^2}{2n}$ $\displaystyle \log_{10}n = 0.05n$ $\displaystyle n = 10^{0.05n}$ You can solve it numerically from here. • Jul 27th 2011, 10:04 PM kiwi5 Re: solving quadratic equation involving log Thanks a lot for the fast replies. I also got up to n = 10^(0.05n) and did not know how to proceed any further. What is meant by solving it numerically, exactly? Does it basically mean a brute-force approach? Cheers • Jul 27th 2011, 10:09 PM pickslides Re: solving quadratic equation involving log Yep, brute force, open up a spreadsheet you'll find $n \approx 29$ • Jul 28th 2011, 08:33 AM mithgar Re: solving quadratic equation involving log	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 9, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.9981248378753662, "perplexity": 1243.5549959308591}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2016-50/segments/1480698544140.93/warc/CC-MAIN-20161202170904-00215-ip-10-31-129-80.ec2.internal.warc.gz"}
http://www.koreascience.or.kr/article/ArticleFullRecord.jsp?cn=DHGGDU_2000_v24n4_599	Determination of Background Gray-level for Accurate Measurement of Particles in using Image Processing Method Title & Authors Determination of Background Gray-level for Accurate Measurement of Particles in using Image Processing Method Koh, Kwang-Uoong; Lee, Sang-Yong; Abstract In this study, experiments have been performed to examine the effects of background gray-level on the depth-of-field and on the in-focus criteria. The normalized value of contrast(VC) and the gradient indicator(GI) were used as the in-focus criteria for the small and the large size-ranges of particles, respectively. The slightly larger number of pixels were detected with the brighter background. The maximum of the normalized value of contrast(VCmax) is decreased with the brighter background and its deviation from that with the background gray-level of 160 turned out to be about $\small{pm}$15% when the background gray-level changes from 100 to 200. However, the maximum gradient indicator(GImax) changes with the background gray-level within only $\small{pm}$5%. The depth-of-field for the VC-applicable particle-size range is largely dependent on the background gray-level. On the other hand, the depth-of-field for the GI-applicable particle-size range changes only slightly with the background gray-level. To keep the normalized standard deviation of the particle size within 0.1, the background gray-level should be set 160$\small{pm}$20 for both the VC-applicable and GI-applicable ranges which cover the particle size between $\small{10{\mu}m}$ and $\small{300{\mu}m}$. Keywords Image Processing;In-focus Criterion;Particle Size Measurement;Gradient Indicator(Gl);Normalized Value of Contrast(VC);Depth-of-field;Background Gray-level; Language Korean Cited by References 1. Chigier, N., 1983, 'Drop Size and Velocity Instrumentation,' Prog. Energy Combust. Sci., Vol. 9, pp. 155 -177 2. 이상용, 1996, 액체의 미립화, 민음사 3. Ahlers, K. D. and Alexander, D. R., 1985, 'Microcomputer Based Digital Image Processing System Developed to Count and Size Laser-Generated Small Particle Images,' Opt. Eng., Vol. 24, No.6, pp, 1060-1065 4. Kim, I. G. and Lee, S. Y., 1990, 'A Simple Technique for Sizing and Counting of Spray Drops Using Digital Image Processing,' Exp. Thermal Fluid Sci., Vol. 3, pp. 214-221 5. Ow, C. S. and Crane, R. I., 1981, 'Pattern Recognition Procedures for a Television-Minicomputer Spray Droplet Sizing System,' J. lnst. Energy, Vol. 54, No. 430, pp. 119 -123 6. Weiss, B. A., Derov, P., DeBiase, D. and Simmons, H. C., 1984, 'Fluid Particle Sizing Using a Fully Automated Optical Imaging System, Opt. Eng., Vol. 23, No.5, pp. 561-566 7. 김주연, 추정호, 이상용, 1998, '입경 측정을 위한 영상처리기법의 개선,' 대한기계학회 논문집, Vol. 22, No. 5, pp, 561-566 8. Lee, S. Y., Park, B. S. and Kim, I. G., 1991, 'Gray Level Factors Used in Image Processing of Two-Dimensional Drop Images,' Atomization and Sprays, Vol. 1, No.4, pp. 389-400 9. Kim, K. S. and Kim, S. S., 1994, 'Drop Sizing and Depth-of-field Correction in TV Imaging,' Atomization and Sprays, Vol. 4, No. 1, pp. 65-78 10. Talley, D. G. and Hassoni, M., 1992, 'Accounting for Depth of Field in Sizing Spherical Particles by Imaging,' Atomization and Sprays, Vol. 2, No. 1, pp. 385 -409 11. Mohammadi, A., Miwa, K., Ishiyama, K. and Abe, M., 1998, 'Measurement of Droplet Size, Shape and Velocity in Diesel Sprays using a Single and Double Nano-spark Photography Method,' JSME International Journal, series B, Vol. 41, No. 1, pp. 7-12 12. 고광웅, 김주연, 이상용, 1999, '입경측정을 위한 영상처리기법에서 입자 초점면 존재 판단기준의 설정,' 대한기계학회 논문집, Vol. 23, No.3, pp. 398 -407	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 5, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.7253309488296509, "perplexity": 11031.237912099923}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2017-04/segments/1484560279176.20/warc/CC-MAIN-20170116095119-00577-ip-10-171-10-70.ec2.internal.warc.gz"}
http://tex.stackexchange.com/questions/102232/let-operation-vs-tkz-euclide	# let operation vs tkz-euclide Before put my question to give some explanation of why I do this question. When I started to use the TeX a matter of luck that I started working with LaTeX (xelatex) and not with LuaTex for example. But now as little more experienced user does not want to leave things to luck. Well my question: Because I want to create several similar shapes and I do not want to go back and to fix them can you tell me in your opinion which method - pack of those presented to this question arc that passes from (B) having a center on (A), automatically calculates (AB) distance offers me more possibilities - options. The method with let operation or the method tkz-euclide of course there is the method with PSTricks (although I did not use it but it is never too late) I do not know if I put my question correctly because let operation is not package ... but I hope you understand. I would like namely to tell me the advantages and disadvantages of each method (I do not want to hurry to give myself my own right choice but I want the users through their vote to decide). I know my question is rather general and perhaps closed ... but my concern is real (because my English does not help me if you understand the meaning of my question please correct where necessary to have better sense) 1ο update: To clarify ... my concern is mainly on the possibilities of let operation and tkz-euclide and not on features differences between tikz and PSTricks, I think this is covered on the links you indicated - tikZ experts will vote for tikZ and PSTricks experts for PSTricks ... and there is no expert in the whole wide world who is it for both and can give a good answer. – Herbert Mar 13 '13 at 8:00 @Herbert certainly this is true .... but let us hear their arguments and then we decide – karathan Mar 13 '13 at 8:12 @Herbert ... here are given the opportunity to anyone who has a package not only what I said to present and support it. – karathan Mar 13 '13 at 8:17 This is similar to tex.stackexchange.com/q/6676/15925 – Andrew Swann Mar 13 '13 at 9:04 – percusse Mar 13 '13 at 12:10 I can help you to clarify the question. You need to add pst-eucl in your question. The most important thing is Because I want to create several similar shapes and I do not want to go back and to fix them can you tell me in your opinion which method offers me more possibilities - options. Part 1) _Tikz Pstricks tkz-euclide pst-eucl_ Firstly you can't compare my little package tkz-euclide with main packages like Pgf-tikz and pstricks. On one hand tkz-euclide is a package based on Pgf-tikz and on other hand pst-eucl is a package based on pstricks. These packages allow the drawing of Euclidean geometric figures using macros for specifying mathematical constraints. If you want to create several similar shapes you need to make a choice between a general tool like pgf or pstricks and a specialized package like tkz-euclide or pst-eucl. I agree with Herbert, it's not easy to give a correct answer. I can only say that I prefer tikz because I like the syntax, the documentation but this is just my opinion and these arguments are not necessarily objectives. Perhaps you can also find it strange that my package syntax is different from that of tikz. To understand why... I can also tell you why I wrote tkz-euclide. My idea was like you to create several similar Euclidean geometric figures. A fine tool was pst-eucl so I decided to create a similar tool based on tikz. There are a lot of similitudes between pst-eucl and tkz-euclide. I made a mix ... the names of the macros are based on pst-eucl and the options are based on tikz. The syntax is also a mix. An important thing is that you can mix tikz and tkz-euclide (see my answer on your first question) Conclusion : tkz-euclide is a tool to create similar geometric figures without knowing the complete documentation of tikz. And it's the same thing for pst-eucl and pstricks. Part 2) Update _let operation vs tkz-euclide_ The question is now ore precise. In a perfect world, tkz-euclide is unnecessary. A fine solution would be to write a library euclide to provide some useful tools to get geometrical figures with simple codes. I wrote the first version of tkz, before some libraries of pgf/tikz without the let operation without the intersections library. Now I need to update the package to add new macros for the user and the possibility to use name path and something like let. Some disadvantages of tkz-euclide a) The package is based on tikz but the syntax is different b) if you work with tkz-euclide, you can't use something like let or name path. It's possible to mix syntax and codes but I agree it's not satisfactory. c) Like Tikz calculations depend of TeX and it's a bad thing. Perhaps lua can change a lot of things. I agree with Garbage Collector, Pstricks with postscript is more powerful to make complex calculations. If you only want to draw geometrical figures the package can facilitate the creation of severals shapes. If you want to use tikz A recent example (yesterday), the next code shows a bug : \documentclass{article} \usepackage{tkz-euclide} \usetkzobj{all} \usetikzlibrary{through,intersections} \begin{document} \begin{tikzpicture} \tkzInit[xmin=-0.5,xmax=14.5,ymin=-0.5,ymax=7] \tkzClip \tkzDefPoints{0/0/A, 13/0/B} \tkzDefMidPoint(A,B) \tkzGetPoint{M} \tkzDefLine[orthogonal=through B](A,B) \tkzGetPoint{C} \tkzInterLC(B,C)(B,M) \tkzGetSecondPoint{C} \tkzInterLC(A,C)(C,B) \tkzGetFirstPoint{D} %\node [name path=ci,circle through=(B)] at (C) {}; %\path [name path=A--C] (A) -- (C); %\path [name intersections={of=ci and A--C,by={D}}]; \tkzInterLC(A,B)(A,D) \tkzGetSecondPoint{S} \tkzDrawSegment[color=red](A,S) \tkzDrawSegment[color=blue](S,B) \tkzDrawSegment[thin](A,C) \tkzDrawSegment[thin](B,C) \tkzDrawArc[delta=10](C,D)(B) \tkzDrawArc[delta=10](B,C)(M) \tkzDrawArc[delta=10](A,S)(D) \tkzDrawPoints(A,B,C,D,S,M) \tkzLabelPoints[above left](A,B,C,D,S,M) \end{tikzpicture} \end{document} The result seems to be fine but if you look at the figure in B with a zoom, you see that : It's probably a rounding error. The mistake comes from the macro \tkzInterLC. A solution is to use some codes from Tikz, an I can replace : \tkzInterLC(A,C)(C,B) \tkzGetFirstPoint{D} by \node [name path=ci,circle through=(B)] at (C) {}; \path [name path=A--C,red] (A) -- (C); \path [name intersections={of=ci and A--C,by={D}}]; You can see that the code from tikz is very different and less concise. This is ironic. I used the fp package with the tkz packages to avoid these kinds of problems (there are other problems like this with tikz) but it seems to be insufficient. Conclusion. Tikz is very useful for a lot of things and I think it's a good idea to study this tool. If you don't have a lot of time and if you want to draw only geometrical figures tkz-euclide can help you. It's obvious that it's possible to draw all the pictures with only Tikz but sometimes it's not easy when you want to draw complex figures (but Tikz is not a mathematical tool !). - My english is not very good as it might be a good thing someone corrects my mistakes. – Alain Matthes Mar 13 '13 at 18:57 Your response to my concern is very important (as author of tkz-euclide). I am really confused ... perhaps begin to put a series in my mind. – karathan Mar 13 '13 at 19:20 Could you please modify my question if you think I should correct it, welcome any changes as I have written. :) – karathan Mar 13 '13 at 19:30 This is another longish comment. I think you are overwhelmed with the variety of options within TikZ which I consider it to be a great advantage. First this let operation... TikZ/PGF has a layered structure. TikZ part is the frontend where you literally type what you want to do and I can't overemphasize how much thought went into that (having a big influence from PSTricks is also quite visible). But the stuff that is literal and easy to use is mapped back to lower level PGF commands, example: \draw (0,0) -- (1,1); is, roughly mapped to \pgfpathmoveto{\pgfpointorigin} \pgfpathlineto{\pgfpoint{1cm}{1cm}} \pgfusepath{stroke} This is the lower level that is being mentioned in the manual etc. These are once more mapped to a stream of system level commands like (I'm really approximating here) \pgfsys@moveto{0pt}{0pt} \pgfsys@lineto{1cm}{1cm} \pgfsys@stroke These last ones are actually great convenience since they translate into PDF or PS specials depending on your compilation driver where PSTricks use only the mighty PostScript. Now when you start a let operation it causes a \pgfextra{...} instruction which pauses the current path construction computes some stuff such as length and angle as we did in the previous question and records it into some macros such as \p1,\n2 etc. Then resumes the path with those macro values remembered. Coming back to the PSTricks discussion, I think you already have an idea how powerful it is compared to TikZ but it's usability and the steepness of the learning curve is often gets in the way. But that's not a major obstacle but let's leave that discussion for the linked questions. We all hail to Herbert. There is also Asymptote which is yet another monster but that's again irrelevant. We also have the TKZ-family which is a layer in the opposite direction namely it's built on top of TikZ. Again they are the great accomplishments of our Alain Matthes (or Altermundus as we have known him) In other words, its commands invoke TikZ and PGF commands in the background. So it might happen that some of them might use a let or \pgfextra{} behind the scenes however the usage is super easy and it really does a great job immitating pst-eucl without typing out a let or whatever each time you want to mark an angle etc. Long story short, it's all two and a half main families; TikZ/PGF, PSTricks and Asymptote. within these families you have lots of varieties but still they all come back to the same primitive commands. So, you only need to decide on what you want to do and choose the easiest way out. - Assume we have constraints as follows: 1. We need better typography with microtype package. 2. Sometimes we need to annotate some parts of the text in a document or in your presentation with beamer. 3. We intensively need to draw standalone diagrams. 4. Sometimes we need to draw 3D diagrams involving 3D projection, etc. My consideration is as follows 1. Use microtype package and compile the main TeX input file with pdflatex. 2. As we use pdflatex for compiling the main TeX file, any annotation must be done with TikZ. In most cases, the annotations are so simple that grasping basic knowledge of TikZ should be more than enough. 3. For 2D drawing, both TikZ and PSTricks are great and powerful. We can choose either one. Write the diagram with standalone documentclass, compile with proper compiler and make sure all standalone diagrams are in PDF such that they can be imported from the main TeX input file. 4. PSTricks is superior in 3D drawing. See Manuel Luque's blog to see how sophisticated PSTricks in 3D drawing. Write the diagram with standalone document class, compile with latex-dvips-ps2pdf (faster) or xelatex (slower) to get PDF outputs that consumable for the main TeX input file. ## Summary: • If you are bound to all constraints above • and if you have limited time and memory, I think devoting time for mastering PSTricks should be in the correct path. :-) Or Waiting for someone to create better 3D suppport for TikZ will waste time. • you need to consider that putting PSTricks as the main tool and TikZ as the second tool (just for inline annotations in pdflatex compilation) should be more efficient than putting TikZ as the main tool and PSTricks as the second tool (just for 3D drawing support). • If you don't need 3D capability, use TikZ only. • If you don't need inline anotation in the text or presentation with beamer, use PSTricks only. Note: It is my personal opinion and please correct my bad English sentences (if any). - This is not because a package is more powerful than another, it is superior. It's your opinion but you need to consider the syntax, the documentation and the ease of use. These considerations depend of each user and I think it's not possible to give a correct answer. I'm not sure it's a good idea to choice a package with 3D consideration. You can also get 3D figures with Asymptote if you need a powerful tool. – Alain Matthes Mar 13 '13 at 22:02 @AlainMatthes: PSTricks syntax seems to be good enough (but there is inconsistency, for sure) but I admit its adopted naming conventions are rather inconsistent (plus counter intuitive) and the documentations are a bit difficult to understand (because of the language and less detailed explanation). :-) – kiss my armpit Mar 13 '13 at 22:25	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 1, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.9219594597816467, "perplexity": 1241.047553888914}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.3, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2015-48/segments/1448398460982.68/warc/CC-MAIN-20151124205420-00262-ip-10-71-132-137.ec2.internal.warc.gz"}
http://mathoverflow.net/questions/17738/conjugacy-classes-in-the-absolute-galois-group?sort=newest	# Conjugacy classes in the absolute galois group We consider $G_{\mathbb Q} = Gal(\mathbb {\bar Q}/\mathbb Q)$. The Frobenius elements corresponding to each prime are well-studied. But these are really not elements; these are only defined as some conjugacy classes(upto inertia, etc..) Question: Are these the only conjugacy classes in the absolute Galois group? If there are others, please give examples or methods to construct them. The conjugacy classes are of course defined algebraically; this question is not asking for results of the form that the Frobenii form a dense set. - Firstly, Frobenius elements aren't even conjugacy classes, as you know. So you had better look at quotients $Gal(K/\mathbf{Q})$ of the Galois group which are unramified outside some set $S$. Now you have Frobenius conjugacy classes for all $p$ not in $S$. But now there's a dichotomy. If the quotient is finite, then we see every conj class infinitely often. If the quotient is infinite, then the Frobenius conj classes are dense, as you know, but again trivially there are conj classes that aren't Frobenius elements, because there are only countably many of them, and there will almost always (and perhaps always? not sure) be uncountably many conj classes in the Galois group---for example if $K$ is the maximal extension unramified outside $S$ and $S$ is non-empty then $K$ contains the $p$-cyclotomic extension for some prime $p\in S$ and so the Galois group has a quotient isomorphic to $\mathbf{Z}_p^\times$, and this group is uncountable and the Frobenius conj classes here are just the elements $\ell\in\mathbf{Z}_p^\times$ for $\ell$ running through the primes other than $p$. So now we can see that not only are there uncountably many conj classes that aren't Frobenius elements, we can see uncountably many that aren't in the group generated by the Frobenius elements. I have no idea how to construct these guys in any sort of natural way. - This is a side comment, but I think it's plausible that if G is any infinite profinite group, then there are uncountably many conjugacy classes in G. In fact, I believe that in such a G the Haar measure of any conjugacy class is zero (but please correct me if I am wrong). – senti_today Mar 10 '10 at 20:45 @senti_today : The first statement is true, because the number of conjugacy classes in a finite group cannot remain bounded as the size of the group increases. The second statement is false: Reflections inside a dihedral group are a conjugacy class of measure $\frac{1}{2}$, and you can convert this to an infinite example. – moonface Mar 10 '10 at 23:16 @moonface: I am not sure I follow your first comment. How does it imply that the number of conjugacy classes is not countable? In the second comment, you probably mean "dihedral group of order not divisible by 4" (otherwise there are two conjugacy classes of reflections, if I'm not mistaken). If I understand you correctly, the sort of example you have in mind is: consider $\mathbb{Z}/2\mathbb{Z}$ acting on $\mathbb{Z}_p$ via $x\mapsto-x$, where $p$ is an odd prime, and form the semidirect product. Then the nontrivial coset of $\mathbb{Z}_p$ is a single conjugacy class of Haar measure 1/2. – senti_today Mar 10 '10 at 23:49 Yes, dihedrals of 2xodd order, and that's exactly what I had in mind. About the first comment, I don't follow it either (I had hastily assumed that any inverse limit of finite sets with increasing size and surjective transition maps is uncountable...) Thanks for catching. – moonface Mar 11 '10 at 2:38 I agree with the answer of Kevin Buzzard -- you better look only at quotients $Gal(K/Q)$ unramified outside some (finite) set $S$ to make the question make sense as it is. But regardless, you can ask about the conjugacy classes in the absolute Galois group, and what they "mean". An answer was given many years ago by Ax (I guess in one of his Annals papers, 1968 or 1969), and there are elaborations and new results in the thesis of James Gray, now published in the J. of Symbolic Logic as "Coding complete theories in Galois groups" (his thesis is also available freely online). The reason why these "other conjugacy classes" (which are essentially all of them) are difficult to construct is that the associated fixed fields are the algebraic (over $Q$) subfields of pseudofinite fields of characteristic zero. In Theorem 1.27 of his thesis, Gray states that there is a [natural, homeomorphic in the appropriate topology] bijection between the set of conjugacy classes in $Gal(\bar Q / Q)$ and the Stone space of completions of $ACFA_0$ -- the theory of algebraically closed fields of characteristic zero with generic automorphism. Given such a completion of $ACFA_0$, realized by a model $(K, \sigma)$ where $K$ is algebraically closed, and $\sigma$ is a generic automorphism (see MacIntyre, "Generic automorphisms of fields" for the definition of generic used here), the fixed field $K^\sigma$ is a pseudofinite field of characteristic zero. Now, while two conjugacy classes in $Gal(\bar Q / Q)$ are quite simple to describe -- the trivial conjugacy class and the conjugacy class of order 2 elements -- other conjugacy classes contain elements of infinite order. The associated fixed fields (in this infinite-order case) in $\bar Q$ are psuedofinite fields, which are difficult to get your hands on. Probably the best way is to take an ultraproduct (for a non-principal ultrafilter on the set of prime numbers) of finite fields, and take the algebraic elements within. This is certainly nonconstructive, relying heavily on Zorn's lemma. Still, such fields have arithmetic significance. The model theory related to $ACFA_0$ has had a great deal of impact on number theory lately, and Fried-Jarden also touch on related matters in their "Field Arithmetic" book. -	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.8612490892410278, "perplexity": 242.23569768684587}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2014-49/segments/1416931008289.40/warc/CC-MAIN-20141125155648-00036-ip-10-235-23-156.ec2.internal.warc.gz"}
http://www.fonthaus.com/help/installing-fonts	#### Installing Fonts This section explains how to install PostScript, TrueType, and OpenType fonts for both Mac and PC. We assume you are familiar with basic computer operations, such as clicking and dragging, using menus, and moving icons. If you are unfamiliar with any of these operations, please refer to your operating system user guide. Before installing your fonts, we would like to encourage you to make one backup copy of your font and store it on a CD, external hard drive or other removable media. We recommend installing only one format of a font, either OpenType, TrueType, or PostScript. Installing two or more formats of the same font may cause problems when you try to use, view, or print the font. If you use a font management utility to manage your fonts, follow the instructions for the utility to install and remove fonts. After installing fonts, you may need to restart an application or reselect the printer in the application to make the fonts appear in the font list. ##### Macintosh - Installing PostScript Type 1 Fonts PostScript fonts consist of two parts: a screen font (also known as a bitmap font) and a printer font (also known as an outline font). Although the screen and printer fonts are separate files, they are related. You must install at least one size of a screen font for that font to appear in the font menu of your applications. Each font may also include an Adobe Font Metrics (AFM) file. This is a text file that contains character metric and kerning information that is used by some applications to determine character spacing. Most applications can retrieve metrics and kerning information from the screen font suitcase and do not need this file. Do not install this file unless your application requires it. Before these fonts can be installed, they must de-compressed using a software product called "Stuff-It". All MAC files that are downloaded from the web site are in a .hqx format (Compressed). See: Uncompressing Font Files Installing Fonts on System 9 or below: - Open up the Hard Disk - Open up the System folder - Open up the fonts folder - Highlight and drag the screen font (Suitcase with "A" on it) and the printer font (not the .AFM file) into the FONTS folder. Installing Fonts on System X Operating System: - Open up the Hard Disk - Open up the Library folder - Open up the Fonts folder - Highlight and drag the screen font (Suitcase with “A” on it) and the printer font (not the .AFM file) into the FONTS folder. ##### Macintosh - Installing TrueType Fonts TrueType suitcases contain the suffix "LET" or "TT" in the suitcase name to distinguish them from PostScript versions of the same typeface and to make TrueType font identification easier. These suffixes will appear in the font menu of any application using TrueType fonts. - Open your font's TrueType folder. - Drag the TrueType font suitcase onto the System Folder icon on your hard disk. Note: If you attempt to drag a font suitcase onto the System Folder icon while an application is open, a message appears, asking you to close any open applications. Click OK, quit any open applications, and repeat step 2. A message appears, telling you that fonts must be installed in either the System file (System 9.0.x or below). Click OK. ##### Macintosh - Installing OpenType Fonts - The file you download from FontHaus.com will end with a “.zip” extension. - Drag this file over the StuffIt Expander application to uncompress the file. See: Uncompressing Font Files - This should produce a new uncompressed folder. Open the folder. - Drag the font file (the file that ends in .OTF) into your fonts folder. - To access your fonts folder on OS X, open your hard disk and the Library folder inside. - The Fonts folder is inside the Library folder. - To access your fonts folder on OS 9 or earlier, open up the hard disk and the system folder inside. The fonts folder is inside the system folder. ##### Macintosh - Removing Fonts To remove a screen font or a TrueType font under System 7.1.x or later Start by double-clicking the Fonts folder icon (inside the System folder) to open it. Then drag the font icon(s) out of the Fonts folder window and into another folder or the Trash. Close the Fonts folder. To remove a screen font or a TrueType font under System 7.0.x Start by double-clicking the System file icon (inside the System folder) to open it. Then drag the font icon(s) out of the System file window and into another folder or the Trash. Close the System file. To remove a PostScript printer font under System 7.0.x Start by double-clicking the Extensions folder (inside the System folder) to open it. Then drag the font icon(s) out of the Extensions folder and into another folder or the Trash. Close the Extensions folder. To remove a PostScript printer font under System 7.1.x or later Start by double-clicking the Fonts folder (inside the System folder) to open it. Then drag the font icon(s) out of the Fonts folder and into another folder or the Trash. Close the Fonts folder. NOTE: Some display typefaces are very ornate and may contains a large number of control points in the font outlines. If you are using Type 1 fonts and are having trouble printing, you might try using the TrueType version of the font. This is because of differences in the way that the two formats are downloaded to your printer. Managing Fonts with Suitcase, MasterJuggler, and ATM FontHaus fonts are fully compatible with Symantec’s Suitcase, Alsys’ MasterJuggler, and Adobe System’s ATM and ATM Deluxe, utilities for managing and installing fonts. To install and manage fonts with these utilities, please check their respective user guides. ##### Windows - Installing PostScript Type 1, TrueType and OpenType Fonts If you have Windows 95, 98, NT or 2000 ME, you will need to install that font using Adobe Type Manager. If you don't have Adobe Type Manager, you can download a FREE "lite" version here. This is how the font should be installed using Adobe Type Manager. 2. On right hand side under "Source", point to where the font files live. Example: c:\fonthaus 3. If the fonts live in c:\fonthaus, point to that folder, and double click on the font folder. 4. The font should now appear in the window. 5. Highlight the font and click on ADD. 6. This will install the font and be available in all Windows applications. ##### Windows - Installing TrueType, Postscript and OpenType Fonts using Windows XP or 2000 Pro TrueType fonts use the extension "TTF" in file names to distinguish them from PostScript versions of the same typeface and to make TrueType font identification easier. To install TrueType fonts in Windows, the following steps should be taken; 1. Go into Windows by going to START, SETTINGS, CONTROL PANEL. 2. Double click on the FONTS folder 3. Go to FILE, and down to “"Install New Fonts". 4. Point to where the de-compressed TrueType font files live (C:\fonthaus) 5. Highlight the font and click on OK. This will install the font Note: A printer icon appears to the left of a font name in the font menu of any application using PostScript Type 1 fonts; "TT" appears to the left of a font name in the font menu of any application using TrueType fonts.	{"extraction_info": {"found_math": false, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.932110071182251, "perplexity": 6655.077375241938}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2018-05/segments/1516084886397.2/warc/CC-MAIN-20180116090056-20180116110056-00446.warc.gz"}
https://dsp.stackexchange.com/questions/43747/computer-vision-how-to-correctly-calibrate-my-camera-with-a-wide-angle-lens-us/43770	# computer vision - How to correctly calibrate my camera with a wide angle lens using openCV? I am trying to calibrate a camera with a fisheye lens. I therefor used the fisheye lens module, but keep getting strange results no matter what distortion parameters I fix. This is the input image I use: https://i.imgur.com/apBuAwF.png where the red circles indicate the corners I use to calibrate my camera. This is the best I could get, output: https://imgur.com/a/XeXk5 I currently don't know by heart what the camera sensor dimensions are, but based on the focal length in pixels that is being calculated in my nitrinsic matrix, I deduce my sensor size is approximately 3.3mm (assuming my physical focal length is 1.8mm), which seems realistic to me. Yet, when undistorting my input image I get nonsense. Could someone tell me what I may be doing incorrectly? the matrices and rms being output by the calibration: K:[263.7291703200009, 0, 395.1618975493187; 0, 144.3800397321767, 188.9308218101271; 0, 0, 1] D:[0, 0, 0, 0] rms: 9.27628 my code: #include <opencv2/opencv.hpp> #include "opencv2/core.hpp" #include "opencv2/imgcodecs.hpp" #include "opencv2/imgproc.hpp" #include "opencv2/highgui.hpp" #include "opencv2/ccalib/omnidir.hpp" using namespace std; using namespace cv; vector<vector<Point2d> > points2D; vector<vector<Point3d> > objectPoints; Mat src; //so that I don't have to select them manually every time void initializePoints2D() { points2D[0].push_back(Point2d(234, 128)); points2D[0].push_back(Point2d(300, 124)); points2D[0].push_back(Point2d(381, 126)); points2D[0].push_back(Point2d(460, 127)); points2D[0].push_back(Point2d(529, 137)); points2D[0].push_back(Point2d(207, 147)); points2D[0].push_back(Point2d(280, 147)); points2D[0].push_back(Point2d(379, 146)); points2D[0].push_back(Point2d(478, 153)); points2D[0].push_back(Point2d(551, 165)); points2D[0].push_back(Point2d(175, 180)); points2D[0].push_back(Point2d(254, 182)); points2D[0].push_back(Point2d(377, 185)); points2D[0].push_back(Point2d(502, 191)); points2D[0].push_back(Point2d(586, 191)); points2D[0].push_back(Point2d(136, 223)); points2D[0].push_back(Point2d(216, 239)); points2D[0].push_back(Point2d(373, 253)); points2D[0].push_back(Point2d(534, 248)); points2D[0].push_back(Point2d(624, 239)); points2D[0].push_back(Point2d(97, 281)); points2D[0].push_back(Point2d(175, 322)); points2D[0].push_back(Point2d(370, 371)); points2D[0].push_back(Point2d(578, 339)); points2D[0].push_back(Point2d(662, 298)); for(int j=0; j<25;j++) { circle(src, points2D[0].at(j), 5, Scalar(0, 0, 255), 1, 8, 0); } imshow("src with circles", src); waitKey(0); } int main(int argc, char** argv) { Mat srcSaved; resize(src, src, Size(), 0.5, 0.5); src.copyTo(srcSaved); vector<Point3d> objectPointsRow; vector<Point2d> points2DRow; objectPoints.push_back(objectPointsRow); points2D.push_back(points2DRow); for(int i=0; i<5;i++) { for(int j=0; j<5;j++) { objectPoints[0].push_back(Point3d(5j,5i,1)); } } initializePoints2D(); cv::Matx33d K; cv::Vec4d D; std::vector<cv::Vec3d> rvec; std::vector<cv::Vec3d> tvec; int flag = 0; flag \|= cv::fisheye::CALIB_RECOMPUTE_EXTRINSIC; flag \|= cv::fisheye::CALIB_CHECK_COND; flag \|= cv::fisheye::CALIB_FIX_SKEW; flag \|= cv::fisheye::CALIB_FIX_K1; flag \|= cv::fisheye::CALIB_FIX_K2; flag \|= cv::fisheye::CALIB_FIX_K3; flag \|= cv::fisheye::CALIB_FIX_K4; double rms =cv::fisheye::calibrate( objectPoints, points2D, src.size(), K, D, rvec, tvec, flag, cv::TermCriteria(3, 20, 1e-6) ); Mat output; cerr<<"K:"<<K<<endl; cerr<<"D:"<<D<<endl; cv::fisheye::undistortImage(srcSaved, output, K, D); cerr<<"rms: "<<rms<<endl; imshow("output", output); waitKey(0); cerr<<"image .size: "<<srcSaved.size()<<endl; } If anybody has an idea, feel free to either share some code in Python either in C++. Whatever floats your boat. EDIT: As you may have notice I don't use a black and white checkerboard for the calibration, but corners from tiles constituting my carpet. At the end of the day the goal -I think- is to get corner coordinates which represent samples from the distortion radii . The carpet is to some extent the same as the checkerboard, the only difference -once again I think- is the fact that you have less high frequency edges at those eg corners on the carpet than on a black and white checkerboard. I know the number of pictures is very limited, ie only 1. I expect the image to be undistorted to some extent, but I also expect the undistortion to be very well done. But in this case the image output looks like total nonsense. Thanks If you haven't followed this tutorial on camera calibration with OpenCV, do it. It's well explained and the code is pretty much ready to go. And if your goal is to calibrate your camera using the carpet, maybe check first if it works with the checkerboard. Also a few things: • some factors in the K matrix are relative to the size of the pictures you use, check if they're the exact same. • the reference points you used with your carpet also seems wrong to me: 3 squares along X axis but only 2 along Y axis. • and as you've stated, the number of pictures is very limited, I recommend you using at least 5 pictures. Quoting the tutorial on camera calibration from the OpenCV doc: ... in practice we have a good amount of noise present in our input images, so for good results you will probably need at least 10 good snapshots of the input pattern in different positions. If you could use the code from the tutorial and tell me what goes wrong I could help you then. If you could also post a link with the actual image you use (not a screenshot) so that I can test your code. PS: Too bad for you I had the exact C++ function that did what you want but it looks like I somehow lost it.	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 1, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.17865611612796783, "perplexity": 3370.937116787912}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2020-45/segments/1603107887810.47/warc/CC-MAIN-20201025041701-20201025071701-00141.warc.gz"}
http://www.aimsciences.org/article/doi/10.3934/dcds.2011.29.1419	# American Institute of Mathematical Sciences October 2011, 29(4): 1419-1441. doi: 10.3934/dcds.2011.29.1419 ## Symbolic extensions and partially hyperbolic diffeomorphisms 1 Dep. Matemática PUC-Rio, Marquês de São Vicente 225 22453-900, Rio de Janeiro, Brazil 2 Department of Mathematics, Brigham Young University, Provo, UT 84602, United States Received November 2009 Revised August 2010 Published December 2010 We show there are no symbolic extensions $C^1$-generically among diffeomorphisms containing nonhyperbolic robustly transitive sets with a center indecomposable bundle of dimension at least 2. Similarly, $C^1$-generically homoclinic classes with a center indecomposable bundle of dimension at least 2 that satisfy a technical assumption called index adaptation have no symbolic extensions. Citation: Lorenzo J. Díaz, Todd Fisher. Symbolic extensions and partially hyperbolic diffeomorphisms. Discrete & Continuous Dynamical Systems - A, 2011, 29 (4) : 1419-1441. doi: 10.3934/dcds.2011.29.1419 ##### References: [1] F. Abdenur, C. Bonatti, S. Crovisier, L. J. Díaz and G. Wen, Periodic points and homoclinic classes,, Ergod. Th. Dynamic. Systems, 27 (2007), 1. Google Scholar [2] M. Asaoka, Hyperbolic sets exhibiting $C^1$-persistent homoclinic tangency for higher dimensions,, Proc. Amer. Math. Soc., 136 (2008), 677. doi: 10.1090/S0002-9939-07-09115-0. Google Scholar [3] C. Bonatti and L. J. Díaz, Persistent nonhyperbolic transitive diffeomorphisms,, Ann. of Math., 143 (1996), 357. doi: 10.2307/2118647. Google Scholar [4] C. Bonatti and L. J. Díaz, Connexions hétéroclines et généricité d'une infinité de puits ou de sources,, Ann. Scient. Éc. Norm. Sup., 32 (1999), 135. Google Scholar [5] C. Bonatti and S. Crovisier, Recurrence et généricité,, Invent. Math., 158 (2004), 33. Google Scholar [6] C. Bonatti and L. J. Díaz, On maximal transitive sets of generic diffeomorphisms,, Publ. Math. Inst. Hautes Études Sci., 96 (2002), 171. Google Scholar [7] C. Bonatti, L. J. Díaz and T. Fisher, Supergrowth of the number of periodic orbits for non-hyperbolic homoclinic classes,, Discrete and Cont. Dynamic. Systems, 20 (2008), 589. Google Scholar [8] C. Bonatti, L. J. Díaz and E. Pujals, A $C^1$-generic dichotomy for diffeomorphisms; weak forms of hyperbolicity or infinitely many sinks or sources,, Annals of Math., 158 (2003), 355. doi: 10.4007/annals.2003.158.355. Google Scholar [9] C. Bonatti, L. J. Díaz, and M. Viana, "Dynamics Beyond Uniform Hyperbolicity. A Global Geometric and Probabilistic Perspective,", volume \textbf{102} of Encyclopaedia of Mathematical Sciences, 102 (2005). Google Scholar [10] C. Bonatti and M. Viana, SRB measures for partially hyperbolic systems whose central direction is mostly contracting,, Israel J. Math., 115 (2000), 157. doi: 10.1007/BF02810585. Google Scholar [11] Ch. Bonatti, L. J. Díaz, E.R. Pujals and J. Rocha, Robustly transitive sets and heterodimensional cycles,, Astérisque, 286 (2003), 187. Google Scholar [12] M. Boyle and T. Downarowicz, Symbolic extension entropy: $C^r$ examples, products and flows,, Discrete Contin. Dyn. Syst., 16 (2006), 329. doi: 10.3934/dcds.2006.16.329. Google Scholar [13] M. Boyle, D. Fiebig and U. Fiebig, Residual entropy, conditional entropy, and subshift covers,, Forum Math., 14 (2002), 713. doi: 10.1515/form.2002.031. Google Scholar [14] M. Brin and Stuck G, "Introduction to Dynamical Systems,", Cambridge University Press, (2002). doi: 10.1017/CBO9780511755316. Google Scholar [15] D. Burguet, $C^2$ surface diffeomorphisms have symbolic extensions,, preprint, (). Google Scholar [16] K. Burns, personal, communication., (). Google Scholar [17] J. Buzzi, Intrinsic ergodicity for smooth interval maps,, Isreal J. Math., 100 (1997), 125. doi: 10.1007/BF02773637. Google Scholar [18] J. Buzzi, T. Fisher, M. Sambarino and C. Vásquez, Intrinsic ergodicity for certain partially hyperbolic derived from Anosov systems,, preprint., (). Google Scholar [19] A. Candel and L. Conlon, "Foliations I,", volume \textbf{23} of Graduate Studies in Mathematics, 23 (2000). Google Scholar [20] C. Carbalo, C. Morales and M. J. Pacifico, Homoclinic classes for generic $C^1$ vector fields,, Ergod. Th. Dynamic. Systems, 23 (2003), 403. Google Scholar [21] W. Cowieson and L.-S. Young, SRB measures as zero-noise limits,, Ergod. Th. Dynamic. Systems, 25 (2005), 1115. Google Scholar [22] L. J. Díaz, E. Pujals and R. Ures, Partial hyperbolicity and robust transitivity,, Acta Math., 183 (1999), 1. doi: 10.1007/BF02392945. Google Scholar [23] T. Downarowicz and A. Maass, Smooth interval maps have symbolic extensions,, Inventiones Math., 176 (2009), 617. doi: 10.1007/s00222-008-0172-4. Google Scholar [24] T. Downarowicz and S. Newhouse, Symbolic extensions in smooth dynamical systems,, Inventiones Math., 160 (2005), 453. doi: 10.1007/s00222-004-0413-0. Google Scholar [25] N. Gourmelon, Generation of homoclinic tangencies by $C^1$-perturbations,, Discrete Contin. Dyn. Syst., 26 (2010), 1. doi: 10.3934/dcds.2010.26.1. Google Scholar [26] S. Hayashi, Connecting invariant manifolds and the solution of the $C^1$ stability and $\omega$-stability conjectures for flows,, Annals of Math., 145 (1997), 81. doi: 10.2307/2951824. Google Scholar [27] A. Katok and B. Hasselblatt, "Introduction to the Modern Theory of Dynamical Systems,", Cambridge University Press, (1995). Google Scholar [28] G. Keller, "Equilibrium States in Ergodic Theory,", London Mathematical Society Student Texts, (1998). Google Scholar [29] R. Mañé, Contributions to the stability conjecture,, Topology, 17 (1978), 383. doi: 10.1016/0040-9383(78)90005-8. Google Scholar [30] M. Misiurewicz, Diffeomorphim without any measure of maximal entropy,, Bull. Acad. Pol. Sci., 21 (1973), 903. Google Scholar [31] S. Newhouse, Hyperbolic limit sets,, Trans. Amer. Math. Soc., 167 (1972), 125. doi: 10.1090/S0002-9947-1972-0295388-6. Google Scholar [32] S. Newhouse, Continuity properties of entropy,, Annals of Math., 129 (1989), 215. doi: 10.2307/1971492. Google Scholar [33] M. J. Pacifico and J. Vieitez, Robust entropy-expansiveness implies generic domination,, preprint, (). Google Scholar [34] M. J. Pacifico and J. Vieitez, Entropy-expansiveness and domination for surface diffeomorphisms,, Rev. Mat. Complut., 21 (2008), 293. Google Scholar [35] E. Pujals and M. Sambarino, Homoclinic tangencies and hyperbolicity for surface diffeomorphisms,, Annals of Math., 151 (2000), 961. doi: 10.2307/121127. Google Scholar [36] R. Saghin and Z. Xia, The entropy conjecture for partially hyperbolic diffeomorphisms with 1-D center,, Topology Appl., 157 (2010), 29. doi: 10.1016/j.topol.2009.04.053. Google Scholar [37] M. Shub, Dynamical systems, filtrations and entropy,, Bull. Amer. Math. Soc., 80 (1974), 27. doi: 10.1090/S0002-9904-1974-13344-6. Google Scholar [38] M. Shub, "Global Stability of Dynamical Systems,", Springer-Verlag, (1987). Google Scholar [39] K. Sigmund, Generic properties of invariant measures for Axiom-A-diffeomorphisms,, Inventiones Math., 11 (1970), 99. doi: 10.1007/BF01404606. Google Scholar [40] C. P. Simon, Instability in Diff$(T^3)$ and the nongenericity of rational zeta function,, Trans. Amer. Math. Soc., 174 (1972), 217. Google Scholar [41] P. Walters, "An Introduction to Ergodic Theory,", volume \textbf{79} of Graduate Texts in Mathematics, 79 (1982). Google Scholar show all references ##### References: [1] F. Abdenur, C. Bonatti, S. Crovisier, L. J. Díaz and G. Wen, Periodic points and homoclinic classes,, Ergod. Th. Dynamic. Systems, 27 (2007), 1. Google Scholar [2] M. Asaoka, Hyperbolic sets exhibiting $C^1$-persistent homoclinic tangency for higher dimensions,, Proc. Amer. Math. Soc., 136 (2008), 677. doi: 10.1090/S0002-9939-07-09115-0. Google Scholar [3] C. Bonatti and L. J. Díaz, Persistent nonhyperbolic transitive diffeomorphisms,, Ann. of Math., 143 (1996), 357. doi: 10.2307/2118647. Google Scholar [4] C. Bonatti and L. J. Díaz, Connexions hétéroclines et généricité d'une infinité de puits ou de sources,, Ann. Scient. Éc. Norm. Sup., 32 (1999), 135. Google Scholar [5] C. Bonatti and S. Crovisier, Recurrence et généricité,, Invent. Math., 158 (2004), 33. Google Scholar [6] C. Bonatti and L. J. Díaz, On maximal transitive sets of generic diffeomorphisms,, Publ. Math. Inst. Hautes Études Sci., 96 (2002), 171. Google Scholar [7] C. Bonatti, L. J. Díaz and T. Fisher, Supergrowth of the number of periodic orbits for non-hyperbolic homoclinic classes,, Discrete and Cont. Dynamic. Systems, 20 (2008), 589. Google Scholar [8] C. Bonatti, L. J. Díaz and E. Pujals, A $C^1$-generic dichotomy for diffeomorphisms; weak forms of hyperbolicity or infinitely many sinks or sources,, Annals of Math., 158 (2003), 355. doi: 10.4007/annals.2003.158.355. Google Scholar [9] C. Bonatti, L. J. Díaz, and M. Viana, "Dynamics Beyond Uniform Hyperbolicity. A Global Geometric and Probabilistic Perspective,", volume \textbf{102} of Encyclopaedia of Mathematical Sciences, 102 (2005). Google Scholar [10] C. Bonatti and M. Viana, SRB measures for partially hyperbolic systems whose central direction is mostly contracting,, Israel J. Math., 115 (2000), 157. doi: 10.1007/BF02810585. Google Scholar [11] Ch. Bonatti, L. J. Díaz, E.R. Pujals and J. Rocha, Robustly transitive sets and heterodimensional cycles,, Astérisque, 286 (2003), 187. Google Scholar [12] M. Boyle and T. Downarowicz, Symbolic extension entropy: $C^r$ examples, products and flows,, Discrete Contin. Dyn. Syst., 16 (2006), 329. doi: 10.3934/dcds.2006.16.329. Google Scholar [13] M. Boyle, D. Fiebig and U. Fiebig, Residual entropy, conditional entropy, and subshift covers,, Forum Math., 14 (2002), 713. doi: 10.1515/form.2002.031. Google Scholar [14] M. Brin and Stuck G, "Introduction to Dynamical Systems,", Cambridge University Press, (2002). doi: 10.1017/CBO9780511755316. Google Scholar [15] D. Burguet, $C^2$ surface diffeomorphisms have symbolic extensions,, preprint, (). Google Scholar [16] K. Burns, personal, communication., (). Google Scholar [17] J. Buzzi, Intrinsic ergodicity for smooth interval maps,, Isreal J. Math., 100 (1997), 125. doi: 10.1007/BF02773637. Google Scholar [18] J. Buzzi, T. Fisher, M. Sambarino and C. Vásquez, Intrinsic ergodicity for certain partially hyperbolic derived from Anosov systems,, preprint., (). Google Scholar [19] A. Candel and L. Conlon, "Foliations I,", volume \textbf{23} of Graduate Studies in Mathematics, 23 (2000). Google Scholar [20] C. Carbalo, C. Morales and M. J. Pacifico, Homoclinic classes for generic $C^1$ vector fields,, Ergod. Th. Dynamic. Systems, 23 (2003), 403. Google Scholar [21] W. Cowieson and L.-S. Young, SRB measures as zero-noise limits,, Ergod. Th. Dynamic. Systems, 25 (2005), 1115. Google Scholar [22] L. J. Díaz, E. Pujals and R. Ures, Partial hyperbolicity and robust transitivity,, Acta Math., 183 (1999), 1. doi: 10.1007/BF02392945. Google Scholar [23] T. Downarowicz and A. Maass, Smooth interval maps have symbolic extensions,, Inventiones Math., 176 (2009), 617. doi: 10.1007/s00222-008-0172-4. Google Scholar [24] T. Downarowicz and S. Newhouse, Symbolic extensions in smooth dynamical systems,, Inventiones Math., 160 (2005), 453. doi: 10.1007/s00222-004-0413-0. Google Scholar [25] N. Gourmelon, Generation of homoclinic tangencies by $C^1$-perturbations,, Discrete Contin. Dyn. Syst., 26 (2010), 1. doi: 10.3934/dcds.2010.26.1. Google Scholar [26] S. Hayashi, Connecting invariant manifolds and the solution of the $C^1$ stability and $\omega$-stability conjectures for flows,, Annals of Math., 145 (1997), 81. doi: 10.2307/2951824. Google Scholar [27] A. Katok and B. Hasselblatt, "Introduction to the Modern Theory of Dynamical Systems,", Cambridge University Press, (1995). Google Scholar [28] G. Keller, "Equilibrium States in Ergodic Theory,", London Mathematical Society Student Texts, (1998). Google Scholar [29] R. Mañé, Contributions to the stability conjecture,, Topology, 17 (1978), 383. doi: 10.1016/0040-9383(78)90005-8. Google Scholar [30] M. Misiurewicz, Diffeomorphim without any measure of maximal entropy,, Bull. Acad. Pol. Sci., 21 (1973), 903. Google Scholar [31] S. Newhouse, Hyperbolic limit sets,, Trans. Amer. Math. Soc., 167 (1972), 125. doi: 10.1090/S0002-9947-1972-0295388-6. Google Scholar [32] S. Newhouse, Continuity properties of entropy,, Annals of Math., 129 (1989), 215. doi: 10.2307/1971492. Google Scholar [33] M. J. Pacifico and J. Vieitez, Robust entropy-expansiveness implies generic domination,, preprint, (). Google Scholar [34] M. J. Pacifico and J. Vieitez, Entropy-expansiveness and domination for surface diffeomorphisms,, Rev. Mat. Complut., 21 (2008), 293. Google Scholar [35] E. Pujals and M. Sambarino, Homoclinic tangencies and hyperbolicity for surface diffeomorphisms,, Annals of Math., 151 (2000), 961. doi: 10.2307/121127. Google Scholar [36] R. Saghin and Z. Xia, The entropy conjecture for partially hyperbolic diffeomorphisms with 1-D center,, Topology Appl., 157 (2010), 29. doi: 10.1016/j.topol.2009.04.053. Google Scholar [37] M. Shub, Dynamical systems, filtrations and entropy,, Bull. Amer. Math. Soc., 80 (1974), 27. doi: 10.1090/S0002-9904-1974-13344-6. Google Scholar [38] M. Shub, "Global Stability of Dynamical Systems,", Springer-Verlag, (1987). Google Scholar [39] K. Sigmund, Generic properties of invariant measures for Axiom-A-diffeomorphisms,, Inventiones Math., 11 (1970), 99. doi: 10.1007/BF01404606. Google Scholar [40] C. P. Simon, Instability in Diff$(T^3)$ and the nongenericity of rational zeta function,, Trans. Amer. Math. Soc., 174 (1972), 217. Google Scholar [41] P. Walters, "An Introduction to Ergodic Theory,", volume \textbf{79} of Graduate Texts in Mathematics, 79 (1982). Google Scholar [1] Dante Carrasco-Olivera, Bernardo San Martín. Robust attractors without dominated splitting on manifolds with boundary. Discrete & Continuous Dynamical Systems - A, 2014, 34 (11) : 4555-4563. doi: 10.3934/dcds.2014.34.4555 [2] Ian Melbourne, V. Niţicâ, Andrei Török. A note about stable transitivity of noncompact extensions of hyperbolic systems. Discrete & Continuous Dynamical Systems - A, 2006, 14 (2) : 355-363. doi: 10.3934/dcds.2006.14.355 [3] Viorel Niţică. Stable transitivity for extensions of hyperbolic systems by semidirect products of compact and nilpotent Lie groups. Discrete & Continuous Dynamical Systems - A, 2011, 29 (3) : 1197-1204. doi: 10.3934/dcds.2011.29.1197 [4] Sergio Muñoz. Robust transitivity of maps of the real line. Discrete & Continuous Dynamical Systems - A, 2015, 35 (3) : 1163-1177. doi: 10.3934/dcds.2015.35.1163 [5] Eleonora Catsigeras, Heber Enrich. SRB measures of certain almost hyperbolic diffeomorphisms with a tangency. Discrete & Continuous Dynamical Systems - A, 2001, 7 (1) : 177-202. doi: 10.3934/dcds.2001.7.177 [6] Danijela Damjanović. Central extensions of simple Lie groups and rigidity of some abelian partially hyperbolic algebraic actions. Journal of Modern Dynamics, 2007, 1 (4) : 665-688. doi: 10.3934/jmd.2007.1.665 [7] David Burguet, Todd Fisher. Symbolic extensionsfor partially hyperbolic dynamical systems with 2-dimensional center bundle. Discrete & Continuous Dynamical Systems - A, 2013, 33 (6) : 2253-2270. doi: 10.3934/dcds.2013.33.2253 [8] Eleonora Catsigeras, Xueting Tian. Dominated splitting, partial hyperbolicity and positive entropy. Discrete & Continuous Dynamical Systems - A, 2016, 36 (9) : 4739-4759. doi: 10.3934/dcds.2016006 [9] Wenxiang Sun, Xueting Tian. Dominated splitting and Pesin's entropy formula. Discrete & Continuous Dynamical Systems - A, 2012, 32 (4) : 1421-1434. doi: 10.3934/dcds.2012.32.1421 [10] Xinsheng Wang, Lin Wang, Yujun Zhu. Formula of entropy along unstable foliations for $C^1$ diffeomorphisms with dominated splitting. Discrete & Continuous Dynamical Systems - A, 2018, 38 (4) : 2125-2140. doi: 10.3934/dcds.2018087 [11] Pedro Duarte, Silvius Klein. Topological obstructions to dominated splitting for ergodic translations on the higher dimensional torus. Discrete & Continuous Dynamical Systems - A, 2018, 38 (11) : 5379-5387. doi: 10.3934/dcds.2018237 [12] Shaobo Gan, Kazuhiro Sakai, Lan Wen. $C^1$ -stably weakly shadowing homoclinic classes admit dominated splittings. Discrete & Continuous Dynamical Systems - A, 2010, 27 (1) : 205-216. doi: 10.3934/dcds.2010.27.205 [13] Pengfei Zhang. Partially hyperbolic sets with positive measure and $ACIP$ for partially hyperbolic systems. Discrete & Continuous Dynamical Systems - A, 2012, 32 (4) : 1435-1447. doi: 10.3934/dcds.2012.32.1435 [14] Rafael Potrie. Partially hyperbolic diffeomorphisms with a trapping property. Discrete & Continuous Dynamical Systems - A, 2015, 35 (10) : 5037-5054. doi: 10.3934/dcds.2015.35.5037 [15] Zhenqi Jenny Wang. Local rigidity of partially hyperbolic actions. Journal of Modern Dynamics, 2010, 4 (2) : 271-327. doi: 10.3934/jmd.2010.4.271 [16] Zhenqi Jenny Wang. Local rigidity of partially hyperbolic actions. Electronic Research Announcements, 2010, 17: 68-79. doi: 10.3934/era.2010.17.68 [17] Jingyu Li, Chuangchuang Liang. Viscosity dominated limit of global solutions to a hyperbolic equation in MEMS. Discrete & Continuous Dynamical Systems - A, 2016, 36 (2) : 833-849. doi: 10.3934/dcds.2016.36.833 [18] Wenxiang Sun, Yun Yang. Hyperbolic periodic points for chain hyperbolic homoclinic classes. Discrete & Continuous Dynamical Systems - A, 2016, 36 (7) : 3911-3925. doi: 10.3934/dcds.2016.36.3911 [19] Michael Field, Ian Melbourne, Matthew Nicol, Andrei Török. Statistical properties of compact group extensions of hyperbolic flows and their time one maps. Discrete & Continuous Dynamical Systems - A, 2005, 12 (1) : 79-96. doi: 10.3934/dcds.2005.12.79 [20] Luiz Felipe Nobili França. Partially hyperbolic sets with a dynamically minimal lamination. Discrete & Continuous Dynamical Systems - A, 2018, 38 (6) : 2717-2729. doi: 10.3934/dcds.2018114 2018 Impact Factor: 1.143	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.7494592070579529, "perplexity": 5383.858119710971}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2019-43/segments/1570986672548.33/warc/CC-MAIN-20191017022259-20191017045759-00498.warc.gz"}
https://dsp.stackexchange.com/questions/41171/whitened-matched-filter	# Whitened Matched Filter I am seeking for an advice on whitened matched filtering technique. I have looked into the literature and I do understand its the purpose and how to select the filter in order to achieve the desired response. However, what I don't understand is that if the signal is matched to the channel filtered signal plus noise using the matched filter, and then if we apply the whitening filter, we get the inverse again which should actually be the channel filtered signal and noise. So in essence we end up where we started from. I am sure I am missing something but any comments will be highly appreciated. Thanks Milos In the ideal AWGN channel we have the received signal is $r(t)=s(t)+n(t)$, where $s(t)$ is the transmitted signal and $n(t)$ is white Gaussian noise. In this case, the transmitted symbols can be estimated using a matched filter whose output is sampled at the symbol rate. Note that in general the noise at the output of the matched filter is correlated, and no longer white; however, at the sampling times the noise is uncorrelated. In the ISI channel we have $r(t)=c(t) \ast s(t) + n(t)$, where $c(t)$ is the channel response. We can think of this system as an AWGN channel where the transmitted signal is $g(t)=c(t) \ast s(t)$, and then we can use $g^*(-t)$ as a matched filter. However, in this case we no longer have uncorrelated noise samples. Correlated noise is more harmful, and thus this situation is undesirable. Note that the whitening filter does not revert what the matched filter did. The reason is that the purpose of the filter is not to turn the noise back into white noise; its purpose is to decorrelate the noise at the sampling instants. If the transmitted symbols are $a_k$ for integer $k$, and the (discrete) whitening filter has taps $f_n,\,n=0,1,\ldots,L$, then the output of the whitening filter is $$v_k=\sum_{n=0}^L f_n a_{k-n} + w_k,$$ where the noise samples $w_k$ are uncorrelated. The symbols $a_k$ can then be optimally obtained from $v_k$ by the Viterbi algorithm, or (perhaps sub-optimally, but easily) from another type equalizer (ZF, LS, etc.). • @MilosMilosavljevic Indeed I misunderstood your question. I have edited my answer; hopefully it's more useful now. The key point is that the whitening filter does not turn the noise back into white noise; it only decorrelates the noise samples at times $kT$ where $T$ is the symbol rate.	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 1, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.8881288170814514, "perplexity": 234.457502177712}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2021-43/segments/1634323587719.64/warc/CC-MAIN-20211025154225-20211025184225-00169.warc.gz"}
https://www.mysciencework.com/publication/show/observations-mimosis0-first-dedicated-cps-prototype-cbm-mvd-74a9106b	# Observations on MIMOSIS-0, the first dedicated CPS prototype for the CBM MVD Authors Type Preprint Publication Date Sep 12, 2019 Submission Date Sep 12, 2019 Identifiers DOI: 10.1016/j.nima.2019.162653 Source arXiv The Micro Vertex Detector (MVD) of the future Compressed Baryonic Matter (CBM) experiment at FAIR will have to provide a spatial precision of $\sim 5~\rm \mu m$ in combination with a material budget of 0.3\% - 0.5\% X$_0$ for a full detector station. Simultaneously, it will have to handle the rate and radiation load of operating the fixed target experiment at an average collision rate of 100 kHz (4 - 10 AGeV Au+Au collisions) or 10 MHz (up to 28 GeV p-A collisions). The harsh requirements call for a dedicated detector technology, which is the next generation CMOS Monolithic Active Pixel Sensor MIMOSIS. We report about the requirements for the sensor, introduce the design approach being followed to cope with it and show first test results from a first sensor prototype called MIMOSIS-0 .	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.7680036425590515, "perplexity": 4313.549619605767}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2020-40/segments/1600400198287.23/warc/CC-MAIN-20200920161009-20200920191009-00009.warc.gz"}
https://lavelle.chem.ucla.edu/forum/viewtopic.php?f=148&t=44395&p=154054	## 7B.9 $\frac{d[R]}{dt}=-k[R]; \ln [R]=-kt + \ln [R]_{0}; t_{\frac{1}{2}}=\frac{0.693}{k}$ Maggie Doan 1I Posts: 61 Joined: Fri Sep 28, 2018 12:24 am ### 7B.9 For the first order reaction A $\rightarrow$ 3B + C, When [A]0 = .015 mol/l, the concentration of B increases to .018 mol/ L in 3.0 min. a) What is the rate of constant for the reaction expressed as the rate of loss of A? I got the answer 1.7 minutes but the answer is .17 minutes. I was wondering how they got the answer. Nicklas_Wright_1A Posts: 60 Joined: Fri Sep 28, 2018 12:23 am ### Re: 7B.9 If you use the equation you should get the right answer. I recommend rechecking your math as you probably put a decimal point in the wrong place. Destiny Diaz 4D Posts: 51 Joined: Fri Sep 28, 2018 12:28 am ### Re: 7B.9 the mistake is more likely in your unit conversions, I would just double check those.	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 2, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.8285757899284363, "perplexity": 3028.5381998008393}, "config": {"markdown_headings": true, "markdown_code": false, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 20, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2020-34/segments/1596439737883.59/warc/CC-MAIN-20200808135620-20200808165620-00125.warc.gz"}
https://cmua.uniandes.edu.co/index.php/en/microscopy/stm	Scanning Tunneling Microscope The Scanning Tunneling Microscope was the first born in the SPM family. When two electrodes are brought very close together (~nm) and they have a potential difference Vb, there is a fair probability that some electrons will tunnel across the electrodes gap. The STM uses the tunneling current exiting between these electrodes as the interaction that can render the surface topographies of a particular specimen. When a constant current and a control system are put in place, the probe raster the sample and describe it's topography as illustrated in the figure below. Operation principle of the STM: A tip scans the surfaces at a constant current It. A change in the surface topography produces a proportional change in the scanning height called lateral resolution (\delta). The scientific background section describes thoroughly the behavior and physics behind the STM Go to top	{"extraction_info": {"found_math": false, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.8360071778297424, "perplexity": 1278.4950307867184}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 20, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2021-17/segments/1618039594808.94/warc/CC-MAIN-20210423131042-20210423161042-00410.warc.gz"}
https://astronomy.stackexchange.com/questions/26017/good-source-for-the-relationship-between-absolute-magnitude-diameter-and-albed?noredirect=1	# Good source for the relationship between absolute magnitude, diameter, and albedo? In this answer I have rearranged an equation from somewhere, and now I can not relocate the source. My re-aranged form is: $$M_{Abs} = 5 \left(\log_{10}(1329) -\frac{1}{2}\log_{10}(\text{albedo}) -\log_{10}(D_{km})\right)$$ This is the relationship between the absolute magnitude of an object and its diameter and albedo, assuming it is spherical. Question: What is a good source for any form of this equation to which I can link in my answer? • This shouldn't be hard to derive. Twice as large = 4 times as bright, double the albedo = double the brightness, convert both to changes in magnitude, and apply to original absolute magnitude. – barrycarter Apr 23 '18 at 21:53 • Found while reading for another Q: Wikipedia: Absolute magnitude: Planets – Mike G Jun 25 '19 at 4:57 • @MikeG Yep, thanks! While I don't see the exact expression there verbatim but I see enough pieces of it in similar form that it is certainly there in spirit. Thanks! – uhoh Jun 25 '19 at 5:03 The JPL CNEOS asteroid size estimator and various asteroid albedo papers cite Harris and Harris 1997. That paper is behind a paywall, but Stuart and Binzel 2004 attribute this formula to it: $$H = C - 5 \log_{10} D - 2.5 \log_{10} p_V$$ where $H$ is absolute magnitude, $p_V$ is albedo, and $C$ = 15.618. • That's numerically equivalent and so it will do, thank you! I'm still going to try to find the source that has the exact expression log${}_{10}$(1329) in my own quixocity because it bothers me that I've lost a reference (I suspect due to a variant of this). – uhoh Apr 23 '18 at 22:47	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 1, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.7213257551193237, "perplexity": 968.8978613032734}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2020-05/segments/1579250591431.4/warc/CC-MAIN-20200117234621-20200118022621-00403.warc.gz"}
http://translate.vernier.com/experiments/chem-a/35/rate_determination_and_activation_energy/	Vernier Software & Technology # Rate Determination and Activation Energy ## Introduction An important part of the kinetic analysis of a chemical reaction is to determine the activation energy, Ea. Activation energy can be defined as the energy necessary to initiate an otherwise spontaneous chemical reaction so that it will continue to react without the need for additional energy. An example of activation energy is the combustion of paper. The reaction of cellulose and oxygen is spontaneous, but you need to initiate the combustion by adding activation energy from a lit match. In this experiment you will investigate the reaction of crystal violet with sodium hydroxide. Crystal violet, in aqueous solution, is often used as an indicator in biochemical testing. The reaction of this organic molecule with sodium hydroxide can be simplified by abbreviating the chemical formula for crystal violet as CV. As the reaction proceeds, the violet-colored CV+ reactant will slowly change to a colorless product, following the typical behavior of an indicator. You will measure the color change with a Vernier Colorimeter or a Vernier Spectrometer. You can assume that absorbance is directly proportional to the concentration of crystal violet according to Beer’s law. The molar concentration of the sodium hydroxide, NaOH, solution will be much greater than the concentration of crystal violet. This ensures that the reaction, which is first order with respect to crystal violet, will be first order overall (with respect to all reactants) throughout the experiment. You will monitor the reaction at different temperatures, while keeping the initial concentrations of the reactants the same for each trial. In this way, you will observe and measure the effect of temperature change on the rate of the reaction. From this information you will be able to calculate the activation energy, Ea, or the reaction. ## Objectives In this experiment, you will • React solutions of crystal violet and sodium hydroxide at four different temperatures. • Measure and record the effect of temperature on the reaction rate and rate constant. • Calculate the activation energy, Ea, for the reaction. ## Sensors and Equipment This experiment features the following Vernier sensors and equipment. ### Option 4 You may also need an interface and software for data collection. What do I need for data collection?	{"extraction_info": {"found_math": false, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.8434632420539856, "perplexity": 1119.9066527947214}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2020-29/segments/1593655886121.45/warc/CC-MAIN-20200704104352-20200704134352-00367.warc.gz"}
https://codereview.stackexchange.com/questions/114725/my-first-haskell-dice-rolling	# My first Haskell: dice rolling Yesterday morning I decided to stop procrastinating and start learning me some Haskell. So far I've made this, which is a simple cli 'dice rolling' utility that can be used like: $./dice 3d20 You rolled: 17 The code looks like this: import Data.List.Split import Data.Char import Control.Monad import Control.Monad.Random import System.Environment type Dice = (Int, Int) diceCode :: String -> Dice diceCode die = (parts!!0, parts!!1) where parts = [read x :: Int \| x <- take 2 (splitOn "D" (map toUpper die))] rollDie :: (RandomGen g) => Int -> Rand g Int rollDie sides = getRandomR (1, sides) rollDice :: (RandomGen g) => Dice -> Rand g Int rollDice dice = liftM sum (sequence(replicate rolls (rollDie sides))) where rolls = fst dice sides = snd dice main = do args <- getArgs roll <- evalRandIO (rollDice (diceCode (args!!0))) putStrLn ("You rolled: " ++ show roll) I was able to get the diceCode 'parsing' function by myself without too much trouble. The rollDie function is almost straight from an example in the Control.Monad.Random docs, which helped a lot. I struggled for quite a while to find a recipe for summing the rolls in rollDice... it seemed to me I ought to use msum but I couldn't find a way to make it work. liftM sum seems to do exactly what I wanted though. I also found the use of tuples quite cumbersome. In Python I could just do: rolls, sides = dice but I seem to have to use the horribly-named fst and snd functions to access the members in Haskell (?) I guess the next part of my adventure is to try and incorporate this into a larger program, eg a simple game. It seems like the monadically-wrapped random int values are going to force the rest of the code to be 'monad-aware' (i.e. lots of use of liftM) and I wonder if there is a way to avoid this? ## 1 Answer The list comprehension you use in diceCode is a bit overkill: after all, you only want to split the list of characters into two. You can use break instead. Here I have to use fmap tail to act on the second list because break retains the value it breaks the list at (the 'd' character here). This would be a good place to handle the sort of errors that would arise if there is no 'd' in the string. diceCode :: String -> Dice diceCode die = (read rolls, read sides) where (rolls, sides) = fmap tail$ break ('D' ==) $fmap toUpper die Your rollDice is a bit complex. Here is how I would rewrite it: • (rolls, sides) on the left hand side exposes the two components of the tuple • [1..rolls] generates a list of length rolls • mapM (const$ rollDie sides) replaces all the numbers in that list with an invocation of rollDie sides and performs the same job as sequence thus returning an Random g [Int] • sum <$> (or fmap sum$) goes under the Random g part and sums the elements in the [Int] value. Putting all this together we get: rollDice :: (RandomGen g) => Dice -> Rand g Int rollDice (rolls, sides) = sum <$> mapM (const$ rollDie sides) [1..rolls] The rest of the code is quite idiomatic. One thing I was a bit concerned about is the fact that a Dice is represented as a pair of Ints: to understand which is which, you need to read the code manipulating them and if you make a mistake the compiler won't warn you: they have the same type! It's quite annoying. One thing you could do is use a record type instead in order to name the two fields: data Dice' = Dice' { rolls :: Int , sides :: Int } This way you can access them by their names, build the Dice' using the named syntax, etc. • thanks, I will digest this a bit. first question - I'm just googling what is fmap and why not map... it seems like fmap is more 'general' and I should always just use it instead of map? stackoverflow.com/a/6824333/202168 Dec 22 '15 at 11:24 • I don't understand whyfmap tail only strips the first char from the second half and not from the first half too. I tried in ghci fmap tail ([1,2,3],[4,1,2,3,4]) returns ([1,2,3],[1,2,3,4]) ...I don't understand why this result Dec 22 '15 at 11:35 • following your hint in 4th bullet point I wrote this line rollDice (rolls, sides) = fmap sum $sequence$ replicate rolls (rollDie sides) which seems to work fine... however I don't understand why fmap sum is appropriate here (or even works). liftM sum made sense to me but now I am confused. Dec 22 '15 at 12:01 • on the other hand, I just found this works rollDice (rolls, sides) = sum <$> (sequence$ replicate rolls (rollDie sides)) ...this makes sense to me if I understand <$> as a sort of 'monadic $' or ...an infix liftM? I had to add parentheses around the right-hand-side to get it to compile Dec 22 '15 at 12:06 • fmap and liftM are the same thing. As you noticed,(<$>) is a nice infix operator for it. It does not have the same precedence as $ hence the fact that you needed to add parentheses to get haskell to parse the expression the right way. Dec 22 '15 at 12:19	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 0, "mathjax_asciimath": 1, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.6199127435684204, "perplexity": 2080.143497118072}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2022-05/segments/1642320305288.57/warc/CC-MAIN-20220127193303-20220127223303-00585.warc.gz"}
http://en.wikipedia.org/wiki/Jacques_Philippe_Marie_Binet	# Jacques Philippe Marie Binet Jacques Binet Jacques Philippe Marie Binet (February 2, 1786 – May 12, 1856) was a French mathematician, physicist and astronomer born in Rennes; he died in Paris, France, in 1856. He made significant contributions to number theory, and the mathematical foundations of matrix algebra which would later lead to important contributions by Cayley and others. In his memoir on the theory of the conjugate axis and of the moment of inertia of bodies he enumerated the principle now known as Binet's theorem. He is also recognized as the first to describe the rule for multiplying matrices in 1812, and Binet's formula expressing Fibonacci numbers in closed form is named in his honour, although the same result was known to Abraham de Moivre a century earlier. Binet graduated from l'École Polytechnique in 1806, and returned as a teacher in 1807. He advanced in position until 1816 when he became an inspector of studies at l'École. He held this post until November 13, 1830, when he was dismissed by the recently crowned King Louis-Philippe of France, probably because of Binet's strong support of the previous King, Charles X. In 1823 Binet succeeded Delambre in the chair of astronomy at the Collège de France.[1] He was made a Chevalier in the Légion d'Honneur in 1821, and was elected to the Académie des Sciences in 1843. ## Binet's Fibonacci number formula This formula provides the $n^\text{th}$ term in the Fibonacci sequence, and is defined using the recurrence formula: • $u_n = u_{n-1} + u_{n-2},\text{ for }n > 1, \,$ where • $u_0 = 0 \,$ • $u_1 = 1 \,$ $u_n = \frac{(1 + \sqrt{5})^n - (1 - \sqrt{5})^n}{2^n \sqrt{5}}$ [2]	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 5, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.7840405702590942, "perplexity": 1206.4067177328707}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2014-23/segments/1404776439565.18/warc/CC-MAIN-20140707234039-00047-ip-10-180-212-248.ec2.internal.warc.gz"}
https://www.slim.eos.ubc.ca/content/stable-sparse-expansions-non-convex-optimization	# Stable sparse expansions via non-convex optimization Title Stable sparse expansions via non-convex optimization Publication Type Conference Year of Publication 2008 Authors Ozgur Yilmaz Conference Name SINBAD 2008 Keywords Presentation, SINBAD, SLIM Abstract We present theoretical results pertaining to the ability of p-(quasi)norm minimization to recover sparse and compressible signals from incomplete and noisy measurements. In particular, we extend the results of Candes, Romberg and Tao for 1-norm to the p $łl$ 1 case. Our results indicate that depending on the restricted isometry constants and the noise level, p-norm minimization with certain values of p $łl$ 1 provides better theoretical guarantees in terms of stability and robustness compared to 1-norm minimization. This is especially true when the restricted isometry constants are relatively large, or equivalently, when the data is significantly undersampled. URL https://www.slim.eos.ubc.ca/Publications/Private/Conferences/SINBAD/2008/yilmaz2008SINBADsse/yilmaz2008SINBADsse.pdf Citation Key yilmaz2008SINBADsse	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.8005951046943665, "perplexity": 1388.4940310568018}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2018-43/segments/1539583511314.51/warc/CC-MAIN-20181017220358-20181018001858-00341.warc.gz"}
http://jas21.com/athenaeum/athenaeum241.htm	# ӔN̉K搶- Ɍ̓Ǐ > R > ɌgV̓Ǐ ## @ @ ӔN̉K搶 @ @ @ @ @ ИvzƒˎR{ ɌFȉ́AKŕ25N 727 (y) ɍs񍐃WłB @ @ @ @ J V (Ȃ ) ㋳{棋^{m̉L 3e̒A @ @ @ @ wKFҁE{҂̐UƎvzx ({oŁA2012.1.10) @ @ @ @ ẅ脟K]`x ({oŁA2013.1.20) @ @ @ @ wK]`ꍂfwIҁx @ @ @ @ @ @ (ё{kޱA2013.2.20) @ @ @ @ ɌĂuИvzƒˎR{v̂̕łB @ @ @ @ 玑ɂȂ₤ɁAڂ݂܂i񍐌Ɏ኱₵܂jB @ @ @ @ K搶̈椎҂͑Sɍ̂ŁA̕X椂߂₤ɂƍlցA @ @ @ @ ɋL^邱Ƃɂ܂B hDИvz (Ўv) dK搶 (1901^34.11.6\|1988^a63.6.12)F iPjL^ɟk銈F @ @ iȉA݁x@萎w݂x^ЁwИvzxj C) Ўv̋NFސẺ͍ĎY搶Ղ @ (N{̘)FYoung Japan @ @ @ @ @ 1840Nɉpێ}̎肪gDNp} Young England Ɉޖ @ @ @ @ @ ՗O ϯ¨ Young Italia gDB @ 1939^a14.1.25 ͍ĎYA隠{xE\| @ @ @ @ ͍̍剺BuT 1 ͍@Ř @ @ @ @ ` (₪) āA񍐌ɋc_錤ᢓW @ 1941^a16. 2. 5@ vް Māw{DSZ_x(_) s @ 1944^a19. 1.23@ ͍ᢓWF @ @ @ @ @ @ @ @ @ @ @ ޲ ؑN^ؽ y^챼ޱ 萉ÕF @ @ @ @ @ @ @ @ 2.15@ ͍ĎYA}B͍AR @ @ @ @ @ @ @ @ @ @ @ u15vWtÂ ) ЎvdK搶FJuEĂ̐瑁hE_椏E椏 @ 1946^a21.11. 1@ yEΏǕE萉ÕF 20n`J @ @ @ @ @ @ @ @ @ @ @ 7Aǒ萉ÕF@ dK搶c @ @ @ @ @ @ @ @ @ @ @ (͌E񍐝^c^F͍Âə҉邾) @ 1947^a22. 4.@ @ ܍ڂ̍j̍F҂ 7 (RcY^tY^ؑN^ @ @ @ @ @ @ @ @ @ @ @ y@ ^ΏǕ^萁@ ÕF^ؐ) @ @ @ @ @ @ @ @ @ @ @ li̐^R^И`^吭i^Eaێ @ 1948^a23. 4.@ @ dK 46΁A @ @ @ @ @ @ @ @ @ @ @ N̖MČ؈ُ҂A⛔Â̐gƂȂB @ @ @ @ @ @ @ @ 9.10@ wИvzx(B5 4) njᢍs @ @ @ @ @ @ @ @ @ @ @ uFvWAɌgV @ 1949^a24. 2.25@ wx6jdKu椏Gvf (M 2 3) @ @ @ @ @ @ @ @ @ @ @ (ށEݼwДbxVЁ^{wŲ݂ᢌxnЂ 2e) @ @ @ @ @ @ @ @ 5. 3@ 萐xݗ (xc Иƛ{Z) ް 30l @ @ @ @ @ @ @ @ 7.@ @ dK 47΁A_ˑ{zC @ @ @ @ @ @ @ @ @ @ @ { {EИȋ_u` @ @ @ @ @ @ @ 10.16@ 萐xuFdKul`v^u 1 F^ @ @ @ @ @ @ @ 11.15@ ЎvAՎ`FrYEc𗝎ɒǉ @ 1950^a25. 1.@ @ wИvzx(B5) ^ (8Ł`14) @ @ @ @ @ @ @ @ 3.28@ V_ˑ{SZ{̍iᢕ\FɌgVAi (sHdȑ) @ @ @ @ @ @ @ @ @ @ @ ̓AdKwƑ̖x椗AhB @ @ @ @ @ @ @ @ 4. 5@ ɌgVAdK搶K˂ďZg{ɂłqR̂ł߂܂炸 @ @ @ @ @ @ @ @ @ @ @ 18-19歲ʂ̊ ظ ځB2疾܂ŗs̗RB @ @ @ @ @ @ @ @ @ @ @ c̏ЉƎ̖hnȂʒmЂB @ @ @ @ @ @ @ @ 4.14@ ɌgVAdK搶ɏʁFZg{ (_ˑ{{) 2Ǩ @ @ @ @ @ @ @ @ @ @ @ ȗōBؑN̋󂫎ԂƂ̒B5.7 () ɌB @ @ @ @ @ @ @ @ 5. 7@ 萐x 1NLOu ( 4Ku) F13:00 JÁ^O 500 @ @ @ @ @ @ @ @ @ @ @ @ @ @ dKuؽ `v @ @ @ yJuzF ɌgV̗vi2-5^5j, 11ŁjFȉdK搶̕ @ @ @ @ @ @ @ @ @ @ @ p`͍Ȃٌڂׂ݂JlB̐lX͐l̖ړI @ @ @ @ @ @ @ @ @ @ @ KƍlւĂ̂łBނ͌ǂ͗z`֍s˂΂ȂȂ̂ @ @ @ @ @ @ @ @ @ @ @ z`屢ɉ߂B`͕Ղœ퐶ɗnłB @ @ @ @ @ @ @ @ @ @ @ ̑命ɂ̐lXɂƂĂ͌`痝z`ɍŝőPłB @ @ @ @ @ @ @ @ @ @ @ `͗z`ւ̒ʘHƂĉivIӋ`B`̐X @ @ @ @ @ @ @ @ @ @ @ 󂯂ĂȂXɂ́A`̂₤ȓOꂵ`El`𕁋y @ @ @ @ @ @ @ @ @ @ @ Oꂹ߂邱Ƃ͎ɕKvłB @ @ @ @ @ @ @ @ @ @ @ @ @ @ ؐua̞И`ᢓWsϓv @ @ @ @ @ @ @ @ @ @ @ @ @ @ ؑNuƂɂāv @ @ @ @ @ @ ci21-7^7Ǔj,26)F̍uŖؑ́A @ @ @ @ @ @ @ @ @ @ @ uvz猾Ăe猾ĂA{̼ޮ݁EāEفAɍ݂v @ @ @ @ @ @ @ @ @ @ @ dK]ˁB @ 1951^a26. 7.@ @ dK 49΁A_ˑ{{ɏAC @ 1953^a28. 6.15@ 萐x ({ 3K)FKuИvƏ@v(5-6/7 f) @ @ @ @ @ @ @ 9.-12. 萐ŰفFutc^÷ā͍ĎYwЉ􌴗x @ @ @ @ @ @ @ @ @ @ @ 9.14`12.14 12ďI @ @ @ @ @ @ @ 10.31@ 萐xɁuyjvᢑF萐ݏŽ (͍{h{c۔n{h) @ @ @ @ @ @ @ @ @ @ @ ndK搶҉^lyjߌɌJ @ @ @ @ @ @ @ 11.28@ 萐xuyjvᢑF萐ݏŽ (͍{h{c۔n{h) @ 1954^a29. 2.@ @ _ˑ{ dKEkFvAИvz̗ɑIC @ @ @ @ @ @ @ 4.-10. 萐ŰفFutc @ @ @ @ @ @ @ @ @ @ @ ÷āDurbin,The Politics of Democratic Socialism,1940. @ @ @ @ @ @ @ @ @ @ @ ȏ͘B (6-10,27)F萐Ű 4Ș޳ާ݁w\|ɑւāx @ @ @ @ @ @ @ @ @ @ @ wV炵ИxAcOwИ`ƎRx̍]sĘ҂܂A @ @ @ @ @ @ @ @ @ @ @ 9.11 Durbin ÷ n߂܂B @ @ @ @ @ @ @ @ 4.24@ ͍ĎY\LO萐u ()F @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ ؑ@ Nu{Ɛv @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ kFvuVИ`̗v @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ dK@ u͍Ǝ߂̗z`vi6-6fځj @ @ @ @ @ @ @ @ 8.21/22/23 V_EREFaui6-8/9jF @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ dK@ uИvƏ@v @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ kRIvuSZvV̕v @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ c@ u`̉^v @ @ @ @ @ @ @ 10.@ @ ɌgV (_ˑ{{@ݛ{) F ɏi @ 1955^a30.5.9-7.11 (10A) Tj 18:00-21:00 Иț{ÓTu (萐) @ @ @ @ @ @ @ @ @ @ @ ÷ 5ew̪ޱݎИ`_Wx(c)^݁wИ̊TOx @ @ @ @ @ @ @ @ @ @ @ (ؐ) ^ϱفwSZ{x(kFv)^ݽށwٗbEqy @ @ @ @ @ @ @ @ @ @ @ ݕ̈ʗ_x(؉av)^Ʋwϲݼ ޾ټāx(䗘) @ @ @ @ @ @ @ @ 7.11@ Иț{ÓTuA𗡂ɏI @ @ @ @ @ @ @ @ 7.5-11. 萐ЁA瑁ōh Durbin 椗B桏oŕo @ @ @ @ @ @ @ @ 7.12@ Иț{ÓTuA ({ 3Fjōk J @ @ @ @ @ @ @ @ @ @ @ ÷āʲwnւ̓x(nЁAJY) @ @ @ @ @ @ @ @ @ @ @ utcE䗘 @ @ @ @ @ @ @ 10.10- O萐ŰٕWF10.10 uTj 18:30-20:30 (10) @ @ @ @ @ @ @ 10.24@ O萐Ű 2ځAuẲ͍ ɕCGvxȋc_WJ @ @ @ @ @ @ @ 11. 7@ _ˑ{x̍hAdK搶Ƃ킩قō (7-12,10)F @ @ @ @ @ @ @ @ @ @ @ _ˑ{xł͘䏕 (SZИ{) 𒆐S ީāEʲ݁wY @ @ @ @ @ @ @ @ @ @ @ `ȨсE`x椏㔂Ă邪A11.6-7 ɌÓTq˂ @ @ @ @ @ @ @ @ @ @ @ ޗǂɗV񂾁BZt瓂񎛂AӂɎvЂȂ20N @ @ @ @ @ @ @ @ @ @ @ x̌JƂӏtЂ̌ÎقK^ɜ܂ꂽBț{ƐE @ @ @ @ @ @ @ @ @ @ @ V̑萌Wĝc܂㔂̘_cɉāAɌ͉vғI @ @ @ @ @ @ @ @ @ @ @ n_҂̗L@IƂӛȈdvA`ؘ͌҂Ƃ @ @ @ @ @ @ @ @ @ @ @ ͖O܂ł_҂sʂĲ޵۷ްI΍𒴂镁ՓIᢌɓw @ @ @ @ @ @ @ @ @ @ @ ׂƂA͐EVɛț{̒ʐƁAɗ_ț{ւ̒ @ @ @ @ @ @ @ @ @ @ @ ̕KvB (7) ͎ᑐق͍̌̉̕ɕ׋ɘ҂ @ @ @ @ @ @ @ @ @ @ @ ꂽdK搶q˂ĂbfЁA搶̏ꂽ\|͂̕ɉ͍ @ @ @ @ @ @ @ @ @ @ @ Â񂾁Bߌ㉜RAVᑐR̒ォ猩Ȃޓޗǖ~n̔V @ @ @ @ @ @ @ @ @ @ @ ğd{Aɔӂ萐Űقɒy҂B(`،Y) @ 1956^a31.5.-12. l萐Ű @ @ @ @ @ @ @ @ @ @ @ @ A׽ (N{) Ѱƴwli`xutdKEc @ @ @ @ @ cf. l萐Űق (9-1/1857.1j,48)FN 5Ɏn @ @ @ @ @ @ @ @ @ @ @ 1210̎И{׽ ŌɏI܂B @ @ @ @ @ @ @ @ @ @ @ @ N{׽ Ѱƴwli`x ĂĂ䂯ȂA @ @ @ @ @ @ @ @ @ @ @ Ѱƴ li` Ƙ҂Ȃ Ƃ߂ @ @ @ @ @ @ @ @ @ @ @ ꕔ (啔?) o܂B ÷ ̑I莸s @ @ @ y瑁h1)z8-6 (6j) 35łɁuĊ (萐)v̕WLf @ @ @ @ @ @ @ @ @ @ ꏊF{͓S瑁瑁A{wR̉Ɓx (piuفv) @ @ @ @ @ @ @ @ @ @ pFʔ 200Ah 1 300 @ @ @ @ @ @ @ @ 7.14-16 瑁h1) ( 5j^ 8-8) ҉ 57 (j 31/ 26) @ @ @ @ @ @ @ @ @ @ @ @ u`u^ꔑҁ^񔑎 ƎRIł (Ζ҂ɍD]) @ @ @ @ @ @ @ @ @ 14 (y) 18:00WAE[H @ @ @ @ @ @ @ @ @ @ @ @ uJ熁vc^uc}̈AvR̉ _lĎYْ @ @ @ @ @ @ @ @ @ @ @ @ հӱ鎩ȏЉ ڸش ( ް) @ @ @ @ @ @ @ @ @ 15 () ߑO@ u`uߑИ̊{Iv䗘 @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ ussɂƍ߂ƎИvēcP @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ uƂւ̓vc @ @ @ @ @ @ @ @ @ @ @ @ @ ߌ@ u`u͍ĎYƑqcSOvdK (8-9f) @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ ^䓚Ec @ @ @ @ @ @ @ @ @ @ @ @ @ Ӂ@ @ x (KĐRcExƖ) ^ڸش @ @ @ @ @ @ @ @ @ 16 () ߑO@ R (wǂRo) @ @ @ @ @ @ @ @ @ @ @ @ @ ߌ@ Ș^\|^U (Еqē񝾁rȂ牺R) @ @ @ yݹāz( 5j,1)Feu`͎ԕsA\|[カ^u`Iœ^ @ @ @ @ @ @ @ @ ٰߓc]ށ^H沂şޑ^ڸش Ƃ肽^ @ @ @ @ @ @ @ @ ҉ғmE搶ƍk^ʓma\XƂꂽ^ @ @ @ @ @ @ @ @ ҉ėǂ etc. @ 1957^a32. _ˎx椏𘬍i9-1,42)F @ @ @ @ @ @ @ @ @ @ @ ÷ādKw@Ɛlxw⛔Ixwb̒ǋx(Ɍ㋳{) @ @ @ @ @ @ @ @ @ @ @ RcBdK oȁB2.12 uTΗj 6-8J @ @ @ @ @ @ @ @ 2.12@ _ˎx椏1) (V)FdK𚡂ގRc (i`،Y) @ @ @ y_ˎxւz(9-3/3j,41)F́A2.12 () 6 8܂ @ @ @ @ @ @ @ @ @ @ @ _ːVٓ萐dͻ޽Ecōs͂ꂽB @ @ @ @ @ @ @ @ @ @ @ oȎҁdKȉ20B÷Ăɓ炸ȏЉƍksA @ @ @ @ @ @ @ @ @ @ @ EƂƐb萌WāAZp҂ƎƂ̔rMSɘ_cꂽB @ @ @ @ @ @ @ @ @ @ @ 񁁐_ˑ{{B @ @ @ @ @ @ @ @ @ @ @ wb̒ǋx́u䂪lV̝̑Jv𒆐Sɕ׋B @ @ @ @ @ @ @ @ @ @ @ ꏊ͑Ɠꏊ (`،Y) @ @ @ @ @ @ @ @ 2.26@ _ˎx椏2) ({)FdKubA҉҂Ƃ̘_c @ @ @ y_椏2)oȋL^z( 12j 2)FdK搶̂ŁAVAɌ @ @ @ @ @ @ @ @ @ @ @ dK搶𒆐SɁwb̒ǋx̉䂪lV̕՗̌b @ @ @ @ @ @ @ @ @ @ @ 搶S鄂ɊlԐ̐MAȈAɂb܂B @ @ @ @ @ @ @ @ @ @ @ ʂĐlԐ͐Mł̂ł炤B @ @ @ @ @ @ @ @ @ @ @ łĂ悢̂ł炤B @ @ @ @ @ @ @ @ @ @ @ e̖̒獂簂Ȃ{IES鄏̎₠B @ @ @ @ @ @ @ @ @ @ @ _c e݂̍Aꐫɂ ӌɊ潑(T) @ @ @ @ @ @ @ @ 2.26@ _ˎx椏2) ({)FdKubAubƙ҉҂Ƃ̘_c @ @ @ @ @ @ @ @ 3.12@ _ˎx椏3) (V)F (ȌuTɊJÁ^dK搶𚡂 2) @ @ @ @ @ @ @ @ 4.22@ 15:00` xJuFdKuИvƏ@v @ @ @ @ @ @ @ @ @ @ @ (xIOu^N椏E񍐘ȂǂJ) @ @ @ @ @ @ @ @ @ @ @ ӁAdKA_ˎx椏ɏo @ @ @ y萐z(9-5/5j,32) F4.22 () ߌ 3 s{@Sԋ @ @ @ @ @ @ @ @ @ @ @ _ˑ{{dK̍uB @ @ @ @ @ @ @ @ @ @ @ ͍N߂犈n߂s{ИvzÂ̛{uŁA @ @ @ @ @ @ @ @ @ @ @ ؐ̈AƎИvz̏Љ̂ƁA @ @ @ @ @ @ @ @ @ @ @ dKuИvƏ@vƑ肵āA @ @ @ @ @ @ @ @ @ @ @ @ƎИvƂ͙_Ȃ̂ł͂ȂƂ @ @ @ @ @ @ @ @ @ @ @ 鈤椎҂̋^ɓւ`ŁA_҂ɂĈł鏊ȂB @ @ @ @ @ @ @ @ @ @ @ ŌɎēcPut̕qׂĕB @ @ @ @ @ @ @ @ @ @ @ ̂ Ȃ ҂͞B҉Җ400 (g) @ @ @ @ @ @ @ @ 7. 8@ _ˎx椏 (OŏI)FO{ŗ[HBdK搶Ɋӂ @ @ @ @ @ @ @ @ @ @ @ `؋L ( 16j2)Fu搶̂ɂ笕f椏̂ƁA @ @ @ @ @ @ @ @ @ @ @ 搶̏uԒˎR[v ˰ yɂȂ ׼قɎX̂ @ @ @ @ @ @ @ @ @ @ @ XɂƂĒR͂łAɂƂĂ͑̂ȂƂł @ @ @ @ @ @ @ @ @ @ @ vӁBlɐ[X\グv @ @ @ @ @ @ @ @ 7. @ @ dK 55΁A_ˑ{{ 4I @ @ @ y瑁h2)z9-5,36Ł^9-6, 26łɁuĊ (萐)v ^WL @ @ @ @ @ @ @ @ @ @ 13H 350^45AủHځ`̉HځvŐ\ @ @ @ @ @ @ @ @ @ @ ҉ 42 ()Fn恁n_ޗǂ̂قADyEEEÉ @ @ @ @ @ @ @ @ @ @ (j28/14)@ @ xEE_ˁEcEE_ˑ @ @ @ @ @ @ @ @ 7.13-16@ ( 17j^9-8)F13-14 ʌ^15-16 { @ @ @ @ @ @ @ @ @ 13 (y) ӁAE[H^cE_lْ A^ȏЉ^k^ @ @ @ @ @ @ @ @ @ 14 () ߑO@ u`u㔁Eli`ƎИ`vdK @ @ @ @ @ @ @ @ @ @ @ @ @ ߌ@ u`uИ`Ɩ`vc @ @ @ @ @ @ @ @ @ @ @ @ @ ^䓚Ec @ @ @ @ @ @ @ @ @ @ @ @ @ Ӂ@ @ ڸش (ް) @ @ @ @ @ @ @ @ @ 15 () ߑO@ u`ulԂ̕ɂāvdK @ @ @ yɌ̍u`Ӂz 1)Ѱƴ 椏ł̘buli̕łʁv^ @ @ @ @ @ @ @ @ @ @ ̎莆u\͂̕s𒴂li̕𛉊ɂ͂ǂ΂悢v @ @ @ @ @ @ @ @ @ āFlԂ͕sɐĂ邪̂ɕւ̗~B @ @ @ @ @ @ @ @ @ @ łȂ΂ȂʂƎvւΎvӂق s𛉊₤ɂȂB @ @ @ @ @ @ @ @ @ @ ݞHAulԂ ǂyŕ ǂyŕsA @ @ @ @ @ @ @ @ @ @ ulԂ ǂyŕłׂ ǂyŕsłׂ @ @ @ @ @ @ @ @ @ @ uʂčl@˂΂Ȃʁv @ @ @ @ @ @ @ @ @ @ 2)Ȃ̉\ɛMF\ƂĂ PɓB @ @ @ @ @ @ @ @ @ @ (qcSOuvwɂāv)B @ @ @ @ @ @ @ @ @ @ {c̈̑ȎИ𗝘_́AɉċȕvƋɁA @ @ @ @ @ @ @ @ @ @ As̐F܂łB@vzɂ ʂ݂̌B @ @ @ @ @ @ @ @ @ @ 3)ꕍ̕skOAꕍfǂȂkO @ @ @ @ @ @ @ @ @ @ ɗ炸[B (Иvz) I]܂A@̕ɂB @ @ @ @ @ @ @ @ @ @ \|@̋ϓł͎И𐶊ɉğޑo҂ȂB @ @ @ @ @ @ @ @ @ @ 4)ulԂ̕vɛF̕sBFĂl͏ȂA @ @ @ @ @ @ @ @ @ @ xɍB啔̐lX͕~sɎĂB @ @ @ @ @ @ @ @ @ @ ߂ułȂ΂ȂʁvƍlւĂƕꂸA @ @ @ @ @ @ @ @ @ @ J날sÎ󂵂悤ƂӐS\ւɂȂƁA𓾂₷B @ @ @ @ @ @ @ @ @ @ @ @ @ ߌ@ u`u{{ɂāF ޽ľװ{ɂāv@ @ @ @ @ @ @ @ @ @ @ @ @ @ Ӂ@ @ c𚡂ŋcF{̕␧EOߑ㐫_c̒S @ @ @ @ @ @ @ @ @ 16 () ߑO@ oR^HAU @ yOaj̙҉Lz ( 17jA57.8.15j 2) F(É@4) @ @ @ @ @ @ @ @ @ @ @ @ @ 1)򍞂ł݂ď߂ĒmИvz̑ۂ́A̘r @ @ @ @ @ @ @ @ @ @ @ @ @ MSɎИvzɂČ悤ƂlB̏Wł邱ƂłB @ @ @ @ @ @ @ @ @ @ @ @ @ ΂̏o₤ȔMӂAłďirɐli`҂炵ԓx @ @ @ @ @ @ @ @ @ @ @ @ @ blB΂łB @ @ @ @ @ @ @ @ @ @ @ @ @ 2)҉ėǂ̂́Aheu`E_Ȃǌꂵ̂ς @ @ @ @ @ @ @ @ @ @ @ @ @ łȂAԓIPT[ĎXȐlBƘbւƂłB @ @ @ @ @ @ @ @ @ @ @ @ @ ə҉҂݂Ђɞق߂ ڸش ƂłB @ y@ ]̙҉Lz ( A3)F(x) 瑁܂ŋDԁEdԁE޽ Ƙ㋂ @ @ @ @ @ @ @ @ @ @ @ @ @ 15PBSfj̐ΒiAuR̉Ɓv̌Ɉꂽ @ @ @ @ @ @ @ @ @ @ @ @ @ قȕ\āu҂ėǂv ݂ݎvB @ @ @ @ @ @ @ @ @ @ @ @ @ 猩m͉c搶ƈɌ񂾂Aق̕XƑO @ @ @ @ @ @ @ @ @ @ @ @ @ mĂ₤ȟBȏЉANɂĂ邤 @ @ @ @ @ @ @ @ @ @ @ @ @ N₩ɕяlԌQ͂ɂИvzɑ䂵B @ @ @ @ @ @ @ @ @ @ @ @ @ ͛瑁̎RX̍XցAOȂT̎p̂ @ @ @ @ @ @ @ @ @ @ @ @ @ Ƃӈۂ́A̍ő̝nB @ @ @ @ @ @ @ @ @ @ @ @ @ ړIɌ΂ꂽl萌W̐D栂ւ₤Ȃ́A @ @ @ @ @ @ @ @ @ @ @ @ @ ƖYȂB y܉萐Űفz( 18j 2ʁ^ 9-9,50)F2JnBʲсw̐fЁx ÷ ēcEE @ @ @ @ @ @ @ @ @ @ @ @ @ dK 3uto ̉Au㔂uTjߌ 6:30`8:30 ` @ @ @ @ @ @ @ @ @ @ @ @ @ قōsӁv\|mB y䗘̉zz( 69j 1)FudK搶ɂāv @ @ @ @ @ @ @ @ @ @ @ @ @ Ɉۂ̐[vЏo a30N 33NИvz萐x @ @ @ @ @ @ @ @ @ @ @ @ @ uTɊJĂ萐Ű 搶 ꏏə҉ƂłB @ @ @ @ @ @ @ @ @ @ @ @ @ Ű ͑N (a30N31N) ʲ ́wnւ̓xA @ @ @ @ @ @ @ @ @ @ @ @ @ N (31N32N) ϯާ ́wИ{xA @ @ @ @ @ @ @ @ @ @ @ @ @ ON (32N33N) ʲ ́w̐ffxAꂼ ÷ ƂA @ @ @ @ @ @ @ @ @ @ @ @ @ ut Nڂ c A @ @ @ @ @ @ @ @ @ @ @ @ @ N ON Ƃ ēcPsƐ{utƎłB @ @ @ @ @ @ @ @ @ @ @ @ @ ꏊ N ONڂ `قŁA @ @ @ @ @ @ @ @ @ @ @ @ @ Nڂ VقłB @ @ @ @ @ @ @ @ @ @ @ @ @ dK搶 MSɏoȂAȂǂ Ǜ{ȍuqɂXA @ @ @ @ @ @ @ @ @ @ @ @ @ ܂ႢʘƋɋc_ւꂽ̂łB @ @ @ @ @ @ @ @ @ @ @ @ @ ̌pɂ́AȂ̑哹߂Ď~܂ȂA @ @ @ @ @ @ @ @ @ @ @ @ @ ǂȑfpȈӌłhӂȂĎA @ @ @ @ @ @ @ @ @ @ @ @ @ Rȋ҂̖ʉeݏoĂB @ @ @ @ @ @ @ @ @ @ @ @ @ drAɐl̎ႢlBւĐ搶ƌꏏ @ @ @ @ @ @ @ @ @ @ @ @ @ ~c粂̋iXɓA˰ ݂Ȃ @ @ @ @ @ @ @ @ @ @ @ @ @ ȟck̈ꎞ߂ĂƂvЏołB @ ɌF N{ESZ{EИ{ OA䂳͎И{^cB @ @ @ @ @ @ @ 10. 1 () _椏 ĊJFuTΗj ߌ 6`9^÷āFE.H.wVИx @ @ @ @ @ @ @ @ @ @ @ @ @ 椏̂ƁAiX֌J݁Ac_㔂{k_ @ @ @ @ @ @ @ @ @ @ @ @ @ oȎ҂20ÂW߂ĐϗāA[HȂǂŊҌ @ @ @ yÑq (_ˎx) _ˎxz(9-12/12j,44) F @ @ @ @ @ @ @ @ @ @ @ @ @ 1)_˕߂ɘFAN2A_ˎxo҂܂B @ @ @ @ @ @ @ @ @ @ @ @ @ dK搶𚡂椏ƂӖ͂ ȐlXuTΗj̔ @ @ @ @ @ @ @ @ @ @ @ @ @ 椏Aw@Ɛlxw⛔Ix ÷ @ @ @ @ @ @ @ @ @ @ @ @ @ l_E@_ElS鄘_ьЂ܂B @ @ @ @ @ @ @ @ @ @ @ @ @ 㔼dK搶̐_ˑ{{ɊX态XA @ @ @ @ @ @ @ @ @ @ @ @ @ NwlᢌAPTA ̔@ Ɨ₩ꂽ肵܂B @ @ @ @ @ @ @ @ @ @ @ @ @ 椏搶z̐ԒˎRi 낼 ҉ ĂȂA @ @ @ @ @ @ @ @ @ @ @ @ @ ں޺ݻ A ق @ @ @ @ @ @ @ @ @ @ @ @ @ 悢椏 7܂B @ @ @ @ @ @ @ @ @ @ @ @ @ 2) 7 8 9ɘiĐ_ˑ{xƍLu̎w @ @ @ @ @ @ @ @ @ @ @ @ @ ݹٽ ́wzț{ցx 椂݁AɊ潑 Ɍ_͂ @ @ @ @ @ @ @ @ @ @ @ @ @ c_܂B_{Ԍ̛{ƁASŕ׋Ă @ @ @ @ @ @ @ @ @ @ @ @ @ wƂ̑֕̈̕ЂmA{̑؂Ɋv܂B @ @ @ @ @ @ @ @ @ @ @ @ @ Ă̒101椏͉ĕȓɗǂhł܂B @ @ @ @ @ @ @ @ @ @ @ @ @ 3)10.2 E.H. ́wVИx ÷ _ːVفA㏤D @ @ @ @ @ @ @ @ @ @ @ @ @ ̙_ւŏ펞 15l̏oȂ𓾂 Ɍ r椏 @ @ @ @ @ @ @ @ @ @ @ @ @ JĂ܂B11.26 () ɂ ضl E.H. Fl Prof.Spalding @ @ @ @ @ @ @ @ @ @ @ @ @ āAۓss_˂炵椏܂B @ @ @ @ @ @ @ @ @ @ @ @ @ ̕ ײČőOɐmjւɘ҂ĂRA @ @ @ @ @ @ @ @ @ @ @ @ @ Ўv̑QiIȍs 낢Ƙbfւƞق݂łB @ @ @ @ @ @ @ @ @ @ @ @ @ ̊cɂ O {̙҉]A @ @ @ @ @ @ @ @ @ @ @ @ @ }ɁwVИx椂ݎn߂lBƂB @ @ @ @ @ @ @ @ @ @ @ @ @ 񍐒v܂B @ @ @ @ @ @ @ 10.@ dK搶Axōu ( 21j,2)F @ @ @ @ @ @ @ 11.26 () _椏FOut ߰ިݸދA㞐 @ @ @ @ @ @ @ 12.10 () _椏F߰ިݸދAwVИxɂ ub @ @ @ @ @ @ @ @ @ @ @ @ @ (pA桂Ȃ) @ @ @ @ @ @ @ @ @ @ @ @ @ ⊈潑B8:00 A߂̋iX 9:30 ܂ ut𚡂şck @ @ @ @ @ @ @ 12.16 () _椏YNF؞ 13ҏW @ 1958^a33. 1.14 _椏F扮 2KA19:00-21:00 @ @ @ @ @ @ @ @ 1.28 _椏F扮 2K @ @ @ @ @ @ @ @ 2. 1 yj ް݁wИ`̐_xu] 2ځA @ @ @ @ @ @ @ @ @ @ ܏͝^cdKAsɂ艄 @ @ @ @ @ @ @ @ 2.11 _椏i扮 2K)F14:30`21:00 wVИx ÷āB @ @ @ @ @ @ @ @ @ @ l`I ` O`ւzڂA @ @ @ @ @ @ @ @ @ @ R@̕]Jɂ_c @ @ @ @ @ @ @ @ 2.25 _椏i扮 2K)F14:30`21:00 @ yÑqu椏̒ł̓Xvz( 24jA58.3.15j 2) Fm肽̂ŁA @ @ @ @ @ @ @ @ @ @ Ўv椏ɂlŔ򍞂ŎȂ̒qd̊ꂫȂA @ @ @ @ @ @ @ @ @ @ ɔNAD̗FB @ɍsAdĒ̛{K̗ǂɊA @ @ @ @ @ @ @ @ @ @ 椏悤Ƃ̂ƁA椂 ÷ q㔂ȂA ˭ް @ @ @ @ @ @ @ @ @ @ w{`SZ݁̕xƁw{̎vzx(gV) 0 @ @ @ @ @ @ @ @ @ @ w̏W椂ł܂Bӌ͕S㇘łB @ @ @ @ @ @ @ @ @ @ _ˎx E.H. ́wVИx L̓ƍ͂ @ @ @ @ @ @ @ @ @ @ O椏̒ŁAɛ銴󐫂݂̓A @ @ @ @ @ @ @ @ @ @ ̒̊SƂȂƂȂĂ韆łB @ @ @ @ @ @ @ @ @ @ ̐lÂǂɌĂ钆ŁAkĂ͂ȂA @ @ @ @ @ @ @ @ @ @ ׋čsƎvӓXłB @ @ @ @ @ @ @ @ 6. 2 _椏i 27,1ʁ^10-6,28)F爰قɝ̍XB @ @ @ @ @ @ @ @ @ @ ̓sō 2񂾂ΗjłȂjɂ @ @ @ @ @ @ @ @ 6.16 _椏F18:30-21:00@ wVИx椗 @ @ @ @ @ @ @ @ 7.12 (y)@ _椏 (10-8,28)F 椏ÎŁA @ @ @ @ @ @ @ @ @ @ ̒Ñx [HkJÁB @ @ @ @ @ @ @ @ @ @ 9椏 ĊJB÷āсwR̓x @ @ @ y瑁h3)z( 27j 2ʁ^10 (萐)vWLfځ^1 3H 400^23 @ @ @ @ @ @ @ @ 瑁h3) 񍐋L ( 29j 1-2ʁ^ 10-9,28) ҉ 39 (j19/20) @ @ @ @ @ @ @ @ 7.19 (y) ӁAcE_lْ̈A^ȏЉ^E_ˎx^ڸش @ @ @ @ @ @ @ @ @ 20 () ߑO@ u`uɂāvdK @ @ @ @ @ @ @ @ @ @ @ @ @ ߌ@ ҉ᢕ\ufՂ̌ʂɂāvck @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ uaɏoȂāvq @ @ @ @ @ @ @ @ @ @ @ @ @ Ӂ@ @ @ @ @ @ @ uޭ۸׼ lԁvMJ@ @ @ @ @ @ @ @ @ @ @ @ @ @ 22:00 ܂ c @ @ @ @ @ @ @ @ @ 21 () ߑO@ Rԁ^oR @ @ @ @ @ @ @ @ @ @ @ @ @ ߌ@ U @ yO̙҉Lz ( 29jA58.8.15j 1)F(_ˑ@) Ўvɟ^ȑԓxA @ @ @ @ @ @ @ @ @ @ @ @ @ łĖ邭e݈ՂjȕAɏ̐^ȊA @ @ @ @ @ @ @ @ @ @ @ @ @ ɂ͉̐ƂȂ܂BxAh̛͂܂A @ @ @ @ @ @ @ @ @ @ @ @ @ ̐܂̈ꑈꑂقISę҂܂B @ @ @ @ @ @ @ @ @ @ @ @ @ dK搶̓萂u`AcEEMJǑᢕ\ @ @ @ @ @ @ @ @ @ @ @ @ @ ^䓚AɌw̍ߍAVࣖȗVYARoccA @ @ @ @ @ @ @ @ @ @ @ @ @ ĕʂBInѓO ϲݼēI󟆂tƂȂ̂ƂȂ @ @ @ @ @ @ @ @ @ @ @ @ @ 粂Ύju܂ӓ܂Łv񂵂̕ʂ̈ꎞA @ @ @ @ @ @ @ @ @ @ @ @ @ ͎Ɋ[̂łB޾ټ @ @ @ @ @ @ @ @ @ @ @ @ @ ϲݼēI󟆂F߁Aǔj͂ȗs̈ɐ^ȉԂoA @ @ @ @ @ @ @ @ @ @ @ @ @ x͂Ȏ悻ɐl̐vӐȐlԑToƂ́A @ @ @ @ @ @ @ @ @ @ @ @ @ Đ瑁hYȂ̂ɒv܂B @ ydK搶̙jȈʁz ( AuҏSLv)F @ @ @ @ @ @ @ @ @ @ @ @ @ 瑁h̍ŏIAHꑫɟddKEc_搶Ɠ䎁 @ @ @ @ @ @ @ @ @ @ @ @ @ g܂ӓ܂" ̍ŌƂAdK搶Xqʂ @ @ @ @ @ @ @ @ @ @ @ @ @ g撣[" ƌĉ̂ɂ͊B{uR̉Ɓv @ @ @ @ @ @ @ @ @ @ @ @ @ 萂班oƁAlBKi (̐Sfj̊Ki) @ @ @ @ @ @ @ @ @ @ @ @ @ ~؂Ƃp̂ŁA݂Ȃŉ̂㔂Ȃ҂ĂA @ @ @ @ @ @ @ @ @ @ @ @ @ gbz[" Ƃ Ă߁Agbz[" ƓւgoJ[" @ @ @ @ @ @ @ @ @ @ @ @ @ ԂĂB҂ɃoJ[Ƃ͉!?@ ߂͓䎁炵A @ @ @ @ @ @ @ @ @ @ @ @ @ xł͒u񂼂ƎvĂAŕɂƁA @ @ @ @ @ @ @ @ @ @ @ @ @ dK搶̐ (?) ɂ̂ŁAgoJ[b" Ɠ{΁A @ @ @ @ @ @ @ @ @ @ @ @ @ gKo[b" ƕƂӛ{ɊRBdK搶䎩gA @ @ @ @ @ @ @ @ @ @ @ @ @ ܂ŌčsuR̉Ɓvْ̊Ɏ玩Ԃ̑ @ @ @ @ @ @ @ @ @ @ @ @ @ goJ[b" Ɠ{ꂽłB @ @ @ @ @ @ @ @ @ @ @ @ @ goJ[Ƃ͌̌tƂ݂" @ @ @ @ @ @ @ @ @ @ @ ɌF͗NJԂB @ y쑺q̙҉Lz ( 30jA58.9.15j 2) F(Б{) @ @ @ @ @ @ @ @ @ @ @ @ @ uق瑁hc搶ւ̎莆v7.22LB @ @ @ @ @ @ @ @ @ @ @ @ @ 1)A瑁hĂёɟdĂ̂́A܂ق @ @ @ @ @ @ @ @ @ @ @ @ @ ̂ł܂̐ɖ߂ꂳɂ܂BuقȂv @ @ @ @ @ @ @ @ @ @ @ @ @ uق܂ɂ݂ȐӂɈꂽ̗ǂlBȂv @ @ @ @ @ @ @ @ @ @ @ @ @ d̓dԂ̒ŁAB͂ȌtJԂĂ܂B @ @ @ @ @ @ @ @ @ @ @ @ @ ĎRŐLѐLтƂИvz̕B̕׋ԂɈցA @ @ @ @ @ @ @ @ @ @ @ @ @ B͉PT̂Ȃ{ɏInĂ邱ƂA @ @ @ @ @ @ @ @ @ @ @ @ @ ̛ɋÂł܂炸A A{΂˂΂ȂʂƈӌvA @ @ @ @ @ @ @ @ @ @ @ @ @ R ̧ R₵ĕʂ܂B @ @ @ @ @ @ @ @ @ @ @ @ @ 2)Sʂ̒ łY̂́A19ӂ̐̉ł̓cłB @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ (tc搶Ƃ̋c_ȗ) @ @ @ @ @ @ @ @ @ @ @ @ @ 3)dK搶́uɂāvA dK搶 b̓e @ @ @ @ @ @ @ @ @ @ @ @ @ AxXƐꂽ΂ȌA ɛ搶̌虛 @ @ @ @ @ @ @ @ @ @ @ @ @ ԓxɐSł܂Bɐ搶 ͍ĎY搶uċx͐l @ @ @ @ @ @ @ @ @ @ @ @ @ ̈ꂩɑc؂Ȃ̂łB̂ɁA̔N̉ċx݂͂ǂ߂ @ @ @ @ @ @ @ @ @ @ @ @ @ NSĂ͂茾ւ₤ɉ߂Ȃvƌ͂ꂽƂ @ @ @ @ @ @ @ @ @ @ @ @ @ YʂƋA͌Ɗ]Ɗ铓RvЂłB @ @ @ @ @ @ @ @ @ @ @ @ @ čAK̟drXɓAӟȂɏIɌĂ @ @ @ @ @ @ @ @ @ @ @ @ @ Aw䂪S̉́xƂӑẢdKƂӖ܂B @ @ @ @ @ @ @ @ @ @ @ @ @ ȂɂƂĂӂƊJłɂ܂B @ @ @ @ @ @ @ @ @ @ @ @ @ ulԂ͒NłႢɂ͔\͂̕sɜނ̂łBłB @ @ @ @ @ @ @ @ @ @ @ @ @ N͔\͂̕sAJoւꂽ̔\͂@Ɋp @ @ @ @ @ @ @ @ @ @ @ @ @ ׂɜ݋ꂵ񂾁v @ @ @ @ @ @ @ @ @ @ @ @ @ 4)͖łBdK搶ŏɋuޯް ̂lԂɂȂ @ @ @ @ @ @ @ @ @ @ @ @ @ Ƃ ȎgɂȂ邱ƂłvƂ́AǂȏGɑĂAɎȂ @ @ @ @ @ @ @ @ @ @ @ @ @ \MÅJᢂɓw͂邱Ƃƌ܂B낢lւ @ @ @ @ @ @ @ @ @ @ @ @ @ 邱Ƃ̑łB @ @ @ @ @ @ @ @ @ @ @ @ @ 5)ȈӋ`WЂɂUВA瑁łBɂSБՂ܂ @ @ @ @ @ @ @ @ @ @ @ @ @ ƂӒv܂B䌒NF肵Ă܂B @ @ @ @ @ @ @ @ @ @ @ @ @ ` _椏 (10-11,26)FȌ uTؗj̔ӂ s @ @ @ @ @ @ @ 9.19@ @ @ @ dK搶𚡂 ́wR̓x椂ł܂B @ @ @ @ @ @ @ @ @ @ @ @ @ 30l˔j鐷ԂłB @ @ @ @ @ @ @ 10. 9@ _椏 ( 32j,2)F @ @ @ 10.23@ _椏 ()FсwR̓x @ @ @ @ @ @ @ 11. 6@ _椏 ( 33j,2)FсwR̓x @ @ @ 11.20@ _椏 ()FсwR̓x @ @ @ @ @ @ @ 12. 4@ _椏 ( 34j,1)FсwR̓x @ @ @ @ @ @ @ 12.18@ _ˎxYN ( 34j,1ʁ^11-1,24)F̌قŊJ @ 1959^a34. 1.27@ _椏 ( 35j,1ʁ^11-2,24)FuTΗjJ (÷ā) @ @ @ @ @ @ @ @ 2.10@ _椏 ( 36j,2)FсwR̓x @ @ @ @ @ @ @ @ 2.24@ _椏 (^37j,2)F̓udK搶㞐ȁv @ @ @ @ @ @ @ @ 3.10@ _椏 ( 37j,2)FсwR̓x @ @ @ @ @ @ @ @ 3.24 () _椏 сwR̓x܏́u Ҷƽсv @ @ @ @ @ @ @ @ 4. 7 () _椏 ( 37j,2ʁ^11-5,26) F18:30-21:30 @ @ @ @ @ @ @ @ @ @ @ сwR̓x@ Źu¨ Sv @ @ @ @ @ @ @ @ @ @ @ dK搶w̉ JÁB֔Ԃᢕ\ĂAŋߓڂɊ潑Ȉӌ @ @ @ @ @ @ @ @ @ @ @ 骂͂ċɂ߂ėLӋ`ȘB椏̂30 ÷ 𗣂ĉf`]A @ @ @ @ @ @ @ @ @ @ @ ]A񍐁AΕ]ॕ񍐁AॏW҉񍐁Ae @ @ @ @ @ @ @ @ @ @ @ ҉񍐓elXȘb邱ƂɂĂB̏WЂ ް @ @ @ @ @ @ @ @ @ @ @ FƂāAȂ߁AwE{Eذ ̎O҂΂ @ @ @ @ @ @ @ @ @ @ @ ӌ骂͂ƂASł ̗ ɂ߂ěƎv͂B @ @ @ @ @ @ @ @ 6.@ @ dK 57΁A_ˑ{{ Cޗ @ @ @ y瑁h4)z 39j/11-6,24łɁulĊ (萐)vWL^13H 400 @ @ @ @ @ @ @ @ 7.18-20@ 瑁h4) ( 41j,2-3ʁ^ 11-8,26) ҉ 43 (j24/19) @ @ @ @ @ @ @ @ @ 18 (y) Ӂ@ @ R@YxE_lْ̈A @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ u`u{`̝̖eƎИ`̛ҁvc @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ 潑ȓc^ȏЉ^^ްс^AiɂيOŌ荇Ӂj @ @ @ @ @ @ @ @ @ 19 () ߑO@ u`uYɂlԂ̌vdK @ @ @ @ @ @ @ @ @ @ @ @ @ ߌ@ E_˙_x^eniEEVE_ˁEE @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ E_ˑEޗǏqj̊󋵕񍐁^xc ٰߓc @ @ @ @ @ @ @ @ @ @ @ @ @ Ӂ@ @ O[vc̓e񍐁^c @ @ @ @ @ @ @ @ @ 20 () ߑO@ F񍐁uț{Zp̎IᢓWɂ{SZ̋vΕ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ ufm~l[VɂāvJ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ uZpƂĂ̑Ovؑ@ @ @ @ @ @ @ @ @ @ @ @ @ dKEc_搶uvuAɂꂾ̘bł҂ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ ɂ͋Ȃv̂ƋRoA14:00 HAU @ ylڂ}ւ瑁hz( 41jA59.8.15j 2) FɌgVLuevX[v @ yӔV̂ւz( 3)F1)҉A̍h͓Z㞂ĂB @ @ @ @ @ @ @ @ @ @ @ @ ut̘bcŎ~߂ĂȂB2)F񍐂͏[B̂₤ @ @ @ @ @ @ @ @ @ @ @ @ [ 3̕񍐎҂ɛ鍡ᢓWւ̊]ďIւꂽ̂ @ @ @ @ @ @ @ @ @ @ @ @ тłB3)RoB4)ŔAdKEc_搶ƋɂA @ @ @ @ @ @ @ @ @ @ @ @ ԂɓĒBɌ񏉂ߋklXɌꂽB @ @ @ @ @ @ @ @ @ @ @ @ u₤ȂA޶۰vu₤ȂA޶۰v dK搶߂ @ @ @ @ @ @ @ @ @ @ @ @ u޶۰v ܂ҔNAŏIS鄂₤ȏ[҂āA @ @ @ @ @ @ @ @ @ @ @ @ Ăсu޶۰vЂɂĘ҂̂ƎvB @ @ @ @ @ @ @ 11.13@ _椏 ( 45j,2)F哇Nҁw̎vzxhlԂ̎Rɂ @ @ @ @ @ @ @ 11.27@ _椏 ( )F哇w̎vzxIIB̊v @ @ @ @ @ @ @ 12.11@ _椏 (12-1,39)FN̍ŏI @ @ @ @ @ @ @ 12.26@ 萐x (_ˁEE) eF_ˎx Ñq @ 1960^a35. 1.22 () _椏 (12-2E3,64)FdKoȁAA݂ɐVt̕B@ @ @ @ @ @ @ @ @ @ @ ̂ 哇Nҁw̎vzxÓulƚƁvɂ ӌB @ @ @ y瑁h5)z j (7.10)/12-6,26łɁu܉Ċ (萐)v̕WLf @ @ @ @ @ @ @ @ @ @ ðρFИ`̍Ğ^13H 400 @ @ @ @ @ @ @ @ 7.30-8.1@ 瑁h5) ( 53j^ 12-9) @ @ @ @ @ @ @ @ @ @ @ @ @҉ 67 (ߋōL^^̙҉) @ @ @ @ @ @ @ @ @ 30 (y)@ @ @ u`uИ`SZIӖvc @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ u{ɂ鐭}vs @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ ȏЉ^ڸش @ @ @ @ @ @ @ @ @ 31 () ߑO@ u`uИ`̐lVvdK @ @ @ @ @ @ @ @ @ @ @ @ @ ߌ@ O[vc (ϗEESZʂ疯И`) @ @ @ @ @ @ @ @ @ @ @ @ @ Ӂ@ @ c^ڸش @ @ @ @ @ @ @ @ 8. 1 () ߑO@ ҉ҕ񍐁uИ`ƋΙҋvЎY @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ uc𐭎̍Ğvck @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ oR^U @ yΕ@ ̙҉Lz (wИvzx12-9j 23-24) F1)̍h̖ړÍAsЂ΂΂ @ @ @ @ @ @ @ @ @ @ @ ĂF̐er𚤂A҉҂̑݌[ᢂ_ӂ́B2) @ @ @ @ @ @ @ @ @ @ @ NXɂȂĂA_eNX[ĂĂB߂͍u` @ @ @ @ @ @ @ @ @ @ @ A҉҂̈ӌē_dɈڍsBh͙҉҂ @ @ @ @ @ @ @ @ @ @ @ Ǝ^䓚ŐϋɓIo𑣂AD܂B3)Ă̝ɓu @ @ @ @ @ @ @ @ @ @ @ RɓuW܂Č芎̂ӟ͊iʁBN߂ĘAčs @ @ @ @ @ @ @ @ @ @ @ ̖AИ`ɂ͂ċȂɂS炸A @ @ @ @ @ @ @ @ @ @ @ h̕ɂ͖Ɏ䂫ꂽ͞B @ @ @ @ @ @ @ @ @ @ @ F̐eȑł茤ȑł邱̍hɁAƂS @ @ @ @ @ @ @ @ @ @ @ ɂ̙҉҂܂B @ @ @ @ @ @ @ 11.26@ dKuu@ɂĂ̎̍l֕v(uA18:30` ) @ 1961^a36. 1.-3. dK 59΁ASfaŕa @ @ @ @ @ @ @ @ 7.8-13@ pzKSxmőĊ{ŰيJ @ @ @ @ @ @ @ @ @ @ @ @(̂ݛ{^) @ @ @ @ @ @ @ @ @ @ @ cf.Љ@ rquxmŰًLv(13-8,20-22) @ @ @ @ @ @ @ @ @ @ @ @ ɌgVuxmŰ ̂Ɓv(13-8,23-25) @ y瑁h6)z7.29-31 uZĊ (萐)vdK搶ŝs @ @ @ @ @ @ @ @ 9.- @ _椏AdK𒆐S ٽށwܲĶװx椂 () @ @ @ @ @ @ @ 11.19@ _ˎs e𓰂 җj^wdK搶ژ^xzz @ @ @ @ @ @ @ 12. 2@ Ўv Ou ( 70j,2)FdKuИv̓N{v @ 1962^a37. 2.17@ dKu͍搶̎vЏov(14-3,4-7)Fg̐iD݂炷ƁA @ @ @ @ @ @ @ @ @ @ @ łΐU̟k͏Vɕĕ邵B̏V̂Ȃ椂 @ @ @ @ @ @ @ @ @ @ @ 菑肷eƕ́Aǂň؂̐lX̐liƍKBɌqA @ @ @ @ @ @ @ @ @ @ @ И̐iWƌq̂łȂĂ͂ȂȂBłȂAg̐ls @ @ @ @ @ @ @ @ @ @ @ AV̐̂̂ӖƂȂ̂łB͍搶́ÂƂAg @ @ @ @ @ @ @ @ @ @ @ ĎłMdȋPƂāAɟkĉ₤Ɏv͂B @ @ @ @ @ @ @ @ 4.@ @ dKu`̓N{v(14-4,2-20)F߁@ BjVƓN{ @ @ @ @ @ @ @ @ @ @ @ ߁@ `IJlVƓN{ @ @ @ @ @ @ @ @ 7.@ @ dKu`̐lVv(14-7,58-72)F @ @ @ @ @ @ @ @ 9.-@ _椏AE.H.wjƂ͉x椂ݎn߂ (EÑ) @ @ @ @ @ @ @ 10.@ @ dKuȐSES̖F`̐lVE̓v(14-10,66-81) @ @ @ @ @ @ @ 12.17@ _椏AE.H.wjƂ͉x椗Ae߰èJ @ 1963^a38. 1.@ @ dKulԐɂ镽F`̐lVE̎Ov(15-1,2-18) @ @ @ @ @ @ @ @ 4.@ @ dKulԐɂ鍇IvƔ񍇗IvF̎lv(15-4,37-52) @ @ @ @ @ @ @ @ 4.22- _椏 (EOj)^ڲwR̋G߁x(gX) @ @ @ @ @ @ @ @ 7.@ @ dKulԐɂ鋦ւ̌Xूւ̌XF̌܁v(15-7,30-43) @ @ @ @ @ @ @ 10.@ @ dKulԐɂF`̐lVE̘Zv(15-10,33-50) @ @ @ @ @ @ @ 10.13@ HGW (ԉ~) dKoȁA{̈ۂɂڂӌJ @ 1964^a39. 1.@ @ dKuOS̔񍇗Ɩ`E̎v(16-1,26-40) @ @ @ @ @ @ @ @ 4.@ @ ɌgVu͍ĎY̋{_v(16-4,14-33) @ @ @ @ @ @ @ @ @ @ @ dKuOS̔񍇗Ɩ` (2)F̔v(16-4,41-61) @ @ @ @ @ @ @ @ 7.@ @ dKuϽЭƹ݂Ɩ`O (3)F̋v(16-7,44-43) @ @ @ @ @ @ @ 10.@ @ dKuϽEӸ׼ƑO̐lԐO (4)F̏\v(16-10,29-50) @ 1965^a40. 1.@ @ dKuϽEӸ׼̞ܗ͍\ƑO̔\F11v(17-1,40-58) @ @ @ @ @ @ @ @ 2.27@ Ru҂lԑvcdK ʙ҉ (17-4,19-27) @ @ @ @ @ @ @ @ 4.@ @ dKuI萐S̖脟`̐lVF12v(17-4,50-72) @ @ @ @ @ @ @ @ 7.@ @ dKu`̐lVvƕF13v(17-7,61-78) @ @ @ @ @ @ @ 10.@ @ dKuJ.S.ق́wR_xɂlV`̐lVF14 () v @ @ @ @ @ @ @ @ @ @ @ (17-10,29-48) @ 1968^a43. 8.@ @ dKu͍搶̎莆v(20-8,13-22) IIDˎR{dK搶F(̓L) @ @ ˎR{ւzC̏Љ c (dKEɌgVE`،Y 3lꏏ) @ @ c ({ИƒZ{E{{SZw) @ @ @ ˎR{ˎR{{̐XgEˎR{{ČFV_ƐeA @ @ @ ˎR{{{̑n瑊kəoĂB @ @ @ ˎR{{{̍\zɉ͍ĎY̋{_fĂ̂́A @ @ @ coĂłB @ @ dK搶́ASf֓AˎR{̛{Ƃ̎X̛{Oɉ҉ꂽB @ @ @ ꏏŁAVZtł̈ꔑAoXɘĂ̏ڗsȂǂ͖YA @ @ @ ̂ƂłȂBdK搶̓Lɂ͋L^Ă锤B @ @ c̒ˎR{ɂ́An̕₤ȊĂB @ @ @ 鏕AujՓɉƂɋƁAĂ₤ɎvӁvƏq債قǁA @ @ @ {̐l萌W͖ĂB @ @ @ ͌ɒق̏A{̓[~Ƃ萌WȂARɏo肵ğckĂB @ 1965^a40. 3.31@ dK 64΁A_ˑ{NސEB @ @ @ @ @ @ @ @ 4. 1@ ˎR{ɏACB^cȖځuИvzjvuИ𐧓x̌v @ @ @ @ @ @ @ @ 7. 8@ dK搶̂bƁAŉĐQꂵvЂƂ͈xȂRB @ @ @ @ @ @ @ @ @ @ @ SA܂ (F͋{{ɂ̂TAԒˎRR)B @ @ @ @ @ @ @ 11. 2 () bKFdK搶̂bB{ 3l񍐁BðρF`EݻсE @ 1966^a41. 4.22 () ߌAFV{Ăɘ҂āAĖւȂƂ̘bB @ @ @ @ @ @ @ @ @ @ @ S債Ă̂ň󂯂B߂ނ𓾂܂B @ @ @ @ @ @ @ @ @ @ @ ƂɁAdK搶ƂӁB @ @ @ @ @ @ @ @ 5.@ @ dK 65΁A𕹔C @ @ @ @ @ @ @ @ 7.@ @ S؍[ǂœ\| @ @ @ @ @ @ @ @ 9.@ @ @ @ @ @ @ @ @ 10.17 () dK搶 (Ď) @ 1967^a42. 4.@ @ dK 66΁ASߗǍD u`ĊJ^uオvƂ̎S @ @ @ @ @ @ @ @ @ @ @ ^cȖځИ𐧓x̌^[~ĥ݁BИvzj Ɍ^c @ @ @ @ @ @ @ @ 4.17 () ˎR{JuBߌAdK搶̍u`uИ𐧓x̌vuB @ @ @ @ @ @ @ @ @ @ @ 搶̂bԂAsЂƑSR̂炸 (オ邱ƂȂ)B @ @ @ @ @ @ @ @ @ @ @ uOИ̖グBOИ͐lԂɝ̉߂邩A @ @ @ @ @ @ @ @ @ @ @ Ăǂӛ\|̎d邩vuИț{҄S鄉ț{E暓IƂ @ @ @ @ @ @ @ @ @ @ @ ڋ߂AИvzƂƂĐڋ߂B܂AИ𐧓x̑P_B @ @ @ @ @ @ @ @ @ @ @ PƂ͂ǂӂƂBǂӐlԂ̂PƂBꂪOҁB @ @ @ @ @ @ @ @ @ @ @ 𓥂܂Č҂őOИ_v @ 1968^a43. 3.@ @ w`̐lVxo @ @ @ @ @ @ @ @ 4.25@ dK搶̌䏵 (ޗǂ̘̒V܁uv)F`؁Er{EHX @ @ @ @ @ @ @ @ @ @ @ ƈꏏ v 5 @ @ @ @ @ @ @ @ 7. 4@ 17:00` dK搶w`̐lVxoŋLO @ @ @ @ @ @ @ @ @ @ @ @ @ @ @ (SBcEЏ㖾E`،YEɌgV)F @ 1969^a44. 6.12@ dK 67΁AˎR{ 301ɉāuИ𐧓x̌vu` } @ @ @ @ @ @ @ @ @ @ @ S 11:55^aS؍[ @ @ @ @ @ @ @ @ @ @ @ Ō̌tujDूh߂ɂ͂w͂ᶂȂĂ͂ȂȂv @ @ @ @ @ @ @ @ 6.19@ 14:00 ޗpقɉĒˎR{ @ @ @ @ @ @ @ @ @ @ @ ̂ƁAޗǎs킩فu͍搶̕v @ @ @ @ @ @ @ @ @ @ udK搶Âԁvk @ @ @ @ @ @ @ @ @ @ @ @ @ (wИvzx21-7/a44.7j 21-32Ōf) @ @ @ @ @ @ @ @ @ @ @ @ @ (uɌgV椏vɏW^Z) @ 1988^a63.11.13@ dK` (ˎR{ 4Kc) @ @ @ @ @ @ @ @ @ @ @ 񍐁ɌgVug߂ɌdK搶v (25/2013.8.1 j	{"extraction_info": {"found_math": false, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.9992725253105164, "perplexity": 178.87118575632036}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 20, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2019-18/segments/1555578517682.16/warc/CC-MAIN-20190418141430-20190418163430-00447.warc.gz"}
https://bitbucket.org/al45tair/netifaces	# netifaces 0.10.6 ## 1. What is this? It's been annoying me for some time that there's no easy way to get the address(es) of the machine's network interfaces from Python. There is a good reason for this difficulty, which is that it is virtually impossible to do so in a portable manner. However, it seems to me that there should be a package you can easy_install that will take care of working out the details of doing so on the machine you're using, then you can get on with writing Python code without concerning yourself with the nitty gritty of system-dependent low-level networking APIs. This package attempts to solve that problem. ## 2. How do I use it? First you need to install it, which you can do by typing: tar xvzf netifaces-0.10.6.tar.gz cd netifaces-0.10.6 python setup.py install Note that you will need the relevant developer tools for your platform, as netifaces is written in C and installing this way will compile the extension. Once that's done, you'll need to start Python and do something like the following: >>> import netifaces Then if you enter >>> netifaces.interfaces() ['lo0', 'gif0', 'stf0', 'en0', 'en1', 'fw0'] you'll see the list of interface identifiers for your machine. You can ask for the addresses of a particular interface by doing >>> netifaces.ifaddresses('lo0') Hmmmm. That result looks a bit cryptic; let's break it apart and explain what each piece means. It returned a dictionary, so let's look there first: { 18: [...], 2: [...], 30: [...] } Each of the numbers refers to a particular address family. In this case, we have three address families listed; on my system, 18 is AF_LINK (which means the link layer interface, e.g. Ethernet), 2 is AF_INET (normal Internet addresses), and 30 is AF_INET6 (IPv6). But wait! Don't use these numbers in your code. The numeric values here are system dependent; fortunately, I thought of that when writing netifaces, so the module declares a range of values that you might need. e.g. >>> netifaces.AF_LINK 18 Again, on your system, the number may be different. So, what we've established is that the dictionary that's returned has one entry for each address family for which this interface has an address. Let's take a look at the AF_INET addresses now: >>> addrs = netifaces.ifaddresses('lo0') You might be wondering why this value is a list. The reason is that it's possible for an interface to have more than one address, even within the same family. I'll say that again: you can have more than one address of the same type associated with each interface. Right, so, we can see that this particular interface only has one address, and, because it's a loopback interface, it's point-to-point and therefore has a peer address rather than a broadcast address. Let's look at a more interesting interface. >>> addrs = netifaces.ifaddresses('en0') This interface has two addresses (see, I told you...) Both of them are regular IPv4 addresses, although in one case the netmask has been changed from its default. The netmask may not appear on your system if it's set to the default for the address range. Now, say we want, instead of the IP addresses, to get the MAC address; that is, the hardware address of the Ethernet adapter running this interface. We can do >>> addrs[netifaces.AF_LINK] Note that this may not be available on platforms without getifaddrs(), unless they happen to implement SIOCGIFHWADDR. Note also that you just get the address; it's unlikely that you'll see anything else with an AF_LINK address. Oh, and don't assume that all AF_LINK addresses are Ethernet; you might, for instance, be on a Mac, in which case: >>> addrs = netifaces.ifaddresses('fw0') No, that isn't an exceptionally long Ethernet MAC address---it's a FireWire address. As of version 0.10.0, you can also obtain a list of gateways on your machine: >>> netifaces.gateways() {2: [('10.0.1.1', 'en0', True), ('10.2.1.1', 'en1', False)], 30: [('fe80::1', 'en0', True)], 'default': { 2: ('10.0.1.1', 'en0'), 30: ('fe80::1', 'en0') }} This dictionary is keyed on address family---in this case, AF_INET---and each entry is a list of gateways as (address, interface, is_default) tuples. Notice that here we have two separate gateways for IPv4 (AF_INET); some operating systems support configurations like this and can either route packets based on their source, or based on administratively configured routing tables. For convenience, we also allow you to index the dictionary with the special value 'default', which returns a dictionary mapping address families to the default gateway in each case. Thus you can get the default IPv4 gateway with >>> gws = netifaces.gateways() >>> gws['default'][netifaces.AF_INET] ('10.0.1.1', 'en0') Do note that there may be no default gateway for any given address family; this is currently very common for IPv6 and much less common for IPv4 but it can happen even for AF_INET. BTW, if you're trying to configure your machine to have multiple gateways for the same address family, it's a very good idea to check the documentation for your operating system very carefully, as some systems become extremely confused or route packets in a non-obvious manner. I'm very interested in hearing from anyone (on any platform) for whom the gateways() method doesn't produce the expected results. It's quite complicated extracting this information from the operating system (whichever operating system we're talking about), and so I expect there's at least one system out there where this just won't work. ## 3. This is great! What platforms does it work on? It gets regular testing on OS X, Linux and Windows. It has also been used successfully on Solaris, and it's expected to work properly on other UNIX-like systems as well. If you are running something that is not supported, and wish to contribute a patch, please use BitBucket to send a pull request. ## 4. What license is this under? It's an MIT-style license. Here goes:	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 1, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.21340779960155487, "perplexity": 2043.2153624832085}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2017-39/segments/1505818687592.20/warc/CC-MAIN-20170921011035-20170921031035-00415.warc.gz"}
https://www.sebastianstoeckl.com/tags/parameter-uncertainty/	# Parameter uncertainty ## Parameter uncertainty and Financial Markets In this project, we will research many aspects derived from the paper of Garlappi et al. (2007)	{"extraction_info": {"found_math": false, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.9631940722465515, "perplexity": 3979.804885426626}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2018-51/segments/1544376824119.26/warc/CC-MAIN-20181212203335-20181212224835-00303.warc.gz"}
http://mathhelpforum.com/advanced-algebra/13581-irreducible.html	# Math Help - Irreducible 1. ## Irreducible By looking at f (x+1) I think I can prove this but not exactly sure how. Here is the question: Prove for any prime number p, f(x)=x^p-1=x^p-2)+ ... + x+1 is irreducible in Q[x]. 2. .. Attached Thumbnails	{"extraction_info": {"found_math": false, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 0, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.9618009924888611, "perplexity": 2219.5492890878095}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.3, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2015-48/segments/1448398464386.98/warc/CC-MAIN-20151124205424-00160-ip-10-71-132-137.ec2.internal.warc.gz"}
https://www.science.gov/topicpages/h/ht+cas+observed.html	#### Sample records for ht cas observed 1. Orbital period determination in an eclipsing dwarf nova HT Cas NASA Astrophysics Data System (ADS) Bąkowska, Karolina; Olech, Arkadiusz 2014-09-01 HT Cassiopeiae was discovered over seventy years ago (Hoffmeister 1943). Unfortunately, for 35 years this object did not receive any attention, until the eclipses of HT Cas were observed by Bond. After a first analysis, Patterson (1981) called HT Cas "a Rosetta stone among dwarf novae". Since then, the literature on this star is still growing, reaching several dozens of publications. We present an orbital period determination of HT Cas during the November 2010 super-outburst, but also during a longer time span, to check its stability. 2. RXTE Observations of Cas A NASA Technical Reports Server (NTRS) Rothschild, R. E.; Lingenfelter, R. E.; Heindl, W. A.; Blanco, P. R.; Pelling, M. R.; Gruber, D. E.; Allen, G. E.; Jahoda, K.; Swank, J. H.; Woosley, S. E.; Nomoto, K.; Higdon, J. C.; Dermer, Charles D. (Editor); Strickman, Mark S. (Editor); Kurfess, James D. (Editor) 1997-01-01 The exciting detection by the COMPTEL instrument of the 1157 keV Ti-44 line from the supernova remnant Cas A sets important new constraints on supernova dynamics and nucleosynthesis. The Ti-44 decay also produces x-ray lines at 68 and 78 keV, whose flux should be essentially the same as that of the gamma ray line. The revised COMPTEL flux of 4 x l0(exp -5) cm(exp -2)s(exp -1) is very near the sensitivity limit for line detection by the HEXTE instrument on RXTE. We report on the results from two RXTE observations - 20 ks during In Orbit Checkout in January 1996 and 200 ks in April 1996. We also find a strong continuum emission suggesting cosmic ray electron acceleration in the remnant. 3. Hot Spot Manifestation in Eclipsing Dwarf Nova HT Cassiopeiae NASA Astrophysics Data System (ADS) Bąkowska, K.; Olech, A. 2014-09-01 We report the detection of a hot spot in the light curves of the eclipsing dwarf nova HT Cas during its superoutburst in 2010 November. Analysis of the eight reconstructed light curves of the hot spot eclipses showed directly that the brightness of the hot spot was changing significantly during the superoutburst. Thereby, detected hot spot manifestation in HT Cas is the newest observational evidence for the EMT model for dwarf novae. 4. Anxiolytic-like effects observed in rats exposed to the elevated zero-maze following treatment with 5-HT2/5-HT3/5-HT4 ligands PubMed Central Bell, Rob; Duke, Aaron A.; Gilmore, Paula E.; Page, Deaglan; Bègue, Laurent 2014-01-01 The present study examined the effects of administering selective 5-HT antagonists and agonists to rats tested in the elevated zero-maze (EZM) model of anxiety. The EZM paradigm has advantages over the elevated plus-maze (EPM) paradigm with respect to measuring anxiety, yet has been utilized less frequently. Three experiments were conducted each with a diazepam control (0.25, 0.5 and 0.75 mg/kg). In the first experiment, we administered the 5-HT2C antagonist RS 102221 (0.5, 1.0, and 2.0 mg/kg) and 5-HT2C agonist MK-212 (0.25, 0.5 and 0.75 mg/kg); in the second experiment, we administered the 5-HT3 antagonist Y-25130 (0.1, 1.0 and 3.0 mg/kg) and 5-HT3 agonist SR 57227A (0.1, 1.0 and 3.0 mg/kg), and in the third experiment, we administered the 5-HT4 antagonist RS 39604 (0.01, 0.1, 1.0 mg/kg) and 5-HT4 agonist RS 67333 (0.01, 0.1 and 0.5 mg/kg). The administration of 5-HT2/3/4 subtype antagonists all generated behavioral profiles indicative of anxiolytic-like effects in the EZM, which was apparent from examination of both traditional and ethological measures. While little effect was observed from 5-HT2 and 5-HT3 agonists, the 5-HT4 agonist RS 67333 was found to produce a paradoxical anxiolytic-like effect similar to that produced by the 5-HT4 antagonist RS 39604. We conclude by discussing the implications of these findings. PMID:24457553 5. COMPTEL observations of Ti-44 gamma-ray line emission from Cas A NASA Technical Reports Server (NTRS) Iyudin, A. F.; Diehl, R.; Bloemen, H.; Hermsen, W.; Lichti, G. G.; Morris, D.; Ryan, J.; Schoenfelder, V.; Steinle, H.; Varendorff, M. 1994-01-01 The Compton Telescope (COMPTEL) telescope aboard the Compton Gamma-Ray Observatory (CGRO) is capable of imaging gamma-ray line sources in the MeV region with a sensitivity of the order 10(exp -5) photons/(sq cm s). During two observations periods in July 1992 and February 1993 the Galactic plane in the region of the young supernova remnant Cas A was observed, showing evidence for line emission at 1.16 MeV from the decay of Ti-44 at a significance level of approximately 4 sigma. This is the first time a supernova remnant has been detected in the gamma-ray line from Ti-44 decay. Adopting a distance of 2.8 kpc to the Cas A remnant, the measured line flux (7.0 +/- 1.7) x 10(exp -5) photons/(sq cm s), can be translated into a Ti-44 mass ejected during the Cas A supernova explosion, between (1.4 +/- 0.4) x 10(exp -4) solar mass and (3.2 +/- 0.8) x 10(exp -4) solar mass, depending on the precise value of the Ti-44 mean life time and on the precise date of the event. Implications of this result for supernova nucleosynthesis models are discussed. 6. A Class Exercise: Studying the Eclipsing Binary Star RZ Cas Through Visual Observations NASA Astrophysics Data System (ADS) Balonek, T. J.; Davis, S. M. 2000-05-01 As part of the sophomore-junior level "Astronomical Techniques" course at Colgate University, students learn just how much science they can do with simple tools: a pair of binoculars, a clock, and pencil and paper. The students study the Algol type visual eclipsing binary star system RZ Cassiopeiae: observing and making a light curve for the primary minimum, determining the time of minimum using several techniques, calculating the binary star system's orbital period, and determining changes in the system's period over a thirty year interval by constructing an O-C curve. Through a series of preparatory exercises, the students learn how to read star maps and use the unaided eye, binoculars and telescopes to locate star fields and make visual magnitude measurements. By making multiple measurements of stars in the field of RZ Cas on several nights, the students determine the accuracy they can achieve in estimating the visual magnitude of a star -- typically 0.2 magnitude. (Some students even accidentally discover that one of the stars in the field is a variable star!) With this experience, the students use binoculars to observe the four hour primary eclipse of RZ Cas (magnitude 6.2 - 7.7), making magnitude measurements every five minutes. A light curve is then plotted. Several methods are used to determine the time of minimum, which is then converted to heliocentric Julian day. Using times of minima determined by former students (and the instructor) in previous years dating from 1968 to the present, the students determine the average period to a tenth of a second second. By constructing an O-C curve from the class's data and that obtained by the AAVSO, changes in the period of RZ Cas are noticeable -- possibly due to mass transfer in the system. It will be interesting for future classes to build on this knowledge using the primitive tools of our not so distant past. 7. Neurochemical Correlates of Accumbal Dopamine D2 and Amygdaloid 5-HT1B Receptor Densities on Observational Learning of Aggression PubMed Central Suzuki, Hideo; Lucas, Louis R. 2015-01-01 Social learning theory postulates that individuals learn to engage in aggressive behavior through observing an aggressive social model. Prior studies have shown that repeatedly observing aggression, also called “chronic passive exposure to aggression,” changes accumbal dopamine D2 receptor (D2R) and amygdaloid 5-HT1B receptor (5-HT1BR) densities in observers. But, the association between these outcomes remains unknown. Thus, our study used a rat paradigm to comprehensively examine the linkage between aggression, D2R density in the nucleus accumbens core (AcbC) and shell (AcbSh), and 5-HT1BR density in the medial (MeA), basomedial (BMA), and basolateral (BLA) amygdala following chronic passive exposure to aggression. Male Sprague-Dawley rats (N = 72) were passively exposed to either aggression or non-aggression acutely (1 day) or chronically (23 days). When observer rats were exposed to aggression chronically, they showed increased aggressive behavior and reduced D2R density in the bilateral AcbSh. On the other hand, exposure to aggression, regardless of exposure length, increased 5-HT1BR density in the bilateral BLA. Finally, low D2R in the AcbSh significantly interacted with high 5-HT1BR density in the BLA in predicting high levels of aggression in observer rats. Our results advance our understanding of the neurobiological mechanisms for observational learning of aggression, highlighting that dopamine-serotonin interaction, or AcbSh-BLA interaction, may contribute to a risk factor for aggression in observers who chronically witness aggressive interactions. PMID:25650085 8. Neurochemical correlates of accumbal dopamine D2 and amygdaloid 5-HT 1B receptor densities on observational learning of aggression. PubMed Suzuki, Hideo; Lucas, Louis R 2015-06-01 Social learning theory postulates that individuals learn to engage in aggressive behavior through observing an aggressive social model. Prior studies have shown that repeatedly observing aggression, also called "chronic passive exposure to aggression," changes accumbal dopamine D2 receptor (D2R) and amygdaloid 5-HT1B receptor (5-HT1BR) densities in observers. But, the association between these outcomes remains unknown. Thus, in our study, we used a rat paradigm to comprehensively examine the linkage between aggression, D2R density in the nucleus accumbens core (AcbC) and shell (AcbSh), and 5-HT1BR density in the medial (MeA), basomedial (BMA), and basolateral (BLA) amygdala following chronic passive exposure to aggression. Male Sprague-Dawley rats (N = 72) were passively exposed to either aggression or nonaggression acutely (1 day) or chronically (23 days). When observer rats were exposed to aggression chronically, they showed increased aggressive behavior and reduced D2R density in bilateral AcbSh. On the other hand, exposure to aggression, regardless of exposure length, increased the 5-HT1BR density in bilateral BLA. Finally, low D2R in the AcbSh significantly interacted with high 5-HT1BR density in the BLA to predict high levels of aggression in observer rats. Our results advance our understanding of the neurobiological mechanisms in the observational learning of aggression, highlighting that dopamine-serotonin interaction, or AcbSh-BLA interaction, may contribute to a risk factor for aggression in observers who chronically witness aggressive interactions. 9. NASA Controller Acceptability Study 1(CAS-1) Experiment Description and Initial Observations NASA Technical Reports Server (NTRS) Chamberlain, James P.; Consiglio, Maria C.; Comstock, James R., Jr.; Ghatas, Rania W.; Munoz, Cesar 2015-01-01 This paper describes the Controller Acceptability Study 1 (CAS-1) experiment that was conducted by NASA Langley Research Center personnel from January through March 2014 and presents partial CAS-1 results. CAS-1 employed 14 air traffic controller volunteers as research subjects to assess the viability of simulated future unmanned aircraft systems (UAS) operating alongside manned aircraft in moderate-density, moderate-complexity Class E airspace. These simulated UAS were equipped with a prototype pilot-in-the-loop (PITL) Detect and Avoid (DAA) system, specifically the Self-Separation (SS) function of such a system based on Stratway+ software to replace the see-and-avoid capabilities of manned aircraft pilots. A quantitative CAS-1 objective was to determine horizontal miss distance (HMD) values for SS encounters that were most acceptable to air traffic controllers, specifically HMD values that were assessed as neither unsafely small nor disruptively large. HMD values between 0.5 and 3.0 nautical miles (nmi) were assessed for a wide array of encounter geometries between UAS and manned aircraft. The paper includes brief introductory material about DAA systems and their SS functions, followed by descriptions of the CAS-1 simulation environment, prototype PITL SS capability, and experiment design, and concludes with presentation and discussion of partial CAS-1 data and results. 10. Real-time observation of DNA recognition and rejection by the RNA-guided endonuclease Cas9 PubMed Central Singh, Digvijay; Sternberg, Samuel H.; Fei, Jingyi; Doudna, Jennifer A.; Ha, Taekjip 2016-01-01 Binding specificity of Cas9–guide RNA complexes to DNA is important for genome-engineering applications; however, how mismatches influence target recognition/rejection kinetics is not well understood. Here we used single-molecule FRET to probe real-time interactions between Cas9–RNA and DNA targets. The bimolecular association rate is only weakly dependent on sequence; however, the dissociation rate greatly increases from <0.006 s−1 to >2 s−1 upon introduction of mismatches proximal to protospacer-adjacent motif (PAM), demonstrating that mismatches encountered early during heteroduplex formation induce rapid rejection of off-target DNA. In contrast, PAM-distal mismatches up to 11 base pairs in length, which prevent DNA cleavage, still allow formation of a stable complex (dissociation rate <0.006 s−1), suggesting that extremely slow rejection could sequester Cas9–RNA, increasing the Cas9 expression level necessary for genome-editing, thereby aggravating off-target effects. We also observed at least two different bound FRET states that may represent distinct steps in target search and proofreading. PMID:27624851 11. Le syndrome d'Othello: un cas observé à Ouagadougou PubMed Central Kaboré, Bawindsongré Jean; Napon, Christian 2013-01-01 Les auteurs rapportent le premier cas de délire de jalousie encore décrit sous l'acronyme de syndrome d'Othello, à Ouagadougou. Il s'est agit d'un patient qui au décours d'un accident vasculaire cérébral ischémique constitué, a développé un délire de jalousie. Une revue de la littérature permet de comprendre que l'affection, rarement rapportée est de plus en plus décrite au décours de maladies neurologiques aigues ou chroniques, et que le lobe frontal joue vraisemblablement un rôle majeur. PMID:24570777 12. La tuberculose cutanée: observation de six cas confirmés au CHU Souro SANOU (CHUSS) de Bobo-Dioulasso (Burkina Faso) PubMed Central Andonaba, Jean Baptiste; Barro-Traoré, Fatou; Yaméogo, Téné; Diallo, Boukary; Korsaga-Somé, Nina; Traoré, Adama 2013-01-01 La localisation cutanée de la maladie tuberculeuse demeure une forme rare et représente seulement 2,1% des localisations. L'objet de cette étude est de rapporter le profil épidémiologique, anatomoclinique et évolutif des cas de tuberculose ganglio-cutanée diagnostiqués dans un CHU au Burkina Faso. La fréquence de la tuberculose cutanée est très faible au CHUSS. Six cas ont été diagnostiqués entre 2004 et 2010, soit une fréquence de un cas par an. La durée d’évolution des cas allait de deux jusqu’à dix ans avant leur diagnostic. Les lésions observées étaient: trois scrofulodermes, trois gommes, une tuberculose testiculaire associée à un mal de Pott, un cas de polyadénopathies et des cicatrices atropho-rétractiles dans la plupart des cas. Sur le plan anatomopathologique, des granulomes tuberculoïdes ont été mis en évidence dans tous les cas avec une forte réaction tuberculinique à l'IDR. Sous antituberculeux pendant six mois, l’évolution a été bonne dans tous les cas mais au prix de séquelles cutanées cicatricielles inesthétiques. Son ampleur reste peut-être encore méconnue. Le renforcement du plateau technique du CHU et une bonne collaboration interdisciplinaire contribuerait à un meilleur diagnostic et prise en charge de cette affection. PMID:24648863 13. Mucocèle appendiculaire: à propos d'un cas observé à Lubumbashi PubMed Central Wakunga, Eric; Mukuku, Olivier; Bugeme, Marcellin; Tshiband, Moïse; Kipili, Audifax; Mobambo, Pitchou; Arung, Willy; Wakunga, Warach 2014-01-01 La mucocèle appendiculaire est une entité pathologique rare, mais potentiellement dangereuse, elle se présente sous différentes formes cliniques. Nous rapportons ici un cas d'une patiente âgée de 49 ans sans antécédents chirurgicaux chez qui nous avons découvert d'une façon fortuite cette affection. La clinique était celle d'un syndrome appendiculaire aigu patent et elle révélait une masse dans la fosse iliaque droite. Les examens de laboratoire ont montré une hyperleucocytose et une vitesse de sédimentation augmentée. L’échographie a démontré une masse kystique péricaecal. La patiente a subi une appendicectomie avec cæcectomie partielle et la pièce opératoire appendiculaire mesurait 153 mm de longueur et 64 mm de diamètre. L'analyse anatomopathologique de celle-ci a confirmé le diagnostic de mucocèle appendiculaire sans cellules de malignité. Les suites opératoires ont été simples et la patiente est sortie au cinquième jour postopératoire. PMID:25368725 14. Serotonin (5-HT) 5-HT2A Receptor (5-HT2AR):5-HT2CR Imbalance in Medial Prefrontal Cortex Associates with Motor Impulsivity. PubMed Anastasio, Noelle C; Stutz, Sonja J; Fink, Latham H L; Swinford-Jackson, Sarah E; Sears, Robert M; DiLeone, Ralph J; Rice, Kenner C; Moeller, F Gerard; Cunningham, Kathryn A 2015-07-15 A feature of multiple neuropsychiatric disorders is motor impulsivity. Recent studies have implicated serotonin (5-HT) systems in medial prefrontal cortex (mPFC) in mediating individual differences in motor impulsivity, notably the 5-HT2AR receptor (5-HT2AR) and 5-HT2CR. We investigated the hypothesis that differences in the ratio of 5-HT2AR:5-HT2CR protein expression in mPFC would predict the individual level of motor impulsivity and that the engineered loss of the 5-HT2CR would result in high motor impulsivity concomitant with elevated 5-HT2AR expression and pharmacological sensitivity to the selective 5-HT2AR antagonist M100907. High and low impulsive rats were identified in a 1-choice serial reaction time task. Native protein levels of the 5-HT2AR and the 5-HT2CR predicted the intensity of motor impulsivity and the 5-HT2AR:5-HT2CR ratio in mPFC positively correlated with levels of premature responses in individual outbred rats. The possibility that the 5-HT2AR and 5-HT2CR act in concert to control motor impulsivity is supported by the observation that high phenotypic motor impulsivity associated with a diminished mPFC synaptosomal 5-HT2AR:5-HT2CR protein:protein interaction. Knockdown of mPFC 5-HT2CR resulted in increased motor impulsivity and triggered a functional disruption of the local 5-HT2AR:5-HT2CR balance as evidenced by a compensatory upregulation of 5-HT2AR protein expression and a leftward shift in the potency of M100907 to suppress impulsive behavior. We infer that there is an interactive relationship between the mPFC 5-HT2AR and 5-HT2CR, and that a 5-HT2AR:5-HT2CR imbalance may be a functionally relevant mechanism underlying motor impulsivity. 15. Serotonin (5-HT) 5-HT2A Receptor (5-HT2AR):5-HT2CR Imbalance in Medial Prefrontal Cortex Associates with Motor Impulsivity PubMed Central Anastasio, Noelle C.; Stutz, Sonja J.; Fink, Latham H. L.; Swinford-Jackson, Sarah E.; Sears, Robert M; DiLeone, Ralph J.; Rice, Kenner C.; Moeller, F. Gerard; Cunningham, Kathryn A. 2016-01-01 A feature of multiple neuropsychiatric disorders is motor impulsivity. Recent studies have implicated serotonin (5-HT) systems in medial prefrontal cortex (mPFC) in mediating individual differences in motor impulsivity, notably the 5-HT2AR receptor (5-HT2AR) and 5-HT2CR. We investigated the hypothesis that differences in the ratio of 5-HT2AR:5-HT2CR protein expression in mPFC would predict the individual level of motor impulsivity and that the engineered loss of the 5-HT2CR would result in high motor impulsivity concomitant with elevated 5-HT2AR expression and pharmacological sensitivity to the selective 5-HT2AR antagonist M100907. High and low impulsive rats were identified in a 1-choice serial reaction time task. Native protein levels of the 5-HT2AR and the 5-HT2CR predicted the intensity of motor impulsivity and the 5-HT2AR:5-HT2CR ratio in mPFC positively correlated with levels of premature responses in individual outbred rats. The possibility that the 5-HT2AR and 5-HT2CR act in concert to control motor impulsivity is supported by the observation that high phenotypic motor impulsivity associated with a diminished mPFC synaptosomal 5-HT2AR:5-HT2CR protein:protein interaction. Knockdown of mPFC 5-HT2CR resulted in increased motor impulsivity and triggered a functional disruption of the local 5-HT2AR:5-HT2CR balance as evidenced by a compensatory upregulation of 5-HT2AR protein expression and a leftward shift in the potency of M100907 to suppress impulsive behavior. We infer that there is an interactive relationship between the mPFC 5-HT2AR and 5-HT2CR, and that a 5-HT2AR:5-HT2CR imbalance may be a functionally-relevant mechanism underlying motor impulsivity. PMID:26120876 16. Recent Observations of the Neglected Southern Eclipsing Binary Systems V343 Cen, UY Mus, HT Aps, and V1961 Sgr NASA Astrophysics Data System (ADS) Faulkner, D. R.; Samec, R. G.; Stoddard, M. L.; McKenzie, R.; Rebar, D.; Lavoie, G. D.; Moody, S.; Miller, J.; Van Hamme, W. 2002-12-01 As a part of our continuing search for solar type binaries with impacting gas streams, we present light curves of V343 Cen, UY Mus, HT Aps, and V1961 Sgr. These are all neglected variables whose observing histories show little or no observations since their discovery. The CCD observations were taken at the 0.9-m at CTI0 in the UBVRI Johnson-Cousins system. The observations were taken in on 2002, May 31-June 8 and 2001, May 16 - 23 respectively. UY Mus is a near contact binary with a large difference in eclipse depths of V = 0.67 mag. Otherwise the curve appears symmetric. The times of minimum light determined from our data are HJD Min I = 242047.62316(6) and Min II = 2452050.4874(3) where the value in parentheses is the standard error in the last decimal place. V1961 Sgr (GCVS 6848 485) is a W UMa binary with a difference in eclipse depths of V = 0.11 mag and a possible variable spot area causing a V = 0.04 mag variation in MAX I from night to night. HT Aps is a near contact solar type binary with a large difference in eclipse depths of V= 0.47 mag and a somewhat asymmetric (difference in maxima, V= 0.4 mag) light curve. It is a possibly a candidate for a binary with a gas stream. One time of minimum light determined from our data is HJD Min I = 2452331.63725 (12). V343 Cen is a near contact binary with a large difference in eclipse depths of V= 0.42 mag and distortions that give evidence of a gas stream collision. The difference in maxima is V = 0.07 mag. The curve shows little variation over the 4 day interval of observation. Light curves analyses, new period determinations and photometric data will be presented for these variables. Acknowledgements: We wish to thank the American Astronomical Society for their continued support of our undergraduate research programs through their small research grants. Faulkner and Samec were visiting Astronomers, Cerro Tololo InterAmerican Observatory, National Optical Astronomical Observatories, which are operated by the 17. Observation of T-2 and HT-2 glucosides from Fusarium sporotrichioides by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) USDA-ARS?s Scientific Manuscript database Cultures of Fusarium sporotrichioides were extracted and subjected to evaluation by high performance liquid chromatography – tandem mass spectrometry (LC-MS/MS). Along with the expected T-2 and HT-2 toxins, compounds 162 m/z higher than the toxins were observed. Fragmentation behavior of the larger ... 18. Prospects for observing supernova products from Cas A and the Vela region with SPI NASA Astrophysics Data System (ADS) Strong, A. W.; Diehl, R.; Georgii, R.; Iyudin, A. F.; Schönfelder, V. 2001-09-01 The study of gamma-ray line afterglows from supernova radioactivities is a major objective for the SPI Spectrometer on INTEGRAL. The decay lines of 44Ti and 26Al are the main candidates. We discuss prospects for observing two SNR with observation times similar to those available in the core program. Since the lines are expected to be Doppler broadened, we study the effect of line-width on the detectability of SNR. 19. L'observance thérapeutique dans les dermatoses chroniques: à propos de 200 cas PubMed Central Amraoui, Nissrine; Gallouj, Salim; Berraho, Mohamed Amine; Najjari, Chakib; Mernissi, Fatima zohra 2015-01-01 Introduction L'observance thérapeutique est la capacité à prendre correctement son traitement, tel qu'il est prescrit par le médecin. Elle est peu étudiée en dermatologie. Méthodes Le but de notre étude est d’évaluer l'observance chez les patients suivis au service de dermatologie du Centre Hospitalier Universitaire Hassan II de Fès pour une dermatose chronique et de rechercher les facteurs liés à une mauvaise observance à travers une étude incluant 200 patients suivis depuis au moins 6 mois. L’évaluation de l'observance s'est faite essentiellement à l'aide d'un entretien et les facteurs liés à l'observance ont été recherchés par un questionnaire. Résultats 68% de nos patients étaient observant, la mauvaise observance était associée à un niveau socio économique et d’étude bas, à une vie solitaire, à une durée de suivi longue, aux effets secondaires et au coût élevé des traitements, à l'absence d'efficacité, à une faible visibilité des lésions, à une ordonnance complexe, à une explication faible de la maladie, et à des difficultés d'accès à la consultation. Le taux d'observance retrouvé dans notre étude est un taux satisfaisant selon les données de la littérature, notre étude a confirmée certaines facteurs connues et a mis le point sur d'autres facteurs peu étudiés tel un traitement traditionnel associé, la part de chaque forme de traitement dans le respect de l'ordonnance, les dermatoses les plus touchées par les difficulté d'observance a savoir les dermatoses bulleuses et le psoriasis, et l'intérêt du pharmacien. Conclusion Cette analyse de la fréquence de ce phénomène et des facteurs essentiels qui l'influencent permet de cibler la prise en charge à travers une personnalisation de l'entretien médical, une adaptation du suivi au contexte de nos patients et à la nature de notre institution de santé. PMID:26848363 20. Direct Observation of Fracture of Cas-Glass/SiC Composites and Processing of Toughened Alumina DTIC Science & Technology 1992-09-01 to the load-displacement behaviour include indirect techniques such as acoustic emission and edge replication microscopy ( Zawada et at, 1991; Harris...18b). Zawada et aL (1991) also observed that 900 ply cracks precede 00 cracks in tests on the same cross-ply material with unnotched specimens; Pryce...have been some loss of stiffness. Similar behaviour has been found in fatigue with unnotched specimens of this material by Zawada et aL (1991). - 58 1. The new outburst of the EXor V1180 Cas as observed at X and NIR wavelengths NASA Astrophysics Data System (ADS) Nucita, Achille 2013-09-01 EXORs are pre-main sequence stars that show recurrent luminosity changes of short duration superposed to longer quiescence periods, see e.g. Audard et al. 2014. Although a general consensus exists about the nature of such outbursts (i.e. events of enhanced magnetospheric accretion from the circumstellar disk), the physical mechanisms regulating the outbursts and how these latter affect the circumstellar disk structure and its evolution are not clarified yet. We recently started an observational programme on this class of objects (EXORCISM, EXOR OptiCal and Infrared Systematic Monitoring, Antoniucci et al. 2013). Optical and near-IR studies of EXORs rapidly increased in the last decade but little is known about the X-ray properties, in particular whether X-rays come from the corona of the star (being in this case unaffected by the outbursts) or, conversely, originate in accretion events. 2. Shockley-Read-Hall recombination in P3HT:PCBM solar cells as observed under ultralow light intensities SciTech Connect Tzabari, Lior; Tessler, Nir 2011-03-15 We present light intensity dependent measurements of the quantum efficiency of P3HT:PCBM photovoltaic devices. Unlike previous studies we focus on ultralow light intensities down to 10{sup -3} mW/cm{sup 2}. We find that although when the devices are excited at intensities close to 1 Sun they exhibit very little bias or light intensity dependence, this is clearly not the case for light intensities below 1 mW/cm{sup 2}, where the cell's efficiency becomes highly dependent on the bias and light intensity. Using a simple model for the device efficiency we can fit the experimental data across a wide range of parameters and thus separate the effects of generation efficiency (geminate recombination) and charge recombination. Our finding suggests that recombination through trap (charge transfer) states is an important loss mechanism and we are able to quantify the density and depth of these states. 3. Shockley-Read-Hall recombination in P3HT:PCBM solar cells as observed under ultralow light intensities NASA Astrophysics Data System (ADS) Tzabari, Lior; Tessler, Nir 2011-03-01 We present light intensity dependent measurements of the quantum efficiency of P3HT:PCBM photovoltaic devices. Unlike previous studies we focus on ultralow light intensities down to 10-3 mW/cm2. We find that although when the devices are excited at intensities close to 1 Sun they exhibit very little bias or light intensity dependence, this is clearly not the case for light intensities below 1 mW/cm2, where the cell's efficiency becomes highly dependent on the bias and light intensity. Using a simple model for the device efficiency we can fit the experimental data across a wide range of parameters and thus separate the effects of generation efficiency (geminate recombination) and charge recombination. Our finding suggests that recombination through trap (charge transfer) states is an important loss mechanism and we are able to quantify the density and depth of these states. 4. Swift X-Ray Telescope Observations of the Nova-like Cataclysmic Variables MV Lyr, BZ Cam, and V592 Cas NASA Astrophysics Data System (ADS) Balman, Şölen; Godon, Patrick; Sion, Edward M. 2014-10-01 We present a total of ~45 ks (3 × 15 ks) of Swift X-Ray Telescope (XRT) observations for three nonmagnetic nova-like (NL) cataclysmic variables (CVs; MV Lyr, BZ Cam, V592 Cas) in order to study characteristics of boundary layers (BLs) in CVs. The nonmagnetic NLs are found mostly in a state of high mass accretion rate (>=1 × 10-9 M ⊙ yr-1), and some show occasional low states. Using the XRT data, we find optically thin multiple-temperature cooling flow type emission spectra with X-ray temperatures (kT max) of 21-50 keV. These hard X-ray-emitting BLs diverge from simple isobaric cooling flows, indicating X-ray temperatures that are of virial values in the disk. In addition, we detect power-law emission components from MV Lyr and BZ Cam and plausibly from V592 Cas, which may be a result of the Compton scattering of the optically thin emission from the fast wind outflows in these systems and/or Compton upscattering of the soft disk photons. The X-ray luminosities of the (multitemperature) thermal plasma emission in the 0.1-50.0 keV range are (0.9-5.0) × 1032 erg s-1. The ratio of the X-ray and disk luminosities (calculated from the UV-optical wavelengths) yields an efficiency (Lx /L disk) ~ 0.01-0.001. Given this non-radiative ratio for the X-ray-emitting BLs with no significant optically thick blackbody emission in the soft X-rays (consistent with ROSAT observations), together with the high/virial X-ray temperatures, we suggest that high-state NL systems may have optically thin BLs merged with ADAF-like flows and/or X-ray coronae. In addition, we note that the axisymmetric bipolar and/or rotation-dominated fast-wind outflows detected in these three NLs (particularly BZ Cam and V592 Cas) or some other NL may also be explained in the context of ADAF-like BL regions. 5. Swift X-ray telescope observations of the nova-like cataclysmic variables MV Lyr, BZ Cam, and V592 Cas SciTech Connect Balman, Şölen; Godon, Patrick; Sion, Edward M. E-mail: [email protected] 2014-10-10 We present a total of ∼45 ks (3 × 15 ks) of Swift X-Ray Telescope (XRT) observations for three nonmagnetic nova-like (NL) cataclysmic variables (CVs; MV Lyr, BZ Cam, V592 Cas) in order to study characteristics of boundary layers (BLs) in CVs. The nonmagnetic NLs are found mostly in a state of high mass accretion rate (≥1 × 10{sup –9} M {sub ☉} yr{sup –1}), and some show occasional low states. Using the XRT data, we find optically thin multiple-temperature cooling flow type emission spectra with X-ray temperatures (kT {sub max}) of 21-50 keV. These hard X-ray-emitting BLs diverge from simple isobaric cooling flows, indicating X-ray temperatures that are of virial values in the disk. In addition, we detect power-law emission components from MV Lyr and BZ Cam and plausibly from V592 Cas, which may be a result of the Compton scattering of the optically thin emission from the fast wind outflows in these systems and/or Compton upscattering of the soft disk photons. The X-ray luminosities of the (multitemperature) thermal plasma emission in the 0.1-50.0 keV range are (0.9-5.0) × 10{sup 32} erg s{sup –1}. The ratio of the X-ray and disk luminosities (calculated from the UV-optical wavelengths) yields an efficiency (L{sub x} /L {sub disk}) ∼ 0.01-0.001. Given this non-radiative ratio for the X-ray-emitting BLs with no significant optically thick blackbody emission in the soft X-rays (consistent with ROSAT observations), together with the high/virial X-ray temperatures, we suggest that high-state NL systems may have optically thin BLs merged with ADAF-like flows and/or X-ray coronae. In addition, we note that the axisymmetric bipolar and/or rotation-dominated fast-wind outflows detected in these three NLs (particularly BZ Cam and V592 Cas) or some other NL may also be explained in the context of ADAF-like BL regions. 6. CAS77 and CAS7276: A Review. ERIC Educational Resources Information Center Harrison, Isom, Jr. This paper describes the content, organization, specifications, and methods of use of the CAS77 and CAS7276 online files of worldwide chemical literature, databases produced by Chemical Abstracts Service and available from System Development Corporation (SDC). The scope of the databases, their unit record, their data elements, their modes of… 7. Existence of Brain 5-HT1A-5-HT2A Isoreceptor Complexes with Antagonistic Allosteric Receptor-Receptor Interactions Regulating 5-HT1A Receptor Recognition. PubMed Borroto-Escuela, Dasiel O; Li, Xiang; Tarakanov, Alexander O; Savelli, David; Narváez, Manuel; Shumilov, Kirill; Andrade-Talavera, Yuniesky; Jimenez-Beristain, Antonio; Pomierny, Bartosz; Díaz-Cabiale, Zaida; Cuppini, Riccardo; Ambrogini, Patrizia; Lindskog, Maria; Fuxe, Kjell 2017-08-31 Studies on serotonin-selective reuptake inhibitors have established that disturbances in the ascending 5-HT neuron systems and their 5-HT receptor subtypes and collateral networks to the forebrain contribute to the etiology of major depression and are targets for treatment. The therapeutic action of serotonin-selective reuptake inhibitors is of proven effectiveness, but the mechanisms underlying their effect are still unclear. There are many 5-HT subtypes involved; some need to be blocked (e.g., 5-HT2A, 5-HT3, and 5-HT7), whereas others need to be activated (e.g., postjunctional 5-HT1A and 5-HT4). These state-of-the-art developments are in line with the hypothesis that the development of major depression can involve an imbalance of the activity between different types of 5-HT isoreceptors. In the current study, using in situ proximity ligation assay (PLA), we report evidence for the existence of brain 5-HT1A-5-HT2A isoreceptor complexes validated in cellular models with bioluminescence resonance energy transfer (BRET(2)) assay. A high density of PLA-positive clusters visualizing 5-HT1A-5-HT2A isoreceptor complexes was demonstrated in the pyramidal cell layer of the CA1-CA3 regions of the dorsal hippocampus. A marked reduction in the density of PLA-positive clusters was observed in the CA1 and CA2 regions 24 h after a forced swim test session, indicating the dynamics of this 5-HT isoreceptor complex. Using a bioinformatic approach, previous work indicates that receptors forming heterodimers demonstrate triplet amino acid homologies. The receptor interface of the 5-HT1A-5-HT2A isoreceptor dimer was shown to contain the LLG and QNA protriplets in the transmembrane and intracellular domain, respectively. The 5-HT2A agonist TCB2 markedly reduced the affinity of the 5-HT1A agonist ipsapirone for the 5-HT1A agonist binding sites in the frontal lobe using the 5-HT1A radioligand binding assay. This action was blocked by the 5-HT2A antagonist ketanserin. It is proposed that 8. Influence of sodium substitutes on 5-HT-mediated effects at mouse 5-HT3 receptors PubMed Central Barann, M; Schmidt, K; Göthert, M; Urban, B W; Bönisch, H 2004-01-01 The influence of sodium ion substitutes on the 5-hydroxytryptamine (5-HT)-induced flux of the organic cation [14C]guanidinium through the ion channel of the mouse 5-HT3 receptor and on the competition of 5-HT with the selective 5-HT3 receptor antagonist [3H]GR 65630 was studied, unless stated otherwise, in mouse neuroblastoma N1E-115 cells. Under physiological conditions (135 mM sodium), 5-HT induced a concentration-dependent [14C]guanidinium influx with an EC50 (1.3 μM) similar to that in electrophysiological studies. The stepwise replacement of sodium by increasing concentrations of the organic cation hydroxyethyl trimethylammonium (choline) concentration dependently caused both a rightward shift of the 5-HT concentration–response curve and an increase in the maximum effect of 5-HT. Complete replacement of sodium resulted in a 34-fold lower potency of 5-HT and an almost two times higher maximal response. A low potency of 5-HT in choline buffer was also observed in other 5-HT3 receptor-expressing rodent cell lines (NG 108-15 or NCB 20). Replacement of Na+ by Li+ left the potency and maximal effects of 5-HT almost unchanged. Replacement by tris (hydroxymethyl) methylamine (Tris), tetramethylammonium (TMA) or N-methyl-D-glucamine (NMDG) caused an increase in maximal response to 5-HT similar to that caused by choline. The potency of 5-HT was only slightly reduced by Tris, to a high degree decreased by TMA (comparable to the decrease by choline), but not influenced by NMDG. The potency of 5-HT in inhibiting [3H]GR65630 binding to intact cells was 35-fold lower when sodium was completely replaced by choline, but remained unchanged after replacement by NMDG. The results are compatible with the suggestion that choline competes with 5-HT for the 5-HT3 receptor; the increase in maximal response may be partly due to a choline-mediated delay of the 5-HT-induced desensitization. For studies of 5-HT-evoked [14C]guanidinium flux through 5-HT3 receptor channels, NMDG appears 9. Investigation of brightness changes of MZ Cas and TZ Cas in B- and V-light NASA Technical Reports Server (NTRS) Lukatskaya, F. I.; Kheylo, E. S. 1973-01-01 The results are presented concerning statistical processing of two-color observations of MZ Cas and TZ Cas. Light histograms, dispersion and statistical amplitudes are given. Light variations of the variables are represented by normal stochastic processes. Observational data are tabulated. 10. Effects of 5-HT2B, 5-HT3 and 5-HT4 receptor antagonists on gastrointestinal motor activity in dogs PubMed Central Morita, Hiroki; Mochiki, Erito; Takahashi, Nobuyuki; Kawamura, Kiyoshi; Watanabe, Akira; Sutou, Toshinaga; Ogawa, Atsushi; Yanai, Mitsuhiro; Ogata, Kyoichi; Fujii, Takaaki; Ohno, Tetsuro; Tsutsumi, Souichi; Asao, Takayuki; Kuwano, Hiroyuki 2013-01-01 AIM: To study the effects of 5-hydroxytryptamine (5-HT) receptor antagonists on normal colonic motor activity in conscious dogs. METHODS: Colonic motor activity was recorded using a strain gauge force transducer in 5 dogs before and after 5-HT2B, 5-HT3 and 5-HT4 receptor antagonist administration. The force transducers were implanted on the serosal surfaces of the gastric antrum, terminal ileum, ileocecal sphincter and colon. Test materials or vehicle alone was administered as an intravenous bolus injection during a quiescent period of the whole colon in the interdigestive state. The effects of these receptor antagonists on normal gastrointestinal motor activity were analyzed. RESULTS: 5-HT2B, 5-HT3 and 5-HT4 receptor antagonists had no contractile effect on the fasting canine terminal ileum. The 5-HT3 and 5-HT4 receptor antagonists inhibited phase III of the interdigestive motor complex of the antrum and significantly inhibited colonic motor activity. In the proximal colon, the inhibitory effect was dose dependent. Dose dependency, however, was not observed in the distal colon. The 5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity. CONCLUSION: The 5-HT3 and 5-HT4 receptor antagonists inhibited normal colonic motor activity. The 5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity. PMID:24151388 11. 5-HT system and cognition. PubMed Meneses, A 1999-12-01 The study of 5-hydroxytryptamine (5-HT) system has benefited from the identification, classification and cloning of multiple 5-HT receptors (5-HT1 to 5-HT7). Growing evidence suggests that 5-HT is important in learning and memory and all its receptors might be implicated in this. Actually, 5-HT pathways, 5-HT reuptake site/transporter complex and 5-HT receptors show regional distribution in brain areas implicated in learning and memory. Likewise, the stimulation or blockade of presynaptic 5-HT1A, 5-HT1B, 5-HT(2A/2C) and 5-HT3 receptors, postsynaptic 5-HT(2B/2C) and 5-HT4 receptors and 5-HT uptake/transporter sites modulate these processes. Available evidence strongly suggests that the 5-HT system may be important in normal function, the treatment and/or pathogenesis of cognitive disorders. Further investigation will help to specify the 5-HT system nature involvement in cognitive processes, pharmacotherapies, their mechanisms and action sites and to determine under which conditions they could operate. In this regard, it is probable that selective drugs with agonists, neutral antagonist, agonists or inverse agonist properties for 5-HT1A, 5-HT(1B/1D), 5-HT(2A/2B/2C), 5-HT4 and 5-HT7 receptors could constitute a new therapeutic opportunity for learning and memory alterations. 12. Observational Study Of The Pacific Western Boundary Currents And The Indonesian Throughflow by the CAS Strategic Priority Project NASA Astrophysics Data System (ADS) Yuan, D.; Wang, J. 2014-12-01 The warm pool in the western Pacific Ocean has significant impact on the evolution of ENSO and the East Asian monsoon. Ocean circulation in the western Pacific Ocean and in Indonesian seas plays an important role in the interannual climate variations and predictability of the tropical Indo-Pacific Ocean. A major observational program of the Chinese Academy of Sciences is recently launched to study the western Pacific Ocean circulation and the warm pool to test these scientific hypotheses. The physical oceanography project called the "Western Pacific Ocean Circulation and the Warm Pool Variability" is by far the largest and the most intensive observational program in history in the western Pacific ocean study. In this talk, the background and scientific hypotheses of the project, the observational design in the western Pacific Ocean, Indonesian seas, and the eastern Indian Ocean region, and some preliminary results of the program will be presented. The talk serves to encourage more scientists to collaborate in the studies of the ocean circulation and climate in the western Pacific and eastern Indian Oceans. 13. Contractile 5-HT1 receptors in human isolated pial arterioles: correlation with 5-HT1D binding sites. PubMed Central Hamel, E.; Bouchard, D. 1991-01-01 1. The 5-hydroxytryptamine (5-HT) receptor responsible for inducing vasoconstriction in human isolated pial arterioles has been pharmacologically characterized. 2. Of several 5-HT agonists tested, 5-carboxamidotryptamine (5-CT) was the most potent and the rank order of agonist potency can be summarized as: 5-CT greater than 5-HT greater than RU 24969 = alpha-methyl-5-HT = methysergide much greater than MDL 72832 = 2-methyl-5-HT much greater than 2-dipropylamino-8-hydroxy-1,2,3,4-tetrahydro-naphthalene (8-OH-DPAT). With few exceptions, the maximal contractile responses of these agonists were comparable to that induced by 5-HT. 3. A correlation analysis performed between the agonists vascular potency (pD2 values) and their affinities (pKD values) published at various subtypes of 5-HT binding sites showed a positive significant correlation with rat cortical 5-HT1B (r = 0.86; P less than 0.01) and human caudate 5-HT1D (r = 0.98; P less than 0.005) subtypes. 4. Selective antagonists at 5-HT2 (ketanserin, mianserin, MDL 11939) and 5-HT3 (MDL 72222) sites were totally devoid of inhibitory activity on the 5-HT-induced contraction, an observation which agreed with the agonist data and further excluded activation of these receptors. In contrast, the 5-HT1-like/5-HT2 antagonist methiothepin and the non-selective 5-HT1D compound metergoline inhibited with high affinity the contraction induced by 5-HT with respective pA2 values of 8.55 +/- 0.16 and 6.88 +/- 0.05. This contractile response was, however, insensitive to 5-HT1B (propranolol) and 5-HT1C (mesulergine, mianserin) antagonists.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2043924 14. Observation of T-2 Toxin and HT-2 Toxin Glucosides from Fusarium sporotrichioides by Liquid Chromatography Coupled to Tandem Mass Spectrometry (LC-MS/MS) PubMed Central Busman, Mark; Poling, Stephen M.; Maragos, Chris M. 2011-01-01 The trichothecenes produced by solid and liquid cultures of Fusarium sporotrichioides were evaluated with high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Along with the expected T-2 toxin HT-2 toxin and neosolaniol, two additional compounds were detected, which had ions 162 m/z higher than those in the mass spectra of T-2 toxin or HT-2 toxin. Fragmentation behavior of these two compounds was similar to that of T-2 toxin and HT-2 toxin. Based on LC-MS/MS behavior, it is proposed that the two compounds are T-2 toxin 3-O-glucoside and HT-2 toxin 3-O-glucoside. Production of the two glucosides was measured in kernels from wheat and oat inoculated with F. sporotrichiodes, as well as in cultures grown in liquid media and on cracked corn or rice. Production of glucosides in wheat and oats suggest that they may also be present in naturally contaminated cereals. PMID:22295176 15. Platelet 5-hydroxytryptamine (5-HT) transporter and 5-HT2A receptor binding after chronic hypercorticosteronemia, (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane administration or neurotoxin-induced depletion of central nervous system 5-HT in the rat. PubMed Owens, M J; Ballenger, C A; Knight, D L; Nemeroff, C B 1996-09-01 There is considerable evidence that the number of platelet 5-hydroxytryptamine (5-HT) transporter binding sites, as measured by [3H]imipramine binding, are significantly decreased, and platelet 5-HT2 receptor density is increased, in drug-free patients with major depression. To investigate whether these changes in the platelet 5-HT transporter or 5-HT2 receptor sites resulted from known or hypothesized biochemical changes observed in major depression, we examined, in the rat, whether a chronic hyperglucocorticoid state, or decreases or increases in central nervous system 5-HT neurotransmission, altered binding of the selective ligands [3H]citalopram and [125I] (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane to platelet and brain 5-HT transporters and 5-HT2 receptors, respectively. Chronic (6 weeks) hypercorticosteronemia did not alter either brain or platelet 5-HT transporter or 5-HT2A receptor binding. Similarly, 8-week administration of the 5-HT2A/5-HT2C agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, at a dose which down-regulates brain 5-HT2A/2C receptors, did not alter brain or platelet 5-HT transporters or platelet 5-HT2A receptors. Additionally, para-chloroamphetamine-(11 weeks) or fenfluramine-induced chronic (1.5-10 weeks) depletion of central nervous system 5-HT did not alter platelet 5-HT transporter or 5-HT2A receptor binding. Finally, there was no correlation between the number of 5-HT transporters in brain and platelets in any of the control or treatment groups. These findings suggest that the observed changes in platelet 5-HT transporter and 5-HT2A receptor binding in depressed patients are more apt to be of genetic origin (i.e., trait-dependent) rather than an epiphenomenon of hypercortisolemia or altered central nervous system 5-HT status. 16. Constitutively Active 5-HT Receptors: An Explanation of How 5-HT Antagonists Inhibit Gut Motility in Species Where 5-HT is Not an Enteric Neurotransmitter? PubMed Central Spencer, Nick J. 2015-01-01 Antagonists of 5-Hydroxytryptamine (5-HT) receptors are well known to inhibit gastrointestinal (GI)-motility and transit in a variety of mammals, including humans. Originally, these observations had been interpreted by many investigators (including us) as evidence that endogenous 5-HT plays a major role in GI motility. This seemed a logical assumption. However, the story changed dramatically after recent studies revealed that 5-HT antagonists still blocked major GI motility patterns (peristalsis and colonic migrating motor complexes) in segments of intestine depleted of all 5-HT. Then, these results were further supported by Dr. Gershons' laboratory, which showed that genetic deletion of all genes that synthesizes 5-HT had minor, or no inhibitory effects on GI transit in vivo. If 5-HT was essential for GI motility patterns and transit, then one would expect major disruptions in motility and transit when 5-HT synthesis was genetically ablated. This does not occur. The inhibitory effects of 5-HT antagonists on GI motility clearly occur independently of any 5-HT in the gut. Evidence now suggests that 5-HT antagonists act on 5-HT receptors in the gut which are constitutively active, and don't require 5-HT for their activation. This would explain a long-standing mystery of how 5-HT antagonists inhibit gut motility in species like mice, rats, and humans where 5-HT is not an enteric neurotransmitter. Studies are now increasingly demonstrating that the presence of a neurochemical in enteric neurons does not mean they function as neurotransmitters. Caution should be exercised when interpreting any inhibitory effects of 5-HT antagonists on GI motility. PMID:26732863 17. [CAS General Standards 2012 ERIC Educational Resources Information Center Council for the Advancement of Standards in Higher Education, 2011 2011-01-01 The mission of the Council for the Advancement of Standards in Higher Education (CAS) is to promote the improvement of programs and services to enhance the quality of student learning and development. CAS is a consortium of professional associations who work collaboratively to develop and promulgate standards and guidelines and to encourage… 18. [CAS General Standards 2012 ERIC Educational Resources Information Center Council for the Advancement of Standards in Higher Education, 2011 2011-01-01 The mission of the Council for the Advancement of Standards in Higher Education (CAS) is to promote the improvement of programs and services to enhance the quality of student learning and development. CAS is a consortium of professional associations who work collaboratively to develop and promulgate standards and guidelines and to encourage… 19. In vivo genome editing using Staphylococcus aureus Cas9 PubMed Central Ran, F. Ann; Cong, Le; Yan, Winston X.; Scott, David A.; Gootenberg, Jonathan S.; Kriz, Andrea J.; Zetsche, Bernd; Shalem, Ophir; Wu, Xuebing; Makarova, Kira S.; Koonin, Eugene; Sharp, Phillip A.; Zhang, Feng 2015-01-01 The RNA-guided endonuclease Cas9 has emerged as a versatile genome-editing platform. However, the size of the commonly used Cas9 from Streptococcus pyogenes (SpCas9) limits its utility for basic research and therapeutic applications that employ the highly versatile adeno-associated virus (AAV) delivery vehicle. Here, we characterize six smaller Cas9 orthologs and show that Cas9 from Staphylococcus aureus (SaCas9) can edit the genome with efficiencies similar to those of SpCas9, while being >1kb shorter. We packaged SaCas9 and its sgRNA expression cassette into a single AAV vector and targeted the cholesterol regulatory gene Pcsk9 in the mouse liver. Within one week of injection, we observed >40% gene modification, accompanied by significant reductions in serum Pcsk9 and total cholesterol levels. We further demonstrate the power of using BLESS to assess the genome-wide targeting specificity of SaCas9 and SpCas9, and show that SaCas9 can mediate genome editing in vivo with high specificity. PMID:25830891 20. 5-HT spatial distribution imaging with multiphoton excitation of 5-HT correlative visible fluorescence in live cells NASA Astrophysics Data System (ADS) Zhang, Zhihong; Zeng, Shaoqun; Liu, Yafeng; Zhou, Wei; Chen, Tongsheng; Luo, Qingming 2002-04-01 The autofluorescence of 5-Hydroxytryptamine (5-HT) loaded rat mucosal mast cells (RBL-2H3 cells) is imaged with multiphoton excitation laser scanning microscope (MPELSM). 5-HT correlative visible fluorescence (Fco-vis) excited with 740-nm multiphoton excitation is observed in live cells for the first time, and the generating mechanism of 5-HT Fco-vis is studied. The spatial distribution of 5-HT in live cells is imaged at high spatial resolution in our experiment, which provides a new way to study the correlation between 5-HT spatial distribution and content, and the cellular functional state in live tissue or cells. 1. Cas1-Cas2 complex formation mediates spacer acquisition during CRISPR-Cas adaptive immunity. PubMed Nuñez, James K; Kranzusch, Philip J; Noeske, Jonas; Wright, Addison V; Davies, Christopher W; Doudna, Jennifer A 2014-06-01 The initial stage of CRISPR-Cas immunity involves the integration of foreign DNA spacer segments into the host genomic CRISPR locus. The nucleases Cas1 and Cas2 are the only proteins conserved among all CRISPR-Cas systems, yet the molecular functions of these proteins during immunity are unknown. Here we show that Cas1 and Cas2 from Escherichia coli form a stable complex that is essential for spacer acquisition and determine the 2.3-Å-resolution crystal structure of the Cas1-Cas2 complex. Mutations that perturb Cas1-Cas2 complex formation disrupt CRISPR DNA recognition and spacer acquisition in vivo. Active site mutants of Cas2, unlike those of Cas1, can still acquire new spacers, thus indicating a nonenzymatic role of Cas2 during immunity. These results reveal the universal roles of Cas1 and Cas2 and suggest a mechanism by which Cas1-Cas2 complexes specify sites of CRISPR spacer integration. 2. Une étude cas-témoins pour déterminer les facteurs de non-observance du suivi médical chez les patients diabétiques à Kinshasa, en 2010 PubMed Central Mense, Kennedy; Mapatano, Mala Ali; Mutombo, Paulin Beya; Muyer, Marie Claire 2014-01-01 Introduction Le diabète est un problème majeur de santé publique et un fardeau économique mondial qui n’épargne pas la RD-Congo. Bien que sa prise en charge soit codifiée, la plupart des diabétiques n'arrivent pas à respecter les rendez-vous de suivi. Cette étude vise principalement à identifier les déterminants de la non-observance du suivi médical chez les diabétiques à Kinshasa. Méthodes Il s'agit d'une étude cas-témoins où les cas sont les patients diabétiques non observant le suivi médical et les témoins, ceux répondant régulièrement au suivi médical. Couvrant la période du 1erjanvier au 31 décembre 2010, l’étude a porté sur un échantillon aléatoire de 154 sujets répartis entre 77 cas et 77 témoins. Résultats Les données indiquent une association entre la non-observance du suivi médical et le revenu (niveau de vie) des ménages. Les cas provenant des ménages à faible revenu courent six fois plus le risque d’être non-observants. Par contre, entre le niveau de connaissance et la non-observance l'association notée n’était pas statistiquement significative. Le respect des rendez-vous pourrait être amélioré de 77% si le revenu des ménages des diabétiques était augmenté. Le coût total mensuel du suivi médical est estimé à 27,2 USD, alors que le revenu permanant des ménages se situe à 306,6 USD. Conclusion Le bas niveau de vie mais pas celui de l'ignorance est un déterminant de la non-observance des visites de suivi du malade diabétique. PMID:25309658 3. Foreign DNA capture during CRISPR–Cas adaptive immunity PubMed Central Nuñez, James K.; Harrington, Lucas B.; Kranzusch, Philip J.; Engelman, Alan N.; Doudna, Jennifer A. 2015-01-01 Bacteria and archaea generate adaptive immunity against phages and plasmids by integrating foreign DNA of specific 30–40 base pair (bp) lengths into clustered regularly interspaced short palindromic repeats (CRISPR) loci as spacer segments1–6. The universally conserved Cas1–Cas2 integrase complex catalyzes spacer acquisition using a direct nucleophilic integration mechanism similar to retroviral integrases and transposases7–13. How the Cas1–Cas2 complex selects foreign DNA substrates for integration remains unknown. Here we present X-ray crystal structures of the Escherichia coli Cas1–Cas2 complex bound to cognate 33 nucleotide (nt) protospacer DNA substrates. The protein complex creates a curved binding surface spanning the length of the DNA and splays the ends of the protospacer to allow each terminal nucleophilic 3′–OH to enter a channel leading into the Cas1 active sites. Phosphodiester backbone interactions between the protospacer and the proteins explain the sequence-nonspecific substrate selection observed in vivo2–4. Our results uncover the structural basis for foreign DNA capture and the mechanism by which Cas1–Cas2 functions as a molecular ruler to dictate the sequence architecture of CRISPR loci. PMID:26503043 4. Foreign DNA capture during CRISPR-Cas adaptive immunity. PubMed Nuñez, James K; Harrington, Lucas B; Kranzusch, Philip J; Engelman, Alan N; Doudna, Jennifer A 2015-11-26 Bacteria and archaea generate adaptive immunity against phages and plasmids by integrating foreign DNA of specific 30-40-base-pair lengths into clustered regularly interspaced short palindromic repeat (CRISPR) loci as spacer segments. The universally conserved Cas1-Cas2 integrase complex catalyses spacer acquisition using a direct nucleophilic integration mechanism similar to retroviral integrases and transposases. How the Cas1-Cas2 complex selects foreign DNA substrates for integration remains unknown. Here we present X-ray crystal structures of the Escherichia coli Cas1-Cas2 complex bound to cognate 33-nucleotide protospacer DNA substrates. The protein complex creates a curved binding surface spanning the length of the DNA and splays the ends of the protospacer to allow each terminal nucleophilic 3'-OH to enter a channel leading into the Cas1 active sites. Phosphodiester backbone interactions between the protospacer and the proteins explain the sequence-nonspecific substrate selection observed in vivo. Our results uncover the structural basis for foreign DNA capture and the mechanism by which Cas1-Cas2 functions as a molecular ruler to dictate the sequence architecture of CRISPR loci. 5. Simulated transient behavior of HT9 cladding SciTech Connect Cannon, N.S.; Huang, F.H.; Hamilton, M.L. 1988-09-01 6. The First Direct Measurement to the Diameter of a Population II Star; Observationally Determined Fundamental Properties of µ Cas A with the CHARA Array NASA Astrophysics Data System (ADS) Boyajian, Tabetha S.; McAlister, H. A. 2007-12-01 Possessing the longest optical interferometric baselines in the world, the CHARA Array is uniquely suited to measure the diameters of stars, which are generally unresolved by other optical interferometers. Using the longest baselines of the CHARA Array, we have measured the angular diameter of the subdwarf µ Cas A, the first such determination for a halo population star. We compare this result to new diameters for the K0 V stars, σ Dra and HD 10780, and find that the metal-poor star, µ Cas A, has an effective temperature (Teff=5353±26; K), radius (R=0.779±0.004 Rsun), and absolute luminosity (L=0.4475±0.0097 Lsun) comparable to the other two stars with later spectral types. We show that these results provide a key to understanding the fundamental relationships for stars with low metallicity. In addition, we present the current results to our survey of nearby, main sequence, A, F, and G-type stars with the CHARA Array in order to determine highly accurate angular diameters. The accuracy and target sample range are aimed at refining, as well as expanding, the existing diameter measurements, which are used in the calibration of numerous less direct methods based on photometric parameters to predict stellar diameters and effective temperatures of stars. Currently, we have measured diameters to thirty-two new objects. Research at the CHARA Array is supported by the College of Arts and Sciences at Georgia State University and by the National Science Foundation through NSF Grant AST 0606958. 7. Convergence of Melatonin and Serotonin (5-HT) Signaling at MT2/5-HT2C Receptor Heteromers* PubMed Central Kamal, Maud; Gbahou, Florence; Guillaume, Jean-Luc; Daulat, Avais M.; Benleulmi-Chaachoua, Abla; Luka, Marine; Chen, Patty; Kalbasi Anaraki, Dina; Baroncini, Marc; Mannoury la Cour, Clotilde; Millan, Mark J.; Prevot, Vincent; Delagrange, Philippe; Jockers, Ralf 2015-01-01 Inasmuch as the neurohormone melatonin is synthetically derived from serotonin (5-HT), a close interrelationship between both has long been suspected. The present study reveals a hitherto unrecognized cross-talk mediated via physical association of melatonin MT2 and 5-HT2C receptors into functional heteromers. This is of particular interest in light of the “synergistic” melatonin agonist/5-HT2C antagonist profile of the novel antidepressant agomelatine. A suite of co-immunoprecipitation, bioluminescence resonance energy transfer, and pharmacological techniques was exploited to demonstrate formation of functional MT2 and 5-HT2C receptor heteromers both in transfected cells and in human cortex and hippocampus. MT2/5-HT2C heteromers amplified the 5-HT-mediated Gq/phospholipase C response and triggered melatonin-induced unidirectional transactivation of the 5-HT2C protomer of MT2/5-HT2C heteromers. Pharmacological studies revealed distinct functional properties for agomelatine, which shows “biased signaling.” These observations demonstrate the existence of functionally unique MT2/5-HT2C heteromers and suggest that the antidepressant agomelatine has a distinctive profile at these sites potentially involved in its therapeutic effects on major depression and generalized anxiety disorder. Finally, MT2/5-HT2C heteromers provide a new strategy for the discovery of novel agents for the treatment of psychiatric disorders. PMID:25770211 8. Convergence of melatonin and serotonin (5-HT) signaling at MT2/5-HT2C receptor heteromers. PubMed Kamal, Maud; Gbahou, Florence; Guillaume, Jean-Luc; Daulat, Avais M; Benleulmi-Chaachoua, Abla; Luka, Marine; Chen, Patty; Kalbasi Anaraki, Dina; Baroncini, Marc; Mannoury la Cour, Clotilde; Millan, Mark J; Prevot, Vincent; Delagrange, Philippe; Jockers, Ralf 2015-05-01 Inasmuch as the neurohormone melatonin is synthetically derived from serotonin (5-HT), a close interrelationship between both has long been suspected. The present study reveals a hitherto unrecognized cross-talk mediated via physical association of melatonin MT2 and 5-HT2C receptors into functional heteromers. This is of particular interest in light of the "synergistic" melatonin agonist/5-HT2C antagonist profile of the novel antidepressant agomelatine. A suite of co-immunoprecipitation, bioluminescence resonance energy transfer, and pharmacological techniques was exploited to demonstrate formation of functional MT2 and 5-HT2C receptor heteromers both in transfected cells and in human cortex and hippocampus. MT2/5-HT2C heteromers amplified the 5-HT-mediated Gq/phospholipase C response and triggered melatonin-induced unidirectional transactivation of the 5-HT2C protomer of MT2/5-HT2C heteromers. Pharmacological studies revealed distinct functional properties for agomelatine, which shows "biased signaling." These observations demonstrate the existence of functionally unique MT2/5-HT2C heteromers and suggest that the antidepressant agomelatine has a distinctive profile at these sites potentially involved in its therapeutic effects on major depression and generalized anxiety disorder. Finally, MT2/5-HT2C heteromers provide a new strategy for the discovery of novel agents for the treatment of psychiatric disorders. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc. 9. Cas9 Functionally Opens Chromatin PubMed Central Barkal, Amira A.; Srinivasan, Sharanya; Hashimoto, Tatsunori; Gifford, David K.; Sherwood, Richard I. 2016-01-01 Using a nuclease-dead Cas9 mutant, we show that Cas9 reproducibly induces chromatin accessibility at previously inaccessible genomic loci. Cas9 chromatin opening is sufficient to enable adjacent binding and transcriptional activation by the settler transcription factor retinoic acid receptor at previously unbound motifs. Thus, we demonstrate a new use for Cas9 in increasing surrounding chromatin accessibility to alter local transcription factor binding. PMID:27031353 10. Accouchement gémellaire différé: à propos de deux cas observés à la maternité du Centre Hospitalier de Creil PubMed Central Ndoua, Claude Cyrille Noa; Fattouh, Meyssam; Mirdat, Shamsa; Kemfang, Jean Dupont; Kasia, Jean Marie; Pace, Christophe Di 2014-01-01 L'accouchement gémellaire différé définit un accouchement en deux ou plusieurs temps, avec l'expulsion spontanée d'un premier fœtus au deuxième ou au troisième trimestre, et un prolongement de la grossesse pour obtenir un accouchement du ou des fœtus restants en gestation le plus proche possible du terme. Cette technique est mise en œuvre, en cas de grossesse gémellaire pour prévenir la prématurité du fœtus restant après l'expulsion très prématurée d'un premier fœtus. Nous rapportons deux cas observés à la maternité du Centre Hospitalier de Creil avec des latences respectives de 3 et 52 jours pour lesquels nous discutons la prise en charge. PMID:25722777 11. Overview of CRISPR-Cas9 Biology. PubMed Ratner, Hannah K; Sampson, Timothy R; Weiss, David S 2016-12-01 Prokaryotes use diverse strategies to improve fitness in the face of different environmental threats and stresses, including those posed by mobile genetic elements (e.g., bacteriophages and plasmids). To defend against these elements, many bacteria and archaea use elegant, RNA-directed, nucleic acid-targeting adaptive restriction machineries called CRISPR -: Cas (CRISPR-associated) systems. While providing an effective defense against foreign genetic elements, these systems have also been observed to play critical roles in regulating bacterial physiology during environmental stress. Increasingly, CRISPR-Cas systems, in particular the Type II systems containing the Cas9 endonuclease, have been exploited for their ability to bind desired nucleic acid sequences, as well as direct sequence-specific cleavage of their targets. Cas9-mediated genome engineering is transcending biological research as a versatile and portable platform for manipulating genetic content in myriad systems. Here, we present a systematic overview of CRISPR-Cas history and biology, highlighting the revolutionary tools derived from these systems, which greatly expand the molecular biologists' toolkit. 12. Cas9 Variants Expand the Target Repertoire in Caenorhabditis elegans PubMed Central Bell, Ryan T.; Fu, Becky X. H.; Fire, Andrew Z. 2016-01-01 The proliferation of CRISPR/Cas9-based methods in Caenorhabditis elegans has enabled efficient genome editing and precise genomic tethering of Cas9 fusion proteins. Experimental designs using CRISPR/Cas9 are currently limited by the need for a protospacer adjacent motif (PAM) in the target with the sequence NGG. Here we report the characterization of two modified Cas9 proteins in C. elegans that recognize NGA and NGCG PAMs. We found that each variant could stimulate homologous recombination with a donor template at multiple loci and that PAM specificity was comparable to that of wild-type Cas9. To directly compare effectiveness, we used CRISPR/Cas9 genome editing to generate a set of assay strains with a common single-guide RNA (sgRNA) target sequence, but that differ in the juxtaposed PAM (NGG, NGA, or NGCG). In this controlled setting, we determined that the NGA PAM Cas9 variant can be as effective as wild-type Cas9. We similarly edited a genomic target to study the influence of the base following the NGA PAM. Using four strains with four NGAN PAMs differing only at the fourth position and adjacent to the same sgRNA target, we observed that efficient homologous replacement was attainable with any base in the fourth position, with an NGAG PAM being the most effective. In addition to demonstrating the utility of two Cas9 mutants in C. elegans and providing reagents that permit CRISPR/Cas9 experiments with fewer restrictions on potential targets, we established a means to benchmark the efficiency of different Cas9::PAM combinations that avoids variations owing to differences in the sgRNA sequence. PMID:26680661 13. Cas9 Variants Expand the Target Repertoire in Caenorhabditis elegans. PubMed Bell, Ryan T; Fu, Becky X H; Fire, Andrew Z 2016-02-01 The proliferation of CRISPR/Cas9-based methods in Caenorhabditis elegans has enabled efficient genome editing and precise genomic tethering of Cas9 fusion proteins. Experimental designs using CRISPR/Cas9 are currently limited by the need for a protospacer adjacent motif (PAM) in the target with the sequence NGG. Here we report the characterization of two modified Cas9 proteins in C. elegans that recognize NGA and NGCG PAMs. We found that each variant could stimulate homologous recombination with a donor template at multiple loci and that PAM specificity was comparable to that of wild-type Cas9. To directly compare effectiveness, we used CRISPR/Cas9 genome editing to generate a set of assay strains with a common single-guide RNA (sgRNA) target sequence, but that differ in the juxtaposed PAM (NGG, NGA, or NGCG). In this controlled setting, we determined that the NGA PAM Cas9 variant can be as effective as wild-type Cas9. We similarly edited a genomic target to study the influence of the base following the NGA PAM. Using four strains with four NGAN PAMs differing only at the fourth position and adjacent to the same sgRNA target, we observed that efficient homologous replacement was attainable with any base in the fourth position, with an NGAG PAM being the most effective. In addition to demonstrating the utility of two Cas9 mutants in C. elegans and providing reagents that permit CRISPR/Cas9 experiments with fewer restrictions on potential targets, we established a means to benchmark the efficiency of different Cas9::PAM combinations that avoids variations owing to differences in the sgRNA sequence. 14. Inflammation and peripheral 5-HT7 receptors: the role of 5-HT7 receptors in carrageenan induced inflammation in rats. PubMed Albayrak, Abdulmecit; Halici, Zekai; Cadirci, Elif; Polat, Beyzagul; Karakus, Emre; Bayir, Yasin; Unal, Deniz; Atasoy, Mustafa; Dogrul, Ahmet 2013-09-05 The aim of this study was: (1) to investigate possible role for 5-HT7 receptors in carrageenan induced inflammatory paw oedema in rats; (2) to determine the presence of 5-HT7 receptors in rat paw tissue; (3) to observe the effects of 5-HT7 receptor agonist and antagonist administration on inflammation; and (4) to determine a unique mechanism for inflammatory processes via 5-HT7 receptors. Effects of 5-HT7 receptor agonist, antagonist and indomethacin were investigated in carrageenan induced paw oedema in rats. Blood and tissue samples were collected and evaluated biochemically for serum cytokine levels, tissue oxidant-antioxidant balance and histopathologically for inflammatory cell accumulation. We performed Real Time PCR analyses for tissue 5-HT7 receptor and COX mRNA expressions. The 5-HT7 receptor agonist AS-19 exerted significant anti-inflammatory effect both alone and in combination with indomethacin. Antagonist, SB269970, did not affect inflammation alone but decreased the effects of agonist when co-administered. 5-HT7 mRNA levels were higher in the carrageenan group than healthy control. Carrageenan+indometacin group decreased the mRNA expression of 5-HT7 when compared to carrageenan group. While agonist administration decreased 5-HT7 mRNA expression when compared to carrageenan group. Agonist decreased paw COX expression. Agonist also decreased serum cytokine levels and tissue oxidative stress. In conclusion, this study demonstrated for the first time that 5-HT7 receptors are expressed in rat paw tissue and that this expression responds to inflammatory stimuli. The 5-HT7 receptor may be a promising new therapeutic target for prevention of inflammation and inflammatory disorders and may also provide a new glimpse into inflammation pathophysiology. 15. Not all predicted CRISPR-Cas systems are equal: isolated cas genes and classes of CRISPR like elements. PubMed Zhang, Quan; Ye, Yuzhen 2017-02-06 The CRISPR-Cas systems in prokaryotes are RNA-guided immune systems that target and deactivate foreign nucleic acids. A typical CRISPR-Cas system consists of a CRISPR array of repeat and spacer units, and a locus of cas genes. The CRISPR and the cas locus are often located next to each other in the genomes. However, there is no quantitative estimate of the co-location. In addition, ad-hoc studies have shown that some non-CRISPR genomic elements contain repeat-spacer-like structures and are mistaken as CRISPRs. Using available genome sequences, we observed that a significant number of genomes have isolated cas loci and/or CRISPRs. We found that 11%, 22% and 28% of the type I, II and III cas loci are isolated (without CRISPRs in the same genomes at all or with CRISPRs distant in the genomes), respectively. We identified a large number of genomic elements that superficially reassemble CRISPRs but don't contain diverse spacers and have no companion cas genes. We called these elements false-CRISPRs and further classified them into groups, including tandem repeats and Staphylococcus aureus repeat (STAR)-like elements. This is the first systematic study to collect and characterize false-CRISPR elements. We demonstrated that false-CRISPRs could be used to reduce the false annotation of CRISPRs, therefore showing them to be useful for improving the annotation of CRISPR-Cas systems. 16. How type II CRISPR-Cas establish immunity through Cas1-Cas2-mediated spacer integration. PubMed Xiao, Yibei; Ng, Sherwin; Nam, Ki Hyun; Ke, Ailong 2017-09-04 CRISPR (clustered regularly interspaced short palindromic repeats) and the nearby cas (CRISPR-associated) operon establish an RNA-based adaptive immunity system in prokaryotes(1-5). Molecular memory is created when a short foreign DNA-derived prespacer is integrated into the CRISPR array as a new spacer(6-9). Whereas the RNA-guided CRISPR interference mechanism varies widely among CRISPR-Cas systems, the spacer integration mechanism is essentially identical(7-9). The conserved Cas1 and Cas2 proteins form an integrase complex consisting two distal Cas1 dimers bridged by a Cas2 dimer in the middle(6,10). The prespacer is bound by Cas1-Cas2 as a dual forked DNA, and the terminal 3'-OH of each 3'-overhang serves as an attacking nucleophile during integration(11-14). Importantly, the prespacer is preferentially integrated into the leader-proximal region of the CRISPR array(1,7,10,15), guided by the leader sequence and a pair of inverted repeats (IRs) inside the CRISPR repeat(7,15-20). Spacer integration in the most well-studied Escherichia coli Type I-E CRISPR system further relies on the bacterial Integration Host Factor (IHF)(21,22). In Type II-A CRISPR, however, Cas1-Cas2 alone integrates spacer efficiently in vitro(18); other Cas proteins (Cas9 and Csn2) play accessory roles in prespacer biogenesis(17,23). Focusing on the Enterococcus faecalis Type II-A system(24), here we report four structure snapshots of Cas1-Cas2 during spacer integration. EfaCas1-Cas2 selectively binds to a splayed 30-bp prespacer bearing 4-nt 3'-overhangs. Three molecular events take place upon encountering a target: Cas1-Cas2/prespacer first searches for half-sites stochastically, then preferentially interacts with the leader-side CRISPR repeat and catalyzes a nucleophilic attack that connects one strand of the leader-proximal repeat to the prespacer 3'-overhang. Recognition of the spacer half-site requires DNA bending and leads to full integration. We derive a mechanistic framework 17. Incubation of cocaine cue reactivity associates with neuroadaptations in the cortical serotonin (5-HT) 5-HT2C receptor (5-HT2CR) system. PubMed Swinford-Jackson, S E; Anastasio, N C; Fox, R G; Stutz, S J; Cunningham, K A 2016-06-02 18. 5-HT precursor loading, but not 5-HT receptor agonists, increases motor function after spinal cord contusion in adult rats. PubMed Hayashi, Y; Jacob-Vadakot, S; Dugan, E A; McBride, S; Olexa, R; Simansky, K; Murray, M; Shumsky, J S 2010-01-01 Serotonergic (5-HT) receptors are upregulated following spinal cord transection. Stimulation by administration of serotonergic receptor agonists has been successful in improving hindlimb function. We tested whether this strategy would be successful in incomplete injury models (moderate or severe thoracic contusion) where descending projections are partially spared which should produce less denervation-induced receptor upregulation. Adult rats received midthoracic moderate (MOD: 25 mm drop) or severe (SEV: 50 mm drop) contusion injuries. Distribution of 5-HT and its transporter and expression of 5-HT(2C) receptors were evaluated in lumbar spinal cord and motor response to 5-HT receptor activation was assessed using open field locomotion (BBB) score, percent weight supported treadmill stepping (%WS) and evaluation of hindlimb muscle activation (tremor and serotonin syndrome). 5-HT immunostaining 3 months post-contusion revealed few 5-HT fibers caudal to the severe contusion, and more spared caudal to the moderate contusion. The distribution of 5-HT transporter paralleled 5-HT staining, but was more greatly reduced. Thus serotonin reuptake may be less efficient in the injured spinal cord. Immunostaining for the 5-HT(2C) receptor in the dorsal and ventral horns at L5 showed significant upregulation in SEV, compared to sham or MOD rats. Neither 5-HT(2C) nor 5-HT(1A) receptor agonists, alone or in combination, nor the serotonin transporter inhibitor d-fenfluramine modified BBB scores or %WS in either group. Despite the increased sensitivity of post-synaptic targets, agonist treatment did not improve function in SEV rats. We conclude that selective 5-HT(2C) or 5-HT(1A) receptor activation was not effective in improving hindlimb function after incomplete lesions. In contrast, the 5-HT precursor 5-hydroxytryptophan (L-5-HTP), which leads to activation of all classes of 5-HT receptors, increased both %WS and hindlimb activity in the MOD group. While no side effects were 19. Structures of Cas9 endonucleases reveal RNA-mediated conformational activation. PubMed Jinek, Martin; Jiang, Fuguo; Taylor, David W; Sternberg, Samuel H; Kaya, Emine; Ma, Enbo; Anders, Carolin; Hauer, Michael; Zhou, Kaihong; Lin, Steven; Kaplan, Matias; Iavarone, Anthony T; Charpentier, Emmanuelle; Nogales, Eva; Doudna, Jennifer A 2014-03-14 Type II CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) systems use an RNA-guided DNA endonuclease, Cas9, to generate double-strand breaks in invasive DNA during an adaptive bacterial immune response. Cas9 has been harnessed as a powerful tool for genome editing and gene regulation in many eukaryotic organisms. We report 2.6 and 2.2 angstrom resolution crystal structures of two major Cas9 enzyme subtypes, revealing the structural core shared by all Cas9 family members. The architectures of Cas9 enzymes define nucleic acid binding clefts, and single-particle electron microscopy reconstructions show that the two structural lobes harboring these clefts undergo guide RNA-induced reorientation to form a central channel where DNA substrates are bound. The observation that extensive structural rearrangements occur before target DNA duplex binding implicates guide RNA loading as a key step in Cas9 activation. 20. Characterization of 5-HT receptors mediating constriction of porcine carotid arteriovenous anastomoses; involvement of 5-HT1B/1D and novel receptors PubMed Central De Vries, Peter; Villalón, Carlos M; Heiligers, Jan P C; Saxena, Pramod R 1998-01-01 It was previously shown that porcine cranial arteriovenous anastomoses (AVAs) constrict to 5-hydroxytryptamine (5-HT), ergotamine, dihydroergotamine, as well as sumatriptan and that sumatriptan acts exclusively via 5-HT1B/1D receptors. The present study was devoted to establish the contribution of 5-HT1B/1D receptors in the constriction of AVAs elicited by 5-HT (in presence of 0.5 mg kg−1 ketanserin), ergotamine and dihydroergotamine in anaesthetized pigs.Intracarotid infusion of 5-HT (2 μg kg−1 min−1) and intravenous doses of ergotamine (2.5–20 μg kg−1) and dihydroergotamine (3–100 μg kg−1) reduced AVA and increased nutrient blood flows and vascular conductances. The vasodilator response to 5-HT, observed mainly in the skin and ear, was much more prominent than that of the ergot alkaloids.Treatment with the 5-HT1B/1D receptor antagonist GR127935 (0.5 mg kg−1, i.v.) significantly attenuated both ergot-induced AVA constriction and arteriolar dilatation, whereas GR127935 only slightly affected the carotid vascular effects of 5-HT.The results suggest that 5-HT constricts carotid AVAs primarily via receptors, which seem to differ from those (5-HT1B/1D) stimulated by sumatriptan. The ergot alkaloids produce AVA constriction for a substantial part via 5-HT1B/1D receptors, but also stimulate unidentified receptors. Both these non-5-HT1B/1D receptors may be targets for the development of novel antimigraine drugs.The moderate vasodilator response to the ergot derivatives seems to be mediated, at least in part, by 5-HT1B/1D receptors, whereas the arteriolar dilatation caused by 5-HT may be mediated by other, possibly 5-HT7 receptors. PMID:9605562 1. Cerebral 5-HT release correlates with [(11)C]Cimbi36 PET measures of 5-HT2A receptor occupancy in the pig brain. PubMed Jørgensen, Louise M; Weikop, Pia; Villadsen, Jonas; Visnapuu, Tanel; Ettrup, Anders; Hansen, Hanne D; Baandrup, Anders O; Andersen, Flemming L; Bjarkam, Carsten R; Thomsen, Carsten; Jespersen, Bo; Knudsen, Gitte M 2017-02-01 Positron emission tomography (PET) can, when used with appropriate radioligands, non-invasively generate temporal and spatial information about acute changes in brain neurotransmitter systems. We for the first time evaluate the novel 5-HT2A receptor agonist PET radioligand, [(11)C]Cimbi-36, for its sensitivity to detect changes in endogenous cerebral 5-HT levels, as induced by different pharmacological challenges. To enable a direct translation of PET imaging data to changes in brain 5-HT levels, we calibrated the [(11)C]Cimbi-36 PET signal in the pig brain by simultaneous measurements of extracellular 5-HT levels with microdialysis and [(11)C]Cimbi-36 PET after various acute interventions (saline, citalopram, citalopram + pindolol, fenfluramine). In a subset of pigs, para-chlorophenylalanine pretreatment was given to deplete cerebral 5-HT. The interventions increased the cerebral extracellular 5-HT levels to 2-11 times baseline, with fenfluramine being the most potent pharmacological enhancer of 5-HT release, and induced a varying degree of decline in [(11)C]Cimbi-36 binding in the brain, consistent with the occupancy competition model. The observed correlation between changes in the extracellular 5-HT level in the pig brain and the 5-HT2A receptor occupancy indicates that [(11)C]Cimbi-36 binding is sensitive to changes in endogenous 5-HT levels, although only detectable with PET when the 5-HT release is sufficiently high. 2. Characterization and evolution of Salmonella CRISPR-Cas systems. PubMed Shariat, Nikki; Timme, Ruth E; Pettengill, James B; Barrangou, Rodolphe; Dudley, Edward G 2015-02-01 Prokaryotic CRISPR-Cas (clustered regularly interspaced short palindromic repeats and CRISPR-associated genes) systems provide adaptive immunity from invasive genetic elements and encompass three essential features: (i) cas genes, (ii) a CRISPR array composed of spacers and direct repeats and (iii) an AT-rich leader sequence upstream of the array. We performed in-depth sequence analysis of the CRISPR-Cas systems in >600 Salmonella, representing four clinically prevalent serovars. Each CRISPR-Cas feature is extremely conserved in the Salmonella, and the CRISPR1 locus is more highly conserved than CRISPR2. Array composition is serovar-specific, although no convincing evidence of recent spacer acquisition against exogenous nucleic acids exists. Only 12% of spacers match phage and plasmid sequences and self-targeting spacers are associated with direct repeat variants. High nucleotide identity (>99.9%) exists across the cas operon among isolates of a single serovar and in some cases this conservation extends across divergent serovars. These observations reflect historical CRISPR-Cas immune activity, showing that this locus has ceased undergoing adaptive events. Intriguingly, the high level of conservation across divergent serovars shows that the genetic integrity of these inactive loci is maintained over time, contrasting with the canonical view that inactive CRISPR loci degenerate over time. This thorough characterization of Salmonella CRISPR-Cas systems presents new insights into Salmonella CRISPR evolution, particularly with respect to cas gene conservation, leader sequences, organization of direct repeats and protospacer matches. Collectively, our data suggest that Salmonella CRISPR-Cas systems are no longer immunogenic; rather, their impressive conservation indicates they may have an alternative function in Salmonella. 3. Characterization and evolution of Salmonella CRISPR-Cas systems. PubMed Shariat, Nikki; Timme, Ruth E; Pettengill, James B; Barrangou, Rodolphe; Dudley, Edward G 2015-02-01 Prokaryotic CRISPR-Cas (clustered regularly interspaced short palindromic repeats and CRISPR-associated genes) systems provide adaptive immunity from invasive genetic elements and encompass three essential features: (i) cas genes, (ii) a CRISPR array composed of spacers and direct repeats and (iii) an AT-rich leader sequence upstream of the array. We performed in-depth sequence analysis of the CRISPR-Cas systems in >600 Salmonella, representing four clinically prevalent serovars. Each CRISPR-Cas feature is extremely conserved in the Salmonella, and the CRISPR1 locus is more highly conserved than CRISPR2. Array composition is serovar-specific, although no convincing evidence of recent spacer acquisition against exogenous nucleic acids exists. Only 12 % of spacers match phage and plasmid sequences and self-targeting spacers are associated with direct repeat variants. High nucleotide identity (>99.9 %) exists across the cas operon among isolates of a single serovar and in some cases this conservation extends across divergent serovars. These observations reflect historical CRISPR-Cas immune activity, showing that this locus has ceased undergoing adaptive events. Intriguingly, the high level of conservation across divergent serovars shows that the genetic integrity of these inactive loci is maintained over time, contrasting with the canonical view that inactive CRISPR loci degenerate over time. This thorough characterization of Salmonella CRISPR-Cas systems presents new insights into Salmonella CRISPR evolution, particularly with respect to cas gene conservation, leader sequences, organization of direct repeats and protospacer matches. Collectively, our data suggest that Salmonella CRISPR-Cas systems are no longer immunogenic; rather, their impressive conservation indicates they may have an alternative function in Salmonella. 4. Application of CRISPR/Cas9 to Autophagy Research. PubMed O'Prey, J; Sakamaki, J; Baudot, A D; New, M; Van Acker, T; Tooze, S A; Long, J S; Ryan, K M 2017-01-01 The ability to efficiently modulate autophagy activity is paramount in the study of the field. Conventional broad-range autophagy inhibitors and genetic manipulation using RNA interference (RNAi), although widely used in autophagy research, are often limited in specificity or efficacy. In this chapter, we address the problems of conventional autophagy-modulating tools by exploring the use of three different CRISPR/Cas9 systems to abrogate autophagy in numerous human and mouse cell lines. The first system generates cell lines constitutively deleted of ATG5 or ATG7 whereas the second and third systems express a Tet-On inducible-Cas9 that enables regulated deletion of ATG5 or ATG7. We observed the efficiency of autophagy inhibition using the CRISPR/Cas9 strategy to surpass that of RNAi, and successfully generated cells with complete and sustained autophagy disruption through the CRISPR/Cas9 technology. 5. Bi-directional modulation of BNST neurons by 5-HT: Molecular expression and functional properties of excitatory 5-HT receptor subtypes PubMed Central Guo, Ji-Dong; Hammack, Sayamwong E.; Hazra, Rimi; Levita, Liat; Rainnie, Donald G. 2009-01-01 Activation of neurons in the anterolateral bed nucleus of the stria terminalis (BNSTALG) plays an important role in mediating the behavioral response to stressful and anxiogenic stimuli. Application of 5-HT elicits complex postsynaptic responses in BNSTALG neurons, which includes 1) membrane hyperpolarization (5-HTHyp), 2) hyperpolarization followed by depolarization (5-HTHyp-Dep), 3) depolarization (5-HTDep) or 4) no response (5-HTNR). We have shown that the inhibitory response is mediated by activation of postsynaptic 5-HT1A receptors. Here, we used a combination of in vitro whole-cell patch-clamp recording and single cell reverse transcriptase polymerase chain reaction (RT-PCR) to determine the pharmacological properties and molecular profile of 5-HT receptor subtypes mediating the excitatory response to 5-HT in BNSTALG neurons. We show that the depolarizing component of both the 5-HTHyp/Dep and the 5-HTDep response was mediated by activation of 5-HT2A, 5-HT2C and/or 5-HT7 receptors. Single cell RT-PCR data revealed that 5-HT7 receptors (46%) and 5-HT1A receptors (41%) are the most prevalent receptor subtypes expressed in BNSTALG neurons. Moreover, 5-HT receptor subtypes are differentially expressed in Type I – III BNSTALG neurons. Hence, 5-HT2C receptors are almost exclusively expressed by Type III neurons, whereas 5-HT7 receptors are expressed by Type I and II neurons, but not Type III neurons. Conversely, 5-HT2A receptors are found predominantly in Type II neurons. Finally, bi-directional modulation of individual neurons occurs only in Type I and II neurons. Significantly the distribution of 5-HT receptor subtypes in BNSTALG neurons predicted the observed expression pattern of 5-HT responses determined pharmacologically. Together, these results suggest that 5-HT can differentially modulate the excitability of Type I – III neurons, and further suggest that bi-directional modulation of BNSTALG neurons occurs primarily through an interplay between 5-HT1A and 6. Dual nuclease activity of a Cas2 protein in CRISPR-Cas subtype I-B of Leptospira interrogans. PubMed Dixit, Bhuvan; Ghosh, Karukriti Kaushik; Fernandes, Gary; Kumar, Pankaj; Gogoi, Prerana; Kumar, Manish 2016-04-01 Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130 carries a set of cas genes associated with CRISPR-Cas subtype I-B. Herein, we report for the first time active transcription of a set of cas genes (cas1 to cas8) of L. interrogans where cas4, cas1, cas2 and cas6, cas3, cas8, cas7, cas5 are clustered together in two independent operons. As an initial step toward comprehensive understanding of CRISPR-Cas system in spirochete, the biochemical study of one of the core Leptospira Cas2 proteins (Lep_Cas2) showed nuclease activity on both DNA and RNA in a nonspecific manner. Additionally, unlike other known Cas2 proteins, Lep_Cas2 showed metal-independent RNase activity and preferential activity on RNA over DNA. These results provide insight for understanding Cas2 diversity existing in the prokaryotic adaptive immune system. 7. Serotonin (5-HT) regulates neurite outgrowth through 5-HT1A and 5-HT7 receptors in cultured hippocampal neurons. PubMed Rojas, Paulina S; Neira, David; Muñoz, Mauricio; Lavandero, Sergio; Fiedler, Jenny L 2014-08-01 Serotonin (5-HT) production and expression of 5-HT receptors (5-HTRs) occur early during prenatal development. Recent evidence suggests that, in addition to its classical role as a neurotransmitter, 5-HT regulates neuronal connectivity during mammalian development by modulating cell migration and neuronal cytoarchitecture. Given the variety of 5-HTRs, researchers have had difficulty clarifying the specific role of each receptor subtype in brain development. Signalling mediated by the G-protein-coupled 5-HT1A R and 5-HT7 R, however, has been associated with neuronal plasticity. Thus, we hypothesized that 5-HT promotes neurite outgrowth through 5-HT1A R and 5-HT7 R. The involvement of 5-HT1A R and 5-HT7 R in the morphology of rat hippocampal neurons was evaluated by treating primary cultures at 2 days in vitro with 5-HT and specific antagonists for 5-HT1A R and 5-HT7 R (WAY-100635 and SB269970, respectively). The stimulation of hippocampal neurons with 100 nM 5-HT for 24 hr produced no effect on either the number or the length of primary neurites. Nonetheless, after 5HT7 R was blocked, the addition of 5-HT increased the number of primary neurites, suggesting that 5HT7 R could inhibit neuritogenesis. In contrast, 5-HT induced secondary neurite outgrowth, an effect inhibited by 1 μM WAY-100635 or SB269970. These results suggest that both serotonergic receptors participate in secondary neurite outgrowth. We conclude that 5-HT1A R and 5-HT7 R regulate neuronal morphology in primary hippocampal cultures by promoting secondary neurite outgrowth. 8. Nucleosomes impede Cas9 access to DNA in vivo and in vitro PubMed Central Horlbeck, Max A; Witkowsky, Lea B; Guglielmi, Benjamin; Replogle, Joseph M; Gilbert, Luke A; Villalta, Jacqueline E; Torigoe, Sharon E; Tjian, Robert; Weissman, Jonathan S 2016-01-01 The prokaryotic CRISPR (clustered regularly interspaced palindromic repeats)-associated protein, Cas9, has been widely adopted as a tool for editing, imaging, and regulating eukaryotic genomes. However, our understanding of how to select single-guide RNAs (sgRNAs) that mediate efficient Cas9 activity is incomplete, as we lack insight into how chromatin impacts Cas9 targeting. To address this gap, we analyzed large-scale genetic screens performed in human cell lines using either nuclease-active or nuclease-dead Cas9 (dCas9). We observed that highly active sgRNAs for Cas9 and dCas9 were found almost exclusively in regions of low nucleosome occupancy. In vitro experiments demonstrated that nucleosomes in fact directly impede Cas9 binding and cleavage, while chromatin remodeling can restore Cas9 access. Our results reveal a critical role of eukaryotic chromatin in dictating the targeting specificity of this transplanted bacterial enzyme, and provide rules for selecting Cas9 target sites distinct from and complementary to those based on sequence properties. DOI: http://dx.doi.org/10.7554/eLife.12677.001 PMID:26987018 9. Hybrid solar cells from P3HT and silicon nanocrystals. PubMed Liu, Chin-Yi; Holman, Zachary C; Kortshagen, Uwe R 2009-01-01 We are reporting new hybrid solar cells based on blends of silicon nanocrystals (Si NCs) and poly-3(hexylthiophene) (P3HT) polymer in which a percolating network of the nanocrystals acts as the electron-conducting phase. The properties of composite Si NCs/P3HT devices made by spin-coating Si NCs and P3HT from a common solvent were studied as a function of Si NC size and Si NC/P3HT ratio. The open-circuit voltage and short-circuit current are observed to depend on the Si NC size due to changes in the bandgap and surface-area-to-volume ratio. Under simulated one-sun A.M. 1.5 direct illumination (100 mW/cm2), devices made with 35 wt % Si NCs 3-5 nm in size showed 1.15% power conversion efficiency. 10. 5-HT1-like receptor-mediated contraction in the human internal mammary artery. PubMed Yildiz, O; Ciçek, S; Ay, I; Tatar, H; Tuncer, M 1996-07-01 We wished to characterize the 5-hydroxytryptamine (5-HT) receptors mediating vasoconstriction in the human internal mammary artery (IMA). Segments of the IMA obtained from patients undergoing coronary by-pass surgery were suspended in an organ bath and exposed to 5-HT and sumatriptan (SUM), a 5-HT1-like receptor agonist, in the presence and absence of potassium chloride (KCl) and angiotensin II. 5-HT induced concentration-dependent contractions in all quiescent and pre-contracted preparations. SUM induced small contractions in 70% of quiescent IMA rings, whereas it elicited marked and concentration-dependent contractions in all of the preparations given a moderate tone by a threshold concentration of KCl and angiotensin II. The efficacy of SUM was higher in precontracted arteries. Concentration-effect curves (CEC) of 5-HT and SUM were not affected by the 5-HT3-receptor antagonist tropisetron (1 microM). The nonselective antagonist, methiothepin (30 nM), shifted the CEC of SUM to the right. 5-HT2A-receptor antagonist, ketanserin (1 microM) inhibited responses to 5-HT, whereas it affected only the responses to the smaller concentrations of SUM. When methiothepin (30 nM) was applied in the presence of ketanserin (1 microM), a further inhibition in the responses to 5-HT was observed. These results suggest that 5-HT1-like receptors mediate the contractile action of SUM and contribute to that of 5-HT in IMA. 11. Interactions of metoclopramide and ergotamine with human 5-HT3A receptors and human 5-HT reuptake carriers PubMed Central Walkembach, Jan; Brüss, Michael; Urban, Bernd W; Barann, Martin 2005-01-01 The actions of metoclopramide and ergotamine, drugs which are used as a combined migraine medication, on human (h)5-HT3A receptors and 5-HT reuptake carriers, stably expressed in HEK-293 cells, were studied with patch-clamp- and ([3H]5-HT)-uptake techniques. At clinical concentrations, metoclopramide inhibited peak and integrated currents through h5-HT3A receptors concentration-dependently (IC50=0.064 and 0.076 μM, respectively) when it was applied in equilibrium (60 s before and during 5-HT (30 μM) exposure). The onset and offset time constants of metoclopramide action were 1.3 and 2.1 s, respectively. The potency of metoclopramide when exclusively applied during the agonist pulse decreased more than 200-fold (IC50=19.0 μM, peak current suppression). Metoclopramide (0.10 μM) did not alter the EC50 of 5-HT-induced peak currents. In contrast to the lack of competitive interaction between metoclopramide and 5-HT in this functional assay, metoclopramide inhibited specific [3H]GR65630 binding to human h5-HT3A receptors in a surmountable manner. This seeming discrepancy between functional studies and radioligand binding experiments may be accounted for by (1) the slow kinetics of inhibition of peak currents by metoclopramide compared with the fast onset and offset kinetics of 5-HT-induced currents and (2) the low efficacy of metoclopramide in inhibiting radioligand binding (e.g. only 20% binding inhibition compared to 79% peak current suppression by 200 nM metoclopramide). At low concentrations (1–10 nM), ergotamine had no effect on 5-HT (30 μM)-induced peak currents. Above clinical concentrations, ergotamine (>3 μM) inhibited them. When both drugs were applied together (0.10 μM metoclopramide+0.001 to 0.01 μM ergotamine), an inhibition of both, peak and integrated current responses was observed. Neither metoclopramide (⩽30 μM) nor ergotamine (⩽30 μM) had an effect on the 5-HT reuptake carrier as they did not alter the 12. Incubation of cocaine cue reactivity associates with neuroadaptations in the cortical serotonin (5-HT) 5-HT2C receptor (5-HT2CR) system PubMed Central Swinford-Jackson, Sarah E.; Anastasio, Noelle C.; Fox, Robert G.; Stutz, Sonja J.; Cunningham, Kathryn A. 2016-01-01 Intensification of craving elicited by drug-associated cues during abstinence occurs over time in human cocaine users while elevation of cue reactivity (“incubation”) is observed in rats exposed to extended forced abstinence from cocaine self-administration. Incubation in rodents has been linked to time-dependent neuronal plasticity in the medial prefrontal cortex (mPFC). We tested the hypothesis that incubation of cue reactivity during abstinence from cocaine self-administration is accompanied by lower potency and/or efficacy of the selective 5-HT2CR agonist WAY163909 to suppress cue reactivity and a shift in the subcellular localization profile of the mPFC 5-HT2CR protein. We observed incubation of cue reactivity (measured as lever presses reinforced by the discrete cue complex) between Day 1 and Day 30 of forced abstinence from cocaine relative to sucrose self-administration. Pharmacological and biochemical analyses revealed that the potency of the selective 5-HT2CR agonist WAY163909 to suppress cue reactivity, the expression of synaptosomal 5-HT2CR protein in the mPFC, and the membrane to cytoplasmic expression of the 5-HT2CR in mPFC were lower on Day 30 vs. Day 1 of forced abstinence from cocaine self-administration. Incubation of cue reactivity assessed during forced abstinence from sucrose self-administration did not associate with 5-HT2CR protein expression in the mPFC. Collectively, these outcomes are the first indication that neuroadaptations in the 5-HT2CR system may contribute to incubation of cocaine cue reactivity. PMID:26926963 13. Direct CRISPR spacer acquisition from RNA by a natural reverse-transcriptase-Cas1 fusion protein PubMed Central Sidote, David J.; Markham, Laura M.; Sanchez-Amat, Antonio; Bhaya, Devaki; Lambowitz, Alan M.; Fire, Andrew Z. 2016-01-01 CRISPR (Clustered Regularly Interspaced Short Palindromic Repeat) systems mediate adaptive immunity in diverse prokaryotes. CRISPR-associated Cas1 and Cas2 proteins have been shown to enable adaptation to new threats in Type I and II CRISPR systems by the acquisition of short segments of DNA (“spacers”) from invasive elements. In several Type III CRISPR systems, Cas1 is naturally fused to a reverse transcriptase (RT). In the marine bacterium Marinomonas mediterranea (MMB-1), we show that an RT-Cas1 fusion enables the acquisition of RNA spacers in vivo in an RT-dependent manner. In vitro, the MMB-1 RT-Cas1 and Cas2 proteins catalyze ligation of RNA segments into the CRISPR array, followed by reverse transcription. These observations outline a host-mediated mechanism for reverse information flow from RNA to DNA. PMID:26917774 14. Evidence for the widespread distribution of CRISPR-Cas system in the Phylum Cyanobacteria. PubMed Cai, Fei; Axen, Seth D; Kerfeld, Cheryl A 2013-05-01 Members of the phylum Cyanobacteria inhabit ecologically diverse environments. However, the CRISPR-Cas (clustered regularly interspaced short palindromic repeats, CRISPR associated genes), an extremely adaptable defense system, has not been surveyed in this phylum. We analyzed 126 cyanobacterial genomes and, surprisingly, found CRISPR-Cas in the majority except the marine subclade (Synechococcus and Prochlorococcus), in which cyanophages are a known force shaping their evolution. Multiple observations of CRISPR loci in the absence of cas1/cas2 genes may represent an early stage of losing a CRISPR-Cas locus. Our findings reveal the widespread distribution of their role in the phylum Cyanobacteria and provide a first step to systematically understanding CRISPR-Cas systems in cyanobacteria. 15. Measurement of Flux Density of Cas A at Low Frequencies NASA Astrophysics Data System (ADS) Patil, Ajinkya; Fisher, R. 2012-01-01 Cas A is used as a flux calibrator throughout the radio spectrum. Therefore it is important to know the spectral and secular variations in its flux density. Earlier observations by Scott et. al. (1969) and Baars et. al. (1972) suggested a secular decrease in flux density of Cas A at a rate of about 1% per year at all frequencies. However later observations by Erickson & Perley (1975) and Read (1977) indicated anomalously high flux from Cas A at 38 MHz. Also, these observations suggested that the original idea of faster decay of the flux density rate at low frequencies may be in error or that something more complex than simple decay is affecting the flux density at low frequencies. The source changes at 38 MHz still remains a mystery. We intend to present the results of follow up observations made from 1995 to 1998 with a three element interferometer in Green Bank operating in frequency range 30 to 120 MHz. We will discuss the problems at such low frequencies due to large beamwidth and unstable ionosphere. We will also discuss the strategies we have used so far to to find the flux density of Cas A by calculating the ratio of flux density of Cas A to that of Cyg A, assuming flux density of Cyg A to be constant. Above mentioned work was performed in summer student program sponsored by National Radio Astronomy Observatory. 16. 5-HT 1A/1B receptor-mediated effects of the selective serotonin reuptake inhibitor, citalopram, on sleep: studies in 5-HT 1A and 5-HT 1B knockout mice. PubMed Monaca, Christelle; Boutrel, Benjamin; Hen, René; Hamon, Michel; Adrien, Joëlle 2003-05-01 Selective serotonin reuptake inhibitors (SSRIs) are extensively used for the treatment of depression. Aside from their antidepressant properties, they provoke a deficit in paradoxical sleep (PS) that is most probably mediated by the transporter blockade-induced increase in serotonin concentration in the extracellular space. Such an effect can be accounted for by the action of serotonin at various types of serotonergic receptors involved in PS regulation, among which the 5-HT(1A) and 5-HT(1B) types are the best candidates. According to this hypothesis, we examined the effects of citalopram, the most selective SSRI available to date, on sleep in the mouse after inactivation of 5-HT(1A) or 5-HT(1B) receptors, either by homologous recombination of their encoding genes, or pharmacological blockade with selective antagonists. For this purpose, sleep parameters of knockout mice that do not express these receptors and their wild-type counterparts were monitored during 8 h after injection of citalopram alone or in association with 5-HT(1A) or 5-HT(1B) receptor antagonists. Citalopram induced mainly a dose-dependent inhibition of PS during 2-6 h after injection, which was observed in wild-type and 5-HT(1B)-/- mice, but not in 5-HT(1A)-/- mutants. This PS inhibition was fully antagonized by pretreatment with the 5-HT(1A) antagonist WAY 100635, but only partially with the 5-HT(1B) antagonist GR 127935. These data indicate that the action of the SSRI citalopram on sleep in the mouse is essentially mediated by 5-HT(1A) receptors. Such a mechanism of action provides further support to the clinical strategy of antidepressant augmentation by 5-HT(1A) antagonists, because the latter would also counteract the direct sleep-inhibitory side-effects of SSRIs. 17. Generation of tryptophan hydroxylase 2 gene knockout pigs by CRISPR/Cas9-mediated gene targeting. PubMed Li, Ze; Yang, Hai-Yuan; Wang, Ying; Zhang, Man-Ling; Liu, Xiao-Rui; Xiong, Qiang; Zhang, Li-Ning; Jin, Yong; Mou, Li-Sha; Liu, Yan; Li, Rong-Feng; Rao, Yi; Dai, Yi-Fan 2017-09-03 Unbalanced brain serotonin (5-HT) levels have implications in various behavioral abnormalities and neuropsychiatric disorders. The biosynthesis of neuronal 5-HT is regulated by the rate-limiting enzyme, tryptophan hydroxylase-2 (TPH2). In the present study, the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) system was used to target the Tph2 gene in Bama mini pig fetal fibroblasts. It was found that CRISPR/Cas9 targeting efficiency could be as high as 61.5%, and the biallelic mutation efficiency reached at 38.5%. The biallelic modified colonies were used as donors for somatic cell nuclear transfer (SCNT) and 10 Tph2 targeted piglets were successfully generated. These Tph2 KO piglets were viable and appeared normal at the birth. However, their central 5-HT levels were dramatically reduced, and their survival and growth rates were impaired before weaning. These Tph2 KO pigs are valuable large-animal models for studies of 5-HT deficiency induced behavior abnomality. 18. Comparative analysis of CRISPR-Cas systems in Klebsiella genomes. PubMed Shen, Juntao; Lv, Li; Wang, Xudong; Xiu, Zhilong; Chen, Guoqiang 2017-02-03 Prokaryotic CRISPR-Cas system provides adaptive immunity against invasive genetic elements. Bacteria of the genus Klebsiella are important nosocomial opportunistic pathogens. However, information of CRISPR-Cas system in Klebsiella remains largely unknown. Here, we analyzed the CRISPR-Cas systems of 68 complete genomes of Klebsiella representing four species. All the elements for CRISPR-Cas system (cas genes, repeats, leader sequences, and PAMs) were characterized. Besides the typical Type I-E and I-F CRISPR-Cas systems, a new Subtype I system located in the ABC transport system-glyoxalase region was found. The conservation of the new subtype CRISPR system between different species showed new evidence for CRISPR horizontal transfer. CRISPR polymorphism was strongly correlated both with species and multilocus sequence types. Some results indicated the function of adaptive immunity: most spacers (112 of 124) matched to prophages and plasmids and no matching housekeeping genes; new spacer acquisition was observed within the same sequence type (ST) and same clonal complex; the identical spacers were observed only in the ancient position (far from the leader) between different STs and clonal complexes. Interestingly, a high ratio of self-targeting spacers (7.5%, 31 of 416) was found in CRISPR-bearing Klebsiella pneumoniae (61%, 11 of 18). In some strains, there even were multiple full matching self-targeting spacers. Some self-targeting spacers were conserved even between different STs. These results indicated that some unknown mechanisms existed to compromise the function of self-targets of CRISPR-Cas systems in K. pneumoniae. 19. Methylene blue inhibits function of the 5-HT transporter PubMed Central Oz, Murat; Isaev, Dmytro; Lorke, Dietrich E; Hasan, Muhammed; Petroianu, Georg; Shippenberg, Toni S 2012-01-01 BACKGROUND AND PURPOSE Methylene blue (MB) is commonly employed as a treatment for methaemoglobinaemia, malaria and vasoplegic shock. An increasing number of studies indicate that MB can cause 5-HT toxicity when administered with a 5-HT reuptake inhibitor. MB is a potent inhibitor of monoamine oxidases, but other targets that may contribute to MB toxicity have not been identified. Given the role of the 5-HT transporter (SERT) in the regulation of extracellular 5-HT concentrations, the present study aimed to characterize the effect of MB on SERT. EXPERIMENTAL APPROACH Live cell imaging, in conjunction with the fluorescent SERT substrate 4-(4-(dimethylamino)-styryl)-N-methylpyridinium (ASP+), [3H]5-HT uptake and whole-cell patch-clamp techniques were employed to examine the effects of MB on SERT function. KEY RESULTS In EM4 cells expressing GFP-tagged human SERT (hSERT), MB concentration-dependently inhibited ASP+ accumulation (IC50: 1.4 ± 0.3 µM). A similar effect was observed in N2A cells. Uptake of [3H]5-HT was decreased by MB pretreatment. Furthermore, patch-clamp studies in hSERT expressing cells indicated that MB significantly inhibited 5-HT-evoked ion currents. Pretreatment with 8-Br-cGMP did not alter the inhibitory effect of MB on hSERT activity, and intracellular Ca2+ levels remained unchanged during MB application. Further experiments revealed that ASP+ binding to cell surface hSERT was reduced after MB treatment. In whole-cell radioligand experiments, exposure to MB (10 µM; 10 min) did not alter surface binding of the SERT ligand [125I]RTI-55. CONCLUSIONS AND IMPLICATIONS MB modulated SERT function and suggested that SERT may be an additional target upon which MB acts to produce 5-HT toxicity. PMID:21542830 20. Menthol inhibits 5-HT3 receptor-mediated currents. PubMed Ashoor, Abrar; Nordman, Jacob C; Veltri, Daniel; Yang, Keun-Hang Susan; Shuba, Yaroslav; Al Kury, Lina; Sadek, Bassem; Howarth, Frank C; Shehu, Amarda; Kabbani, Nadine; Oz, Murat 2013-11-01 The effects of alcohol monoterpene menthol, a major active ingredient of the peppermint plant, were tested on the function of human 5-hydroxytryptamine type 3 (5-HT3) receptors expressed in Xenopus laevis oocytes. 5-HT (1 μM)-evoked currents recorded by two-electrode voltage-clamp technique were reversibly inhibited by menthol in a concentration-dependent (IC50 = 163 μM) manner. The effects of menthol developed gradually, reaching a steady-state level within 10-15 minutes and did not involve G-proteins, since GTPγS activity remained unaltered and the effect of menthol was not sensitive to pertussis toxin pretreatment. The actions of menthol were not stereoselective as (-), (+), and racemic menthol inhibited 5-HT3 receptor-mediated currents to the same extent. Menthol inhibition was not altered by intracellular 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid injections and transmembrane potential changes. The maximum inhibition observed for menthol was not reversed by increasing concentrations of 5-HT. Furthermore, specific binding of the 5-HT3 antagonist [(3)H]GR65630 was not altered in the presence of menthol (up to 1 mM), indicating that menthol acts as a noncompetitive antagonist of the 5-HT3 receptor. Finally, 5-HT3 receptor-mediated currents in acutely dissociated nodose ganglion neurons were also inhibited by menthol (100 μM). These data demonstrate that menthol, at pharmacologically relevant concentrations, is an allosteric inhibitor of 5-HT3 receptors. 1. The radii of SU Cas and TU Cas NASA Technical Reports Server (NTRS) Niva, G. D.; Schmidt, E. G. 1980-01-01 It is possible to obtain the masses of Cepheid variables by several methods involving the pulsation theory. However, these masses are frequently smaller than those indicated by the theory of stellar evolution. The cause of this discrepancy is not fully understood. Since the pulsation theory indicates that there is a relation among the mass, the radius and the period, the discrepancy also manifests itself in the radii of these stars. With this in mind, radius determinations for two Cepheids, SU Cas and TU Cas, were undertaken. It is concluded that because of the agreement between the present radius and the beat radius of TU Cas, the pulsation theory is giving correct information about the radii of beat Cepheids. This implies that the luminosities of short period Cepheids have been overestimated. Thus, the solution to the mass discrepancy should perhaps be sought in the theory of stellar evolution or in the possibility of mass loss. 2. Localization of 5-HT1A and 5-HT2A positive cells in the brainstems of control age-matched and Alzheimer individuals. PubMed Yeung, L Y; Kung, H F; Yew, David T 2010-12-01 Serotonin receptor 1A and 2A positive cells in postmortem brainstems were demonstrated via immunohistochemistry in eight control age-matched elderly individuals and eight Alzheimer patients. The 5-HT1A positive cells were found in substantia nigra, pontile nucleus, and vagal as well as dorsal raphe nucleus, while 5-HT2A receptor positive cells were found in motor, sensory and spinal trigeminal nuclei, pontile nucleus, substantia nigra, and nucleus solitarius. A comparison in density of positive cells per unit area was made between control age-matched and Alzheimer individuals. Statistically significant differences (p ≤ 0.01) in density were observed in 5-HT1A cells in pontile, dorsal raphe, and vagal nuclei between control age-matched and Alzheimer, and in 5-HT2A positive cells in the sensory trigeminal nucleus, between control and Alzheimer. This de novo study indicated the presence of 5-HT1A and 5-HT2A receptor positive cells in the above nuclei of human brainstem and revealed differences in density between control age-matched and Alzheimer, indicating possible functional derangements in Alzheimer patients in these areas. In addition, colocalization studies indicated that 5-HT1A receptors were in cholinergic cells and gamma-aminobutyric acid positive fibers were linked to 5-HT2A receptor positive cells. It is hoped that understanding these two important 5-HT receptors and their localization might lead to advances in future therapeutic development. 3. Harnessing heterologous and endogenous CRISPR-Cas machineries for efficient markerless genome editing in Clostridium PubMed Central Pyne, Michael E.; Bruder, Mark R.; Moo-Young, Murray; Chung, Duane A.; Chou, C. Perry 2016-01-01 Application of CRISPR-Cas9 systems has revolutionized genome editing across all domains of life. Here we report implementation of the heterologous Type II CRISPR-Cas9 system in Clostridium pasteurianum for markerless genome editing. Since 74% of species harbor CRISPR-Cas loci in Clostridium, we also explored the prospect of co-opting host-encoded CRISPR-Cas machinery for genome editing. Motivation for this work was bolstered from the observation that plasmids expressing heterologous cas9 result in poor transformation of Clostridium. To address this barrier and establish proof-of-concept, we focus on characterization and exploitation of the C. pasteurianum Type I-B CRISPR-Cas system. In silico spacer analysis and in vivo interference assays revealed three protospacer adjacent motif (PAM) sequences required for site-specific nucleolytic attack. Introduction of a synthetic CRISPR array and cpaAIR gene deletion template yielded an editing efficiency of 100%. In contrast, the heterologous Type II CRISPR-Cas9 system generated only 25% of the total yield of edited cells, suggesting that native machinery provides a superior foundation for genome editing by precluding expression of cas9 in trans. To broaden our approach, we also identified putative PAM sequences in three key species of Clostridium. This is the first report of genome editing through harnessing native CRISPR-Cas machinery in Clostridium. PMID:27157668 4. Harnessing heterologous and endogenous CRISPR-Cas machineries for efficient markerless genome editing in Clostridium. PubMed Pyne, Michael E; Bruder, Mark R; Moo-Young, Murray; Chung, Duane A; Chou, C Perry 2016-05-09 Application of CRISPR-Cas9 systems has revolutionized genome editing across all domains of life. Here we report implementation of the heterologous Type II CRISPR-Cas9 system in Clostridium pasteurianum for markerless genome editing. Since 74% of species harbor CRISPR-Cas loci in Clostridium, we also explored the prospect of co-opting host-encoded CRISPR-Cas machinery for genome editing. Motivation for this work was bolstered from the observation that plasmids expressing heterologous cas9 result in poor transformation of Clostridium. To address this barrier and establish proof-of-concept, we focus on characterization and exploitation of the C. pasteurianum Type I-B CRISPR-Cas system. In silico spacer analysis and in vivo interference assays revealed three protospacer adjacent motif (PAM) sequences required for site-specific nucleolytic attack. Introduction of a synthetic CRISPR array and cpaAIR gene deletion template yielded an editing efficiency of 100%. In contrast, the heterologous Type II CRISPR-Cas9 system generated only 25% of the total yield of edited cells, suggesting that native machinery provides a superior foundation for genome editing by precluding expression of cas9 in trans. To broaden our approach, we also identified putative PAM sequences in three key species of Clostridium. This is the first report of genome editing through harnessing native CRISPR-Cas machinery in Clostridium. 5. New CRISPR-Cas systems discovered. PubMed Yang, Hui; Patel, Dinshaw J 2017-03-01 In bacteria and archaea, CRISPR-Cas adaptive immune systems utilize RNA-guided endonucleases to defend against invasion by foreign nucleic acids of bacteriophage, virus and plasmid origin. In a recent paper published in Nature, Burstein et al. identified the first Cas9 protein in uncultivated archaea and two novel CRISPR-CasX and CRISPR-CasY systems in uncultivated bacteria by capitalizing on analysis of terabase-scale metagenomic datasets from natural uncultivated organisms. 6. Physical, antioxidant and structural characterization of blend films based on hsian-tsao gum (HG) and casein (CAS). PubMed Yang, Hui; Wen, Xiao Long; Guo, Shan Guang; Chen, Ming Tsao; Jiang, Ai Min; Lai, Lih-Shiuh 2015-12-10 The effects of hsian-tsao gum (HG) addition on the physical properties, antioxidant activities and structure of casein (CAS) film have been investigated. It has been observed that HG addition provided CAS film with better mechanical properties and resistant to moisture, stronger barrier properties against light and higher antioxidant activities than pure CAS film. Fourier transformation infrared (FTIR) data indicated that hydrogen bonding interactions and Maillard reactions occurred between CAS and HG, giving rise to a more compact structure than CAS film. The results of X-ray diffraction and differential scanning calorimetry (DSC) indicated that CAS and HG were compatible, and addition of HG destroyed the original crystalline domains of CAS film, and the blend films exhibited higher glass transition temperatures than CAS film. Moreover, nuclear magnetic resonance (NMR) analysis showed that HG addition significantly changed the mobility of water molecule in CAS film. Especially, ratio of the high mobility water of CAS/HG films significantly decreased as compared to CAS film. 7. Discriminative stimulus properties of indorenate, a 5-HT1A, 5-HT1B and 5-HT2C agonist: a study in rats. PubMed Sánchez, H; Velázquez-Martínez, D N 2001-03-01 Indorenate (INDO), initially described as an antihypertensive agent, also has some effects on behaviour, with anxiolytic and anorectic actions being reported. The aim of the present experiment was to examine the activity of INDO at the behavioural level at various serotonin (5-hydroxytryptamine, 5-HT) receptor sites by comparing its stimulus properties with those of other 5-HT receptor agonists and by examining its interactions with some 5-HT antagonists. Rats were trained to discriminate between 10.0 mg/kg INDO (administered intraperitoneally (90 min before the start of the session) from saline. A Fixed Ratio 10 (FR10) schedule of reinforcement was in effect in each drug condition. During generalization test sessions, the discrimination index (DI, responses to drug lever/responses to drug + saline lever) was calculated from the responses emitted before the first reinforcer of the session. DI was a function of the dose of INDO employed. Generalization to the discriminative stimulus properties of INDO was observed with the 5-HT1A receptor agonist 8-OH-DPAT (1.0 mg/kg produced 90% generalization) and the 5-HT(1B/2C) receptor agonist 1-(3-trifluoromethylphenyl) piperazine (TFMPP) (3.0 mg/kg produced up to 75% generalization). Yohimbine (5.6 mg/kg), buspirone (1.0 mg/kg), 6-chloro-2-(1-piperaziny)pyrazine (1.0 mg/kg) and m-chlorophenylpiperazine (mCPP) (1.0 mg/kg) induced a DI of 70%, 50% and 48% and 55%, respectively. In generalization tests, ritanserin (0.01-1.0 mg/kg) induced saline-like responding. NAN-190 (3.0 mg/kg), a 5-HT1A receptor antagonist, was able to reduce the DI of INDO to 50%. Although the 5-HT(2C/2A) receptor antagonists cinanserin (10.0 mg/kg) and metergoline (0.3 mg/kg) were able to reduce the stimulus properties of INDO to 60% and 30%, respectively, only ritanserin (1.0 mg/kg) reduced the stimulus properties of INDO to 25% with a clear dose-response relationship. The results suggest that INDO acts as an agonist at 5-HT1A receptor sites, but its 8. The 5-HT7 receptor is involved in allocentric spatial memory information processing. PubMed Sarkisyan, Gor; Hedlund, Peter B 2009-08-24 The hippocampus has been implicated in aspects of spatial memory. Its ability to generate new neurons has been suggested to play a role in memory formation. Hippocampal serotonin (5-HT) neurotransmission has also been proposed as a contributor to memory processing. Studies have shown that the 5-HT(7) receptor is present in the hippocampus in relatively high abundance. Thus the aim of the present study was to investigate the possible role of the 5-HT(7) receptor in spatial memory using 5-HT(7) receptor-deficient mice (5-HT(7)(-/-)). A hippocampus-associated spatial memory deficit in 5-HT(7)(-/-) mice was demonstrated using a novel location/novel object test. A similar reduction in novel location exploration was observed in C57BL/6J mice treated with the selective 5-HT(7) receptor antagonist SB-269970. These findings prompted an extended analysis using the Barnes maze demonstrating that 5-HT(7)(-/-) mice were less efficient in accommodating to changes in spatial arrangement than 5-HT(7)(+/+) mice. 5-HT(7)(-/-) mice had specific impairments in memory compilation required for resolving spatial tasks, which resulted in impaired allocentric spatial memory whereas egocentric spatial memory remained intact after the mice were forced to switch back from striatum-dependent egocentric to hippocampus-dependent allocentric memory. To further investigate the physiological bases underlining these behaviors we compared hippocampal neurogenesis in 5-HT(7)(+/+) and 5-HT(7)(-/-) mice employing BrdU immunohistochemistry. The rate of cell proliferation in the dentate gyrus was identical in the two genotypes. From the current data we conclude that the 5-HT(7)(-/-) mice performed by remembering a simple sequence of actions that resulted in successfully locating a hidden target in a static environment. 9. CAS-Induced Difficulties in Learning Mathematics? ERIC Educational Resources Information Center Jankvist, Uffe Thomas; Misfeldt, Morten 2015-01-01 In recent years computer algebra systems (CAS) have become an integrated part of the upper secondary school mathematics program. Despite the many positive possibilities of CAS, there also seems to be a flip side of the coin in relation to actual difficulties in learning mathematics, not least because a strong dependence on CAS for mathematical… 10. CAS-Induced Difficulties in Learning Mathematics? ERIC Educational Resources Information Center Jankvist, Uffe Thomas; Misfeldt, Morten 2015-01-01 In recent years computer algebra systems (CAS) have become an integrated part of the upper secondary school mathematics program. Despite the many positive possibilities of CAS, there also seems to be a flip side of the coin in relation to actual difficulties in learning mathematics, not least because a strong dependence on CAS for mathematical… 11. "CAS" Statement of Shared Ethical Principles ERIC Educational Resources Information Center Council for the Advancement of Standards in Higher Education, 2006 2006-01-01 The Council for the Advancement of Standards in Higher Education (CAS) has served as a voice for quality assurance and promulgation of standards in higher education for over 25 years. CAS was established to promote inter-association efforts to address quality assurance, student learning, and professional integrity. CAS includes membership of over… 12. Spectroscopic studies of three Cepheids with high positive pulsation period increments: SZ Cas, BY Cas, and RU Sct NASA Astrophysics Data System (ADS) Usenko, I. A.; Klochkova, V. G. 2015-07-01 Three high-resolution spectra have been taken at different times with the 6-m SAO RAS telescope (LYNX and PFES spectrographs) for three Cepheids exhibiting high positive period increments: the small-amplitude (DCEPS) SZ Cas and BY Cas and the classical (DCEP) RU Sct. SZ Cas and RU Sct are members of the Galactic open clusters χ and h Per and Trump 35, respectively. Analysis of the spectra has shown that the interstellar Na I D1 and D2 lines in all objects are considerably stronger than the atmospheric ones and are redshifted in SZ Cas and BY Cas and blushifted in RU Sct. The core of the H α absorption line in BY Cas has an asymmetric knifelike shape, while RU Sct exhibits an intense emission in the blue wing of this line. Such phenomena are observed in long-period Cepheids and bright hypergiants with an extended envelope. In this case, the strong Mg Ib 5183.62 Å and Ba II 5853.67, 6141.713, and 6496.90 Å lines with low χlow in SZ Cas and RU Sct also show characteristic knifelike profiles with an asymmetry in the red region, while the Ba II 4934.095 Å line shows similar profiles in the blue one. The absorption lines of neutral atoms and singly ionized metals with different lowerlevel excitation potentials exhibit different degrees of asymmetry: from a pronounced one with secondary components in BY Cas (similar to those in the small-amplitude Cepheid BG Cru pulsating in the first overtone and having an envelope) to its insignificance or virtual absence in SZ Cas and RU Sct. Analysis of the secular changes in mean T eff determined from photometric color indices and spectra over the last 55 years for these stars has revealed periodic fluctuations of 200 K for SZ Cas and BY Cas and 500 K for RU Sct. For SZ Cas and RU Sct, T eff determined in some years from some color indices show much lower values, which together with the temperature fluctuations can be associated with mass loss and dust formation. Based on these facts, we hypothesize the existence of 13. Structural basis of ligand recognition in 5-HT3 receptors PubMed Central Kesters, Divya; Thompson, Andrew J; Brams, Marijke; van Elk, René; Spurny, Radovan; Geitmann, Matthis; Villalgordo, Jose M; Guskov, Albert; Helena Danielson, U; Lummis, Sarah C R; Smit, August B; Ulens, Chris 2013-01-01 The 5-HT3 receptor is a pentameric serotonin-gated ion channel, which mediates rapid excitatory neurotransmission and is the target of a therapeutically important class of anti-emetic drugs, such as granisetron. We report crystal structures of a binding protein engineered to recognize the agonist serotonin and the antagonist granisetron with affinities comparable to the 5-HT3 receptor. In the serotonin-bound structure, we observe hydrophilic interactions with loop E-binding site residues, which might enable transitions to channel opening. In the granisetron-bound structure, we observe a critical cation–π interaction between the indazole moiety of the ligand and a cationic centre in loop D, which is uniquely present in the 5-HT3 receptor. We use a series of chemically tuned granisetron analogues to demonstrate the energetic contribution of this electrostatic interaction to high-affinity ligand binding in the human 5-HT3 receptor. Our study offers the first structural perspective on recognition of serotonin and antagonism by anti-emetics in the 5-HT3 receptor. PMID:23196367 14. Locomotor-activated neurons of the cat. I. Serotonergic innervation and co-localization of 5-HT7, 5-HT2A, and 5-HT1A receptors in the thoraco-lumbar spinal cord. PubMed Noga, Brian R; Johnson, Dawn M G; Riesgo, Mirta I; Pinzon, Alberto 2009-09-01 Monoamines are strong modulators and/or activators of spinal locomotor networks. Thus monoaminergic fibers likely contact neurons involved in generating locomotion. The aim of the present study was to investigate the serotonergic innervation of locomotor-activated neurons within the thoraco-lumbar spinal cord following induction of hindlimb locomotion. This was determined by immunohistochemical co-localization of serotonin (5-HT) fibers or 5-HT(7)/5-HT2A/5-HT1A receptors with cells expressing the activity-dependent marker c-fos. Experiments were performed on paralyzed, decerebrate cats in which locomotion was induced by electrical stimulation of the mesencephalic locomotor region. Abundant c-fos immunoreactive cells were observed in laminae VII and VIII throughout the thoraco-lumbar segments of locomotor animals. Control sections from the same segments showed significantly fewer labeled neurons, mostly within the dorsal horn. Multiple serotonergic boutons were found in close apposition to the majority (80-100%) of locomotor cells, which were most abundant in lumbar segments L3-7. 5-HT7 receptor immunoreactivity was observed on cells across the thoraco-lumbar segments (T7-L7), in a dorsoventral gradient. Most locomotor-activated cells co-localized with 5-HT7, 5-HT2A, and 5-HT1A receptors, with largest numbers in laminae VII and VIII. Co-localization of c-fos and 5-HT7 receptor was highest in the L5-L7 segments (>90%) and decreased rostrally (to approximately 50%) due to the absence of receptors on cells within the intermediolateral nucleus. In contrast, 60-80 and 35-80% of c-fos immunoreactive cells stained positive for 5-HT2A and 5-HT1A receptors, respectively, with no rostrocaudal gradient. These results indicate that serotonergic modulation of locomotion likely involves 5-HT(7)/5-HT2A/5-HT1A receptors located on the soma and proximal dendrites of serotonergic-innervated locomotor-activated neurons within laminae VII and VIII of thoraco-lumbar segments. 15. Locomotor-Activated Neurons of the Cat. I. Serotonergic Innervation and Co-Localization of 5-HT7, 5-HT2A, and 5-HT1A Receptors in the Thoraco-Lumbar Spinal Cord PubMed Central Noga, Brian R.; Johnson, Dawn M. G.; Riesgo, Mirta I.; Pinzon, Alberto 2009-01-01 Monoamines are strong modulators and/or activators of spinal locomotor networks. Thus monoaminergic fibers likely contact neurons involved in generating locomotion. The aim of the present study was to investigate the serotonergic innervation of locomotor-activated neurons within the thoraco-lumbar spinal cord following induction of hindlimb locomotion. This was determined by immunohistochemical co-localization of serotonin (5-HT) fibers or 5-HT7/5-HT2A/5-HT1A receptors with cells expressing the activity-dependent marker c-fos. Experiments were performed on paralyzed, decerebrate cats in which locomotion was induced by electrical stimulation of the mesencephalic locomotor region. Abundant c-fos immunoreactive cells were observed in laminae VII and VIII throughout the thoraco-lumbar segments of locomotor animals. Control sections from the same segments showed significantly fewer labeled neurons, mostly within the dorsal horn. Multiple serotonergic boutons were found in close apposition to the majority (80–100%) of locomotor cells, which were most abundant in lumbar segments L3–7. 5-HT7 receptor immunoreactivity was observed on cells across the thoraco-lumbar segments (T7–L7), in a dorsoventral gradient. Most locomotor-activated cells co-localized with 5-HT7, 5-HT2A, and 5-HT1A receptors, with largest numbers in laminae VII and VIII. Co-localization of c-fos and 5-HT7 receptor was highest in the L5–L7 segments (>90%) and decreased rostrally (to ∼50%) due to the absence of receptors on cells within the intermediolateral nucleus. In contrast, 60–80 and 35–80% of c-fos immunoreactive cells stained positive for 5-HT2A and 5-HT1A receptors, respectively, with no rostrocaudal gradient. These results indicate that serotonergic modulation of locomotion likely involves 5-HT7/5-HT2A/5-HT1A receptors located on the soma and proximal dendrites of serotonergic-innervated locomotor-activated neurons within laminae VII and VIII of thoraco-lumbar segments. PMID:19571190 16. Hallucinogenic 5-HT2AR agonists LSD and DOI enhance dopamine D2R protomer recognition and signaling of D2-5-HT2A heteroreceptor complexes. PubMed Borroto-Escuela, Dasiel O; Romero-Fernandez, Wilber; Narvaez, Manuel; Oflijan, Julia; Agnati, Luigi F; Fuxe, Kjell 2014-01-03 Dopamine D2LR-serotonin 5-HT2AR heteromers were demonstrated in HEK293 cells after cotransfection of the two receptors and shown to have bidirectional receptor-receptor interactions. In the current study the existence of D2L-5-HT2A heteroreceptor complexes was demonstrated also in discrete regions of the ventral and dorsal striatum with in situ proximity ligation assays (PLA). The hallucinogenic 5-HT2AR agonists LSD and DOI but not the standard 5-HT2AR agonist TCB2 and 5-HT significantly increased the density of D2like antagonist (3)H-raclopride binding sites and significantly reduced the pKiH values of the high affinity D2R agonist binding sites in (3)H-raclopride/DA competition experiments. Similar results were obtained in HEK293 cells and in ventral striatum. The effects of the hallucinogenic 5-HT2AR agonists on D2R density and affinity were blocked by the 5-HT2A antagonist ketanserin. In a forskolin-induced CRE-luciferase reporter gene assay using cotransfected but not D2R singly transfected HEK293 cells DOI and LSD but not TCB2 significantly enhanced the D2LR agonist quinpirole induced inhibition of CRE-luciferase activity. Haloperidol blocked the effects of both quinpirole alone and the enhancing actions of DOI and LSD while ketanserin only blocked the enhancing actions of DOI and LSD. The mechanism for the allosteric enhancement of the D2R protomer recognition and signalling observed is likely mediated by a biased agonist action of the hallucinogenic 5-HT2AR agonists at the orthosteric site of the 5-HT2AR protomer. This mechanism may contribute to the psychotic actions of LSD and DOI and the D2-5-HT2A heteroreceptor complex may thus be a target for the psychotic actions of hallunicogenic 5-HT2A agonists. Copyright © 2013 Elsevier Inc. All rights reserved. 17. Alprazolam potentiates the antiaversive effect induced by the activation of 5-HT(1A) and 5-HT (2A) receptors in the rat dorsal periaqueductal gray. PubMed de Bortoli, Valquíria Camin; Nogueira, Regina Lúcia; Zangrossi, Hélio 2008-06-01 Serotonin in the dorsal periaqueductal gray (DPAG) through the activation of 5-HT(1A) and 5-HT(2A) receptors inhibits escape, a defensive behavior associated with panic attacks. Long-term treatment with antipanic drugs that nonselectively or selectively blocks the reuptake of serotonin (e.g., imipramine and fluoxetine, respectively) enhances the inhibitory effect on escape caused by intra-DPAG injection of 5-HT(1A) and 5-HT(2A) receptor agonists. It has been proposed that these compounds exert their effect on panic by facilitating 5-HT-mediated neurotransmission in the DPAG. The objective of this study was to investigate whether facilitation of 5-HT neurotransmission in the DPAG is also observed after treatment with alprazolam, a pharmacologically distinct antipanic drug that acts primarily as a high potency benzodiazepine receptor agonist. Male Wistar rats, subchronically (3-6 days) or chronically (14-17 days) treated with alprazolam (2 and 4 mg/kg, i.p.) were intra-DPAG injected with (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT), (+/-)-1-(2,5-dimethoxy-4-iodophenyl) piperazine dihydrochloride (DOI), and midazolam, respectively, 5-HT(1A), 5-HT(2A/2C), and benzodiazepine receptor agonists. The intensity of electrical current that needed to be applied to the DPAG to evoke escape behavior was measured before and after the microinjection of these agonists. Intra-DPAG injection of the 5-HT agonists and midazolam increased the escape threshold in all groups of animals tested, indicating a panicolytic-like effect. The inhibitory effect of 8-OH-DPAT and DOI, but not midazolam, was significantly higher in animals receiving long-, but not short-term treatment with alprazolam. Alprazolam as antidepressants compounds facilitates 5-HT(1A)- and 5-HT(2A)-receptor-mediated neurotransmission in the DPAG, implicating this effect in the mode of action of different classes of antipanic drugs. 18. Host Double Strand Break Repair Generates HIV-1 Strains Resistant to CRISPR/Cas9 PubMed Central Yoder, Kristine E.; Bundschuh, Ralf 2016-01-01 CRISPR/Cas9 genome editing has been proposed as a therapeutic treatment for HIV-1 infection. CRISPR/Cas9 induced double strand breaks (DSBs) targeted to the integrated viral genome have been shown to decrease production of progeny virus. Unfortunately HIV-1 evolves rapidly and may readily produce CRISPR/Cas9 resistant strains. Here we used next-generation sequencing to characterize HIV-1 strains that developed resistance to six different CRISPR/Cas9 guide RNAs (gRNAs). Reverse transcriptase (RT) derived base substitution mutations were commonly found at sites encoding unpaired bases of RNA stem-loop structures. In addition to RT mutations, insertion and/or deletion (indel) mutations were common. Indels localized to the CRISPR/Cas9 cleavage site were major contributors to CRISPR gRNA resistance. While most indels at non-coding regions were a single base pair, 3 base pair indels were observed when a coding region of HIV-1 was targeted. The DSB repair event may preserve the HIV-1 reading frame, while destroying CRISPR gRNA homology. HIV-1 may be successfully edited by CRISPR/Cas9, but the virus remains competent for replication and resistant to further CRISPR/Cas9 targeting at that site. These observations strongly suggest that host DSB repair at CRISPR/Cas9 cleavage sites is a novel and important pathway that may contribute to HIV-1 therapeutic resistance. PMID:27404981 19. Host Double Strand Break Repair Generates HIV-1 Strains Resistant to CRISPR/Cas9. PubMed Yoder, Kristine E; Bundschuh, Ralf 2016-07-12 CRISPR/Cas9 genome editing has been proposed as a therapeutic treatment for HIV-1 infection. CRISPR/Cas9 induced double strand breaks (DSBs) targeted to the integrated viral genome have been shown to decrease production of progeny virus. Unfortunately HIV-1 evolves rapidly and may readily produce CRISPR/Cas9 resistant strains. Here we used next-generation sequencing to characterize HIV-1 strains that developed resistance to six different CRISPR/Cas9 guide RNAs (gRNAs). Reverse transcriptase (RT) derived base substitution mutations were commonly found at sites encoding unpaired bases of RNA stem-loop structures. In addition to RT mutations, insertion and/or deletion (indel) mutations were common. Indels localized to the CRISPR/Cas9 cleavage site were major contributors to CRISPR gRNA resistance. While most indels at non-coding regions were a single base pair, 3 base pair indels were observed when a coding region of HIV-1 was targeted. The DSB repair event may preserve the HIV-1 reading frame, while destroying CRISPR gRNA homology. HIV-1 may be successfully edited by CRISPR/Cas9, but the virus remains competent for replication and resistant to further CRISPR/Cas9 targeting at that site. These observations strongly suggest that host DSB repair at CRISPR/Cas9 cleavage sites is a novel and important pathway that may contribute to HIV-1 therapeutic resistance. 20. The periods and amplitudes of TU Cas NASA Technical Reports Server (NTRS) Hodson, S. W.; Cox, A. N. 1980-01-01 Light curve observations of the double-mode Cepheid TU Cas obtained by 10 different sets of observers on several photometric systems over a time span of 67 years were carefully studied to determine the fundamental and first overtone periods and their amplitudes on the V magnitude scale. The presence of a second overtone radial pulsation is discussed, and it is concluded that a previous detection of this mode was spurious due to the lack of a proper zero point correction for two groups of observations. The amplitudes of the two modes are shown to possibly vary during the entire observing period with the fundamental mode amplitude of 0.69 + or - 0.03 and the overtone amplitude decreasing about 0.2 or 0.3 magnitude. If this Cepheid displays the two pulsation modes because it is mode switching, this switching time scale might be less than a hundred years. 1. The interaction of trichloroethanol with murine recombinant 5-HT3 receptors. PubMed Central Downie, D L; Hope, A G; Belelli, D; Lambert, J J; Peters, J A; Bentley, K R; Steward, L J; Chen, C Y; Barnes, N M 1995-01-01 1. The effects of ethanol, chloral hydrate and trichloroethanol upon the 5-HT3 receptor have been investigated by use of electrophysiological techniques applied to recombinant 5-HT3 receptor subunits (5-HT3R-A or 5-HT3R-As) expressed in Xenopus laevis oocytes. Additionally, the influence of trichloroethanol upon the specific binding of [3H]-granisetron to membrane preparations of HEK 293 cells stably transfected with the murine 5-HT3R-As subunit and 5-HT3 receptors endogenous to NG 108-15 cell membranes was assessed. 2. Ethanol (30-300 mM), chloral hydrate (1-30 mM) and trichloroethanol (0.3-10 mM), produced a reversible, concentration-dependent, enhancement of 5-HT-mediated currents recorded from oocytes expressing either the 5-HT3R-A, or the 5-HT3R-As subunit. 3. Trichloroethanol (5 mM) produced a parallel leftward shift of the 5-HT concentration-response curve, reducing the EC50 for 5-HT from 1 +/- 0.04 microM (n = 4) to 0.5 +/- 0.01 microM (n = 4) for oocytes expressing the 5-HT3R-A. A similar shift, from 2.1 +/- 0.05 microM (n = 11) to 1.3 +/- 0.1 microM (n = 4), was observed in oocytes expressing the 5-HT3R-As subunit. Trichloroethanol (5 mM) had little or no effect upon the maximum current produced by 5-HT for either recombinant receptor. 4. Trichloroethanol (5 mM) similarly reduced the EC50 for 2-methyl-5-HT from 13 +/- 0.4 microM (n = 4) to 4.6 +/- 0.2 microM (n = 4) and from 15 +/- 2 microM (n = 4) to 5 +/- 0.4 microM (n = 4) for oocytes expressing the 5-HT3R-A and 5-HT3R-As subunit respectively. Additionally, trichloroethanol (5 mM) produced a clear enhancement of the maximal current to 2-methyl-5-HT (expressed as a percentage of the maximal current to 5-HT) from 63 +/- 0.7% (n = 4) to 101 +/- 1.6% (n = 4) and from 9 +/- 0.2% (n = 4) to 74 +/- 2% (n = 4) for oocytes expressing the 5-HT3R-A and 5-HT3R-As subunit respectively. 5. Trichloroethanol (2.5 mM) had no effect upon the Kd, or Bmax, of specific [3H]-granisetron binding to membrane homogenates of NG 2. The 5-HT deficiency theory of depression: perspectives from a naturalistic 5-HT deficiency model, the tryptophan hydroxylase 2Arg439His knockin mouse PubMed Central Jacobsen, Jacob P. R.; Medvedev, Ivan O.; Caron, Marc G. 2012-01-01 A decreased level of brain 5-hydroxytryptamine (5-HT) has been theorized to be a core pathogenic factor in depression for half a century. The theory arose from clinical observations that drugs enhancing extracellular levels of 5-HT (5-HTExt) have antidepressant effects in many patients. However, whether such drugs indeed correct a primary deficit remains unresolved. Still, a number of anomalies in putative biomarkers of central 5-HT function have been repeatedly reported in depression patients over the past 40 years, collectively indicating that 5-HT deficiency could be present in depression, particularly in severely ill and/or suicidal patients. This body of literature on putative 5-HT biomarker anomalies and depression has recently been corroborated by data demonstrating that such anomalies indeed occur consequent to severely reduced 5-HTExt levels in a mouse model of naturalistic 5-HT deficiency, the tryptophan hydroxylase 2 His439 knockin (Tph2KI) mouse. In this review, we will critically assess the evidence for 5-HT deficiency in depression and the possible role of polymorphisms in the Tph2 gene as a causal factor in 5-HT deficiency, the latter investigated from a clinical as well as preclinical angle. PMID:22826344 3. Helium-induced weld degradation of HT-9 steel SciTech Connect Wang, Chin-An; Chin, B.A.; Lin, Hua T.; Grossbeck, M.L. 1992-12-31 Helium-bearing Sandvik HT-9 ferritic steel was tested for weldability to simulate the welding of structural components of a fusion reactor after irradiation. Helium was introduced into HT-9 steel to 0.3 and 1 atomic parts per million (appm) by tritium doping and decay. Autogenous single pass full penetration welds were produced using the gas tungsten arc (GTA) welding process under laterally constrained conditions. Macroscopic examination showed no sign of any weld defect in HT-9 steel containing 0.3 appm helium. However, intergranular micro cracks were observed in the HAZ of HT-9 steel containing 1 appm helium. The microcracking was attributed to helium bubble growth at grain boundaries under the influence of high stresses and temperatures that were present during welding. Mechanical test results showed that both yield strength (YS) and ultimate tensile strength (UTS) decreased with increasing temperature, while the total elongation increased with increasing temperature for all control and helium-bearing HT-9 steels. 4. 5-HT2 receptors modulate the expression of antipsychotic-induced dopamine supersensitivity. PubMed Charron, Alexandra; Hage, Cynthia El; Servonnet, Alice; Samaha, Anne-Noël 2015-12-01 Antipsychotic treatment can produce supersensitivity to dopamine receptor stimulation. This compromises the efficacy of ongoing treatment and increases the risk of relapse to psychosis upon treatment cessation. Serotonin 5-HT2 receptors modulate dopamine function and thereby influence dopamine-dependent responses. Here we evaluated the hypothesis that 5-HT2 receptors modulate the behavioural expression of antipsychotic-induced dopamine supersensitivity. To this end, we first treated rats with the antipsychotic haloperidol using a clinically relevant treatment regimen. We then assessed the effects of a 5-HT2 receptor antagonist (ritanserin; 0.01 and 0.1mg/kg) and of a 5-HT2A receptor antagonist (MDL100,907; 0.025-0.1mg/kg) on amphetamine-induced psychomotor activity. Antipsychotic-treated rats showed increased amphetamine-induced locomotion relative to antipsychotic-naïve rats, indicating a dopamine supersensitive state. At the highest dose tested (0.1mg/kg for both antagonists), both ritanserin and MDL100,907 suppressed amphetamine-induced locomotion in antipsychotic-treated rats, while having no effect on this behaviour in control rats. In parallel, antipsychotic treatment decreased 5-HT2A receptor density in the prelimbic cortex and nucleus accumbens core and increased 5-HT2A receptor density in the caudate-putamen. Thus, activation of either 5-HT2 receptors or of 5-HT2A receptors selectively is required for the full expression of antipsychotic-induced dopamine supersensitivity. In addition, antipsychotic-induced dopamine supersensitivity enhances the ability of 5-HT2/5-HT2A receptors to modulate dopamine-dependent behaviours. These effects are potentially linked to changes in 5-HT2A receptor density in the prefrontal cortex and the striatum. These observations raise the possibility that blockade of 5-HT2A receptors might overcome some of the behavioural manifestations of antipsychotic-induced dopamine supersensitivity. 5. Occurrence and Diversity of CRISPR-Cas Systems in the Genus Bifidobacterium PubMed Central Briner, Alexandra E.; Lugli, Gabriele Andrea; Milani, Christian; Duranti, Sabrina; Turroni, Francesca; Gueimonde, Miguel; Margolles, Abelardo; van Sinderen, Douwe; Ventura, Marco; Barrangou, Rodolphe 2015-01-01 CRISPR-Cas systems constitute adaptive immune systems for antiviral defense in bacteria. We investigated the occurrence and diversity of CRISPR-Cas systems in 48 Bifidobacterium genomes to gain insights into the diversity and co-evolution of CRISPR-Cas systems within the genus and investigate CRISPR spacer content. We identified the elements necessary for the successful targeting and inference of foreign DNA in select Type II CRISPR-Cas systems, including the tracrRNA and target PAM sequence. Bifidobacterium species have a very high frequency of CRISPR-Cas occurrence (77%, 37 of 48). We found that many Bifidobacterium species have unusually large and diverse CRISPR-Cas systems that contain spacer sequences showing homology to foreign genetic elements like prophages. A large number of CRISPR spacers in bifidobacteria show perfect homology to prophage sequences harbored in the chromosomes of other species of Bifidobacterium, including some spacers that self-target the chromosome. A correlation was observed between strains that lacked CRISPR-Cas systems and the number of times prophages in that chromosome were targeted by other CRISPR spacers. The presence of prophage-targeting CRISPR spacers and prophage content may shed light on evolutionary processes and strain divergence. Finally, elements of Type II CRISPR-Cas systems, including the tracrRNA and crRNAs, set the stage for the development of genome editing and genetic engineering tools. PMID:26230606 6. Efficient fdCas9 Synthetic Endonuclease with Improved Specificity for Precise Genome Engineering PubMed Central Aouida, Mustapha; Eid, Ayman; Ali, Zahir; Cradick, Thomas; Lee, Ciaran; Deshmukh, Harshavardhan; Atef, Ahmed; AbuSamra, Dina; Gadhoum, Samah Zeineb; Merzaban, Jasmeen; Bao, Gang; Mahfouz, Magdy 2015-01-01 The Cas9 endonuclease is used for genome editing applications in diverse eukaryotic species. A high frequency of off-target activity has been reported in many cell types, limiting its applications to genome engineering, especially in genomic medicine. Here, we generated a synthetic chimeric protein between the catalytic domain of the FokI endonuclease and the catalytically inactive Cas9 protein (fdCas9). A pair of guide RNAs (gRNAs) that bind to sense and antisense strands with a defined spacer sequence range can be used to form a catalytically active dimeric fdCas9 protein and generate double-strand breaks (DSBs) within the spacer sequence. Our data demonstrate an improved catalytic activity of the fdCas9 endonuclease, with a spacer range of 15–39 nucleotides, on surrogate reporters and genomic targets. Furthermore, we observed no detectable fdCas9 activity at known Cas9 off-target sites. Taken together, our data suggest that the fdCas9 endonuclease variant is a superior platform for genome editing applications in eukaryotic systems including mammalian cells. PMID:26225561 7. Light Echoes and Cold Dust in Cas A NASA Astrophysics Data System (ADS) Krause, O.; Rieke, G. H.; Birkmann, S. 2006-06-01 We report on infrared observations of the prototypical supernova remnant Cassiopeia A obtained with the Spitzer Space Telescope. Two images of Cas A taken at 24 micrometers with the MIPS instrument over a 1-year time interval revealed moving structures outside the shell of the supernova remnant to a distance of more than 20 arc minutes. The observed tangential velocities are at roughly the speed of light. The moving structures are infrared echoes, in which interstellar dust is heated by the explosion and by flares from the compact object near the center of the remnant. Far-infrared maps of the remnant at 160 micrometers in combination with molecular line observations demonstrate that most of recently detected submillimetre emission towards Cas A originates from interstellar dust in a molecular cloud complex located in the line of sight between the Earth and the remnant, rather than from a large amount (about three solar masses) of cold (18K) dust within Cas A. The argument that type II supernovae produce copious amounts of dust is therefore not supported by the case of Cas A, which previously appeared to provide the best evidence for this possibility. 8. Is there a propeller neutron star in γ Cas? NASA Astrophysics Data System (ADS) Smith, M. A.; Lopes de Oliveira, R.; Motch, C. 2017-08-01 γ Cas is the prototype of a small population of B0-B1.5 III-V classical Be (cBe) stars that emit anomalous and hard X-rays with a unique array of properties. γ Cas is known to host, like other cBe stars, a decretion disc and also a low-mass companion. Recently, Postnov et al. have posited that this companion is a magnetized rapidly spinning neutron star that deflects direct gravitational accretion from a stellar/disc wind via the 'propeller mechanism'. These authors state that the key X-ray observations are 'remarkably well produced' in this scenario. We re-examine this mechanism in detail and conclude that there are a number of fatal objections in its application to the γ Cas case. Among other considerations these issues include the prediction under the propeller scenario of a much smaller population of γ Cas stars than is observed and the lack of allowance for observed correlations of X-ray and UV and/or optical properties over a variety of time-scales. 9. CRISPR/Cas9 Technologies. PubMed Williams, Bart O; Warman, Matthew L 2017-02-23 The Clustered Regularly Interspaced Palindromic Repeats (CRISPR)/CRISPR-associated protein (Cas) pathway is revolutionizing biological research. Modifications to this primitive prokaryotic immune system now enable scientists to efficiently edit DNA or modulate gene expression in living eukaryotic cells and organisms. Thus, many laboratories can now perform important experiments that previously were considered scientifically risky or too costly. Here, we describe the components of the CRISPR/Cas system that have been engineered for use in eukaryotes. We also explain how this system can be used to genetically modify cell lines and model organisms, or regulate gene expression in order to search for new participants in biological pathways. © 2017 American Society for Bone and Mineral Research. 10. Could the 5-HT1B receptor inverse agonism affect learning consolidation? PubMed Meneses, A 2001-03-01 Diverse evidence indicates that, the 5-HT system might play a role in learning and memory, since it occurs in brain areas mediating such processes and 5-HT drugs modulate them. Hence in this work, in order to explore further 5-HT involvement on learning and memory 5-HT1B receptors' role is investigated. Evidence indicates that SB-224289 (a 5-HT1B receptor inverse agonist) post-training injection facilitated learning consolidation in an associative autoshaping learning task, this effect was partially reversed by GR 127935 (a 5-HT1B/1D receptor antagonist), but unaffected by MDL 100907 (a 5-HT2A receptor antagonist) or ketanserin (a 5-HT1D/2A/7 receptor antagonist) at low doses. Moreover, SB-224289 antagonized the learning deficit produced by TFMPP (a 5-HT1A/1B/1D/2A/2C receptor agonist), GR 46611 (a 5-HT1A/1B/1D receptor agonist), mCPP (a 5-HT2A/2C/3/7 receptor agonist/antagonist) or GR 127935 (at low dose). SB-224289 did not alter the 8-OH-DPAT (a 5-HT1A/7 receptor agonist) learning facilitatory effect. SB-224289 eliminated the deficit learning produced by the anticholinergic muscarinic scopolamine or the glutamatergic antagonist dizocilpine. Administration of both, GR 127935 (5mg/kg) plus ketanserin (0.01 mg/kg) did not modify learning consolidation; nevertheless, when ketanserin dose was increased (0.1-1.0mg/kg) and SB-224289 dose was maintained constant, a learning facilitation effect was observed. Notably, SB-224289 at 1.0mg/kg potentiated a subeffective dose of the 5-HT1B/1D receptor agonist/antagonist mixed GR 127935, which facilitated learning consolidation and this effect was abolished by ketanserin at a higher dose. Collectively, the data confirm and extend the earlier findings with GR 127935 and the effects of non-selective 5-HT(1B) receptor agonists. Clearly 5-HT1B agonists induced a learning deficit which can be reversed with SB-224289. Perhaps more importantly, SB-224289 enhances learning consolidation when given alone and can reverse the deficits 11. Cloning, expression and pharmacology of a truncated splice variant of the human 5-HT7 receptor (h5-HT7(b)) PubMed Central Jasper, J R; Kosaka, A; To, Z P; Chang, D J; Eglen, R M 1997-01-01 The rat 5-hydroxytryptamine (5-HT)7 receptor displays two splice variations, a long form, and a truncated splice isoform, arising from the introduction of a stop codon near the carboxy-terminus. The human 5-HT7 receptor gene contains at least two introns and encodes a 445 amino acid 5-HT receptor. A truncated splice variation in the human 5-HT7 receptor was isolated from a human placental cDNA library. In accordance with current NC-IUPHAR nomenclature guidelines, it is suggested that this receptor be denoted as the h5-HT7(b) receptor and the long form of the receptor as h5-HT7(a). The h5-HT7(b) receptor was stably expressed in HEK 293 cells and ligand affinities were determined by displacement of [3H]-5-carboxyamidotryptamine (5-CT; Kd=0.28±0.06 nM, Bmax=7.3±1.7 pmol mg−1 protein). The rank order of affinities (pKi) for a series of ligands was: 5-carboxamidotryptamine (5-CT, 9.65)>5-hydroxytryptamine (5-HT, 9.41)>methiothepin (8.87)>mesulergine (7.87)>8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT, 6.85)>ketanserin (6.44). The h5-HT7(b) receptor coupled positively to adenylyl cyclase in HEK 293 cells. This response was elicited by a number of agonists with the following order of potency (pEC50): 5-CT (8.7±0.11)>5-MeOT (5-methoxytryptamine; 8.1±0.20)>5-HT (7.5±0.13)>tryptamine (5.6±0.36)>8-OH-DPAT (5.3±0.28)>5-methoxytryptamine (5.0±0.06). This rank order was comparable to that observed in the radioligand binding studies. In a similar fashion to that described for the 5-HT7(a) receptor, PCR studies suggested that the 5-HT7(b) receptor mRNA is found in great abundance throughout the brain, in the small intestine and aorta. It is concluded that the h5-HT7 receptor, like the rat receptor, exists as splice variants exhibiting similar pharmacology, signal transduction and distribution. It is thus likely that there exists a complex physiological role for alternate splicing products of the 5-HT7 receptor gene. PMID:9298538 12. Medial hypothalamic 5-hydroxytryptamine (5-HT)1A receptors regulate neuroendocrine responses to stress and exploratory locomotor activity: application of recombinant adenovirus containing 5-HT1A sequences. PubMed Li, Qian; Holmes, Andrew; Ma, Li; Van de Kar, Louis D; Garcia, Francisca; Murphy, Dennis L 2004-12-01 Our previous studies found that serotonin transporter (SERT) knock-out mice showed increased sensitivity to minor stress and increased anxiety-like behavior but reduced locomotor activity. These mice also showed decreased density of 5-hydroxytryptamine (5-HT1A) receptors in the hypothalamus, amygdala, and dorsal raphe. To evaluate the contribution of hypothalamic 5-HT1A receptors to these phenotypes of SERT knock-out mice, two studies were conducted. Recombinant adenoviruses containing 5-HT1A sense and antisense sequences (Ad-1AP-sense and Ad-1AP-antisense) were used to manipulate 5-HT1A receptors in the hypothalamus. The expression of the 5-HT1A genes is controlled by the 5-HT1A promoter, so that they are only expressed in 5-HT1A receptor-containing cells. (1) Injection of Ad-1AP-sense into the hypothalamus of SERT knock-out mice restored 5-HT1A receptors in the medial hypothalamus; this effect was accompanied by elimination of the exaggerated adrenocorticotropin responses to a saline injection (minor stress) and reduced locomotor activity but not by a change in increased exploratory anxiety-like behavior. (2) To further confirm the observation in SERT-/- mice, Ad-1AP-antisense was injected into the hypothalamus of normal mice. The density and the function of 5-HT1A receptors in the medial hypothalamus were significantly reduced in Ad-1AP-antisense-treated mice. Compared with the control group (injected with Ad-track), Ad-1A-antisense-treated mice showed a significant reduction in locomotor activity, but again no changes in exploratory anxiety-like behaviors, tested by elevated plus-maze and open-field tests. Thus, the present results demonstrate that medial hypothalamic 5-HT1A receptors regulate stress responses and locomotor activity but may not regulate exploratory anxiety-like behaviors. 13. Modulation of the hypoxic sensory response of the carotid body by 5-hydroxytryptamine: role of the 5-HT2 receptor. PubMed Jacono, F J; Peng, Y-J; Kumar, G K; Prabhakar, N R 2005-02-15 Previous studies have shown that glomus cells of the carotid body express 5-hydroxytryptamine (5-HT). The aim of this study was to elucidate the role of 5-HT on the hypoxic sensory response (HSR) of the carotid body. Sensory activity was recorded from multi-fiber (n=16) and single-fiber (n=8) preparations of ex vivo carotid bodies harvested from anesthetized, adult rats. 5-HT (3 microM) had no significant effect on the magnitude or on the onset of the HSR. However, 5-HT consistently prolonged the time necessary for the sensory activity to return to baseline following the termination of the hypoxic challenge. Ketanserin (40 microM), a 5-HT2 receptor antagonist completely prevented 5-HT-induced prolongation of the HSR, whereas had no effect on the control HSR (onset, magnitude, and time for decay without 5-HT). Carotid bodies expressed 5-HT, but hypoxia did not facilitate 5-HT release. These observations suggest that 5-HT is not critical for the HSR of the rat carotid body, but it modulates the dynamics of the HSR via its action on 5-HT2 receptors. 14. Novel insights into the potential involvement of 5-HT7 receptors in endocrine dysregulation in stress-related disorders. PubMed Terrón, José A 2014-01-01 A hyperactive hypothalamic-pituitary-adrenal (HPA) axis is a common feature of stress-related disorders, and the brain serotonin (5-HT) system plays a major role in HPA axis modulation. Glucocorticoids and stress profoundly affect the 5-HT system so it is possible that alterations of endocrine 5-HT mechanisms may underlie HPA axis overdrive in stress-related diseases. Available evidence suggests a role of 5-HT1A, 5-HT2A/2C and 5-HT7 receptors in HPA system activation, and pharmacological blockade of 5-HT7 receptors produces a fast-acting antidepressant-like action and shortens the onset of antidepressant-like effects of various classes of antidepressants. The mechanisms involved in this effect have not been elucidated, but recent findings suggest a role of 5-HT7 receptors in the development of HPA axis overdrive as a result of chronic stress. Remarkably, clinical findings have shown an association between corticosteroid-producing adenomas and expression of ectopic 5-HT7 receptors in corticosteroid-producing adrenocortical cells. These observations might therefore reveal an endocrine mechanism for the antidepressant-like action of 5-HT7 receptor blockers, possibly through normalization of HPA axis function. If such a preliminary hypothesis is confirmed, the potential therapeutic usefulness of 5-HT7 receptor antagonists could extend beyond depression to include other diseases, the pathophysiology of which has been associated with chronic stress and HPA axis dysregulation. 15. Genome modification by CRISPR/Cas9. PubMed Ma, Yuanwu; Zhang, Lianfeng; Huang, Xingxu 2014-12-01 Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein (Cas)9-mediated genome modification enables us to edit the genomes of a variety of organisms rapidly and efficiently. The advantages of the CRISPR-Cas9 system have made it an increasingly popular genetic engineering tool for biological and therapeutic applications. Moreover, CRISPR-Cas9 has been employed to recruit functional domains that repress/activate gene expression or label specific genomic loci in living cells or organisms, in order to explore developmental mechanisms, gene expression regulation, and animal behavior. One major concern about this system is its specificity; although CRISPR-Cas9-mediated off-target mutation has been broadly studied, more efforts are required to further improve the specificity of CRISPR-Cas9. We will also discuss the potential applications of CRISPR-Cas9. © 2014 FEBS. 16. Expanding CRISPR/Cas9 Genome Editing Capacity in Zebrafish Using SaCas9 PubMed Central Feng, Yan; Chen, Cheng; Han, Yuxiang; Chen, Zelin; Lu, Xiaochan; Liang, Fang; Li, Song; Qin, Wei; Lin, Shuo 2016-01-01 The type II CRISPR/Cas9 system has been used widely for genome editing in zebrafish. However, the requirement for the 5′-NGG-3′ protospacer-adjacent motif (PAM) of Cas9 from Streptococcus pyogenes (SpCas9) limits its targeting sequences. Here, we report that a Cas9 ortholog from Staphylococcus aureus (SaCas9), and its KKH variant, successfully induced targeted mutagenesis with high frequency in zebrafish. Confirming previous findings, the SpCas9 variant, VQR, can also induce targeted mutations in zebrafish. Bioinformatics analysis of these new Cas targets suggests that the number of available target sites in the zebrafish genome can be greatly expanded. Collectively, the expanded target repertoire of Cas9 in zebrafish should further facilitate the utility of this organism for genetic studies of vertebrate biology. PMID:27317783 17. Control of Amygdala Circuits by 5-HT Neurons via 5-HT and Glutamate Cotransmission PubMed Central Bannerman, David M. 2017-01-01 The serotonin (5-HT) system and the amygdala are key regulators of emotional behavior. Several lines of evidence suggest that 5-HT transmission in the amygdala is implicated in the susceptibility and drug treatment of mood disorders. Therefore, elucidating the physiological mechanisms through which midbrain 5-HT neurons modulate amygdala circuits could be pivotal in understanding emotional regulation in health and disease. To shed light on these mechanisms, we performed patch-clamp recordings from basal amygdala (BA) neurons in brain slices from mice with channelrhodopsin genetically targeted to 5-HT neurons. Optical stimulation of 5-HT terminals at low frequencies (≤1 Hz) evoked a short-latency excitation of BA interneurons (INs) that was depressed at higher frequencies. Pharmacological analysis revealed that this effect was mediated by glutamate and not 5-HT because it was abolished by ionotropic glutamate receptor antagonists. Optical stimulation of 5-HT terminals at higher frequencies (10–20 Hz) evoked both slow excitation and slow inhibition of INs. These effects were mediated by 5-HT because they were blocked by antagonists of 5-HT2A and 5-HT1A receptors, respectively. These fast glutamate- and slow 5-HT-mediated responses often coexisted in the same neuron. Interestingly, fast-spiking and non-fast-spiking INs displayed differential modulation by glutamate and 5-HT. Furthermore, optical stimulation of 5-HT terminals did not evoke glutamate release onto BA principal neurons, but inhibited these cells directly via activation of 5-HT1A receptors and indirectly via enhanced GABA release. Collectively, these findings suggest that 5-HT neurons exert a frequency-dependent, cell-type-specific control over BA circuitry via 5-HT and glutamate co-release to inhibit the BA output. SIGNIFICANCE STATEMENT The modulation of the amygdala by serotonin (5-HT) is important for emotional regulation and is implicated in the pathogenesis and treatment of affective disorders 18. Control of Amygdala Circuits by 5-HT Neurons via 5-HT and Glutamate Cotransmission. PubMed Sengupta, Ayesha; Bocchio, Marco; Bannerman, David M; Sharp, Trevor; Capogna, Marco 2017-02-15 The serotonin (5-HT) system and the amygdala are key regulators of emotional behavior. Several lines of evidence suggest that 5-HT transmission in the amygdala is implicated in the susceptibility and drug treatment of mood disorders. Therefore, elucidating the physiological mechanisms through which midbrain 5-HT neurons modulate amygdala circuits could be pivotal in understanding emotional regulation in health and disease. To shed light on these mechanisms, we performed patch-clamp recordings from basal amygdala (BA) neurons in brain slices from mice with channelrhodopsin genetically targeted to 5-HT neurons. Optical stimulation of 5-HT terminals at low frequencies (≤1 Hz) evoked a short-latency excitation of BA interneurons (INs) that was depressed at higher frequencies. Pharmacological analysis revealed that this effect was mediated by glutamate and not 5-HT because it was abolished by ionotropic glutamate receptor antagonists. Optical stimulation of 5-HT terminals at higher frequencies (10-20 Hz) evoked both slow excitation and slow inhibition of INs. These effects were mediated by 5-HT because they were blocked by antagonists of 5-HT2A and 5-HT1A receptors, respectively. These fast glutamate- and slow 5-HT-mediated responses often coexisted in the same neuron. Interestingly, fast-spiking and non-fast-spiking INs displayed differential modulation by glutamate and 5-HT. Furthermore, optical stimulation of 5-HT terminals did not evoke glutamate release onto BA principal neurons, but inhibited these cells directly via activation of 5-HT1A receptors and indirectly via enhanced GABA release. Collectively, these findings suggest that 5-HT neurons exert a frequency-dependent, cell-type-specific control over BA circuitry via 5-HT and glutamate co-release to inhibit the BA output.SIGNIFICANCE STATEMENT The modulation of the amygdala by serotonin (5-HT) is important for emotional regulation and is implicated in the pathogenesis and treatment of affective disorders 19. 5-HT(1A) receptors and memory. PubMed Meneses, Alfredo; Perez-Garcia, Georgina 2007-01-01 The study of 5-hydroxytryptamine (5-HT) systems has benefited from the identification, classification and cloning of multiple 5-HT receptors (5-HT(1)-5-HT(7)). Increasing evidence suggests that 5-HT pathways, reuptake site/transporter complex and 5-HT receptors represent a strategic distribution for learning and memory. A key question still remaining is whether 5-HT markers (e.g., receptors) are directly or indirectly contributing to the physiological and pharmacological basis of memory and its pathogenesis or, rather, if they represent protective or adaptable mechanisms (at least in initial stages). In the current paper, the major aim is to revise recent advances regarding mammalian 5-HT(1A) receptors in light of their physiological, pathophysiological and therapeutic implications in memory. An attempt is made to identify and discuss sources of discrepancies by employing an analytic approach to examine the nature and degree of difficulty of behavioral tasks used, as well as implicating other factors (for example, brain areas, training time or duration, and drug administration) which might offer new insights into the understanding and interpretation of these data. In this context, 8-OH-DPAT deserves special attention since for many years it has been the more selective 5-HT drug and, hence, more frequently used. As 5-HT(1A) receptors are key components of serotonergic signaling, investigation of their memory mechanisms and action sites and the conditions under which they might operate, could yield valuable insights. Moreover, selective drugs with agonists, neutral antagonists or inverse agonist properties for 5-HT(1A) (and 5-HT(7)) receptors may constitute a new therapeutic opportunity for learning and memory disorders. 20. [Clustered regularly interspaced short palindromic repeat associated protein genes cas1 and cas2 in Shigella]. PubMed Xue, Zerun; Wang, Yingfang; Duan, Guangcai; Wang, Pengfei; Wang, Linlin; Guo, Xiangjiao; Xi, Yuanlin 2014-05-01 To detect the distribution of clustered regularly interspaced short palindromic repeat (CRISPR) associated protein genes cas1 and cas2 in Shigella and to understand the characteristics of CRISPR with relationship between CRISPR and related characteristics on drug resistance. CRISPR associated protein genes cas1 and cas2 in Shigella were detected by PCR, with its products sequenced and compared. The CRISPR-associated protein genes cas1 and cas2 were found in all the 196 Shigella isolates which were isolated at different times and locations in China. Consistencies showed through related sequencing appeared as follows: cas2, cas1 (a) and cas1 (b) were 96.44%, 97.61% and 96.97%, respectively. There were two mutations including 3177129 site(C→G)and 3177126 site (G→C) of cas1 (b) gene in 2003135 strain which were not found in the corresponding sites of Z23 and 2008113. showed that in terms of both susceptibility and antibiotic-resistance, strain 2003135 was stronger than Z23 and 2008113. CRISPR system widely existed in Shigella, with the level of drug resistance in cas1 (b) gene mutant strains higher than in wild strains. Cas1 (b) gene mutation might be one of the reasons causing the different levels of resistance. 1. 5-HT7 receptor modulates GABAergic transmission in the rat dorsal raphe nucleus and controls cortical release of serotonin. PubMed Kusek, Magdalena; Sowa, Joanna; Kamińska, Katarzyna; Gołembiowska, Krystyna; Tokarski, Krzysztof; Hess, Grzegorz 2015-01-01 The 5-HT7 receptor is one of the several serotonin (5-HT) receptor subtypes that are expressed in the dorsal raphe nucleus (DRN). Some earlier findings suggested that 5-HT7 receptors in the DRN were localized on GABAergic interneurons modulating the activity of 5-HT projection neurons. The aim of the present study was to find out how the 5-HT7 receptor modulates the GABAergic synaptic input to putative 5-HT DRN neurons, and whether blockade of the 5-HT7 receptor would affect the release of 5-HT in the target structure. Male Wistar rats with microdialysis probes implanted in the prefrontal cortex (PFC) received injections of the 5-HT7 receptor antagonist (2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine hydrochloride (SB 269970), which induced an increase in the levels of 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA) in the PFC. In another set of experiments whole-cell recordings from presumed projection neurons were carried out using DRN slices. SB 269970 application resulted in depolarization and in an increase in the firing frequency of the cells. In order to activate 5-HT7 receptors, 5-carboxamidotryptamine (5-CT) was applied in the presence of N-[2-[4-(2-methoxyphenyl)-1piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide (WAY100635). Hyperpolarization of cells and a decrease in the firing frequency were observed after activation of the 5-HT7 receptor. Blockade of 5-HT7 receptors caused a decrease in the mean frequency of spontaneous inhibitory postsynaptic currents (sIPSCs), while its activation induced an increase. The mechanism of these effects appears to involve tonically-active 5-HT7 receptors modulating firing and/or GABA release from inhibitory interneurons which regulate the activity of DRN serotonergic projection neurons. 2. Hydrostatic compaction of Microtherm HT. SciTech Connect Broome, Scott Thomas; Bauer, Stephen J. 2010-09-01 Two samples of jacketed Microtherm{reg_sign}HT were hydrostatically pressurized to maximum pressures of 29,000 psi to evaluate both pressure-volume response and change in bulk modulus as a function of density. During testing, each of the two samples exhibited large irreversible compactive volumetric strains with only small increases in pressure; however at volumetric strains of approximately 50%, the Microtherm{reg_sign}HT stiffened noticeably at ever increasing rates. At the maximum pressure of 29,000 psi, the volumetric strains for both samples were approximately 70%. Bulk modulus, as determined from hydrostatic unload/reload loops, increased by more than two-orders of magnitude (from about 4500 psi to over 500,000 psi) from an initial material density of {approx}0.3 g/cc to a final density of {approx}1.1 g/cc. An empirical fit to the density vs. bulk modulus data is K = 492769{rho}{sup 4.6548}, where K is the bulk modulus in psi, and {rho} is the material density in g/cm{sup 3}. The porosity decreased from 88% to {approx}20% indicating that much higher pressures would be required to compact the material fully. 3. CRISPR-Cas9: from Genome Editing to Cancer Research. PubMed Chen, Si; Sun, Heng; Miao, Kai; Deng, Chu-Xia 2016-01-01 Cancer development is a multistep process triggered by innate and acquired mutations, which cause the functional abnormality and determine the initiation and progression of tumorigenesis. Gene editing is a widely used engineering tool for generating mutations that enhance tumorigenesis. The recent developed clustered regularly interspaced short palindromic repeats-CRISPR-associated 9 (CRISPR-Cas9) system renews the genome editing approach into a more convenient and efficient way. By rapidly introducing genetic modifications in cell lines, organs and animals, CRISPR-Cas9 system extends the gene editing into whole genome screening, both in loss-of-function and gain-of-function manners. Meanwhile, the system accelerates the establishment of animal cancer models, promoting in vivo studies for cancer research. Furthermore, CRISPR-Cas9 system is modified into diverse innovative tools for observing the dynamic bioprocesses in cancer studies, such as image tracing for targeted DNA, regulation of transcription activation or repression. Here, we view recent technical advances in the application of CRISPR-Cas9 system in cancer genetics, large-scale cancer driver gene hunting, animal cancer modeling and functional studies. 4. CRISPR-Cas9: from Genome Editing to Cancer Research PubMed Central Chen, Si; Sun, Heng; Miao, Kai; Deng, Chu-Xia 2016-01-01 Cancer development is a multistep process triggered by innate and acquired mutations, which cause the functional abnormality and determine the initiation and progression of tumorigenesis. Gene editing is a widely used engineering tool for generating mutations that enhance tumorigenesis. The recent developed clustered regularly interspaced short palindromic repeats-CRISPR-associated 9 (CRISPR-Cas9) system renews the genome editing approach into a more convenient and efficient way. By rapidly introducing genetic modifications in cell lines, organs and animals, CRISPR-Cas9 system extends the gene editing into whole genome screening, both in loss-of-function and gain-of-function manners. Meanwhile, the system accelerates the establishment of animal cancer models, promoting in vivo studies for cancer research. Furthermore, CRISPR-Cas9 system is modified into diverse innovative tools for observing the dynamic bioprocesses in cancer studies, such as image tracing for targeted DNA, regulation of transcription activation or repression. Here, we view recent technical advances in the application of CRISPR-Cas9 system in cancer genetics, large-scale cancer driver gene hunting, animal cancer modeling and functional studies. PMID:27994508 5. Oxidation and dispersion of HT in the environment: the August 1986 field experiment at Chalk River. PubMed Brown, R M; Ogram, G L; Spencer, F S 1990-02-01 The short-range environmental dispersion and oxidation of a release of tritiated hydrogen (HT) to the atmosphere has been studied in a field experiment. Emphasis was placed on the processes leading to the appearance of tritiated water (HTO) vapor in the atmosphere because HTO is much more radiotoxic than HT. The following conclusions were reached: No evidence was found for the rapid conversion of HT to HTO in the atmosphere; HTO observed in air, during and after the release, arose mainly from HT oxidation in the soil followed by emission of HTO; HT deposition velocities to soil ranged from 0.041 cm s-1 to 0.13 cm s-1, consistent with previous chamber measurements; the rate of HTO loss from soil, averaged over 21 d, was less than 1% h-1; and HTO concentrations in vegetation water initially increased with time after the release, then by 48 h decreased exponentially at a rate similar to soils. 6. Design, Synthesis, and Structure–Activity Relationships of Highly Potent 5-HT3 Receptor Ligands PubMed Central 2012-01-01 The 5-HT3 receptor, a pentameric ligand-gated ion channel (pLGIC), is an important therapeutic target. During a recent fragment screen, 6-chloro-N-methyl-2-(4-methyl-1,4-diazepan-1-yl)quinazolin-4-amine (1) was identified as a 5-HT3R hit fragment. Here we describe the synthesis and structure–activity relationships (SAR) of a series of (iso)quinoline and quinazoline compounds that were synthesized and screened for 5-HT3R affinity using a [3H]granisetron displacement assay. These studies resulted in the discovery of several high affinity ligands of which compound 22 showed the highest affinity (pKi > 10) for the 5-HT3 receptor. The observed SAR is in agreement with established pharmacophore models for 5-HT3 ligands and is used for ligand–receptor binding mode prediction using homology modeling and in silico docking approaches. PMID:23006041 7. CRISPR/Cas9-mediated targeted mutagenesis in Nicotiana tabacum. PubMed Gao, Junping; Wang, Genhong; Ma, Sanyuan; Xie, Xiaodong; Wu, Xiangwei; Zhang, Xingtan; Wu, Yuqian; Zhao, Ping; Xia, Qingyou 2015-01-01 Genome editing is one of the most powerful tools for revealing gene function and improving crop plants. Recently, RNA-guided genome editing using the type II clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein (Cas) system has been used as a powerful and efficient tool for genome editing in various organisms. Here, we report genome editing in tobacco (Nicotiana tabacum) mediated by the CRISPR/Cas9 system. Two genes, NtPDS and NtPDR6, were used for targeted mutagenesis. First, we examined the transient genome editing activity of this system in tobacco protoplasts, insertion and deletion (indel) mutations were observed with frequencies of 16.2-20.3% after transfecting guide RNA (gRNA) and the nuclease Cas9 in tobacco protoplasts. The two genes were also mutated using multiplexing gRNA at a time. Additionally, targeted deletions and inversions of a 1.8-kb fragment between two target sites in the NtPDS locus were demonstrated, while indel mutations were also detected at both the sites. Second, we obtained transgenic tobacco plants with NtPDS and NtPDR6 mutations induced by Cas9/gRNA. The mutation percentage was 81.8% for NtPDS gRNA4 and 87.5% for NtPDR6 gRNA2. Obvious phenotypes were observed, etiolated leaves for the psd mutant and more branches for the pdr6 mutant, indicating that highly efficient biallelic mutations occurred in both transgenic lines. No significant off-target mutations were obtained. Our results show that the CRISPR/Cas9 system is a useful tool for targeted mutagenesis of the tobacco genome. 8. [ASSOCIATION BETWEEN FOUR SEROTONIC GENES POLYMORPHISM (5HTTL, 5HT1A, 5HT2A, AND MAOA) AND PERSONALITY TRAITS IN WRESTLERS AND CONTROL GROUP]. PubMed Butovskaya, P R; Lazebnij, O E; Fekhretdionva, D I; Vasil'ev, V A; Prosikova, E A; Lysenko, V V; Udina, I G; Butovskaya, M L 2015-01-01 This study presents the data on the polymorphisms of the serotonin system genes (5-HTTL, 5-HT1A, 5-HT2A, and MAOA) in male and female wrestlers and in the control group. The population genetics analysis of the 5HTTL gene showed the highest frequency of the SS genotype 5-HTTLPR in sportsmen (p = 0.04), as well as the trend toward higher frequency of united genotypes of the locus of 5-HTTLPR VNTR and SNP rs25531--SASA (p = 0.06) in comparison with the control group. As for the polymorphisms for other genes 5-HT1A (rs6295), 5-HT2A (rs6311), and MAOA (VNTR), we found no significant differences between the groups tested. Using the NEO PI-R questionnaire we analyzed the possible correlations between the genotypes and the psychological traits in our samples. It was demonstrated that the athletic success in elite sportsmen was associated with lower openness to experience and higher conscientiousness. The interaction effect of the gender and 5-HT2A on the self-rating for openness to experience, interaction effect of the level of the sport success and 5-HT2A, and the interaction effect of the gender and 5-HT1A genotype on self-reported conscientiousness were observed as a trend. 9. Exposure to HT-2 toxin causes oxidative stress induced apoptosis/autophagy in porcine oocytes PubMed Central Zhang, Yue; Han, Jun; Zhu, Cheng-Cheng; Tang, Feng; Cui, Xiang-Shun; Kim, Nam-Hyung; Sun, Shao-Chen 2016-01-01 T-2 toxin is a main type A trichothecene mycotoxin which is the most toxic trichothecence. T-2 toxin has posed various toxic effects on human and animals in vigorous cell proliferation tissues like lymphoid, hematopoietic and gastrointestinal tissues, while HT-2 toxin is the major metabolite which is deacetylated by T-2 toxin. In this study, we focused on the toxic effects of HT-2 on porcine oocyte maturation. We treated the porcine oocyte with HT-2 toxin in vitro, and we first found that HT-2 treatment inhibited porcine oocyte polar body extrusion and cumulus cell expansion. We observed the disrupted meiotic spindle morphology after treatment, which might be due to the reduced p-MAPK protein level. Actin distribution was also disturbed, indicating that HT-2 affects cytoskeleton of porcine oocytes. We next explored the causes for the failure of oocyte maturation after HT-2 treatment. We found that HT-2 treated oocytes showed the increased ROS level, which indicated that oxidative stress had occurred. We also detected autophagy as well as early apoptosis in the treatment oocytes. Due to the fact that oxidative stress could induced apoptosis, our results indicated that HT-2 toxin caused oxidative stress induced apoptosis and autophagy, which further affected porcine oocyte maturation. PMID:27658477 10. Neuroticism and serotonin 5-HT1A receptors in healthy subjects. PubMed Hirvonen, Jussi; Tuominen, Lauri; Någren, Kjell; Hietala, Jarmo 2015-10-30 Neuroticism is a personality trait associated with vulnerability for mood and anxiety disorders. Serotonergic mechanisms likely contribute to neuroticism. Serotonin 5-HT1A receptors are altered in mood and anxiety disorders, but whether 5-HT1A receptors are associated with neuroticism in healthy subjects is unclear. We measured brain serotonin 5-HT1A receptor in 34 healthy subjects in vivo using positron emission tomography (PET) and [carbonyl-(11)C]WAY-100635. Binding potential (BPP) was determined using the golden standard of kinetic compartmental modeling using arterial blood samples and radiometabolite determination. Personality traits were assessed using the Karolinska Scales of Personality. We found a strong negative association between serotonin 5-HT1A receptor BPP and neuroticism. That is, individuals with high neuroticism tended to have lower 5-HT1A receptor binding than individuals with low neuroticism. This finding was confirmed with an independent voxel-based whole-brain analysis. Other personality traits did not correlate with 5-HT1A receptor BPP. Previous observations have reported lower serotonin 5-HT1A receptor density in major depression. This neurobiological finding may be a trait-like phenomenon and partly explained by higher neuroticism in patients with affective disorders. The link between personality traits and 5-HT1A receptors should be studied in patients with major depression. 11. Platelet 5-HT concentration and comorbid depression in war veterans with and without posttraumatic stress disorder. PubMed Mück-Seler, Dorotea; Pivac, Nela; Jakovljević, Miro; Sagud, Marina; Mihaljević-Peles, Alma 2003-07-01 The serotonergic system is implicated in the pathophysiology of posttraumatic stress disorder (PTSD) and depression. The present study focused on platelet serotonin (5-HT) concentration and symptoms of comorbid depression in war veterans with or without PTSD. PTSD and depression were evaluated using Clinician Administered PTSD Scale, Davidson Trauma Scale, Montgomery-Asberg Depression Rating Scale and Hamilton Anxiety Scale. Sixty-five male drug-free war veterans (48 with PTSD and 17 without PTSD) and 65 age- and sex-matched healthy controls were studied. Comorbid depression occurred in 54 and 31% of war veterans with PTSD and without PTSD, respectively. Platelet 5-HT concentration was similar in the groups of depressed and nondepressed war veterans with or without PTSD and healthy controls. Platelet 5-HT concentration was found to differ between war veterans with various degrees of appetite loss. A positive correlation was observed between platelet 5-HT concentration and severity of appetite loss in veterans with PTSD. There was no relationship between platelet 5-HT concentration and severity of other symptoms of PTSD or depression. War veterans included in the study were outpatients. War veterans with PTSD had a high incidence of comorbid depression, that was not related to platelet 5-HT concentration. The marked relationship between platelet 5-HT concentration and severity of appetite loss, suggested that 5-HT system is involved in the regulation of appetite, at least in depressed war veterans with PTSD. 12. Blockade of 5-HT7 receptors reduces tactile allodynia in the rat. PubMed Amaya-Castellanos, Evelyn; Pineda-Farias, Jorge B; Castañeda-Corral, Gabriela; Vidal-Cantú, Guadalupe C; Murbartián, Janet; Rocha-González, Héctor I; Granados-Soto, Vinicio 2011-10-01 This study assessed the role of systemic and spinal 5-HT(7) receptors on rats submitted to spinal nerve injury. In addition, the 5-HT(7) receptors level in dorsal root ganglion and spinal cord was also determined. Tactile allodynia was induced by L5/L6 spinal nerve ligation. Systemic (0.01-10mg/kg) or spinal (0.3-30 μg) administration of the selective 5-HT(7) receptor antagonist SB-269970 but not vehicle reduced in a dose-dependent manner established tactile allodynia. This effect was maintained for about 6h. SB-269970 was more potent and effective by the spinal administration route than through systemic injection. Spinal nerve ligation reduced expression of 5-HT(7) receptors in the ipsilateral but not contralateral dorsal root ganglia. Moreover, 5-HT(7) receptor levels were lower in the ipsilateral dorsal spinal cord of neuropathic rats compared to naïve and sham rats. No changes in the receptor levels were observed in the contralateral dorsal spinal cord and in both regions of the ventral spinal cord. Data suggest that spinal 5-HT(7) receptors play a pronociceptive role in neuropathic rats. Results also indicate that spinal nerve injury leads to a reduced 5-HT(7) receptors level in pain processing-related areas which may result from its nociceptive role in this model. Data suggest that selective 5-HT(7) receptor antagonists may function as analgesics in nerve injury pain states. 13. [5-HT1A/5-HT7 receptor interplay: Chronic activation of 5-HT7 receptors decreases the functional activity of 5-HT1A receptor and its сontent in the mouse brain]. PubMed Kondaurova, E M; Bazovkina, D V; Naumenko, V S 2017-01-01 Serotonin receptors 5-HT1A and 5-HT7 are involved in the development of various psychopathologies. Some data indicate that there is an interplay between 5-HT1A 5-HT7 receptors that could be implicated in the regulation of their function. This work analyzed the effects of chronic 5-HT7 activation on the functional activity of 5-HT7 and 5-HT1A receptors, on the corresponding protein levels, and on the expression of genes encoding 5-HT7 and 5-HT1A receptors in the mouse brain. Chronic administration of the 5-HT7 selective agonist LP44 (20.5 nmol, i.c.v., 14 days) produced considerable desensitization of both 5-HT7 and 5-HT1A receptors. In LP44-treated mice, the hypothermic responses mediated by both 5-HT7 and 5-HT1A receptors were attenuated. Moreover, the levels of 5-HT1A receptor protein in the midbrain and the frontal cortex of LP44-treated mice were significantly decreased. However, the brain levels of 5-HT7 receptor protein did not differ between LP44-treated and control mice. Chronic LP44 treatment did not alter the expression of the 5-HT7 and 5-HT1A receptor genes in all investigated brain structure. These data suggest that 5-HT7 receptors participate in the posttranscriptional regulation of the 5-HT1A receptors functioning. 14. Effects of the graphene content on the conversion efficiency of P3HT:Graphene based organic solar cells NASA Astrophysics Data System (ADS) Bkakri, R.; Chehata, N.; Ltaief, A.; Kusmartseva, O. E.; Kusmartsev, F. V.; Song, M.; Bouazizi, A. 2015-10-01 We investigate the effects of the insertion of graphene in the matrix of regioregular poly (3-hexylthiophene-2,5-diyl) (RR-P3HT) on the conversion efficiency of ITO/P3HT:Graphene/Au solar cells. The X-ray diffraction (XRD) measurements show that progressive addition of graphene reduces the degree of order of P3HT lamellae along the hexyl-side direction (a-axis). The insertion of low graphene content in the P3HT matrix reduces the RMS roughness of the P3HT thin film, and improves the optical absorption properties of the device in the visible range. However for high doping level we observe the formation of graphene aggregates which in turn reduces the optical absorption properties of the device. The observed effects arising after addition of graphene to P3HT, and their relationship with the conversion efficiency of the devices are discussed in this work. 15. Individual Differences in Impulsive Action Reflect Variation in the Cortical Serotonin 5-HT2A Receptor System PubMed Central Fink, Latham HL; Anastasio, Noelle C; Fox, Robert G; Rice, Kenner C; Moeller, F Gerard; Cunningham, Kathryn A 2015-01-01 Impulsivity is an important feature of multiple neuropsychiatric disorders, and individual variation in the degree of inherent impulsivity could play a role in the generation or exacerbation of problematic behaviors. Serotonin (5-HT) actions at the 5-HT2AR receptor (5-HT2AR) promote and 5-HT2AR antagonists suppress impulsive action (the inability to withhold premature responses; motor impulsivity) upon systemic administration or microinfusion directly into the medial prefrontal cortex (mPFC), a node in the corticostriatal circuit that is thought to play a role in the regulation of impulsive action. We hypothesized that the functional capacity of the 5-HT2AR, which is governed by its expression, localization, and protein/protein interactions (eg, postsynaptic density 95 (PSD95)), may drive the predisposition to inherent impulsive action. Stable high-impulsive (HI) and low-impulsive (LI) phenotypes were identified from an outbred rodent population with the 1-choice serial reaction time (1-CSRT) task. HI rats exhibited a greater head-twitch response following administration of the preferential 5-HT2AR agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) and were more sensitive to the effects of the selective 5-HT2AR antagonist M100907 to suppress impulsive action relative to LI rats. A positive correlation was observed between levels of premature responses and 5-HT2AR binding density in frontal cortex ([3H]-ketanserin radioligand binding). Elevated mPFC 5-HT2AR protein expression concomitant with augmented association of the 5-HT2AR with PSD95 differentiated HI from LI rats. The observed differential sensitivity of HI and LI rats to 5-HT2AR ligands and associated distinct 5-HT2AR protein profiles provide evidence that spontaneously occurring individual differences in impulsive action reflect variation in the cortical 5-HT2AR system. PMID:25666313 16. The Aspergillus fumigatus metacaspases CasA and CasB facilitate growth under conditions of endoplasmic reticulum stress. PubMed Richie, Daryl L; Miley, Michael D; Bhabhra, Ruchi; Robson, Geoffrey D; Rhodes, Judith C; Askew, David S 2007-01-01 We have examined the contribution of metacaspases to the growth and stress response of the opportunistic human mould pathogen, Aspergillus fumigatus, based on increasing evidence implicating the yeast metacaspase Yca1p in apoptotic-like programmed cell death. Single metacaspase-deficient mutants were constructed by targeted disruption of each of the two metacaspase genes in A. fumigatus, casA and casB, and a metacaspase-deficient mutant, DeltacasA/DeltacasB, was constructed by disrupting both genes. Stationary phase cultures of wild-type A. fumigatus were associated with the appearance of typical markers of apoptosis, including elevated proteolytic activity against caspase substrates, phosphatidylserine exposure on the outer leaflet of the membrane, and loss of viability. By contrast, phosphatidylserine exposure was not observed in stationary phase cultures of the DeltacasA/DeltacasB mutant, although caspase activity and viability was indistinguishable from wild type. The mutant retained wild-type virulence and showed no difference in sensitivity to a range of pro-apoptotic stimuli that have been reported to initiate yeast apoptosis. However, the DeltacasA/DeltacasB mutant showed a growth detriment in the presence of agents that disrupt endoplasmic reticulum homeostasis. These findings demonstrate that metacaspase activity in A. fumigatus contributes to the apoptotic-like loss of membrane phospholipid asymmetry at stationary phase, and suggest that CasA and CasB have functions that support growth under conditions of endoplasmic reticulum stress. 17. 5-hydroxytryptamine receptor (5-HT1DR) promotes colorectal cancer metastasis by regulating Axin1/β-catenin/MMP-7 signaling pathway PubMed Central Ji, Qing; Liu, Xuan; Zhou, Lihong; Song, Haiyan; Zhou, Xiqiu; Xu, Yangxian; Chen, Zhesheng; Cai, Jianfeng; Ji, Guang; Li, Qi 2015-01-01 Overexpression of 5-hydroxytryptamine (5-HT) in human cancer contributes to tumor metastasis, but the role of 5-HT receptor family in cancer has not been thoroughly explored. Here, we report overexpression of 5-HT1D receptor (5-HT1DR) was associated with Wnt signaling pathway and advanced tumor stage. The underlying mechanism of 5-HT1DR-promoted tumor invasion was through its activation on the Axin1/β-catenin/MMP-7 pathway. In an orthotopic colorectal cancer mouse model, we demonstrated that a 5-HT1DR antagonist (GR127935) effectively inhibited tumor metastasis through targeting Axin1. Furthermore, in intestinal epithelium cells, we observed that 5-HT1DR played an important role in cell invasion via Axin1/β-catenin/MMP-7 pathway. Together, our findings reveal an essential role of the physiologic level of 5-HT1DR in pulmonary metastasis of colorectal cancer. PMID:26214021 18. Pilomatricome: étude de 22 cas PubMed Central Nasreddine, Fatima Zahra; Hali, Fouzia; Chiheb, Soumiya 2016-01-01 Le pilomatricome est une tumeur cutanée fréquente et bénigne du follicule pileux chez l'enfant. C'est une tumeur annexielle souvent méconnue et confondue avec d'autres lésions cutanées. Les localisations habituelles sont la tête et le cou. Le but de ce travail est de rapporter une série de 22 cas comportant des formes inhabituelles colligées au service de dermatologie sur une période allant de Janvier 2006 jusqu'au Mai 2015. L’étude a concerné 16 femmes et 6 hommes. La moyenne d’âge était de 23,3 ans (4-80 ans). La localisation cervico faciale a été observée dans 12 cas, 2 patients avaient des localisations multiples, un garçon de 4ans avait une localisation au niveau fronto-temporal et une fillette de 14 ans avait une localisation au niveau du visage et de l'avant-bras, et un patient de 48 ans avait une localisation sous unguéale. L'aspect clinique était typique dans tous les cas avec des nodules sous cutanés de consistance pierreuse. Tous les patients ont bénéficié d'une exérèse des nodules sous anesthésie locale. L’étude histologique était en faveur d'un épithélioma momifié de Malherbe d'exérèse complète sans signes de malignité. Aucun patient n'a présenté de rechute. L'originalité de notre étude réside dans la présence de localisations exceptionnelles au niveau latéro-vertébral, des membres et sous-unguéale, l’âge de survenue inhabituel à 80 ans et la présence de localisations multiples signalées chez 2 enfants. PMID:27516819 19. CRISPRscan: designing highly efficient sgRNAs for CRISPR/Cas9 targeting in vivo PubMed Central Moreno-Mateos, Miguel A.; Vejnar, Charles E.; Beaudoin, Jean-Denis; Fernandez, Juan P.; Mis, Emily K.; Khokha, Mustafa K.; Giraldez, Antonio J. 2015-01-01 CRISPR/Cas9 technology provides a powerful system for genome engineering. However, variable activity across different single guide RNAs (sgRNAs) remains a significant limitation. We have analyzed the molecular features that influence sgRNA stability, activity and loading into Cas9 in vivo. We observe that guanine enrichment and adenine depletion increase sgRNA stability and activity, while loading, nucleosome positioning and Cas9 off-target binding are not major determinants. We additionally identified truncated and 5′ mismatch-containing sgRNAs as efficient alternatives to canonical sgRNAs. Based on these results, we created a predictive sgRNA-scoring algorithm (CRISPRscan.org) that effectively captures the sequence features affecting Cas9/sgRNA activity in vivo. Finally, we show that targeting Cas9 to the germ line using a Cas9-nanos-3′-UTR fusion can generate maternal-zygotic mutants, increase viability and reduce somatic mutations. Together, these results provide novel insights into the determinants that influence Cas9 activity and a framework to identify highly efficient sgRNAs for genome targeting in vivo. PMID:26322839 20. Cas6 specificity and CRISPR RNA loading in a complex CRISPR-Cas system. PubMed Sokolowski, Richard D; Graham, Shirley; White, Malcolm F 2014-06-01 CRISPR-Cas is an adaptive prokaryotic immune system, providing protection against viruses and other mobile genetic elements. In type I and type III CRISPR-Cas systems, CRISPR RNA (crRNA) is generated by cleavage of a primary transcript by the Cas6 endonuclease and loaded into multisubunit surveillance/effector complexes, allowing homology-directed detection and cleavage of invading elements. Highly studied CRISPR-Cas systems such as those in Escherichia coli and Pseudomonas aeruginosa have a single Cas6 enzyme that is an integral subunit of the surveillance complex. By contrast, Sulfolobus solfataricus has a complex CRISPR-Cas system with three types of surveillance complexes (Cascade/type I-A, CSM/type III-A and CMR/type III-B), five Cas6 paralogues and two different CRISPR-repeat families (AB and CD). Here, we investigate the kinetic properties of two different Cas6 paralogues from S. solfataricus. The Cas6-1 subtype is specific for CD-family CRISPR repeats, generating crRNA by multiple turnover catalysis whilst Cas6-3 has a broader specificity and also processes a non-coding RNA with a CRISPR repeat-related sequence. Deep sequencing of crRNA in surveillance complexes reveals a biased distribution of spacers derived from AB and CD loci, suggesting functional coupling between Cas6 paralogues and their downstream effector complexes. 1. Structural characterization of CAS SH3 domain selectivity and regulation reveals new CAS interaction partners. PubMed Gemperle, Jakub; Hexnerová, Rozálie; Lepšík, Martin; Tesina, Petr; Dibus, Michal; Novotný, Marian; Brábek, Jan; Veverka, Václav; Rosel, Daniel 2017-08-14 CAS is a docking protein downstream of the proto-oncogene Src with a role in invasion and metastasis of cancer cells. The CAS SH3 domain is indispensable for CAS-mediated signaling, but structural aspects of CAS SH3 ligand binding and regulation are not well understood. Here, we identified the consensus CAS SH3 binding motif and structurally characterized the CAS SH3 domain in complex with ligand. We revealed the requirement for an uncommon centrally localized lysine residue at position +2 of CAS SH3 ligands and two rather dissimilar optional anchoring residues, leucine and arginine, at position +5. We further expanded the knowledge of CAS SH3 ligand binding regulation by manipulating tyrosine 12 phosphorylation and confirmed the negative role of this phosphorylation on CAS SH3 ligand binding. Finally, by exploiting the newly identified binding requirements of the CAS SH3 domain, we predicted and experimentally verified two novel CAS SH3 binding partners, DOK7 and GLIS2. 2. Immunohistochemical colocalization of 7B2 and 5HT in the neuroepithelial bodies of the lung of Rana temporaria. PubMed Bodegas, M E; Montuenga, L M; Polak, J M; Sesma, P 1993-07-01 The neuroendocrine cell population of the lung of Rana temporaria has been studied by means of immunocytochemistry. Serotonin (5HT)- and polypeptide 7B2-immunoreactive neuroepithelial bodies have been observed in the epithelial lining of the lung. 5HT- but not 7B2-immunoreactive isolated endocrine cells have also been observed. 3. CAS as Environments for Implementing Mathematical Microworlds. ERIC Educational Resources Information Center Alpers, Burkhard 2002-01-01 Investigates whether computer algebra systems (CAS) are suitable environments for implementing mathematical microworlds. Recalls what constitutes a microworld and explores how CAS can be used for implementation, stating potentials as well as limitations. Provides as an example the microworld "Formula 1", implemented in Maple Software. (Author/KHR) 4. CAS as Environments for Implementing Mathematical Microworlds. ERIC Educational Resources Information Center Alpers, Burkhard 2002-01-01 Investigates whether computer algebra systems (CAS) are suitable environments for implementing mathematical microworlds. Recalls what constitutes a microworld and explores how CAS can be used for implementation, stating potentials as well as limitations. Provides as an example the microworld "Formula 1", implemented in Maple Software. (Author/KHR) 5. Assessment of 5-HT7 Receptor Agonists Selectivity Using Nociceptive and Thermoregulation Tests in Knockout versus Wild-Type Mice PubMed Central Brenchat, Alex; Rocasalbas, Maria; Zamanillo, Daniel; Hamon, Michel; Vela, José Miguel; Romero, Luz 2012-01-01 No study has ever examined the effect of 5-HT7 receptor agonists on nociception by using 5-HT7 receptor knockout mice. Basal sensitivity to noxious heat stimuli and formalin-induced nociception in both phase I and II of the formalin test did not differ in 5-HT7 receptor knockout mice and paired wild-type controls. Similarly, there was no significant difference in basal body temperature between both genotypes. Subcutaneous administration of 5-HT7 receptor agonists AS-19 (10 mg/kg), E-57431 (10 mg/kg), and E-55888 (20 mg/kg) significantly reduced formalin-induced licking/biting behavior during the phase II of the test in wild-type but not in 5-HT7 receptor knockout mice. At these active analgesic doses, none of the three 5-HT7 receptor agonists modified the basal body temperature neither in wild-type nor in 5-HT7 receptor knockout mice. However, a significant decrease in body temperature was observed at a higher dose (20 mg/kg) of AS-19 and E-57431 in both genotypes. Our data strongly suggest that the 5-HT7 receptor agonists AS-19, E-57431, and E-55888 produce antinociception in the formalin test by activating 5-HT7 receptors. These results also strengthen the idea that the 5-HT7 receptor plays a role in thermoregulation, but by acting in concert with other receptors. PMID:22761612 6. Probing Structural Changes in Poly(3-hexylthiophene) (P3HT) During Electrochemical Oxidation with In Situ X-ray Scattering NASA Astrophysics Data System (ADS) Thelen, Jacob L.; Patel, Shrayesh N.; Javier, Anna E.; Balsara, Nitash P. 2014-03-01 Mixtures of poly(3-hexylthiophene)-b-poly(ethylene oxide) (P3HT-b-PEO) block copolymer and lithium bis(trifluromethanesulfonyl) imide (LiTFSI) salt can microphase separate into electron (P3HT) and ion (PEO/LiTFSI) conducting domains. P3HT is a semicrystalline polymer with intrinsically semiconducting electronic properties. Electrochemical oxidation (doping) of the P3HT block provides the P3HT-b-PEO/LiTFSI mixtures with electronic conductivity suitable for lithium battery operation. Due to the presence of the solid-state electrolyte (PEO/LiTFSI) in intimate contact with the microphase separated P3HT domains, electrochemical oxidation of P3HT can be performed entirely in the solid state; therefore, P3HT-b-PEO/LiTFSI provides a unique opportunity to study the structural changes in P3HT induced by oxidation. We use in situ x-ray scattering techniques to probe structural changes in P3HT during electrochemical oxidation and correlate these changes with previously observed enhancements in electron mobility. Supported by the Joint Center for Energy Storage Research (JCESR). 7. Campylobacter jejuni acquire new host-derived CRISPR spacers when in association with bacteriophages harboring a CRISPR-like Cas4 protein PubMed Central Hooton, Steven P. T.; Connerton, Ian F. 2015-01-01 Campylobacter jejuni is a worldwide cause of human diarrhoeal disease. Clustered Repetitively Interspaced Palindromic Repeats (CRISPRs) and associated proteins allow Bacteria and Archaea to evade bacteriophage and plasmid infection. Type II CRISPR systems are found in association with combinations of genes encoding the CRISPR-associated Cas1, Cas2, Cas4 or Csn2, and Cas9 proteins. C. jejuni possesses a minimal subtype II-C CRISPR system containing cas1, cas2, and cas9 genes whilst cas4 is notably absent. Cas4 proteins possess 5′-3′ exonuclease activity to create recombinogenic-ends for spacer acquisition. Here we report a conserved Cas4-like protein in Campylobacter bacteriophages that creates a novel split arrangement between the bacteriophage and host that represents a new twist in the bacteriophage/host co-evolutionary arms race. The continuous association of bacteriophage and host in the carrier state life cycle of C. jejuni provided an opportunity to study spacer acquisition in this species. Remarkably all the spacer sequences observed were of host origin. We hypothesize that Campylobacter bacteriophages can use Cas4-like protein to activate spacer acquisition to use host DNA as an effective decoy to bacteriophage DNA. Bacteria that acquire self-spacers and escape phage infection must overcome CRISPR-mediated autoimmunity either by loss of the interference functions leaving them susceptible to foreign DNA incursion or tolerate changes in gene regulation. PMID:25601859 8. CasA mediates Cas3-catalyzed target degradation during CRISPR RNA-guided interference. PubMed Hochstrasser, Megan L; Taylor, David W; Bhat, Prashant; Guegler, Chantal K; Sternberg, Samuel H; Nogales, Eva; Doudna, Jennifer A 2014-05-06 9. In vitro enzymology of Cas9. PubMed Anders, Carolin; Jinek, Martin 2014-01-01 Cas9 is a bacterial RNA-guided endonuclease that uses base pairing to recognize and cleave target DNAs with complementarity to the guide RNA. The programmable sequence specificity of Cas9 has been harnessed for genome editing and gene expression control in many organisms. Here, we describe protocols for the heterologous expression and purification of recombinant Cas9 protein and for in vitro transcription of guide RNAs. We describe in vitro reconstitution of the Cas9-guide RNA ribonucleoprotein complex and its use in endonuclease activity assays. The methods outlined here enable mechanistic characterization of the RNA-guided DNA cleavage activity of Cas9 and may assist in further development of the enzyme for genetic engineering applications. 10. CAS SciTech Connect Martinez, B.; Pomeroy, G. ) 1989-12-02 The Security Alarm System is a data acquisition and control system which collects data from intrusion sensors and displays the information in a real-time environment for operators. The Access Control System monitors and controls the movement of personnel with the use of card readers and biometrics hand readers. 11. The involvement of 5-HT-like receptors in the regulation of food intake in rainbow trout (Oncorhynchus mykiss). PubMed Pérez Maceira, Jorge J; Mancebo, María J; Aldegunde, Manuel 2014-04-01 It is known that in fish the serotonergic system is part of the neural network that controls feeding and that a pharmacologically induced increase in the brain 5-HT inhibits food intake. However, nothing is known about the 5-HT receptors involved in this inhibitory effect. In this study, we investigated the effects of several 5-HT1 and 5-HT2 receptor agonists on food intake in rainbow trout. In the first experiment, fish were injected i.p. or i.c.v. with two 5-HT1B receptor agonists, anpirtoline (2mg/kg, i.p.) and CP93129 (100 and 200μg/kg, i.c.v.). Neither of these treatments significantly altered food intake. In a second set of experiments, different groups of fish were injected i.p. (1mg/kg) or i.c.v. (30μg/kg) with the 5-HT1A receptor agonist 8-OH-DPAT. In both cases, administration of the 5-HT1A receptor agonist inhibited food intake. In a third set of experiments, we explored the effects of different 5-HT2 receptor agonists. Different groups of fish were injected i.p. or i.c.v. with the mixed 5-HT2B/2C agonist m-CPP (5mg/kg, i.p.), 5-HT2C agonist MK212 (60μg/kg, i.c.v.) and 5-HT2B agonist BW723C86 (50 and 100μg/kg, i.c.v.). Administration of the 5-HT2B/2C and 5HT2C receptor agonists significantly inhibited food intake. Administration of the lowest dose of the 5-HT2B receptor agonist did not have any significant effect, while administration of the highest dose induced a significant increase in food intake. Activation of the 5-HT1A-like (food intake inhibition) and 5-HT1B-like (no effect on food intake) receptors in the rainbow trout induced different effects on food intake from those observed in mammals. We conclude that in rainbow trout the anorexigenic actions of 5-HT are probably mediated by activation of 5-HT1A and 5-H2C-like receptors. 12. 5-HT2C Agonists Modulate Schizophrenia-Like Behaviors in Mice. PubMed Pogorelov, Vladimir M; Rodriguiz, Ramona M; Cheng, Jianjun; Huang, Mei; Schmerberg, Claire M; Meltzer, Herbert Y; Roth, Bryan L; Kozikowski, Alan P; Wetsel, William C 2017-10-01 All FDA-approved antipsychotic drugs (APDs) target primarily dopamine D2 or serotonin (5-HT2A) receptors, or both; however, these medications are not universally effective, they may produce undesirable side effects, and provide only partial amelioration of negative and cognitive symptoms. The heterogeneity of pharmacological responses in schizophrenic patients suggests that additional drug targets may be effective in improving aspects of this syndrome. Recent evidence suggests that 5-HT2C receptors may be a promising target for schizophrenia since their activation reduces mesolimbic nigrostriatal dopamine release (which conveys antipsychotic action), they are expressed almost exclusively in CNS, and have weight-loss-promoting capabilities. A difficulty in developing 5-HT2C agonists is that most ligands also possess 5-HT2B and/or 5-HT2A activities. We have developed selective 5-HT2C ligands and herein describe their preclinical effectiveness for treating schizophrenia-like behaviors. JJ-3-45, JJ-3-42, and JJ-5-34 reduced amphetamine-stimulated hyperlocomotion, restored amphetamine-disrupted prepulse inhibition, improved social behavior, and novel object recognition memory in NMDA receptor hypofunctioning NR1-knockdown mice, and were essentially devoid of catalepsy. However, they decreased motivation in a breakpoint assay and did not promote reversal learning in MK-801-treated mice. Somewhat similar effects were observed with lorcaserin, a 5-HT2C agonist with potent 5-HT2B and 5-HT2A agonist activities, which is approved for treating obesity. Microdialysis studies revealed that both JJ-3-42 and lorcaserin reduced dopamine efflux in the infralimbic cortex, while only JJ-3-42 decreased it in striatum. Collectively, these results provide additional evidence that 5-HT2C receptors are suitable drug targets with fewer side effects, greater therapeutic selectivity, and enhanced efficacy for treating schizophrenia and related disorders than current APDs. 13. The Canadian experimental HT release of June 10, 1987, US measurements SciTech Connect Jalbert, R.A.; Murphy, C.E. 1988-09-01 In June 1987, an experiment was performed at the Chalk River Nuclear Laboratories in Ontario, Canada, to study the oxidation of elemental tritium (HT) released to the environment. The experiment involved a 30-minute release of 3.54 TBq (95.7 Ci)of HT to the atmosphere at an elevation of one meter. Scientists from six countries participated in the experiment. The air measurements showed HT concentrations downwind of the release in general agreement with classical atmospheric diffusion (Gaussian) up to the maximum distance measured (400 m). The HTO/HT ratios were shown to slowly increase downwind (approx. 4 x 10/sup /minus/5/ at 50 m to almost 10/sup /minus/3/ at 400 m) as conversion of HT took place. After the release, HTO concentrations in the atmosphere remained elevated. Vegetation samples were also taken since the vegetation and associated soil system have been implicated in the oxidation of HT. Freeze-dried water from vegetation samples was found to be low in HTO immediately after the release suggesting a low direct uptake of HTO in air by vegetation. The tritiated water concentration increased during the first day, peaking during the second day (about 15--30 kBq/L of water at 50 m from the source), and decreasing by the end of the second day. This pattern suggests oxidation in the soil followed by plant uptake through sorption of soil water. This was confirmed by measurements taken by other groups at the experiment site. The HTO in vegetation decreased with distance downwind with the same pattern as the HT measured during the release indicating that the oxidation of HT was linearly related to the HT concentration in the atmosphere during the exposure period. An adequate description of the process can be made through the observed phenomenon of HT deposition into the soil with subsequent rapid oxidation by soil bacteria. 30 refs., 10 figs., 4 tabs. 14. Glucose-dependent trafficking of 5-HT3 receptors in rat gastrointestinal vagal afferent neurons PubMed Central Babic, Tanja; Troy, Amanda E; Fortna, Samuel R; Browning, Kirsteen N 2012-01-01 Background Intestinal glucose induces gastric relaxation via vagally mediated sensory-motor reflexes. Glucose can alter the activity of gastrointestinal (GI) vagal afferent (sensory) neurons directly, via closure of ATP-sensitive potassium channels, as well as indirectly, via the release of 5-hydroxytryptamine (5-HT) from mucosal enteroendocrine cells. We hypothesized that glucose may also be able to modulate the ability of GI vagal afferent neurons to respond to the released 5-HT, via regulation of neuronal 5-HT3 receptors. Methods Whole cell patch clamp recordings were made from acutely dissociated GI-projecting vagal afferent neurons exposed to equiosmolar Krebs’ solution containing different concentrations of D-glucose (1.25–20mM) and the response to picospritz application of 5-HT assessed. The distribution of 5-HT3 receptors in neurons exposed to different glucose concentrations was also assessed immunohistochemically. Key Results Increasing or decreasing extracellular D-glucose concentration increased or decreased, respectively, the 5-HT-induced inward current as well as the proportion of 5-HT3 receptors associated with the neuronal membrane. These responses were blocked by the Golgi-disrupting agent Brefeldin-A (5µM) suggesting involvement of a protein trafficking pathway. Furthermore, L-glucose did not mimic the response of D-glucose implying that metabolic events downstream of neuronal glucose uptake are required in order to observe the modulation of 5-HT3 receptor mediated responses. Conclusions & Inferences These results suggest that, in addition to inducing the release of 5-HT from enterochromaffin cells, glucose may also increase the ability of GI vagal sensory neurons to respond to the released 5-HT, providing a means by which the vagal afferent signal can be amplified or prolonged. PMID:22845622 15. The 5-HT7 receptor in learning and memory. Importance of the hippocampus PubMed Central Roberts, Amanda J.; Hedlund, Peter B. 2011-01-01 The 5-HT7 receptor is a more recently discovered G-protein-coupled receptor for serotonin. The functions and possible clinical relevance of this receptor are not yet fully understood. The present paper reviews to what extent the use of animal models of learning and memory and other techniques have implicated the 5-HT7 receptor in such processes. The studies have used a combination of pharmacological and genetic tools targeting the receptor to evaluate effects on behavior and cellular mechanisms. In tests such as the Barnes maze, contextual fear conditioning and novel location recognition that involve spatial learning and memory there is a considerable amount of evidence supporting an involvement of the 5-HT7 receptor. Supporting evidence has also been obtained in studies of mRNA expression and cellular signaling as well as in electrophysiological experiments. Especially interesting are the subtle but distinct effects observed in hippocampus-dependent models of place learning where impairments have been described in mice lacking the 5-HT7 receptor or after administration of a selective antagonist. While more work is required, it appears that 5-HT7 receptors are particularly important in allocentric representation processes. In instrumental learning tasks both procognitive effects and impairments in memory have been observed using pharmacological tools targeting the 5-HT7 receptor. In conclusion, the use of pharmacological and genetic tools in animal studies of learning and memory suggest a potentially important role for the 5-HT7 receptor in cognitive processes. PMID:21484935 16. 5-HT2C Receptor Desensitization Moderates Anxiety in 5-HTT Deficient Mice: From Behavioral to Cellular Evidence PubMed Central Martin, Cédric BP; Martin, Vincent S.; Trigo, José M.; Chevarin, Caroline; Maldonado, Rafael; Fink, Latham H.; Cunningham, Kathryn A.; Hamon, Michel; Lanfumey, Laurence 2015-01-01 Background: Desensitization and blockade of 5-HT2C receptors (5-HT2CR) have long been thought to be central in the therapeutic action of antidepressant drugs. However, besides behavioral pharmacology studies, there is little in vivo data documenting antidepressant-induced 5-HT2CR desensitization in specific brain areas. Methods: Mice lacking the 5-HT reuptake carrier (5-HTT-/-) were used to model the consequences of chronic 5-HT reuptake inhibition with antidepressant drugs. The effect of this mutation on 5-HT2CR was evaluated at the behavioral (social interaction, novelty-suppressed feeding, and 5-HT2CR–induced hypolocomotion tests), the neurochemical, and the cellular (RT-qPCR, mRNA editing, and c-fos–induced expression) levels. Results: Although 5-HTT-/- mice had an anxiogenic profile in the novelty-suppressed feeding test, they displayed less 5-HT2CR–mediated anxiety in response to the agonist m-chlorophenylpiperazine in the social interaction test. In addition, 5-HT2CR–mediated inhibition of a stress-induced increase in 5-HT turnover, measured in various brain areas, was markedly reduced in 5-HTT-/- mutants. These indices of tolerance to 5-HT2CR stimulation were associated neither with altered levels of 5-HT2CR protein and mRNA nor with changes in pre-mRNA editing in the frontal cortex. However, basal c-fos mRNA production in cells expressing 5-HT2CR was higher in 5-HTT-/- mutants, suggesting an altered basal activity of these cells following sustained 5-HT reuptake carrier inactivation. Furthermore, the increased c-fos mRNA expression in 5-HT2CR–like immune-positive cortical cells observed in wild-type mice treated acutely with the 5-HT2CR agonist RO-60,0175 was absent in 5-HTT-/- mutants. Conclusions: Such blunted responsiveness of the 5-HT2CR system, observed at the cell signaling level, probably contributes to the moderation of the anxiety phenotype in 5-HTT-/- mice. PMID:25522398 17. 5-HT6 receptors and Alzheimer's disease PubMed Central 2013-01-01 During the past 20 years, the 5-HT6 receptor has received increasing attention and become a promising target for improving cognition. Several studies with structurally different compounds have shown that not only antagonists but also 5-HT6 receptor agonists improve learning and memory in animal models. A large number of publications describing the development of ligands for this receptor have come to light, and it is now quite evident that 5-HT6 receptors have great pharmaceutical potential in terms of related patents. However, 5-HT6 receptor functionality is much more complex than initially defined. According to the existing data, different cellular pathways may be activated, depending on the drug being used. This article reviews preclinical and clinical evidence of the effects that 5-HT6 receptor compounds have on cognition. In addition, the biochemical and neurochemical mechanisms of action through which 5-HT6 receptor compounds can influence cognition will be described. Overall, several 5-HT6-targeted compounds can reasonably be regarded as powerful drug candidates for the treatment of Alzheimer's disease. PMID:23607787 18. 5-HT6 receptors and Alzheimer's disease. PubMed Ramírez, María Javier 2013-01-01 During the past 20 years, the 5-HT6 receptor has received increasing attention and become a promising target for improving cognition. Several studies with structurally different compounds have shown that not only antagonists but also 5-HT6 receptor agonists improve learning and memory in animal models. A large number of publications describing the development of ligands for this receptor have come to light, and it is now quite evident that 5-HT6 receptors have great pharmaceutical potential in terms of related patents. However, 5-HT6 receptor functionality is much more complex than initially defined. According to the existing data, different cellular pathways may be activated, depending on the drug being used. This article reviews preclinical and clinical evidence of the effects that 5-HT6 receptor compounds have on cognition. In addition, the biochemical and neurochemical mechanisms of action through which 5-HT6 receptor compounds can influence cognition will be described. Overall, several 5-HT6-targeted compounds can reasonably be regarded as powerful drug candidates for the treatment of Alzheimer's disease. 19. Organic solar cells: evaluation of the stability of P3HT using time-delayed degradation NASA Astrophysics Data System (ADS) Poh, Chung-How; Poh, Chung-Kiak; Bryant, Glenn; Belcher, Warwick; Dastoor, Paul 2011-12-01 Despite the fact that the performance of organic solar cells is generally susceptible to degradation by moisture exposure, there has been suggestion that the photoactive layer (P3HT) is surprisingly resilient. This work attempts to confirm the stability of P3HT as an organic solar cell material by deliberately introducing water into the photoactive layer. A dramatic step drop in device performance during cell characterization is observed approximately one day after the device has been fabricated. The time-delayed step drop in output efficiency strongly suggests that moisture has little effect on the P3HT conducting polymer. 20. 5-HT2A receptor gene polymorphisms in Croatian subjects with autistic disorder. PubMed Hranilovic, Dubravka; Blazevic, Sofia; Babic, Marina; Smurinic, Maja; Bujas-Petkovic, Zorana; Jernej, Branimir 2010-08-15 Disturbances in the expression/function of the 5-HT2A receptor are implicated in autism. The association of the 5-HT2A receptor gene with autism was studied in the Croatian population. Distribution frequencies for alleles, genotypes and haplotypes of -1438 A/G and His452Tyr polymorphisms were compared in samples of 103 autistic and 214 control subjects. Significant overrepresentation of the G allele and the GG genotype of the -1438 A/G polymorphism was observed in group of autistic subjects, supporting the possible involvement of the 5-HT2A receptor in the development of autism. 1. Anxiolytic-like effect of a serotonergic ligand with high affinity for 5-HT1A, 5-HT2A and 5-HT3 receptors. PubMed Delgado, Mercedes; Caicoya, Anne G; Greciano, Virginia; Benhamú, Bellinda; López-Rodríguez, María Luz; Fernández-Alfonso, María Soledad; Pozo, Miguel A; Manzanares, Jorge; Fuentes, José A 2005-03-21 S-(-)-2-[[4-(napht-1-yl)piperazin-1-yl]methyl]-1,4-dioxoperhydropyrrolo[1,2-alpha]-pyrazine (CSP-2503) is a serotonin (5-HT) receptor ligand with selectivity and high affinity for 5-HT1A, 5-HT2A and 5-HT3 receptors. CSP-2503 reduced rectal temperature and 5-HT neuronal hypothalamic activity in mice, decreased electrical activity of raphe nuclei cells in rats and blocked the enhancement of adenylate cyclase activity induced by forskolin in HeLa cells transfected with the human 5-HT1A receptor. This compound also blocked head-twitches induced by the 5-HT(2A/2C) receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI). Contractions of guinea pig ileum induced by the 5-HT3 receptor agonist 2-methyl-5-HT were prevented by CSP-2503. Moreover, it reduced the bradycardia reflex induced by 2-methyl-5-HT in anaesthetized rats. In the light/dark box and social interaction tests, CSP-2503 presented anxiolytic activity, an action shared by 5-HT1 agonists and 5-HT3 antagonists. Taken together, these results suggest that CSP-2503 is a new 5-HT1 receptor agonist with 5-HT2A and 5-HT3)receptor antagonist activities that might be useful in a number of conditions associated with anxiety. 2. Detection of the secondary star in HT Cassiopeiae NASA Technical Reports Server (NTRS) Marsh, T. R. 1990-01-01 Low-resolution spectra of the eclipsing dwarf nova HT Cas, taken over the range 5000-9800 A show TiO bands and Na I absorption lines from the secondary star. From the TiO band ratio at mid-eclipse it is estimated that the secondary star contributes about 37 percent of the light at 7500 A during the eclipse, and that it has a Boeshaar spectral type M5.4 + or - 0.3. The mass, radius, and luminosity of the secondary star are all consistent with main-sequence values. The TiO band strength diminishes greatly near phase 0.5, but an eclipse by the disk is not sufficient to explain this. The radial velocity is measured from the Na line near 8200 A for most of the spectra and (after a correction for the asymmetric distribution of absorption over the secondary star) its radial velocity semiamplitude K2 = 430 + or - 25 km/sec. 3. RNA targeting with CRISPR-Cas13. PubMed Abudayyeh, Omar O; Gootenberg, Jonathan S; Essletzbichler, Patrick; Han, Shuo; Joung, Julia; Belanto, Joseph J; Verdine, Vanessa; Cox, David B T; Kellner, Max J; Regev, Aviv; Lander, Eric S; Voytas, Daniel F; Ting, Alice Y; Zhang, Feng 2017-10-12 RNA has important and diverse roles in biology, but molecular tools to manipulate and measure it are limited. For example, RNA interference can efficiently knockdown RNAs, but it is prone to off-target effects, and visualizing RNAs typically relies on the introduction of exogenous tags. Here we demonstrate that the class 2 type VI RNA-guided RNA-targeting CRISPR-Cas effector Cas13a (previously known as C2c2) can be engineered for mammalian cell RNA knockdown and binding. After initial screening of 15 orthologues, we identified Cas13a from Leptotrichia wadei (LwaCas13a) as the most effective in an interference assay in Escherichia coli. LwaCas13a can be heterologously expressed in mammalian and plant cells for targeted knockdown of either reporter or endogenous transcripts with comparable levels of knockdown as RNA interference and improved specificity. Catalytically inactive LwaCas13a maintains targeted RNA binding activity, which we leveraged for programmable tracking of transcripts in live cells. Our results establish CRISPR-Cas13a as a flexible platform for studying RNA in mammalian cells and therapeutic development. 4. COMMUNICATION BETWEEN 5-HT AND SMALL GTPases PubMed Central Mercado, Charles P.; Ziu, Endrit; Kilic, Fusun 2011-01-01 Advances over the past decade have improved our understanding of the serotonin (5-HT) biology outside the central nervous system specifically the molecular mechanisms of serotonergic signaling in association with small GTPases. It is now recognized that the communication between 5-HT and GTPases plays important roles in peripheral tissues, vascular cells and are involved in coagulation, hypertension, inflammation, healing and protection. Furthermore, 5-HT receptors as heterotrimeric GTP-binding protein-coupled receptors act as effector protein on the small GTPases. Therefore, the antagonists or agonists of the effector proteins of small GTPases could be useful therapeutic agents for the treatment of several diseases and disorders. PMID:21320798 5. Assisting Students' Cognitive Strategies with the Use of CAS ERIC Educational Resources Information Center Sarvari, Csaba; Lavicza, Zsolt; Klincsik, Mihaly 2010-01-01 This paper examines various cognitive strategies applied while CAS (Computer Algebra System) are used in undergraduate-level engineering mathematics teaching and learning. We posed some questions in relation to such CAS use: What kind of tools can CAS offer to enhance different cognitive strategies of students? How can the use of CAS widen the… 6. Stimulation of 5-HT1A, 5-HT1B, 5-HT2A/2C, 5-HT3 and 5-HT4 receptors or 5-HT uptake inhibition: short- and long-term memory. PubMed Meneses, Alfredo 2007-11-22 In order to determine whether short- (STM) and long-term memory (LTM) function in serial or parallel manner, serotonin (5-hydroxtryptamine, 5-HT) receptor agonists were tested in autoshaping task. Results show that control-vehicle animals were modestly but significantly mastering the autoshaping task as illustrated by memory scores between STM and LTM. Thus, post-training administration of 8-OHDPAT (agonist for 5-HT(1A/7) receptors) only at 0.250 and 0.500 mg/kg impaired both STM and LTM. CGS12066 (agonist for 5-HT(1B)) produced biphasic affects, at 5.0 mg/kg impaired STM but at 1.0 and 10.0 mg/kg, respectively, improved or impaired LTM. DOI (agonist for 5-HT(2A/2C) receptors) dose-dependently impaired STM and, at 10.0 mg/kg only impaired LTM. Both, STM and LTM were impaired by either mCPP (mainly agonist for 5-HT(2C) receptors) or mesulergine (mainly antagonist for 5-HT(2C) receptors) lower dose. The 5-HT(3) agonist mCPBG at 1.0 impaired STM and its higher dose impaired both STM and LTM. RS67333 (partial agonist for 5-HT(4) receptors), at 5.0 and 10.0 mg/kg facilitated both STM and LTM. The higher dose of fluoxetine (a 5-HT uptake inhibitor) improved both STM and LTM. Using as head-pokes during CS as an indirect measure of food-intake showed that of 30 memory changes, 21 of these were unrelated to the former. While some STM or LTM impairments can be attributed to decrements in food-intake, but not memory changes (either increase or decreases) produced by 8-OHDPAT, CGS12066, RS67333 or fluoxetine. Except for animals treated with DOI, mCPBG or fluoxetine, other groups treated with 5-HT agonists 6 h following autoshaping training showed similar LTM and unmodified CS-head-pokes scores. 7. Potentiation of RSU-1069 tumour cytotoxicity by 5-hydroxytryptamine (5-HT). PubMed Chaplin, D J 1986-11-01 It is known that many solid animal tumours have a lower oxygenation level than most normal tissues and, in addition, that this level of oxygenation can be further decreased by systemic administration of 5-hydroxytryptamine (5-HT). The present study has investigated if such selective decrease in tumour oxygenation can be exploited by using the hypoxic cell cytotoxin, RSU-1069. The results obtained show that 5-HT at a dose of 5 mg kg-1, although not cytotoxic alone, can potentiate the cytotoxic effects of RSU-1069 in the Lewis lung carcinoma over the dose range 0.01-0.15 mg g-1. Maximum potentiation occurs when 5-HT is administered after RSU-1069. Potentiation of RSU-1069 cytotoxicity was observed using both the soft agar excision assay as an endpoint as well as in situ growth delay. In addition, the study shows that potentiation of RSU-1069 (0.1 mg g-1) cytotoxicity can be seen with 5-HT doses as low as 0.5 mg kg-1. In contrast to the tumour cytotoxicity results, 5-HT at a dose of 5 mg kg-1 i.p. did not affect the systemic toxicity, as measured by LD50/7d of RSU-1069. Thus, these results indicate that 5-HT can increase the therapeutic efficiency of RSU-1069. Such a finding is consistent with the rationale that selective reduction in tumour blood flow and oxygenation induced by 5-HT can be exploited using the hypoxic cell cytotoxin RSU-1069. 8. 5-HT(2B) receptors are required for serotonin-selective antidepressant actions. PubMed Diaz, S L; Doly, S; Narboux-Nême, N; Fernández, S; Mazot, P; Banas, S M; Boutourlinsky, K; Moutkine, I; Belmer, A; Roumier, A; Maroteaux, L 2012-02-01 The therapeutic effects induced by serotonin-selective reuptake inhibitor (SSRI) antidepressants are initially triggered by blocking the serotonin transporter and rely on long-term adaptations of pre- and post-synaptic receptors. We show here that long-term behavioral and neurogenic SSRI effects are abolished after either genetic or pharmacological inactivation of 5-HT(2B) receptors. Conversely, direct agonist stimulation of 5-HT(2B) receptors induces an SSRI-like response in behavioral and neurogenic assays. Moreover, the observation that (i) this receptor is expressed by raphe serotonergic neurons, (ii) the SSRI-induced increase in hippocampal extracellular serotonin concentration is strongly reduced in the absence of functional 5-HT(2B) receptors and (iii) a selective 5-HT(2B) agonist mimics SSRI responses, supports a positive regulation of serotonergic neurons by 5-HT(2B) receptors. The 5-HT(2B) receptor appears, therefore, to positively modulate serotonergic activity and to be required for the therapeutic actions of SSRIs. Consequently, the 5-HT(2B) receptor should be considered as a new tractable target in the combat against depression. 9. Study of the P3HT/PCBM interface using photoemission yield spectroscopy NASA Astrophysics Data System (ADS) Grzibovskis, Raitis; Vembris, Aivars 2016-04-01 Photogeneration efficiency and charge carrier extraction from active layer are the parameters that determine the efficiency of organic photovoltaics (OPVs). Devices made of organic materials often consist of thin (up to 100nm) layers. At this thickness different interface effects become more pronounced. The electron affinity and ionization energy shift can affect the charge carrier transport across metal-organic interface which can affect the performance of the entire device. In the case of multilayer OPVs, energy level compatibility at the organic-organic interface is as important. Photoemission yield spectroscopy was used for organic-organic interface study by ionization energy measurements. In this work we studied "sandwich" type samples of two well-known organic photovoltaic materials- poly(3- hexylthiophene-2,5-diyl) (P3HT) and [6,6]-phenyl C61 butyric acid methyl ester (PCBM). Ionization energy changes at the P3HT/PCBM interface depending on PCBM layer thickness were studied. P3HT layer was obtained by spin-coating while PCBM was deposited on the P3HT by thermal evaporation in vacuum. No ionization energy shift of P3HT was observed. On the contrary, PCBM at the interface with P3HT created additional 0.40eV barrier for hole transport from PCBM to P3HT. 10. Nucleosomes Inhibit Cas9 Endonuclease Activity in Vitro. PubMed Hinz, John M; Laughery, Marian F; Wyrick, John J 2015-12-08 During Cas9 genome editing in eukaryotic cells, the bacterial Cas9 enzyme cleaves DNA targets within chromatin. To understand how chromatin affects Cas9 targeting, we characterized Cas9 activity on nucleosome substrates in vitro. We find that Cas9 endonuclease activity is strongly inhibited when its target site is located within the nucleosome core. In contrast, the nucleosome structure does not affect Cas9 activity at a target site within the adjacent linker DNA. Analysis of target sites that partially overlap with the nucleosome edge indicates that the accessibility of the protospacer-adjacent motif (PAM) is the critical determinant of Cas9 activity on a nucleosome. 11. Novel class of arylpiperazines containing N-acylated amino acids: their synthesis, 5-HT1A, 5-HT2A receptor affinity, and in vivo pharmacological evaluation. PubMed Zajdel, Paweł; Subra, Gilles; Bojarski, Andrzej J; Duszyńska, Beata; Tatarczyńska, Ewa; Nikiforuk, Agnieszka; Chojnacka-Wójcik, Ewa; Pawłowski, Maciej; Martinez, Jean 2007-04-15 Novel arylpiperazines with N-acylated amino acids, selected on the basis of a preliminary screening of two libraries previously synthesized on SynPhase Lanterns, were prepared in solution and their affinity for 5-HT(1A), 5-HT(2A), and D(2) receptors was evaluated. The compounds bearing (3-acylamino)pyrrolidine-2,5-dione (19-26) and N-acylprolinamide (29-34) moieties showed high affinity for 5-HT(1A) (K(i)=3-47 nM), high-to-low for 5-HT(2A) (K(i)=4.2-990 nM), and low for D(2) receptors (K(i)=0.77-21.19 microM). All the new o-methoxy derivatives of (3-acylamino)pyrrolidine-2,5-diones tested in vivo revealed agonistic activity at postsynaptic 5-HT(1A) receptors, while m-chloro derivatives were classified as antagonists of these sites; similar relations were observed for o-methoxy (29) and m-chlorophenylpiperazine derivatives of N-acylprolinamides. The reported results show that the amino acid-derived terminal fragment modified the in vivo functional profile. Finally, the selected compounds 19 and 20, a 5-HT(1A) partial agonist and a full agonist, respectively, and 26, a mixed 5-HT(1A)/5-HT(2A) antagonist, were evaluated in preclinical animal models of depression and anxiety. The project allowed selecting the lead compound 20 which exhibited an anxiolytic-like effect in the four-plate test in mice and revealed distinct antidepressant-like effects in the forced swimming and tail suspension tests in mice. 12. Addition of P3HT-grafted Silica nanoparticles improves bulk-heterojunction morphology in P3HT-PCBM blends NASA Astrophysics Data System (ADS) Garg, Mohit; Padmanabhan, Venkat 2016-09-01 We present molecular dynamics simulations of a ternary blend of P3HT, PCBM and P3HT-grafted silica nanoparticles (SiNP) for applications in polymer-based solar cells. Using coarse-grained models, we study the effect of SiNP on the spatial arrangement of PCBM in P3HT. Our results suggest that addition of SiNP not only alters the morphology of PCBM clusters but also improves the crystallinity of P3HT. We exploit the property of grafted SiNP to self-assemble into a variety of anisotropic structures and the tendency of PCBM to preferentially adhere to SiNP surface, due to favorable interactions, to achieve morphologies with desirable characteristics for the active layer, including domain size, crystallinity of P3HT, and elimination of isolated islands of PCBM. As the concentration of SiNP increases, the number of isolated PCBM molecules decreases, which in turn improves the crystallinity of P3HT domains. We also observe that by tuning the grafting parameters of SiNP, it is possible to achieve structures ranging from cylindrical to sheets to highly interconnected network of strings. The changes brought about by addition of SiNP shows a promising potential to improve the performance of these materials when used as active layers in organic photovoltaics. 13. Addition of P3HT-grafted Silica nanoparticles improves bulk-heterojunction morphology in P3HT-PCBM blends PubMed Central Garg, Mohit; Padmanabhan, Venkat 2016-01-01 We present molecular dynamics simulations of a ternary blend of P3HT, PCBM and P3HT-grafted silica nanoparticles (SiNP) for applications in polymer-based solar cells. Using coarse-grained models, we study the effect of SiNP on the spatial arrangement of PCBM in P3HT. Our results suggest that addition of SiNP not only alters the morphology of PCBM clusters but also improves the crystallinity of P3HT. We exploit the property of grafted SiNP to self-assemble into a variety of anisotropic structures and the tendency of PCBM to preferentially adhere to SiNP surface, due to favorable interactions, to achieve morphologies with desirable characteristics for the active layer, including domain size, crystallinity of P3HT, and elimination of isolated islands of PCBM. As the concentration of SiNP increases, the number of isolated PCBM molecules decreases, which in turn improves the crystallinity of P3HT domains. We also observe that by tuning the grafting parameters of SiNP, it is possible to achieve structures ranging from cylindrical to sheets to highly interconnected network of strings. The changes brought about by addition of SiNP shows a promising potential to improve the performance of these materials when used as active layers in organic photovoltaics. PMID:27628895 14. Communication interventriculaire ischémique: à propos d'un cas observé dans le service de cardiologie du CHU-Yalgado Ouedraogo de Ouagadougou (Burkina Faso) PubMed Central Yaméogo, Nobila Valentin; Ilboudo, Maurice; Seghda, Arthur; Kologo, Jonas; Millogo, Georges; Toguyéni, Boubakar Jean Yves; Samadoulougou, André; Zabsonré, Patrice 2014-01-01 La rupture myocardique est une complication rare mais souvent fatale de l'infarctus du myocarde aigu récent. Une patiente âgée de 72 ans, présentant une douleur thoracique typiquement angineuse évoluant depuis 34 jours, en insuffisance cardiaque globale était reçue pour une exploration cardio-vasculaire. L'examen physique retrouvait un souffle holosystolique endapexien d'intensité 3/6, irradiant en rayon de roue. La troponine T était élevée à quatre fois la normale et l'ECG objectivait une lésion sous épicardique en antéroseptoapical et une nécrose dans le même territoire. L’échodoppler cardiaque retrouvait un anévrisme septoapicolatéral avec une solution de continuité dans le segment apical du septum interventriculaire (CIV). Traitée par énoxaparine, antiagrégant plaquettaire, diurétique de l'anse, dérivés morphiniques et oxygène, la patiente présente au deuxième jour de son hospitalisation un collapsus cardio-vasculaire et décède dans un tableau de choc cardiogénique malgré l'administration des amines vasopressives à forte dose. La coronarographie n'a pu être réalisée. Ce cas illustre la gravité des complications mécaniques de l'infarctus du myocarde. L'absence de chirurgie cardiaque dans notre pays explique en grande partie l’évolution fatale de cette CIV ischémique. PMID:25922631 15. A newly discovered Bordetella species carries a transcriptionally active CRISPR-Cas with a small Cas9 endonuclease USDA-ARS?s Scientific Manuscript database The Cas9 endonuclease of the Type II-a clustered regularly interspersed short palindromic repeats (CRISPR), of Streptococcus pyogenes (SpCas9) has been adapted as a widely used tool for genome editing and genome engineering. Herein, we describe a gene encoding a novel Cas9 ortholog (BpsuCas9) and th... 16. Effects of DAU 6215, a novel 5-hydroxytryptamine3 (5-HT3) antagonist on electrophysiological properties of the rat hippocampus. PubMed Central Passani, M. B.; Pugliese, A. M.; Azzurrini, M.; Corradetti, R. 1994-01-01 1. The aim of the present study was to test the effects of DAU 6215 (endo-N-(8-methyl-8-azabicyclo-[3.2.1]-octo-3-yl)-2,3-dihydro-2-ox o-1H- benzimidazole-1-carboxamide carboxamide hydrochloride), a newly synthesized, selective 5-hydroxytryptamine3 (5-HT3) antagonist, on the cell membrane properties and on characterized 5-HT-mediated responses of pyramidal neurones in the hippocampal CA1 region. 2. Administration of DAU 6215, even at concentrations several hundred fold its Ki, did not affect the cell membrane properties of pyramidal neurones, nor modify extracellularly recorded synaptic potentials, evoked by stimulating the Schaffer's collaterals. 3. Micromolar concentrations (15-30 microM) of 5-HT elicited several responses in pyramidal neurones that are mediated by distinct 5-HT receptor subtypes. DAU 6215 did not antagonize the 5-HT1A-induced membrane hyperpolarization and conductance increase, a response that was blocked by the selective 5-HT1A antagonist NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-phtalamido)butyl- piperazine). Similarly, DAU 6215 did not affect the membrane depolarization and decrease in amplitude of the afterhyperpolarization, elicited by the activation of putative 5-HT4 receptors. 4. 5-HT increased the frequency of spontaneous postsynaptic potentials (s.p.s.ps) recorded in pyramidal neurones loaded with chloride. In agreement with previous observations, most of the s.p.s.ps were reversed GABAergic events, produced by the activation of 5-HT3 receptors on interneurones, because they persisted in the presence of the glutamate NMDA and non NMDA antagonists, D-aminophosphonovaleric acid (APV; 50 microM) and 6,7-dinitroquinoxaline-2,3-dione (DNQX; 25 microM), and were elicited by the selective 5-HT3 agonist, 2-methyl-5-HT (2-Me-5-HT, 50 microM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8075890 17. MDMA-induced neurotoxicity: long-term effects on 5-HT biosynthesis and the influence of ambient temperature. PubMed O'Shea, Esther; Orio, Laura; Escobedo, Isabel; Sanchez, Veronica; Camarero, Jorge; Green, Alfred Richard; Colado, Maria Isabel 2006-07-01 1. 3,4-Methylenedioxymethamphetamine (MDMA or 'ecstasy') decreases the 5-HT concentration, [3H]-paroxetine binding and tryptophan hydroxylase activity in rat forebrain, which has been interpreted as indicating 5-HT neurodegeneration. This has been questioned, particularly the 5-HT loss, as MDMA can also inhibit tryptophan hydroxylase. We have now evaluated the validity of these parameters as a reflection of neurotoxicity. 2. Male DA rats were administered MDMA (12.5 mg kg(-1), i.p.) and killed up to 32 weeks later. 5-HT content and [3H]-paroxetine binding were measured in the cortex, hippocampus and striatum. Parallel groups of treated animals were administered NSD-1015 for determination of in vivo tryptophan hydroxylase activity and 5-HT turnover rate constant. 3. Tissue 5-HT content and [3H]-paroxetine binding were reduced in the cortex (26-53%) and hippocampus (25-74%) at all time points (1, 2, 4, 8 and 32 weeks). Hydroxylase activity was similarly reduced up to 8 weeks, but had recovered at 32 weeks. The striatal 5-HT concentration and [3H]-paroxetine binding recovered by week 4 and hydroxylase activity after week 1. In all regions, the reduction in 5-HT concentration did not result in an altered 5-HT synthesis rate constant. 4. Administering MDMA to animals when housed at 4 degrees C prevented the reduction in [3H]-paroxetine binding and hydroxylase activity observed in rats housed at 22 degrees C, but not the reduction in 5-HT concentration. 5. These data indicate that MDMA produces long-term damage to serotoninergic neurones, but this does not produce a compensatory increase in 5-HT synthesis in remaining terminals. It also highlights the fact that measurement of tissue 5-HT concentration may overestimate neurotoxic damage. 18. Biochemical profile of YM992, a novel selective serotonin reuptake inhibitor with 5-HT2A receptor antagonistic activity. PubMed Hatanaka, K; Nomura, T; Hidaka, K; Takeuchi, H; Yatsugi, S; Fujii, M; Yamaguchi, T 1996-01-01 YM992, (S)-2-[[(7-fluoro-4-indanyl)oxy]methyl]morpholine monohydrochloride, exhibited the biochemical profile of a selective serotonin (5-HT) reuptake inhibitor (SSRI) with 5-HT2A receptor antagonistic activity. YM922 showed the same high affinity as fluoxetine against the 5-HT reuptake site (Ki = 21 nM) and a similar affinity to that of crazodone against the 5-HT2A receptor (Ki = 86 nM). In other receptor binding studies, an affinity for the adrenergic alpha 1 receptor (Ki = 200 nM) and 5-HT2C receptor (Ki = 680 nM) was observed. In a monoamine uptake study, YM992 showed a selective 5-HT uptake inhibition (IC50 = 0.15 microM), but only very weakly inhibited both noradrenaline (NA) and dopamine (DA) uptake (IC50 = 3.1 microM (NA), > 10 microM (DA)). YM992 was also found to potently inhibit the aggregation of human platelets (IC50 = 1.9 microM), revealing antagonistic activity for the 5-HT2A receptor in vitro. Enhanced serotonergic neurotransmission, in particular that mediated by the 5-HT1A receptor, has recently been reported to be important in the long-term treatment of depressive disorders with antidepressants. In addition, some 5-HT1A receptor-mediated responses are known to be potentiated by co-administration of 5-HT2A receptor antagonists. Thus, YM992, having both selective 5-HT reuptake inhibition and 5-HT2A antagonistic activity, might show potent therapeutic activity as a novel antidepressant in comparison with conventional SSRIs. 19. 5-HT1A and 5-HT7 receptors contribute to lurasidone-induced dopamine efflux. PubMed Huang, Mei; Horiguchi, Masakuni; Felix, Anna R; Meltzer, Herbert Y 2012-05-09 Lurasidone is a novel, atypical antipsychotic drug with serotonin [5-hydroxytryptamine (5-HT)]2A, 5-HT7, dopamine (DA) D2 antagonist, and 5-HT1A receptor partial agonist properties. The ability of lurasidone to reverse the effects of subchronic administration phencyclidine, to impair novel object recognition in rats, an animal model of cognitive impairment in schizophrenia, is dependent, in part, on its 5-HT1A agonist and 5-HT7 receptor antagonist properties. We tested whether 5-HT1A partial agonism or 5-HT7 antagonism, or both, contributed to the ability of lurasidone to enhance cortical and hippocampal DA efflux, which may be related to its ability to improve cognition. Here, we report that lurasidone, 0.25 and 0.5, but not 0.1 mg/kg, subcutaneously, significantly increased DA efflux in the prefrontal cortex and hippocampus in a dose-dependent manner. Lurasidone, 0.5 mg/kg, also produced a smaller increase in DA efflux in the nucleus accumbens. Pretreatment with the 5-HT1A receptor antagonist, WAY100635 (0.2 mg/kg, subcutaneously), partially blocked the lurasidone-induced cortical and hippocampal DA efflux. Further, subeffective doses of the 5-HT1A receptor agonist, tandospirone (0.2 mg/kg), or the 5-HT7 antagonist, SB269970 (0.3 mg/kg), potentiated the ability of a subeffective dose of lurasidone (0.1 mg/kg) to increase DA efflux in the prefrontal cortex. These findings suggest that the effects of lurasidone on the prefrontal cortex and hippocampus, DA efflux are dependent, at least partially, on its 5-HT1A agonist and 5-HT7 antagonist properties and may contribute to its efficacy to reverse the effects of subchronic phencyclidine treatment and improve schizophrenia. 20. Distribution of 5-HT2A receptor immunoreactivity in the rat amygdaloid complex and colocalization with γ-aminobutyric acid. PubMed Bombardi, Cristiano 2011-01-25 The 5-HT2A receptor (5-HT2Ar) is located in a variety of excitatory and inhibitory neurons in many regions of the central nervous system and is a major target for atypical antipsychotic drugs. In the present study, an immunoperoxidase experiment was used to investigate the distribution of 5-HT2Ar immunoreactivity in the rat amygdaloid complex. In the basolateral amygdala, the colocalization of 5-HT2Ar with inhibitory transmitter γ-aminobutyric acid (GABA) was studied using double-immunofluorescence confocal microscopy. The staining pattern obtained was colchicine-sensitive. In fact, pretreatment with colchicine increased the number of 5-HT2Ar-immunoreactive somata. Accordingly, with the exception of the intercalated nuclei, the amygdaloid complex of colchicine-injected rats exhibited a high density of 5-HT2Ar-IR somata. Morphological analyses indicated that 5-HT2Ar was located on both excitatory and inhibitory neurons in the rat amygdaloid complex. In addition, double-immunofluorescence observations revealed that the great majority of GABA-immunoreactive neurons in the basolateral amygdala exhibited 5-HT2Ar immunoreactivity (66.3%-70.6% depending on the nucleus). These data help to clarify the complex role of the 5-HT2Ar in the amygdaloid complex suggesting that this receptor can regulate amygdaloid activity by acting on different neuronal populations. 1. Cas9 specifies functional viral targets during CRISPR-Cas adaptation. PubMed Heler, Robert; Samai, Poulami; Modell, Joshua W; Weiner, Catherine; Goldberg, Gregory W; Bikard, David; Marraffini, Luciano A 2015-03-12 Clustered regularly interspaced short palindromic repeat (CRISPR) loci and their associated (Cas) proteins provide adaptive immunity against viral infection in prokaryotes. Upon infection, short phage sequences known as spacers integrate between CRISPR repeats and are transcribed into small RNA molecules that guide the Cas9 nuclease to the viral targets (protospacers). Streptococcus pyogenes Cas9 cleavage of the viral genome requires the presence of a 5'-NGG-3' protospacer adjacent motif (PAM) sequence immediately downstream of the viral target. It is not known whether and how viral sequences flanked by the correct PAM are chosen as new spacers. Here we show that Cas9 selects functional spacers by recognizing their PAM during spacer acquisition. The replacement of cas9 with alleles that lack the PAM recognition motif or recognize an NGGNG PAM eliminated or changed PAM specificity during spacer acquisition, respectively. Cas9 associates with other proteins of the acquisition machinery (Cas1, Cas2 and Csn2), presumably to provide PAM-specificity to this process. These results establish a new function for Cas9 in the genesis of prokaryotic immunological memory. 2. Foreign DNA acquisition by the I-F CRISPR-Cas system requires all components of the interference machinery. PubMed Vorontsova, Daria; Datsenko, Kirill A; Medvedeva, Sofia; Bondy-Denomy, Joseph; Savitskaya, Ekaterina E; Pougach, Ksenia; Logacheva, Maria; Wiedenheft, Blake; Davidson, Alan R; Severinov, Konstantin; Semenova, Ekaterina 2015-12-15 CRISPR immunity depends on acquisition of fragments of foreign DNA into CRISPR arrays. For type I-E CRISPR-Cas systems two modes of spacer acquisition, naïve and primed adaptation, were described. Naïve adaptation requires just two most conserved Cas1 and Cas2 proteins; it leads to spacer acquisition from both foreign and bacterial DNA and results in multiple spacers incapable of immune response. Primed adaptation requires all Cas proteins and a CRISPR RNA recognizing a partially matching target. It leads to selective acquisition of spacers from DNA molecules recognized by priming CRISPR RNA, with most spacers capable of protecting the host. Here, we studied spacer acquisition by a type I-F CRISPR-Cas system. We observe both naïve and primed adaptation. Both processes require not just Cas1 and Cas2, but also intact Csy complex and CRISPR RNA. Primed adaptation shows a gradient of acquisition efficiency as a function of distance from the priming site and a strand bias that is consistent with existence of single-stranded adaption intermediates. The results provide new insights into the mechanism of spacer acquisition and illustrate surprising mechanistic diversity of related CRISPR-Cas systems. 3. Foreign DNA acquisition by the I-F CRISPR–Cas system requires all components of the interference machinery PubMed Central Vorontsova, Daria; Datsenko, Kirill A.; Medvedeva, Sofia; Bondy-Denomy, Joseph; Savitskaya, Ekaterina E.; Pougach, Ksenia; Logacheva, Maria; Wiedenheft, Blake; Davidson, Alan R.; Severinov, Konstantin; Semenova, Ekaterina 2015-01-01 CRISPR immunity depends on acquisition of fragments of foreign DNA into CRISPR arrays. For type I-E CRISPR–Cas systems two modes of spacer acquisition, naïve and primed adaptation, were described. Naïve adaptation requires just two most conserved Cas1 and Cas2 proteins; it leads to spacer acquisition from both foreign and bacterial DNA and results in multiple spacers incapable of immune response. Primed adaptation requires all Cas proteins and a CRISPR RNA recognizing a partially matching target. It leads to selective acquisition of spacers from DNA molecules recognized by priming CRISPR RNA, with most spacers capable of protecting the host. Here, we studied spacer acquisition by a type I-F CRISPR–Cas system. We observe both naïve and primed adaptation. Both processes require not just Cas1 and Cas2, but also intact Csy complex and CRISPR RNA. Primed adaptation shows a gradient of acquisition efficiency as a function of distance from the priming site and a strand bias that is consistent with existence of single-stranded adaption intermediates. The results provide new insights into the mechanism of spacer acquisition and illustrate surprising mechanistic diversity of related CRISPR–Cas systems. PMID:26586803 4. The Sun Like Star : HT Vir NASA Astrophysics Data System (ADS) Tanriver, Mehmet; Özeren, Ferhat Fikri 2016-12-01 This study is focused on the photometric (light curve) analysis of the Sun like star HT Vir which is a binary star located in the ASAS catalogue, shows variation in W UMa (EW/KW) type. The solution of light curve was executed using the PHOBE code. We conducted an unspotted solution for the HT Vir binary system. The positions in the HR diagram of the components are also discussed. 5. Memory formation and memory alterations: 5-HT6 and 5-HT7 receptors, novel alternative. PubMed Meneses, Alfredo 2014-01-01 Agonists and antagonists of the 5-hydroxytryptamine (serotonin) receptor6 (5-HT6) or receptor7 (5-HT7) might improve memory and/or reverse amnesia, although the mechanisms involved are poorly understood. Hence, the current work summarizes recent reviews and findings involving these receptors. Evidence indicates that diverse 5-HT6 receptor antagonists produce promnesic and/or antiamnesic effect in conditions, such as memory formation, age-related cognitive impairments and memory deficit in preclinical studies, as well as in diseases such as schizophrenia, Parkinson's, and Alzheimer's disease (AD). Memory, aging, and AD modify 5-HT6 receptors and signaling cascades; likewise, the modulation of 5-HT6 drugs on memory seems to be accompanied with neural changes. Moreover, 5-HT7 receptors are localized in brain areas mediating memory, including the cortex, hippocampus (e.g., Zola-Morgan and Squire, 1993) and raphe nuclei; however, the role of these receptors on memory has yet to be fully explored. Hence, findings and reviews are summarized in this work. Evidence suggests that both 5-HT7 receptor agonists and antagonists might have promnesic and anti-amnesic effects. These effects seem to be dependent on the basal level of performance, i.e., normal or impaired. Available evidence suggests that a potential utility of 5-HT6 and 5-HT7 receptor in mild-to-moderate AD patients and other memory dysfunctions as therapeutic targets. 6. Interplay between serotonin 5-HT1A and 5-HT7 receptors in depressive disorders. PubMed Naumenko, Vladimir S; Popova, Nina K; Lacivita, Enza; Leopoldo, Marcello; Ponimaskin, Evgeni G 2014-07-01 Serotonin (5-hydroxytryptamine or 5-HT) is an important neurotransmitter regulating a wide range of physiological and pathological functions via activation of heterogeneously expressed 5-HT receptors. Besides the important role of 5-HT receptors in the pathogenesis of depressive disorders and in their clinical medications, underlying mechanisms are far from being completely understood. This review focuses on possible cross talk between two serotonin receptors, 5-HT1A and the 5-HT7 . Although these receptors are highly co-expressed in brain regions implicated in depression, and most agonists developed for the 5-HT1A or 5-HT7 receptors have cross-reactivity, their functional interaction has not been yet established. It has been recently shown that 5-HT1A and 5-HT7 receptors form homo- and heterodimers both in vitro and in vivo. From the functional point of view, heterodimerization has been shown to play an important role in regulation of receptor-mediated signaling and internalization, suggesting the implication of heterodimerization in the development and maintenance of depression. Interaction between these receptors is also of clinical interest, because both receptors represent an important pharmacological target for the treatment of depression and anxiety. 7. Reduced signal transduction by 5-HT4 receptors after long-term venlafaxine treatment in rats PubMed Central Vidal, R; Valdizan, EM; Vilaró, MT; Pazos, A; Castro, E 2010-01-01 BACKGROUND AND PURPOSE The 5-HT4 receptor may be a target for antidepressant drugs. Here we have examined the effects of the dual antidepressant, venlafaxine, on 5-HT4 receptor-mediated signalling events. EXPERIMENTAL APPROACH The effects of 21 days treatment (p.o.) with high (40 mg·kg−1) and low (10 mg·kg−1) doses of venlafaxine, were evaluated at different levels of 5-HT4 receptor-mediated neurotransmission by using in situ hybridization, receptor autoradiography, adenylate cyclase assays and electrophysiological recordings in rat brain. The selective noradrenaline reuptake inhibitor, reboxetine (10 mg·kg−1, 21 days) was also evaluated on 5-HT4 receptor density. KEY RESULTS Treatment with a high dose (40 mg·kg−1) of venlafaxine did not alter 5-HT4 mRNA expression, but decreased the density of 5-HT4 receptors in caudate-putamen (% reduction = 26 ± 6), hippocampus (% reduction = 39 ± 7 and 39 ± 8 for CA1 and CA3 respectively) and substantia nigra (% reduction = 49 ± 5). Zacopride-stimulated adenylate cyclase activation was unaltered following low-dose treatment (10 mg·kg−1) while it was attenuated in rats treated with 40 mg·kg−1 of venlafaxine (% reduction = 51 ± 2). Furthermore, the amplitude of population spike in pyramidal cells of CA1 of hippocampus induced by zacopride was significantly attenuated in rats receiving either dose of venlafaxine. Chronic reboxetine did not modify 5-HT4 receptor density. CONCLUSIONS AND IMPLICATIONS Our data indicate a functional desensitization of 5-HT4 receptors after chronic venlafaxine, similar to that observed after treatment with the classical selective inhibitors of 5-HT reuptake. PMID:20880406 8. CRISPR-Cas Genome Surgery in Ophthalmology PubMed Central DiCarlo, James E.; Sengillo, Jesse D.; Justus, Sally; Cabral, Thiago; Tsang, Stephen H.; Mahajan, Vinit B. 2017-01-01 Genetic disease affecting vision can significantly impact patient quality of life. Gene therapy seeks to slow the progression of these diseases by treating the underlying etiology at the level of the genome. Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated systems (Cas) represent powerful tools for studying diseases through the creation of model organisms generated by targeted modification and by the correction of disease mutations for therapeutic purposes. CRISPR-Cas systems have been applied successfully to the visual sciences and study of ophthalmic disease – from the modification of zebrafish and mammalian models of eye development and disease, to the correction of pathogenic mutations in patient-derived stem cells. Recent advances in CRISPR-Cas delivery and optimization boast improved functionality that continues to enhance genome-engineering applications in the eye. This review provides a synopsis of the recent implementations of CRISPR-Cas tools in the field of ophthalmology. PMID:28573077 9. Serotonergic 5-HT7 receptors and cognition. PubMed Gasbarri, Antonella; Pompili, Assunta 2014-01-01 The abundant distribution of serotonin (5-HT) in different areas of the central nervous system can explain the involvement of this neurotransmitter in the regulation of several functions, such as sleep, pain, feeding, and sexual and emotional behaviors. Moreover, the serotonergic system is also involved in other more complex roles, such as cognition, including learning and memory processes. Recent studies led to the discovery of various types and subtypes of receptors differentially associated to cognitive mechanisms. 5-HT7 is the most recently discovered receptor for 5-HT; therefore, it is also one of the least well characterized. Studies exist hypothesizing the role of 5-HT7 on the modulation of learning and memory processes and other cognitive functions. Moreover, much attention has been devoted to the possible role of 5-HT7 receptors in psychiatric disorders. Therefore, the aim of this review is to clarify the behavioral role of the recently discovered 5-HT7 type receptor and highlight its involvement in the cognitive functions, with particular attention to the modulation of learning and memory processes, thus providing a basis to obtain new therapeutic agents and strategies for the treatment of cognitive disorders. 10. Phylogeny of Cas9 determines functional exchangeability of dual-RNA and Cas9 among orthologous type II CRISPR-Cas systems PubMed Central Fonfara, Ines; Le Rhun, Anaïs; Chylinski, Krzysztof; Makarova, Kira S.; Lécrivain, Anne-Laure; Bzdrenga, Janek; Koonin, Eugene V.; Charpentier, Emmanuelle 2014-01-01 The CRISPR-Cas-derived RNA-guided Cas9 endonuclease is the key element of an emerging promising technology for genome engineering in a broad range of cells and organisms. The DNA-targeting mechanism of the type II CRISPR-Cas system involves maturation of tracrRNA:crRNA duplex (dual-RNA), which directs Cas9 to cleave invading DNA in a sequence-specific manner, dependent on the presence of a Protospacer Adjacent Motif (PAM) on the target. We show that evolution of dual-RNA and Cas9 in bacteria produced remarkable sequence diversity. We selected eight representatives of phylogenetically defined type II CRISPR-Cas groups to analyze possible coevolution of Cas9 and dual-RNA. We demonstrate that these two components are interchangeable only between closely related type II systems when the PAM sequence is adjusted to the investigated Cas9 protein. Comparison of the taxonomy of bacterial species that harbor type II CRISPR-Cas systems with the Cas9 phylogeny corroborates horizontal transfer of the CRISPR-Cas loci. The reported collection of dual-RNA:Cas9 with associated PAMs expands the possibilities for multiplex genome editing and could provide means to improve the specificity of the RNA-programmable Cas9 tool. PMID:24270795 11. Isolation of the serotoninergic 5-HT4(e) receptor from human heart and comparative analysis of its pharmacological profile in C6-glial and CHO cell lines PubMed Central Mialet, Jeanne; Berque-Bestel, Isabelle; Eftekhari, Pierre; Gastineau, Monique; Giner, Mireille; Dahmoune, Yamina; Donzeau-Gouge, Patrick; Hoebeke, Johan; Langlois, Michel; Sicsic, Sames; Fischmeister, Rodolphe; Lezoualc'h, Frank 2000-01-01 RT–PCR technique was used to clone the human 5-HT4(e) receptor (h5-HT4(e)) from heart atrium. We showed that this h5-HT4(e) receptor splice variant is restricted to brain and heart atrium. Recombinant h5-HT4(e) receptor was stably expressed in CHO and C6-glial cell lines at 347 and 88 fmol mg−1 protein, respectively. Expression of h5-HT4(e) receptors at the cell membrane was confirmed by immunoblotting. The receptor binding profile, determined by competition with [3H]-GR113808 of a number of 5-HT4 ligands, was consistent with that previously reported for other 5-HT4 receptor isoforms. Surprisingly, we found that the rank order of potencies (EC50) of 5-HT4 agonists obtained from adenylyl cyclase functional assays was inversely correlated to their rank order of affinities (Ki) obtained from binding assays. Furthermore, EC50 values for 5-HT, renzapride and cisapride were 2 fold lower in C6-glial cells than in CHO cells. ML10302 and renzapride behaved like partial agonists on the h5-HT4(e) receptor. These results are in agreement with the reported low efficacy of the these two compounds on L-type Ca2+ currents and myocyte contractility in human atrium. A constitutive activity of the h5-HT4(e) receptor was observed in CHO cells in the absence of any 5-HT4 ligand and two 5-HT4 antagonists, GR113808 and ML10375, behaved as inverse agonists. These data show that the h5-HT4(e) receptor has a pharmacological profile which is close to the native h5-HT4 receptor in human atrium with a functional potency which is dependent on the cellular context in which the receptor is expressed. PMID:10683202 12. Adrenergic stimulation-released 5-HT stored in adrenergic nerves inhibits CGRPergic nerve-mediated vasodilatation in rat mesenteric resistance arteries PubMed Central Fujii, Hirohito; Takatori, Shingo; Zamami, Yoshito; Hashikawa-Hobara, Narumi; Miyake, Natsuki; Tangsucharit, Panot; Mio, Mitsunobu; Kawasaki, Hiromu 2012-01-01 BACKGROUND AND PURPOSE 5-HT is taken up by and stored in adrenergic nerves and periarterial nerve stimulation (PNS) releases 5-HT to cause vasoconstriction in rat mesenteric arteries. The present study investigated whether PNS-released 5-HT stored in adrenergic nerves affects the function of perivascular calcitonin gene-related peptide-containing (CGRPergic) nerves. EXPERIMENTAL APPROACH Rat mesenteric vascular beds without endothelium and with active tone were perfused with Krebs solution. Changes in perfusion pressure in response to PNS and CGRP injection were measured before (control) and after perfusion of Krebs solution containing 5-HT (10 µM) for 20 min. Distributions of 5-HT- and TH-immunopositive fibres in mesenteric arteries were studied using immunohistochemical methods. KEY RESULTS PNS (1–4 Hz) frequency dependently caused adrenergic nerve-mediated vasoconstriction followed by CGRPergic nerve-mediated vasodilatation. 5-HT treatment inhibited PNS-induced vasodilatation without affecting exogenous CGRP-induced vasodilatation, while it augmented PNS-induced vasoconstriction. Guanethidine (adrenergic neuron blocker), methysergide (non-selective 5-HT receptor antagonist) and BRL15572 (selective 5-HT1D receptor antagonist) abolished inhibition of PNS-induced vasodilatation in 5-HT-treated preparations. Combined treatment with 5-HT and desipramine (catecholamine transporter inhibitor), but not fluoxetine (selective 5-HT reuptake inhibitor), did not inhibit PNS-induced vasodilatation. Exogenous 5-HT inhibited PNS-induced vasodilatation, which was antagonized by methysergide. In immunohistochemical experiments, 5-HT-immunopositive nerves, colocalized with adrenergic TH-immunopositive nerves, were observed only in 5-HT-treated mesenteric arteries, but not in control preparations or arteries co-treated with desipramine. CONCLUSIONS AND IMPLICATIONS These results suggest that 5-HT can be taken up by and released from adrenergic nerves in vitro by PNS to inhibit 13. Targeted inhibition of serotonin type 7 (5-HT7) receptor function modulates immune responses and reduces the severity of intestinal inflammation. PubMed Kim, Janice J; Bridle, Byram W; Ghia, Jean-Eric; Wang, Huaqing; Syed, Shahzad N; Manocha, Marcus M; Rengasamy, Palanivel; Shajib, Mohammad Sharif; Wan, Yonghong; Hedlund, Peter B; Khan, Waliul I 2013-05-01 Mucosal inflammation in conditions ranging from infective acute enteritis or colitis to inflammatory bowel disease is accompanied by alteration in serotonin (5-hydroxytryptamine [5-HT]) content in the gut. Recently, we have identified an important role of 5-HT in the pathogenesis of experimental colitis. 5-HT type 7 (5-HT7) receptor is one of the most recently identified members of the 5-HT receptor family, and dendritic cells express this receptor. In this study, we investigated the effect of blocking 5-HT7 receptor signaling in experimental colitis with a view to develop an improved therapeutic strategy in intestinal inflammatory disorders. Colitis was induced with dextran sulfate sodium (DSS) or dinitrobenzene sulfonic acid (DNBS) in mice treated with selective 5-HT7 receptor antagonist SB-269970, as well as in mice lacking 5-HT7 receptor (5-HT7(-/-)) and irradiated wild-type mice reconstituted with bone marrow cells harvested from 5-HT7(-/-) mice. Inhibition of 5-HT7 receptor signaling with SB-269970 ameliorated both acute and chronic colitis induced by DSS. Treatment with SB-269970 resulted in lower clinical disease, histological damage, and proinflammatory cytokine levels compared with vehicle-treated mice post-DSS. Colitis severity was significantly lower in 5-HT7(-/-) mice and in mice reconstituted with bone marrow cells from 5-HT7(-/-) mice compared with control mice after DSS colitis. 5-HT7(-/-) mice also had significantly reduced DNBS-induced colitis. These observations provide us with novel information on the critical role of the 5-HT7 receptor in immune response and inflammation in the gut, and highlight the potential benefit of targeting this receptor to alleviate the severity of intestinal inflammatory disorders such as inflammatory bowel disease. 14. Highly efficient Cas9-mediated transcriptional programming. PubMed Chavez, Alejandro; Scheiman, Jonathan; Vora, Suhani; Pruitt, Benjamin W; Tuttle, Marcelle; P R Iyer, Eswar; Lin, Shuailiang; Kiani, Samira; Guzman, Christopher D; Wiegand, Daniel J; Ter-Ovanesyan, Dmitry; Braff, Jonathan L; Davidsohn, Noah; Housden, Benjamin E; Perrimon, Norbert; Weiss, Ron; Aach, John; Collins, James J; Church, George M 2015-04-01 The RNA-guided nuclease Cas9 can be reengineered as a programmable transcription factor. However, modest levels of gene activation have limited potential applications. We describe an improved transcriptional regulator obtained through the rational design of a tripartite activator, VP64-p65-Rta (VPR), fused to nuclease-null Cas9. We demonstrate its utility in activating endogenous coding and noncoding genes, targeting several genes simultaneously and stimulating neuronal differentiation of human induced pluripotent stem cells (iPSCs). 15. Influence of the 5-HT(2C) receptor antagonist SB242,084 on behaviour produced by the 5-HT(2) agonist Ro60-0175 and the indirect 5-HT agonist dexfenfluramine. PubMed Higgins, G A; Ouagazzal, A M; Grottick, A J 2001-06-01 Ro60-0175 has been described as a selective agonist at the 5-HT(2C) receptor, yet it has only 10- fold higher affinity at the 5-HT(2C) compared to the 5-HT(2A) subtype, and equivalent affinity for the 5-HT(2B) receptor. The selective 5-HT(2C) receptor antagonist SB242,084 (0.5 mg kg(-1) i.p.), blocked the hypoactivity and penile grooming induced by Ro60-0175 (1 mg kg(-1) s.c.). The combination of SB242,084 (0.5 mg kg(-1) i.p.) and Ro60-0175 (3 - 10 mg kg(-1)) produced a completely different pattern of behaviours including wet-dog shakes, hyperactivity and back muscle contractions. These latter effects were blocked by the selective 5-HT(2A) receptor antagonist MDL100,907 (0.5 mg kg(-1) i.p.), but not the 5-HT(2B) receptor antagonist SB215,505 (3 mg kg(-1) p.o.). The indirect 5-HT releaser/reuptake inhibitor dexfenfluramine (1 - 10 mg kg(-1) i.p.) produced a mild increase in locomotor activity, penile grooming, and occasional back muscle contractions and wet-dog shakes. Pre-treatment with SB242,084 (0.5 mg kg(-1)), blocked the incidence of penile grooming, and markedly potentiated both the dexfenfluramine-induced hyperactivity, the incidence of back muscle contractions, and to a lesser extent wet-dog shakes. Some toxicity was also evident in animals treated with dexfenfluramine (10 mg kg(-1))/SB242,084 (0.5 mg kg(-1)), but not in any other treatment groups. The hyperactivity and toxicity produced by the dexfenfluramine (10 mg kg(-1))/SB242,084 (0.5 mg kg(-1)) combination was replicated in a further study, and hyperthermia was also recorded. Both hyperthermia and toxicity were blocked by MDL100,907 (0.5 mg kg(-1)) but not SB215,505 (3 mg kg(-1)). An attenuation of the hyperlocomotor response was also observed following MDL100,907. These findings suggest that 5-HT(2C) receptor activation can inhibit the expression of behaviours mediated through other 5-HT receptor subtypes. 16. Efficient targeted mutagenesis in soybean by TALENs and CRISPR/Cas9. PubMed Du, Hongyang; Zeng, Xuanrui; Zhao, Meng; Cui, Xiaopei; Wang, Qing; Yang, Hui; Cheng, Hao; Yu, Deyue 2016-01-10 Gene targeting (GT) is of great significance for advancing basic plant research and crop improvement. Both TALENs (transcription activator-like effectors nucleases) and CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated 9) systems have been developed for genome editing in eukaryotes, including crop plants. In this work, we present the comparative analysis of these two technologies for two soybean genome editing targets, GmPDS11 and GmPDS18. We found GT in soybean hairy roots with a single targeting efficiency range of 17.5-21.1% by TALENs, 11.7-18.1% by CRISPR/Cas9 using the AtU6-26 promoter, and 43.4-48.1% by CRISPR/Cas9 using the GmU6-16g-1 promoter, suggesting that the CRISPR/Cas9 using the GmU6-16g-1 promoter is probably a much more efficient tool compared to the other technologies. Similarly, our double mutation GT efficiency experiment with these three technologies displayed a targeting efficiency of 6.25% by TALENs, 12.5% by CRISPR/Cas9 using the AtU6-26 promoter, and 43.4-48.1% by CRISPR/Cas9 using the GmU6-16g-1 promoter, suggesting that CRISPR/Cas9 is still a better choice for simultaneous editing of multiple homoeoalleles. Furthermore, we observed albino and dwarf buds (PDS knock-out) by soybean transformation in cotyledon nodes. Our results demonstrated that both TALENs and CRISPR/Cas9 systems are powerful tools for soybean genome editing. 17. Expression of OsCAS (Calcium-Sensing Receptor) in an Arabidopsis Mutant Increases Drought Tolerance. PubMed Zhao, Xin; Xu, Mengmeng; Wei, Rongrong; Liu, Yang 2015-01-01 The calcium-sensing receptor (CaS), which is localized in the chloroplasts, is a crucial regulator of extracellular calcium-induced stomatal closure in Arabidopsis. It has homologs in Oryza sativa and other plants. These sequences all have a rhodanese-like protein domain, which has been demonstrated to be associated with specific stress conditions. In this study, we cloned the Oryza sativa calcium-sensing receptor gene (OsCAS) and demonstrated that OsCAS could sense an increase of extracellular Ca2+ concentration and mediate an increase in cytosolic Ca2+ concentration. The OsCAS gene was transformed into an Arabidopsis CaS knockout mutant (Salk) and overexpressed in the transgenic plants. OsCAS promoted stomatal closure. We screened homozygous transgenic Arabidopsis plants and determined physiological indices such as the oxidative damage biomarker malondialdehyde (MDA), relative membrane permeability (RMP), proline content, and chlorophyll fluorescence parameters, after 21 days of drought treatment. Our results revealed lower RMP and MDA contents and a higher Proline content in transgenic Arabidopsis plants after drought stress, whereas the opposite was observed in Salk plants. With respect to chlorophyll fluorescence, the electron transport rate and effective PSII quantum yield decreased in all lines under drought stress; however, in the transgenic plants these two parameters changed fewer and were higher than those in wild-type and Salk plants. The quantum yield of regulated energy dissipation and nonregulated energy dissipation in PSII were higher in Salk plants, whereas these values were lower in the transgenic plants than in the wild type under drought stress. The above results suggest that the transgenic plants showed better resistance to drought stress by decreasing damage to the cell membrane, increasing the amount of osmoprotectants, and maintaining a relatively high photosynthetic capacity. In conclusion, OsCAS is an extracellular calcium-sensing receptor 18. Parameters affecting frequency of CRISPR/Cas9 mediated targeted mutagenesis in rice. PubMed Mikami, Masafumi; Toki, Seiichi; Endo, Masaki 2015-10-01 Frequency of CRISPR/Cas9-mediated targeted mutagenesis varies depending on Cas9 expression level and culture period of rice callus. Recent reports have demonstrated that the CRISPR/Cas9 system can function as a sequence-specific nuclease in various plant species. Induction of mutation in proliferating tissue during embryogenesis or in germline cells is a practical means of generating heritable mutations. In the case of plant species in which cultured cells are used for transformation, non-chimeric plants can be obtained when regeneration occurs from mutated cells. Since plantlets are regenerated from both mutated and non-mutated cells in a random manner, any increment in the proportion of mutated cells in Cas9- and guide RNA (gRNA)-expressing cells will help increase the number of plants containing heritable mutations. In this study, we examined factors affecting mutation frequency in rice calli. Following sequential transformation of rice calli with Cas9- and gRNA- expression constructs, the mutation frequency in independent Cas9 transgenic lines was analyzed. A positive correlation between Cas9 expression level and mutation frequency was found. This positive relationship was observed regardless of whether the transgene or an endogenous gene was used as the target for CRISPR/Cas9-mediated mutagenesis. Furthermore, we found that extending the culture period increased the proportion of mutated cells as well as the variety of mutations obtained. Because mutated and non-mutated cells might proliferate equally, these results suggest that a prolonged tissue culture period increases the chance of inducing de novo mutations in non-mutated cells. This fundamental knowledge will help improve systems for obtaining non-chimeric regenerated plants in many plant species. 19. Vinculin-p130Cas interaction is critical for focal adhesion dynamics and mechano-transduction. PubMed Goldmann, Wolfgang H 2014-03-01 Adherent cells, when mechanically stressed, show a wide range of responses including large-scale changes in their mechanical behaviour and gene expression pattern. This is in part facilitated by activating the focal adhesion (FA) protein p130Cas through force-induced conformational changes that lead to the phosphorylation by src family kinases. Janostiak et al. [Janostiak et al. Cell Mol Life Sci (2013) DOI 10.1007/s00018-013-1450-x] have reported that the phosphorylation site Y12 on the SH3 domain of p130Cas modulates the binding with vinculin, a prominent mechano-coupling protein in FAs. Tension changes in FAs (due to the anchorage of the SH3 domain and C-terminal) bring about an extension of the substrate domain of p130Cas by unmasking the phosphorylation sites. These observations demonstrate that vinculin is an important modulator of the p130Cas-mediated mechano-transduction pathway in cells. The central aim should be now to test that vinculin is critical for p130Cas incorporation into the focal adhesion complex and for transmitting forces to the p130Cas molecule. 20. Homology-directed repair in rodent zygotes using Cas9 and TALEN engineered proteins. PubMed Ménoret, Séverine; De Cian, Anne; Tesson, Laurent; Remy, Séverine; Usal, Claire; Boulé, Jean-Baptiste; Boix, Charlotte; Fontanière, Sandra; Crénéguy, Alison; Nguyen, Tuan H; Brusselle, Lucas; Thinard, Reynald; Gauguier, Dominique; Concordet, Jean-Paul; Cherifi, Yacine; Fraichard, Alexandre; Giovannangeli, Carine; Anegon, Ignacio 2015-10-07 The generation of genetically-modified organisms has been revolutionized by the development of new genome editing technologies based on the use of gene-specific nucleases, such as meganucleases, ZFNs, TALENs and CRISPRs-Cas9 systems. The most rapid and cost-effective way to generate genetically-modified animals is by microinjection of the nucleic acids encoding gene-specific nucleases into zygotes. However, the efficiency of the procedure can still be improved. In this work we aim to increase the efficiency of CRISPRs-Cas9 and TALENs homology-directed repair by using TALENs and Cas9 proteins, instead of mRNA, microinjected into rat and mouse zygotes along with long or short donor DNAs. We observed that Cas9 protein was more efficient at homology-directed repair than mRNA, while TALEN protein was less efficient than mRNA at inducing homology-directed repair. Our results indicate that the use of Cas9 protein could represent a simple and practical methodological alternative to Cas9 mRNA in the generation of genetically-modified rats and mice as well as probably some other mammals. 1. CRISPR-Cas9 Structures and Mechanisms. PubMed Jiang, Fuguo; Doudna, Jennifer A 2017-05-22 Many bacterial clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) systems employ the dual RNA-guided DNA endonuclease Cas9 to defend against invading phages and conjugative plasmids by introducing site-specific double-stranded breaks in target DNA. Target recognition strictly requires the presence of a short protospacer adjacent motif (PAM) flanking the target site, and subsequent R-loop formation and strand scission are driven by complementary base pairing between the guide RNA and target DNA, Cas9-DNA interactions, and associated conformational changes. The use of CRISPR-Cas9 as an RNA-programmable DNA targeting and editing platform is simplified by a synthetic single-guide RNA (sgRNA) mimicking the natural dual trans-activating CRISPR RNA (tracrRNA)-CRISPR RNA (crRNA) structure. This review aims to provide an in-depth mechanistic and structural understanding of Cas9-mediated RNA-guided DNA targeting and cleavage. Molecular insights from biochemical and structural studies provide a framework for rational engineering aimed at altering catalytic function, guide RNA specificity, and PAM requirements and reducing off-target activity for the development of Cas9-based therapies against genetic diseases. 2. CRISPR-Cas: biology, mechanisms and relevance PubMed Central Hille, Frank 2016-01-01 Prokaryotes have evolved several defence mechanisms to protect themselves from viral predators. Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated proteins (Cas) display a prokaryotic adaptive immune system that memorizes previous infections by integrating short sequences of invading genomes—termed spacers—into the CRISPR locus. The spacers interspaced with repeats are expressed as small guide CRISPR RNAs (crRNAs) that are employed by Cas proteins to target invaders sequence-specifically upon a reoccurring infection. The ability of the minimal CRISPR-Cas9 system to target DNA sequences using programmable RNAs has opened new avenues in genome editing in a broad range of cells and organisms with high potential in therapeutical applications. While numerous scientific studies have shed light on the biochemical processes behind CRISPR-Cas systems, several aspects of the immunity steps, however, still lack sufficient understanding. This review summarizes major discoveries in the CRISPR-Cas field, discusses the role of CRISPR-Cas in prokaryotic immunity and other physiological properties, and describes applications of the system as a DNA editing technology and antimicrobial agent. This article is part of the themed issue ‘The new bacteriology’. PMID:27672148 3. Sensitization of restraint-induced corticosterone secretion after chronic restraint in rats: Involvement of 5-HT7 receptors PubMed Central García-Iglesias, Brenda B.; Mendoza-Garrido, María E.; Gutiérrez-Ospina, Gabriel; Rangel-Barajas, Claudia; Noyola-Díaz, Martha; Terrón, José A. 2013-01-01 Serotonin (5-HT) modulates the hypothalamic-pituitary-adrenal (HPA) axis response to stress. We examined the effect of chronic restraint stress (CRS; 20 min/day) as compared to control (CTRL) conditions for 14 days, on: 1) restraint-induced ACTH and corticosterone (CORT) secretion in rats pretreated with vehicle or SB-656104 (a 5-HT7 receptor antagonist); 2) 5-HT7 receptor-like immunoreactivity (5-HT7-LI) and protein in the hypothalamic paraventricular nucleus (PVN) and adrenal glands (AG); 3) baseline levels of 5-HT and 5-hydroxyindolacetic acid (5-HIAA), and 5-HIAA/5-HT ratio in PVN and AG; and 4) 5-HT-like immunoreactivity (5-HT-LI) in AG and tryptophan hydroxylase (TPH) protein in PVN and AG. On day 15, animals were subdivided into Treatment and No treatment groups. Treatment animals received an i.p. injection of vehicle or SB-656104; No Treatment animals received no injection. Sixty min later, Treatment animals were either decapitated with no further stress (0 min) or submitted to acute restraint (10, 30, 60 or 120 min); hormone serum levels were measured. No Treatment animals were employed for the rest of measurements. CRS decreased body weight gain and increased adrenal weight. In CTRL animals, acute restraint increased ACTH and CORT secretion in a time of restraint-dependent manner; both responses were inhibited by SB-656104. Exposure to CRS abolished ACTH but magnified CORT responses to restraint as compared to CTRL conditions; SB-656104 had no effect on ACTH levels but significantly inhibited sensitized CORT responses. In CTRL animals, 5-HT7-LI was detected in magnocellular and parvocellular subdivisions of PVN and sparsely in adrenal cortex. Exposure to CRS decreased 5-HT7-LI and protein in the PVN, but increased 5-HT7-LI in the adrenal cortex and protein in whole AG. Higher 5-HT and 5-HIAA levels were detected in PVN and AG from CRS animals but 5-HIAA/5-HT ratio increased in AG only. Finally, whereas 5-HT-LI was sparsely observed in the adrenal cortex 4. INCREASED 5-HT2A RECEPTOR AVAILABILITY IN THE ORBITOFRONTAL CORTEX OF PHYSICALLY AGGRESSIVE PERSONALITY DISORDERED PATIENTS PubMed Central Rosell, Daniel R.; Thompson, Judy L.; Slifstein, Mark; Xu, Xiaoyan; Frankle, W. Gordon; New, Antonia S.; Goodman, Marianne; Weinstein, Shauna R.; Laruelle, Marc; Dargham, Anissa Abi; Siever, Larry J. 2011-01-01 Background Impulsive physical aggression is a common and problematic feature of many personality disorders. The serotonergic system is known to be involved in the pathophysiology of aggression, and multiple lines of evidence have implicated the 5-HT2A receptor (5-HT2AR). We sought to examine the role of the 5-HT2AR in impulsive aggression specifically in the orbitofrontal cortex (OFC), given that our own studies and an extensive literature indicate that serotonergic disturbances in the OFC are linked to aggression. We have previously hypothesized that increased 5-HT2AR function in the OFC is a state phenomenon which promotes impulsive aggression. Methods 5-HT2AR availability was measured with positron emission tomography and the selective 5-HT2AR antagonist radioligand [11C]MDL100907 in two groups of impulsively aggressive personality disordered patients --14 with current physical aggression, and 15 without current physical aggression --and 25 healthy controls. Clinical ratings of various symptom dimensions were also obtained. Results Orbitofrontal 5-HT2AR availability was greater in patients with current physical aggression compared to patients without current physical aggression and healthy controls; no differences in OFC 5-HT2AR availability were observed between patients without current physical aggression and healthy controls. No significant differences in 5-HT2AR availability were observed in other brain regions examined. Among both groups of impulsively aggressive personality disordered patients combined, OFC 5-HT2AR availability was correlated, specifically, with a state measure of impulsive aggression. Conclusions These findings are consistent with our previously described model in which impulsive aggression is related to dynamic changes in 5-HT2AR function in the OFC. PMID:20434136 5. Memory time-course: mRNA 5-HT1A and 5-HT7 receptors. PubMed Perez-Garcia, Georgina; Meneses, Alfredo 2009-08-24 In an attempt to clarify conflicting results about serotonin (5-hydroxytryptamine, 5-HT) 5-HT(1A) and 5-HT(7) receptors in memory formation, their mRNA expression was determined by RT-PCR in key brain areas for explicit and implicit memory. The time-course (0-120 h) of autoshaped responses was progressive and mRNA 5-HT(1A) or 5-HT(7) receptors expression monotonically augmented or declined in prefrontal cortex, hippocampus and raphe nuclei, respectively. At 24-48 h acutely 8-OH-DPAT (0.062 mg/kg) administration enhanced memory and attenuated mRNA 5-HT(1A)<5-HT(7) receptors expression respect to saline group. WAY100635 (0.3 mg/kg) or SB-269970 (10.0 mg/kg) did not affect the former, partially blocked or reversed the latter, respectively. Furthermore, lower WAY100635 (0.001-0.1 mg/kg) or SB-269970 (1.0-5.0 mg/kg) doses plus 8-OHDPAT not affected memory; however both combinations suppressed or up-regulated mRNA expression 5-HT(1A) or 5-HT(7) receptors. In contrast, AS19 (5.0 mg/kg) facilitated memory consolidation, decreased or increased hippocampal 5-HT(7) and 5-HT(1A) receptors expression. Together these data revealed that, when both 5-HT(1A) and 5-HT(7) receptors were stimulated by 8-OHDPAT under memory consolidation, subtle changes emerged, not evident at behavioral level though detectable at genes expression. Notably, high levels of efficient memory were maintained even when serotonergic tone, via either 5-HT(1A) or 5-HT(7) receptor, was down- or up-regulated. Nevertheless, WAY100635 plus SB-269970 impaired memory consolidation and suppressed their expression. Considering that serotonergic changes are prominent in AD patients with an earlier onset of disease the present approach might be useful in the identification of functional changes associated to memory formation, memory deficits and reversing or even preventing these deficits. 6. Involvement of 5-HT1, 5-HT2, and 5-HT3 receptors in the mediation of the prolactin response to serotonin and 5-hydroxytryptophan. PubMed Jørgensen, H; Knigge, U; Warberg, J 1992-03-01 Serotonin (5-HT) is involved in the neuroendocrine regulation of prolactin (PRL) secretion as a stimulator. Within the last decade several 5-HT receptor types have been identified, but their individual role in the mediation of the PRL response to 5-HT is only partly understood. We investigated in conscious male rats the effect of different 5-HT1, 5-HT2, and 5-HT3 receptor antagonists on the PRL response to 5-HT or to the 5-HT precursor 5-hydroxytrytophan (5-HTP) which was administered in combination with the 5-HT reuptake inhibitor fluoxetine. 5-HT (0.5-5.0 mg/kg BW i.v.) or 5-HTP (25-100 mg/kg i.p.) in combination with saline or fluoxetine (10 mg/kg i.p.) increased the plasma PRL concentration dose-dependently. Pretreatment with the 5-HT1+2 receptor antagonist methysergide (2.5 mg/kg i.p.) prevented the stimulatory effect of 5-HT or 5-HTP + fluoxetine. Pretreatment with the 5-HT2 receptor antagonists ketanserin or LY 53857 (2.5 mg/kg i.p.) inhibited the PRL response to 5-HT by approximately 80% and to 5-HTP + fluoxetine approximately 100%. A higher dose (10 mg/kg) of the 5-HT2 receptor antagonists possessed only 50% inhibitory effect. Pretreatment with the 5-HT3 receptor antagonists ICS 205-930 or GR 38032F (0.05-2.5 mg/kg i.p.) inhibited the PRL response induced by 5-HT or by 5-HTP + fluoxetine. The maximal inhibitory effect (approximately 80%) was obtained by a dose of 0.1 mg/kg of both compounds.(ABSTRACT TRUNCATED AT 250 WORDS) 7. Anchoring the Distance Scale via X-Ray/Infrared Data for Cepheid Clusters: SU Cas NASA Astrophysics Data System (ADS) Majaess, D.; Turner, D. G.; Gallo, L.; Gieren, W.; Bonatto, C.; Lane, D. J.; Balam, D.; Berdnikov, L. 2012-07-01 New X-ray (XMM-Newton) and JHKs (Observatoire du Mont-Mégantic) observations for members of the star cluster Alessi 95, which Turner et al. discovered hosts the classical Cepheid SU Cas, were used in tandem with UCAC3 (proper motion) and Two Micron All Sky Survey observations to determine precise cluster parameters: E(J - H) = 0.08 ± 0.02 and d = 405 ± 15 pc. The ensuing consensus among cluster, pulsation, and trigonometric distances (d=414+/- 5(\\sigma _{\\bar{x}}) +/- 10 (\\sigma) pc) places SU Cas in a select group of nearby fundamental Cepheid calibrators (δ Cep, ζ Gem). High-resolution X-ray observations may be employed to expand that sample as the data proved pertinent for identifying numerous stars associated with SU Cas. Acquiring X-ray observations of additional fields may foster efforts to refine Cepheid calibrations used to constrain H 0. 8. ANCHORING THE DISTANCE SCALE VIA X-RAY/INFRARED DATA FOR CEPHEID CLUSTERS: SU Cas SciTech Connect Majaess, D.; Turner, D. G.; Gallo, L.; Lane, D. J.; Gieren, W.; Bonatto, C.; Balam, D.; Berdnikov, L. 2012-07-10 New X-ray (XMM-Newton) and JHK{sub s} (Observatoire du Mont-Megantic) observations for members of the star cluster Alessi 95, which Turner et al. discovered hosts the classical Cepheid SU Cas, were used in tandem with UCAC3 (proper motion) and Two Micron All Sky Survey observations to determine precise cluster parameters: E(J - H) = 0.08 {+-} 0.02 and d = 405 {+-} 15 pc. The ensuing consensus among cluster, pulsation, and trigonometric distances (d=414{+-}5({sigma}{sub x}-bar){+-}10 ({sigma}) pc) places SU Cas in a select group of nearby fundamental Cepheid calibrators ({delta} Cep, {zeta} Gem). High-resolution X-ray observations may be employed to expand that sample as the data proved pertinent for identifying numerous stars associated with SU Cas. Acquiring X-ray observations of additional fields may foster efforts to refine Cepheid calibrations used to constrain H{sub 0}. 9. Efficient genome editing of genes involved in neural crest development using the CRISPR/Cas9 system in Xenopus embryos. PubMed Liu, Zhongzhen; Cheng, Tina Tsz Kwan; Shi, Zhaoying; Liu, Ziran; Lei, Yong; Wang, Chengdong; Shi, Weili; Chen, Xiongfeng; Qi, Xufeng; Cai, Dongqing; Feng, Bo; Deng, Yi; Chen, Yonglong; Zhao, Hui 2016-01-01 The RNA guided CRISPR/Cas9 nucleases have been proven to be effective for gene disruption in various animal models including Xenopus tropicalis. The neural crest (NC) is a transient cell population during embryonic development and contributes to a large variety of tissues. Currently, loss-of-function studies on NC development in X. tropicalis are largely based on morpholino antisense oligonucleotide. It is worthwhile establishing targeted gene knockout X. tropicails line using CRISPR/Cas9 system to study NC development. We utilized CRISPR/Cas9 to disrupt genes that are involved in NC formation in X. tropicalis embryos. A single sgRNA and Cas9 mRNA synthesized in vitro, were co-injected into X. tropicalis embryos at one-cell stage to induce single gene disruption. We also induced duplex mutations, large segmental deletions and inversions in X. tropicalis by injecting Cas9 and a pair of sgRNAs. The specificity of CRISPR/Cas9 was assessed in X. tropicalis embryos and the Cas9 nickase was used to reduce the off-target cleavages. Finally, we crossed the G0 mosaic frogs with targeted mutations to wild type frogs and obtained the germline transmission. Total 16 target sites in 15 genes were targeted by CRISPR/Cas9 and resulted in successful indel mutations at 14 loci with disruption efficiencies in a range from 9.3 to 57.8 %. Furthermore, we demonstrated the feasibility of generation of duplex mutations, large segmental deletions and inversions by using Cas9 and a pair of sgRNAs. We observed that CRISPR/Cas9 displays obvious off-target effects at some loci in X. tropicalis embryos. Such off-target cleavages was reduced by using the D10A Cas9 nickase. Finally, the Cas9 induced indel mutations were efficiently passed to G1 offspring. Our study proved that CRISPR/Cas9 could mediate targeted gene mutation in X. tropicalis with high efficiency. This study expands the application of CRISPR/Cas9 platform in X. tropicalis and set a basis for studying NC development using genetic 10. PET imaging of the serotonin transporter and 5HT1A receptor in alcohol dependence PubMed Central Martinez, Diana; Slifstein, Mark; Gil, Roberto; Hwang, Dah-Ren; Huang, Yiyun; Perez, Audrey; Frankle, W. Gordon; Laruelle, Marc; Krystal, John; Abi-Dargham, Anissa 2009-01-01 Background Rodent models as well as studies in humans have suggested alterations in serotonin (5HT) innervation and transmission in early onset genetically determined or type II alcoholism. This study examines two indices of serotonergic transmission, 5HT transporter levels and 5-HT1A availability, in vivo, in type II alcoholism. This is the first report of combined tracers for pre and post-synaptic serotonergic transmission in the same alcoholic subjects and the first study of 5HT1A receptors in alcoholism. Method Fourteen alcohol dependent subjects were scanned (11 with both tracers, 1 with [11C]DASB only and two with [11C]WAY100635 only). Twelve healthy controls (HC) subjects were scanned with [11C]DASB and another 13 were scanned with [11C]WAY100635. Binding Potential (BPp, mL/cm3) and the specific to nonspecific partition coefficient (BPND, unitless) were derived for both tracers using 2 tissue compartment model and compared to HC across different brain regions. Relationships to severity of alcoholism were assessed. Results No significant differences were observed in regional BPp or BPND between patients and controls in any of the regions examined. No significant relationships were observed between regional 5HT transporter availability, 5-HT1A availability, and disease severity with the exception of a significant negative correlation between SERT and years of dependence in amygdala and insula. Conclusion This study did not find alterations in measures of 5-HT1A or 5HT transporter levels in patients with type II alcoholism. PMID:18962444 11. Putting the CAS Standards to Work. Training Manual for the CAS Self Assessment Guides. ERIC Educational Resources Information Center Yerian, Jean M.; Miller, Theodore K., Ed. These 18 self-assessment guides and training manual from the Council for the Advancement of Standards (CAS) for Student Services/Development Programs translate the CAS Standards and Guidelines of 1986 into a format for self-study purposes. These self-study guides allow an institution to assure compliance with minimally-acceptable practice, gain an… 12. Photovoltaic performance improvement in planar P3HT/CdS solar cells induced by structural, optical and electrical property modification in thermal annealed P3HT thin films NASA Astrophysics Data System (ADS) Cortina-Marrero, Hugo Jorge; Martínez-Alonso, Claudia; Hechavarría-Difur, Liliana; Hu, Hailin 2013-07-01 Bilayer hybrid solar cells were prepared by solution deposition of CdS thin films on conductive glass substrates (ITO), followed by spin-coating or drop-casting poly (3-hexylthiophene) (P3HT) solution on a CdS surface. After a slow drying process, the P3HT films of different thicknesses (from 100 to 725 nm) were annealed at temperatures (T1) from 110 to 190 °C, called pre-metal contact annealing. Then carbon paint was collocated on top of P3HT and gold was evaporated. The whole structure was annealed for the second time, called post-metal contact annealing, at temperature (T2) between 110 and 190 °C. The continuous increase of the (1 0 0) crystalline plane and the optical absorption coefficient of P3HT films with annealing temperatures indicates the improvement of molecular order inside the polymer films induced by the thermal annealing process. The better ordered P3HT films lead to lower series resistance and higher fill factor in the corresponding solar cells, suggesting the enlargement of charge carrier mobility in annealed P3HT films. On the other hand, the photovoltaic performance is also affected by T2 temperature; a low T2 improves the ohmic contact between P3HT and the metal contact to benefit the charge carrier extraction, whereas a high T2 may deteriorate that union. The same observation was obtained in CdS/P3HT solar cells with P3HT films of different thicknesses. The best energy conversion efficiency of 0.44% was obtained in CdS/P3HT cells with 305 nm thick P3HT annealed at T1 = 190 °C and T2 = 110 °C for 10 min each. 13. Regulation of 5-HT receptors and the hypothalamic-pituitary-adrenal axis. Implications for the neurobiology of suicide. PubMed López, J F; Vázquez, D M; Chalmers, D T; Watson, S J 1997-12-29 Disturbances in the serotonin (5-HT) system is the neurobiological abnormality most consistently associated with suicide. Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is also described in suicide victims. The HPA axis is the classical neuroendocrine system that responds to stress and whose final product, corticosteroids, targets components of the limbic system, particularly the hippocampus. We will review results from animal studies that point to the possibility that many of the 5-HT receptor changes observed in suicide brains may be a result of, or may be worsened by, the HPA overactivity that may be present in some suicide victims. The results of these studies can be summarized as follows: (1) chronic unpredictable stress produces high corticosteroid levels in rats; (2) chronic stress also results in changes in specific 5-HT receptors (increases in cortical 5-HT2A and decreases in hipocampal 5-HT1A and 5-HT1B); (3) chronic antidepressant administration prevents many of the 5-HT receptor changes observed after stress; and (4) chronic antidepressant administration reverses the overactivity of the HPA axis. If indeed 5-HT receptors have a partial role in controlling affective states, then their modulation by corticosteroids provides a potential mechanism by which these hormones may regulate mood. These data may also provide a biological understanding of how stressful events may increase the risk for suicide in vulnerable individuals and may help us elucidate the neurobiological underpinnings of treatment resistance. 14. SER-7, a Caenorhabditis elegans 5-HT7-like Receptor, Is Essential for the 5-HT Stimulation of Pharyngeal Pumping and Egg Laying PubMed Central Hobson, Robert J.; Hapiak, Vera M.; Xiao, Hong; Buehrer, Kara L.; Komuniecki, Patricia R.; Komuniecki, Richard W. 2006-01-01 Serotonin (5-HT) stimulates both pharyngeal pumping and egg laying in Caenorhabditis elegans. Four distinct 5-HT receptors have been partially characterized, but little is known about their function in vivo. SER-7 exhibits most sequence identity to the mammalian 5-HT7 receptors and couples to a stimulation of adenyl cyclase when expressed in COS-7 cells. However, many 5-HT7-specific agonists have low affinity for SER-7. 5-HT fails to stimulate pharyngeal pumping and the firing of the MC motorneurons in animals containing the putative ser-7(tm1325) and ser-7(tm1728) null alleles. In addition, although pumping on bacteria is upregulated in ser-7(tm1325) animals, pumping is more irregular. A similar failure to maintain “fast pumping” on bacteria also was observed in ser-1(ok345) and tph-1(mg280) animals that contain putative null alleles of a 5-HT2-like receptor and tryptophan hydroxylase, respectively, suggesting that serotonergic signaling, although not essential for the upregulation of pumping on bacteria, “fine tunes” the process. 5-HT also fails to stimulate egg laying in ser-7(tm1325), ser-1(ok345), and ser-7(tm1325) ser-1(ok345) animals, but only the ser-7 ser-1 double mutants exhibit an Egl phenotype. All of the SER-7 mutant phenotypes are rescued by the expression of full-length ser-7∷gfp translational fusions. ser-7∷gfp is expressed in several pharyngeal neurons, including the MC, M2, M3, M4, and M5, and in vulval muscle. Interestingly, 5-HT inhibits egg laying and pharyngeal pumping in ser-7 null mutants and the 5-HT inhibition of egg laying, but not pumping, is abolished in ser-7(tm1325);ser-4(ok512) double mutants. Taken together, these results suggest that SER-7 is essential for the 5-HT stimulation of both egg laying and pharyngeal pumping, but that other signaling pathways can probably fulfill similar roles in vivo. PMID:16204223 15. P2X3 receptors induced inflammatory nociception modulated by TRPA1, 5-HT3 and 5-HT1A receptors. PubMed Krimon, Suzy; Araldi, Dionéia; do Prado, Filipe César; Tambeli, Cláudia Herrera; Oliveira-Fusaro, Maria Cláudia G; Parada, Carlos Amílcar 2013-11-01 It has been described that endogenous ATP via activation of P2X3 and P2X2/3 receptors contributes to inflammatory nociception in different models, including the formalin injected in subcutaneous tissue of the rat's hind paw. In this study, we have evaluated whether TRPA1, 5-HT3 and 5-HT1A receptors, whose activation is essential to formalin-induced inflammatory nociception, are involved in the nociception induced by activation of P2X3 receptors on subcutaneous tissue of the rat's hind paw. We have also evaluated whether the activation of P2X3 receptors increases the susceptibility of primary afferent neurons to formalin action modulated by activation of TRPA1, 5-HT3 or 5-HT1A receptors. Nociceptive response intensity was measured by observing the rat's behavior and considering the number of times the animal reflexively raised its hind paw (flinches) in 60min. Local subcutaneous administration of the selective TRPA1, 5-HT3 or 5-HT1A receptor antagonists HC 030031, tropisetron and WAY 100,135, respectively, prevented the nociceptive responses induced by the administration in the same site of the non-selective P2X3 receptor agonist αβmeATP. Administration of the selective P2X3 and P2X2/3 receptor antagonist A-317491 or pretreatment with oligonucleotides antisense against P2X3 receptor prevented the formalin-induced behavioral nociceptive responses during the first and second phases. Also, the co-administration of a subthreshold dose of αβmeATP with a subthreshold dose of formalin induced nociceptive behavior, which was prevented by local administration of tropisetron, HC 030031 or WAY 100, 135. These findings have demonstrated that the activation of P2X3 receptors induces inflammatory nociception modulated by TRPA1, 5-HT3 and 5-HT1A receptors. Also, they suggest that inflammatory nociception is modulated by the release of endogenous ATP and P2X3 receptor activation, which in turn, increases primary afferent nociceptor susceptibility to the action of inflammatory 16. Eruptive star V1180 Cas now in outburst NASA Astrophysics Data System (ADS) Antoniucci, S.; Arkharov, A. A.; Efimova, N.; Kopatskaya, E. N.; Larionov, V. M.; Di Paola, A.; Giannini, T.; Li Causi, G.; Lorenzetti, D.; Vitali, F. 2013-09-01 In the framework of our optical/near-IR EXor monitoring program dubbed EXORCISM (EXOR optiCal Infrared Systematic Monitoring - Antoniucci et al. PPVI), we have been observing since two months the variable star V1180 Cas, associated with the dark cloud Lynds 1340. This source has been originally recognized as a young eruptive object by Kun et al. (2011, ApJ 733, L8), who observed a powerful outburst (5-6 mag in the Ic band) in the period 2005-2008. 17. Design and synthesis of dual 5-HT1A and 5-HT7 receptor ligands. PubMed Ofori, Edward; Zhu, Xue Y; Etukala, Jagan R; Peprah, Kwakye; Jordan, Kamanski R; Adkins, Adia A; Bricker, Barbara A; Kang, Hye J; Huang, Xi-Ping; Roth, Bryan L; Ablordeppey, Seth Y 2016-08-15 5-HT1A and 5-HT7 receptors have been at the center of discussions recently due in part to their major role in the etiology of major central nervous system diseases such as depression, sleep disorders, and schizophrenia. As part of our search to identify dual targeting ligands for these receptors, we have carried out a systematic modification of a selective 5HT7 receptor ligand culminating in the identification of several dual 5-HT1A and 5-HT7 receptor ligands. Compound 16, a butyrophenone derivative of tetrahydroisoquinoline (THIQ), was identified as the most potent agent with low nanomolar binding affinities to both receptors. Interestingly, compound 16 also displayed moderate affinity to other clinically relevant dopamine receptors. Thus, it is anticipated that compound 16 may serve as a lead for further exploitation in our quest to identify new ligands with the potential to treat diseases of CNS origin. 18. Effect of 5-HT(7) antagonist SB-269970 in the modulation of working and reference memory in the rat. PubMed Gasbarri, Antonella; Cifariello, Agata; Pompili, Assunta; Meneses, Alfredo 2008-12-16 It has been established that serotonergic pathways project to cerebral areas involved in learning and memory and that serotonin (5-HT) receptor agonists and antagonists modify these processes. Indeed, most of the 5-HT receptors characterized so far, i.e., 5-HT(1) through 5-HT(7), show a regional distribution in brain areas involved in learning and memory, such as hippocampal formation (HF), amygdala and cortex. Although 5-HT(7) receptor biological functions are still to be clarified, it was recently suggested that it may play a role in the control of learning and memory processes. The aim of our study was to assess the role of 5-HT(7) receptors antagonist SB-269970 on working and reference memory in a radial arm maze task, utilizing a two-phase procedure, comprising an acquisition and test phase, conducted to evaluate working and reference memory, respectively. Our results showed that 5-HT(7) receptors antagonist SB-269970 improved memory, decreasing the number of errors in test phase and, thus, affecting reference memory, while no effects were observed in working memory. These results could be explained taking into consideration the specific localization of 5-HT(7) receptors in the CNS. In fact, high concentrations of 5-HT(7) receptors were found in the HF, which exerts an important role on reference memory, while relatively low concentrations were present in the prefrontal cortex, involved in working memory. Thus, 5-HT(7) receptor blockade had procognitive effect, when the learning task implicated a high degree of difficulty. This conclusion has a major implication in the context that 5-HT receptors play an important role under amnesia states (e.g., Alzheimer's disease) or when the learning is complex. 19. Serotonin regulates β-casein expression via 5-HT7 receptors in human mammary epithelial MCF-12A cells. PubMed Chiba, Takeshi; Kimura, Soichiro; Takahashi, Katsuo; Morimoto, Yasunori; Maeda, Tomoji; Sanbe, Atsushi; Ueda, Hideo; Kudo, Kenzo 2015-01-01 We previously reported that serotonin (5-hydroxytryptamine; 5-HT) suppresses β-casein expression, a differentiation marker in mammary epithelial cells, via inhibition of the signal transducer and activator of transcription 5 (STAT5) phosphorylation in the human mammary epithelial cell line, MCF-12A. In this study, we investigated the expression pattern of the different 5-HT receptor subtypes in MCF-12A cells, and identified the receptors involved in 5-HT-mediated suppression of β-casein protein expression. β-Casein mRNA expression was inhibited by 30 µM 5-HT in a time-dependent manner. Treatment with 30 µM 5-HT for 72 h decreased β-casein protein levels and STAT5 phosphorylation (pSTAT5). The cells expressed four 5-HT receptors subtypes (5-HTR1D, 2B, 3A, and 7) at the mRNA and protein level, and their expression was elevated by prolactin (PRL) treatment. Additionally, the mRNA levels of 5-HTR1D and 5-HTR7 were significantly higher than the other 5-HT receptors in the cells. Tryptophan hydroxylase 1 mRNA was detectable in the cells in the absence of PRL, and PRL treatment significantly increased its expression. β-Casein and pSTAT5/STAT5 levels in the cells co-treated with 5-HT and a selective 5-HTR1D inhibitor, BRL15572, were equal to those observed in cells treated with 5-HT alone. However, in the cells co-treated with 5-HT and a selective 5-HTR7 inhibitor, SB269970, β-casein and pSTAT5/STAT5 levels increased in a SB269970 concentration-dependent manner. In conclusion, we showed that 5-HT regulates β-casein expression via 5-HTR7 in MCF-12A human mammary epithelial cells. 20. Serotonin 5-HT7 receptor increases the density of dendritic spines and facilitates synaptogenesis in forebrain neurons. PubMed Speranza, Luisa; Labus, Josephine; Volpicelli, Floriana; Guseva, Daria; Lacivita, Enza; Leopoldo, Marcello; Bellenchi, Gian Carlo; di Porzio, Umberto; Bijata, Monika; Perrone-Capano, Carla; Ponimaskin, Evgeni 2017-01-25 Precise control of dendritic spine density and synapse formation is critical for normal and pathological brain functions. Therefore, signaling pathways influencing dendrite outgrowth and remodeling remain a subject of extensive investigations. Here we report that prolonged activation of the serotonin 5-HT7 receptor (5-HT7R) with selective agonist LP-211 promotes formation of dendritic spines and facilitates synaptogenesis in postnatal cortical and striatal neurons. Critical role of 5-HT7R in neuronal morphogenesis was confirmed by analysis of neurons isolated from 5-HT7R-deficient mice and by pharmacological inactivation of the receptor. Acute activation of 5-HT7R results in pronounced neurite elongation in postnatal striatal and cortical neurons, thus extending previous data on the morphogenic role of 5-HT7R in embryonic and hippocampal neurons. We also observed decreased number of spines in neurons with either genetically (i.e. 5-HT7R-KO) or pharmacologically (i.e. antagonist treatment) blocked 5-HT7R, suggesting that constitutive 5-HT7R activity is critically involved in the spinogenesis. Moreover, cyclin-dependent kinase 5 (Cdk5) and small GTPase Cdc42 were identified as important downstream effectors mediating morphogenic effects of 5-HT7R in neurons. Altogether, our data suggest that the 5-HT7R-mediated structural reorganization during the postnatal development might have a crucial role for the development and plasticity of forebrain areas such as cortex and striatum, and thereby can be implicated in regulation of the higher cognitive functions. This article is protected by copyright. All rights reserved. 1. Secular Decrease the Flux of Supernova Remnant CAS a on Monitoring Results to Radiotelescope "URAN-4" Ira Nasu NASA Astrophysics Data System (ADS) Gorbynov, A. A.; Ryabov, M. I.; Panishko, S. K. This work is dedicated to the study of secular decrease of the flux of young supernova remnant Cas A according to observations by radio- telescope "URAN-4" of Odessa Observatory IRA NASU from 1987 to 2001 years on frequency of 25 MHz. On the investigation base there is a relationship analysis of flux CasA to the "stable" source - radio-galaxy Cyg A (CasA/Cyg A) which is located on a small angular distance. Results of the observations held on RT "URAN-4" show that there is no noticeable decrease of fluxes in the period 1987-1993, with the relationship ratio (CasA/Cyg A) = 1.5. While considering data from 1987 to 2001 manifested a slight decrease trend in flux equal to 8.4% for the all period. At the same time, according to various investigations the average value flux of Cas A in the interval of frequencies 38-2924 MHz is 0.8% per year. At the meantime in this frequency the range ratio (CasA/Cyg A) has become less than one. Thus, there is a noticable contradiction of secular decrease of the flux Cas A on this radio frequencies in comparison with the predictions of the theory in 1.7% per year. 2. Generation of porcine fetal fibroblasts expressing the tetracycline-inducible Cas9 gene by somatic cell nuclear transfer PubMed Central Liu, Guoqian; Liu, Kai; Wei, Hengxi; Li, Li; Zhang, Shouquan 2016-01-01 Cas9 endonuclease, from so-called clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems of Streptococcus pyogenes, type II functions as an RNA-guided endonuclease and edits the genomes of prokaryotic and eukaryotic organisms, including deletion and insertion by DNA double-stranded break repair mechanisms. In previous studies, it was observed that Cas9, with a genome-scale lentiviral single-guide RNA library, could be applied to a loss-of-function genetic screen, although the loss-of-function genes have yet to be verified in vitro and this approach has not been used in porcine cells. Based on these observations, lentiviral Cas9 was used to infect porcine primary fibroblasts to achieve cell colonies carrying Cas9 endonuclease. Subsequently, porcine fetal fibroblasts expressing the tetracycline-inducible Cas9 gene were generated by somatic cell nuclear transfer, and three 30 day transgenic porcine fetal fibroblasts (PFFs) were obtained. Polymerase chain reaction (PCR), reverse transcription-PCR and western blot analysis indicated that the PFFs were Cas9-positive. In addition, one of the three integrations was located near to known functional genes in the PFF1 cell line, whereas neither of the integrations was located in the PFF1 or PFF2 cell lines. It was hypothesized that these transgenic PFFs may be useful for conditional genomic editing in pigs, and for generating ideal modified porcine models. PMID:27430306 3. PHP-HT (VitaResc Biotech). PubMed Baldwin, A; Wiley, E 2001-04-01 VitaResc (formerly Apex) is developing PHP-HT, pyridoxalated hemoglobin polyoxyethylene conjugate, for the potential treatment of nitric oxide-induced shock (characterized by hypotension), associated with various etiologies, initially in septic shock. A phase I safety study and an initial phase I/II patient trial for NO-induced shock have been completed, and VitaResc has enrolled patients in three of five planned cohorts in a continuation of these trials to include a protocol of continuous infusion and dose escalation [330680,349187,390918]. The results from the dose escalation trials are expected to provide the basis for a randomized, controlled phase II/III pivotal trial of PHP-HT [390918]. VitaResc has licensed PHP-HT exclusively from Ajinomoto for all indications, worldwide, except Japan [275263]. Ajinomoto originally developed the human derived and chemically modified hemoglobin preparation as a blood substitute, but no development has been reported by the company since 1997 [275277,303577]. The other potential indications of PHP-HT include shock associated with burns, pancreatitis, hemodialysis and cytokine therapies [275277]. VitaResc expects the annual market potential of PHP-HT to exceed 1 billion dollars [330680]. 4. 5-HT2 and 5-HT7 receptor agonists facilitate plantar stepping in chronic spinal rats through actions on different populations of spinal neurons PubMed Central Sławińska, Urszula; Miazga, Krzysztof; Jordan, Larry M. 2014-01-01 There is considerable evidence from research in neonatal and adult rat and mouse preparations to warrant the conclusion that activation of 5-HT2 and 5-HT1A/7 receptors leads to activation of the spinal cord circuitry for locomotion. These receptors are involved in control of locomotor movements, but it is not clear how they are implicated in the responses to 5-HT agonists observed after spinal cord injury. Here we used agonists that are efficient in promoting locomotor recovery in paraplegic rats, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OHDPAT) (acting on 5-HT1A/7 receptors) and quipazine (acting on 5-HT2 receptors), to examine this issue. Analysis of intra- and interlimb coordination confirmed that the locomotor performance was significantly improved by either drug, but the data revealed marked differences in their mode of action. Interlimb coordination was significantly better after 8-OHDPAT application, and the activity of the extensor soleus muscle was significantly longer during the stance phase of locomotor movements enhanced by quipazine. Our results show that activation of both receptors facilitates locomotion, but their effects are likely exerted on different populations of spinal neurons. Activation of 5-HT2 receptors facilitates the output stage of the locomotor system, in part by directly activating motoneurons, and also through activation of interneurons of the locomotor central pattern generator (CPG). Activation of 5-HT7/1A receptors facilitates the activity of the locomotor CPG, without direct actions on the output components of the locomotor system, including motoneurons. Although our findings show that the combined use of these two drugs results in production of well-coordinated weight supported locomotion with a reduced need for exteroceptive stimulation, they also indicate that there might be some limitations to the utility of combined treatment. Sensory feedback and some intraspinal circuitry recruited by the drugs can conflict with the 5. Laser-Induced Periodic Surface Structures on P3HT and on Its Photovoltaic Blend with PC71BM. PubMed Cui, Jing; Rodríguez-Rodríguez, Álvaro; Hernández, Margarita; García-Gutiérrez, Mari-Cruz; Nogales, Aurora; Castillejo, Marta; Moseguí González, Daniel; Müller-Buschbaum, Peter; Ezquerra, Tiberio A; Rebollar, Esther 2016-11-23 We describe the conditions for optimal formation of laser-induced periodic surface structures (LIPSS) over poly(3-hexylthiophene) (P3HT) spin-coated films. Optimal LIPSS on P3HT are observed within a particular range of thicknesses and laser fluences. These conditions can be translated to the photovoltaic blend formed by the 1:1 mixture of P3HT and [6,6]-phenyl C71-butyric acid methyl ester (PC71BM) when deposited on an indium tin oxide (ITO) electrode coated with (poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT:PSS). Solar cells formed by using either a bilayer of P3HT structured by LIPSS covered by PC71BM or a bulk heterojunction with a P3HT:PC71BM blend structured by LIPSS exhibit generation of electrical photocurrent under light illumination. These results suggest that LIPSS could be a compatible technology with organic photovoltaic devices. 6. Pharmacological and genetic interventions in serotonin (5-HT)(2C) receptors to alter drug abuse and dependence processes. PubMed Filip, Małgorzata; Spampinato, Umberto; McCreary, Andrew C; Przegaliński, Edmund 2012-10-02 The present review provides an overview on serotonin (5-hydroxytryptamine; 5-HT)(2C) receptors and their relationship to drug dependence. We have focused our discussion on the impact of 5-HT(2C) receptors on the effects of different classes of addictive drugs, illustrated by reference to data using pharmacological and genetic tools. The neurochemical mechanism of the interaction between 5-HT(2C) receptors, with focus on the mesocorticolimbic dopaminergic system, and drugs of abuse (using cocaine as an example) is discussed. Finally, we integrate recent nonclinical and clinical research and information with marketed products possessing 5-HT(2C) receptor binding affinities. Accordingly, available nonclinical data and some clinical observations targeting 5-HT(2C) receptors may offer innovative translational strategies for combating drug dependence.This article is part of a Special Issue entitled: Brain Integration. 7. [Effect and mechanism of LY294002 on growth of fibrosarcoma cell line HT1080]. PubMed Zhou, Hong; Huang, Xiang-Yang; Yang, Ting; Wang, Tao; Xu, Dan; Wen, Fu-Qiang 2010-01-01 To investigate the effect and mechanism of LY294002 on growth of fibrosarcoma cell line HT1080. The proliferation inhibitory rate of HT1080 cells treated by LY294002 at doses of 5, 10, 25, 50, 100 micromol/L for 12 and 24 h, respectively, was evaluated using SunBio Am-Blue method. HT1080 cells were divided into two groups, that is, A and B. The A group was control group without treatment. The B group received LY294002 (100 micromol/L) for 24 h. The changes of cell morphology and quantity were observed by phase contrast microscope. The apoptosis rate of HT1080 cells was detected by flow cytometry. And the protein expression of p-Akt and p-mTOR in HT1080 cells were detected by Western Blotting. The proliferation of HT1080 cells was inhibited in time- and dose- dependent manner by LY294002. After the treatment of 100 micromol/L LY294002 for 24 h, the growth of HT1080 cell line was remarkably inhibited by LY294002. The rate of apoptosis increased. And the protein expression of p-Akt (0.23 +/- 0.01) and p-mTOR (0.32 +/- 0.06) in LY294002 group was lower than p-Akt (0.63 +/- 0.02) and p-mTOR (0.71 +/- 0.02) in control group (P<0. 01). LY294002 can inhibit the growth of HT1080 cells through PI3K-mTOR pathway. PI3K-mTOR pathway presents an appealing therapeutic target on fibrosarcoma. 8. The Havemann-Taylor Fast Radiative Transfer Code (HT-FRTC) and its applications NASA Astrophysics Data System (ADS) Thelen, Jean-Claude; Havemann, Stephan; Lewis, Warren 2015-09-01 The Havemann-Taylor Fast Radiative Transfer Code (HT-FRTC) is a component of the Met Office NEON Tactical Decision Aid (TDA). Within NEON, the HT-FRTC has for a number of years been used to predict the IR apparent thermal contrasts between different surface types as observed by an airborne sensor. To achieve this, the HT-FRTC is supplied with the inherent temperatures and spectral properties of these surfaces (i.e. ground target(s) and background). A key strength of the HT-FRTC is its ability to take into account the detailed properties of the atmosphere, which in the context of NEON tend to be provided by a Numerical Weather Prediction (NWP) forecast model. While water vapour and ozone are generally the most important gases, additional trace gases are now being incorporated into the HT-FRTC. The HT-FRTC also includes an exact treatment of atmospheric scattering based on spherical harmonics. This allows the treatment of several different aerosol species and of liquid and ice clouds. Recent developments can even account for rain and falling snow. The HT-FRTC works in Principal Component (PC) space and is trained on a wide variety of atmospheric and surface conditions, which significantly reduces the computational requirements regarding memory and time. One clear-sky simulation takes approximately one millisecond. Recent developments allow the training to be completely general and sensor independent. This is significant as the user of the code can add new sensors and new surfaces/targets by simply supplying extra files which contain their (possibly classified) spectral properties. The HT-FRTC has been extended to cover the spectral range of Photopic and NVG sensors. One aim here is to give guidance on the expected, directionally resolved sky brightness, especially at night, again taking the actual or forecast atmospheric conditions into account. Recent developments include light level predictions during the period of twilight. 9. Molecular imaging of the 5-HT(1A) receptor in relation to human cognition. PubMed Borg, Jacqueline 2008-12-16 Animal studies and pharmacological studies in man have suggested that the serotonin 5-HT(1A) receptor may serve as a biomarker for cognitive functioning and a target for treatment of cognitive impairment. Consistent findings in man have nonetheless hitherto remained sparse. Positron emission tomography (PET) imaging of the 5-HT(1A) receptor in patients with Alzheimer's disease, schizophrenia and depression implicate an alteration in 5-HT(1A) receptor binding compared to control subjects, but it is yet unknown whether these alterations are related to the cognitive impairment associated with these disorders. Pharmacological challenge studies using 5-HT(1A) agonism and antagonism to manipulate the serotonin system support involvement of the 5-HT(1A) receptor in human cognition, mainly in verbal memory functioning. However, the effect varies across studies and it remains unclear if the 5-HT(1A) receptor serves as a validated target for treatment of cognitive deficits. This lack of confirmation of experimental preclinical data, calls for increased efforts in translational research. Molecular imaging techniques such as PET, holds the potential to facilitate translational neuroscience by confirming observations from animal models in man, and aid development of validated animal models of use for advancement of pharmacological treatment. Furthermore, in combination with molecular genetics, molecular imaging may suggest novel strategies for prevention and intervention, based on an understanding of the molecular mechanisms involved in disease pathogenesis of major neuropsychiatric disorder and associated cognitive impairment. 10. Seizure susceptibility alteration through 5-HT(3) receptor: modulation by nitric oxide. PubMed Gholipour, Taha; Ghasemi, Mehdi; Riazi, Kiarash; Ghaffarpour, Majid; Dehpour, Ahmad Reza 2010-01-01 There is some evidence that epileptic seizures could be induced or increased by 5-hydroxytryptamine (5-HT) attenuation, while augmentation of serotonin functions within the brain (e.g. by SSRIs) has been reported to be anticonvulsant. This study was performed to determine the effect of selective 5-HT(3) channel/receptor antagonist granisetron and agonist SR57227 hydrochloride on the pentylenetetrazole (PTZ)-induced seizure threshold in mice. The possible interaction of this effect with nitrergic system was also examined using the nitric oxide (NO) synthase inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) and the NO precursor l-arginine. SR57227 (10mg/kg, i.p.) significantly increased the seizure threshold compared to control group, while high dose granisetron (10mg/kg, i.p.) proved proconvulsant. Co-administration of sub-effective doses of the 5-HT(3) agonist with l-NAME (5 and 60mg/kg, i.p., respectively) exerted a significant anticonvulsive effect, while sub-effective doses of granisetron (3mg/kg) was observed to have a proconvulsive action with the addition of l-arginine (75mg/kg, i.p.). Our data demonstrate that enhancement of 5-HT(3) receptor function results in as anticonvulsant effect in the PTZ-induced seizure model, and that selective antagonism at the 5-HT(3) receptor yields proconvulsive effects. Furthermore, the NO system may play a role in 5-HT(3) receptor function. 11. A Broad-Spectrum Inhibitor of CRISPR-Cas9. PubMed Harrington, Lucas B; Doxzen, Kevin W; Ma, Enbo; Liu, Jun-Jie; Knott, Gavin J; Edraki, Alireza; Garcia, Bianca; Amrani, Nadia; Chen, Janice S; Cofsky, Joshua C; Kranzusch, Philip J; Sontheimer, Erik J; Davidson, Alan R; Maxwell, Karen L; Doudna, Jennifer A 2017-09-07 CRISPR-Cas9 proteins function within bacterial immune systems to target and destroy invasive DNA and have been harnessed as a robust technology for genome editing. Small bacteriophage-encoded anti-CRISPR proteins (Acrs) can inactivate Cas9, providing an efficient off switch for Cas9-based applications. Here, we show that two Acrs, AcrIIC1 and AcrIIC3, inhibit Cas9 by distinct strategies. AcrIIC1 is a broad-spectrum Cas9 inhibitor that prevents DNA cutting by multiple divergent Cas9 orthologs through direct binding to the conserved HNH catalytic domain of Cas9. A crystal structure of an AcrIIC1-Cas9 HNH domain complex shows how AcrIIC1 traps Cas9 in a DNA-bound but catalytically inactive state. By contrast, AcrIIC3 blocks activity of a single Cas9 ortholog and induces Cas9 dimerization while preventing binding to the target DNA. These two orthogonal mechanisms allow for separate control of Cas9 target binding and cleavage and suggest applications to allow DNA binding while preventing DNA cutting by Cas9. Copyright © 2017 Elsevier Inc. All rights reserved. 12. Potential role of cortical 5-HT(2A) receptors in the anxiolytic action of cyamemazine in benzodiazepine withdrawal. PubMed Benyamina, Amine; Naassila, Mickaël; Bourin, Michel 2012-07-30 The antipsychotic cyamemazine is a potent serotonin 5-HT(2A) receptor (5-HT(2AR)) antagonist. A positron emission tomography (PET) study in human patients showed that therapeutic doses of cyamemazine produced near saturation of 5-HT(2AR) occupancy in the frontal cortex, whereas dopamine D(2) occupancy remained below the level for motor side effects observed with typical antipsychotics. Recently, numerous studies have revealed the involvement of 5-HT(2AR) in the pathophysiology of anxiety and a double-blind, randomized clinical trial showed similar efficacy of cyamemazine and bromazepam in reducing the anxiety associated with benzodiazepine withdrawal. Therefore, we reviewed the above articles about 5-HT(2AR) and anxiety in order to understand better the anxiolytic mechanisms of cyamemazine in benzodiazepine withdrawal. The 5-HT(2AR) is the most abundant serotonin receptor subtype in the cortex. Non-pharmacological studies with antisense oligodeoxynucleotides and genetically modified mice clearly showed that cortical 5-HT(2AR) signaling positively modulates anxiety-like behavior. With a few exceptions, most other studies reviewed here further support this view. Therefore, the anxiolytic efficacy of cyamemazine in benzodiazepine withdrawal can be due to a 5-HT(2AR) antagonistic activity at the cortical level. Copyright © 2012 Elsevier Ltd. All rights reserved. 13. [Influence of iridoid from Valeriana jatamansi on 5-HT and 5-HIAA in rats with irritable bowel syndrome]. PubMed Yan, Xingli; Hong, Ying; Shi, Jinli; Qin, Yi; Zhang, Jianjun; Lin, Qing; Chen, Zhenzhen; Zhao, Ren; Cui, Xiaoli; Gao, Xuemin 2011-05-01 To investigate the mechanism of iridoid from Valeriana jatamansi treating irritable bowel syndrome. Sixty male SD rats were equally divided into 6 groups (2 controls, 1 model and 3 treatment doses) with 10 rats per group. The test groups were administered with iridoid (24.92, 12.46, 6. 23 mg x kg(-1)) while the control groups were administered with fluoxetine (2.5 mg x kg(-1), positive control) or distilled water (negative control). The model was established by chronic stress and independent feeding. The influence of iridoid from V. jatamansi on 5-HT and 5-HIAA in colon, serum and hypothalamic were observed in all groups. In the model group, the content of 5-HT in colon and serum increased significantly, but the content of 5-HT in hypothalamic decreased significantly. The content of 5-HIAA and the value of 5-HT/5-HIAA had no significant change. In three iridoid-treated groups, the content of 5-HT in colon and serum decreased, but the content of 5-HT in hypothalamic increased. The content of 5-HIAA had no significant change. The value of 5-HT/5-HIAA in colon and serum reduced. The mechanism of iridoid from V. jatamansi treating irritable bowel syndrome may be related to the regulation effect to the levels of 5-HT from Gastrointestinal to central nervous system. 14. The 5-HT1-like receptors mediating inhibition of sympathetic vasopressor outflow in the pithed rat: operational correlation with the 5-HT1A, 5-HT1B and 5-HT1D subtypes PubMed Central Villalón, Carlos M; Centurión, David; Rabelo, Gonzalo; de Vries, Peter; Saxena, Pramod R; Sánchez-López, Araceli 1998-01-01 It has been suggested that the inhibition of sympathetically-induced vasopressor responses produced by 5-hydroxytryptamine (5-HT) in pithed rats is mediated by 5-HT1-like receptors. The present study has re-analysed this suggestion with regard to the classification schemes recently proposed by the NC-IUPHAR subcommittee on 5-HT receptors.Intravenous (i.v.) continuous infusions of 5-HT and the 5-HT1 receptor agonists, 8-OH-DPAT (5-HT1A), indorenate (5-HT1A), CP 93,129 (5-HT1B) and sumatriptan (5-HT1B/1D), resulted in a dose-dependent inhibition of sympathetically-induced vasopressor responses.The sympatho-inhibitory responses induced by 5-HT, 8-OH-DPAT, indorenate, CP 93,129 or sumatriptan were analysed before and after i.v. treatment with blocking doses of the putative 5-HT receptor antagonists, WAY 100635 (5-HT1A), cyanopindolol (5-HT1A/1B) or GR 127935 (5-HT1B/1D). Thus, after WAY 100635, the responses to 5-HT and indorenate, but not to 8-OH-DPAT, CP 93,129 and sumatriptan, were blocked. After cyanopindolol, the responses to 5-HT, indorenate and CP 93,129 were abolished, whilst those to 8-OH-DPAT and sumatriptan (except at the lowest frequency of stimulation) remained unaltered. In contrast, after GR 127935, the responses to 5-HT, CP 93,129 and sumatriptan, but not to 8-OH-DPAT and indorenate, were abolished.In additional experiments, the inhibition induced by 5-HT was not modified after 5-HT7 receptor blocking doses of mesulergine.The above results suggest that the 5-HT1-like receptors, which inhibit the sympathetic vasopressor outflow in pithed rats, display the pharmacological profile of the 5-HT1A, 5-HT1B and 5-HT1D, but not that of 5-HT7, receptors. PMID:9692787 15. Comparative receptor mapping of serotoninergic 5-HT3 and 5-HT4 binding sites* NASA Astrophysics Data System (ADS) López-Rodríguez, María L.; Morcillo, María José; Benhamú, Bellinda; Rosado, María Luisa 1997-11-01 The clinical use of currently available drugs acting at the5-HT4 receptor has been hampered by their lack of selectivityover 5-HT3 binding sites. For this reason, there is considerableinterest in the medicinal chemistry of these serotonin receptor subtypes, andsignificant effort has been made towards the discovery of potent and selectiveligands. Computer-aided conformational analysis was used to characterizeserotoninergic 5-HT3 and 5-HT4 receptorrecognition. On the basis of the generally accepted model of the5-HT3 antagonist pharmacophore, we have performed a receptormapping of this receptor binding site, following the active analog approach(AAA) defined by Marshall. The receptor excluded volume was calculated as theunion of the van der Waals density maps of nine active ligands(pKi ≥ 8.9), superimposed in pharmacophoric conformations.Six inactive analogs (pKi < 7.0) were subsequently used todefine the essential volume, which in its turn can be used to define theregions of steric intolerance of the 5-HT3 receptor. Five activeligands (pKi ≥ 9.3) at 5-HT4 receptors wereused to construct an antagonist pharmacophore for this receptor, and todetermine its excluded volume by superimposition of pharmacophoricconformations. The volume defined by the superimposition of five inactive5-HT4 receptor analogs that possess the pharmacophoric elements(pKi ≤ 6.6) did not exceed the excluded volume calculated forthis receptor. In this case, the inactivity may be due to the lack of positiveinteraction of the amino moiety with a hypothetical hydrophobic pocket, whichwould interact with the voluminous substituents of the basic nitrogen ofactive ligands. The difference between the excluded volumes of both receptorshas confirmed that the main difference is indeed in the basic moiety. Thus,the 5-HT3 receptor can only accommodate small substituents inthe position of the nitrogen atom, whereas the 5-HT4 receptorrequires more voluminous groups. Also, the basic nitrogen is located at ca 16. On the origin of the orbital period changes of V523 Cas NASA Astrophysics Data System (ADS) Rovithis-Livaniou, H.; Tsantilas, S.; Kalimeris, A. 2003-03-01 The orbital period changes of V523 Cas were studied based on observational material covering almost a century. Two periodic terms of 99 y and of 33 y were detected, as well as a long-period increase of the order of 3.01 x 10-8 d/y. The latter might be the result of TRO cycles action. For what concerns the two periodic terms, both could be due to light-time effects or they could be the result of magnetic activity cycles. In the first case, V523 Cas will be a quadruple system but this has to be confirmed with further observations. 17. Yellow Hypergiants: A Comparative Study of HR 5171A, Rho Cas, and HR 8752 NASA Astrophysics Data System (ADS) Lobel, A.; de Jager, C.; Nieuwenhuijzen, H.; van Genderen, A. M.; Oudmaijer, R. 2015-12-01 We present a comparative study of the detailed spectroscopic variability of selected Fe i absorption lines observed between 1991 and 1995 in the optical spectra of the bright yellow hypergiants HR 5171A and Rho Cas. We also compare with the high-resolution spectrum of HR 8752. The three cool hypergiants reveal broad lines with very similar shapes. The variations with time in the line shapes and depths of HR 5171A and Rho Cas are very similar. The spectroscopic variability is caused by quasi-periodic atmospheric pulsations that strongly correlates with the observed radial velocity and V-brightness changes. 18. Manipulating the Biosynthesis of Bioactive Compound Alkaloids for Next-Generation Metabolic Engineering in Opium Poppy Using CRISPR-Cas 9 Genome Editing Technology. PubMed Alagoz, Yagiz; Gurkok, Tugba; Zhang, Baohong; Unver, Turgay 2016-08-03 Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated9 (Cas9) endonuclease system is a powerful RNA-guided genome editing tool. CRISPR/Cas9 has been well studied in model plant species for targeted genome editing. However, few studies have been reported on plant species without whole genome sequence information. Currently, no study has been performed to manipulate metabolic pathways using CRISPR/Cas9. In this study, the type II CRISPR/SpCas9 system was used to knock out, via nonhomologous end-joining genome repair, the 4'OMT2 in opium poppy (Papaver somniferum L.), a gene which regulates the biosythesis of benzylisoquinoline alkaloids (BIAs). For sgRNA transcription, viral-based TRV and synthetic binary plasmids were designed and delivered into plant cells with a Cas9 encoding-synthetic vector by Agrobacterium-mediated transformation. InDels formed by CRISPR/Cas9 were detected by sequence analysis. Our results showed that the biosynthesis of BIAs (e.g. morphine, thebaine) was significantly reduced in the transgenic plants suggesting that 4'OMT2 was efficiently knocked-out by our CRISPR-Cas9 genome editing approach. In addition, a novel uncharacterized alkaloid was observed only in CRISPR/Cas9 edited plants. Thus, the applicabilitiy of the CRISPR/Cas9 system was demonstrated for the first time for medicinal aromatic plants by sgRNAs transcribed from both synthetic and viral vectors to regulate BIA metabolism and biosynthesis. 19. Sacroillite tuberculeuse: à propos de deux cas PubMed Central Diallo, Ismaël; Zabsonré, Joëlle Tiendrébéogo; Kambou, Bénilde Marie Ange Tiemtoré; Sondo, Apoline Kongnimissom; Sagna, Yempabou; Ouédraogo, Dieu-Donné 2016-01-01 La sacroiliite tuberculeuse est rare et de diagnostic difficile. Les auteurs rapportent deux cas. Il s'agissait dans le premier cas d'une patiente de 40 ans ayant une infection à VIH ; le diagnostic a été histologique après une biopsie chirurgicale. Le second cas a concerné un patient de 25 ans vivant en milieu carcéral chez qui le diagnostic a été établi sur la base des arguments cliniques, biologiques, radiologiques et l'efficacité du traitement ; l'intradermoréaction à la tuberculine était phlycténulaire. Le scanner a été indispensable au diagnostic lésionnel en montrant une érosion des berges et des abcès des parties molles. Le traitement a été médical et a fait appel aux antituberculeux. PMID:28292032 20. CRISPR-Cas Systems in Prokaryotes. PubMed Burmistrz, Michał; Pyrć, Krzysztof 2015-01-01 Prokaryotic organisms possess numerous strategies that enable survival in hostile conditions. Among others, these conditions include the invasion of foreign nucleic acids such as bacteriophages and plasmids. The clustered regularly interspaced palindromic repeats-CRISPR-associated proteins (CRISPR-Cas) system provides the majority of bacteria and archaea with adaptive and hereditary immunity against this threat. This mechanism of immunity is based on short fragments of foreign DNA incorporated within the hosts genome. After transcription, these fragments guide protein complexes that target foreign nucleic acids and promote their degradation. The aim of this review is to summarize the current status of CRISPR-Cas research, including the mechanisms of action, the classification of different types and subtypes of these systems, and the development of new CRISPR-Cas-based molecular biology tools. 1. Imipenem represses CRISPR-Cas interference of DNA acquisition through H-NS stimulation in Klebsiella pneumoniae PubMed Central Lin, Tzu-Lung; Pan, Yi-Jiun; Hsieh, Pei-Fang; Hsu, Chun-Ru; Wu, Meng-Chuan; Wang, Jin-Town 2016-01-01 Analysis of the genome of Klebsiella pneumoniae NTUH-K2044 strain revealed the presence of two clustered regularly interspaced short palindromic repeats (CRISPR) arrays separated with CRISPR-associated (cas) genes. Carbapenem-resistant K. pneumoniae isolates were observed to be less likely to have CRISPR-Cas than sensitive strains (5/85 vs. 22/132). Removal of the transcriptional repressor, H-NS, was shown to prevent the transformation of plasmids carrying a spacer and putative proto-spacer adjacent motif (PAM). The CRISPR-Cas system also decreased pUC-4K plasmid stability, resulting in plasmid loss from the bacteria with acquisition of new spacers. Analysis of the acquired proto-spacers in pUC-4K indicated that 5′-TTN-3′ was the preferred PAM in K. pneumoniae. Treatment of cells by imipenem induced hns expression, thereby decreasing cas3 expression and consequently repressed CRISPR-Cas activity resulted in increase of plasmid stability. In conclusion, NTUH-K2044 CRISPR-Cas contributes to decrease of plasmid transformation and stability. Through repression of CRISPR-Cas activity by induced H-NS, bacteria might be more able to acquire DNA to confront the challenge of imipenem. PMID:27531594 2. Immunohistochemical characterization of 5-HT(3A) receptors in the Syrian hamster forebrain. PubMed Carrillo, Maria; Ricci, Lesley A; Schwartzer, Jared J; Melloni, Richard H 2010-05-06 The Syrian hamster (Mesocricetus auratus) has been extensively used as an animal model to investigate neuronal networks underlying various behaviors where 5-HT(3A) receptors have been found to play a critical role. To date, however, there is no comprehensive description of the distribution of 5-HT(3A) receptors in the Syrian hamster brain. The current study examined the localization of 5-HT(3A) receptors across the neuraxis of the Syrian hamster forebrain using immunohistochemistry. Overall, 5-HT(3A) receptors were widely and heterogeneously distributed across the neuraxis of the Syrian hamster brain. Notably, the most intense 5-HT(3A) immunolabeling patterns were observed in the cerebral cortex and amygdala. In addition, high variability in receptor density and expression patterns (i.e., perikarya, fibers and/or neuropilar puncta) was observed within the majority of brain areas examined, indicating that the role this receptor has in the modulation of a particular neural function differs depending on brain region. In some regions (i.e., nucleus accumbens) differences in the immunolabeling pattern between rostral, medial and caudal portions were also observed, suggesting functional heterogeneity of this receptor within a single brain region. Together, these results and the localization of this receptor to brain areas involved in the regulation of sexual behavior, aggression, circadian rhythm, drug abuse and anxiety implicate 5-HT(3A) receptors in the modulation of various behaviors and neural functions in the Syrian hamster. Further, these results underscore the importance of evaluating 5-HT(3A) receptors as a pharmacological target for the treatment of various psychopathological disorders. 3. Deconstructing Antiobesity Compound Action: Requirement of Serotonin 5-HT2B Receptors for Dexfenfluramine Anorectic Effects PubMed Central Banas, Sophie M; Doly, Stéphane; Boutourlinsky, Katia; Diaz, Silvina L; Belmer, Arnauld; Callebert, Jacques; Collet, Corinne; Launay, Jean-Marie; Maroteaux, Luc 2011-01-01 The now-banned anorectic molecule, dexfenfluramine, promotes serotonin release through a serotonin transporter-dependent mechanism, and it has been widely prescribed for the treatment of obesity. Previous studies have identified that 5-HT2B receptors have important roles in dexfenfluramine side effects, that is, pulmonary hypertension, plasma serotonin level regulation, and valvulopathy. We thus investigated a putative contribution of 5-HT2B receptors in dexfenfluramine-dependent feeding behavior in mice. Interestingly, the hypophagic response to dexfenfluramine (3–10 mg/kg) observed in wild-type mice (1–4 h) was eliminated in mice lacking 5-HT2B receptors (5-HT2B−/−). These findings were further validated by the lack of hypophagic response to dexfenfluramine in wild-type mice treated with RS127445, a highly selective and potent antagonist (pKi=8.22±0.24). Using microdialysis, we observed that in 5-HT2B−/− awake mice, the dexfenfluramine-induced hypothalamic peak of serotonin release (1 h) was strongly reduced (fourfold) compared with wild type. Moreover, using hypothalamic synaptosomes, we established the serotonergic neuron autonomous properties of this effect: a strong serotonin release was observed upon dexfenfluramine stimulation of synaptosome preparation from wild type but not from mice lacking active 5-HT2B receptors. These findings strongly suggest that activation of presynaptic 5-HT2B receptors is a limiting step in the serotonin transporter dependant-releasing effect of dexfenfluramine, whereas other serotonin receptors act downstream with respect to feeding behavior. PMID:20927048 4. Evolution and classification of the CRISPR-Cas systems. PubMed Makarova, Kira S; Haft, Daniel H; Barrangou, Rodolphe; Brouns, Stan J J; Charpentier, Emmanuelle; Horvath, Philippe; Moineau, Sylvain; Mojica, Francisco J M; Wolf, Yuri I; Yakunin, Alexander F; van der Oost, John; Koonin, Eugene V 2011-06-01 The CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins) modules are adaptive immunity systems that are present in many archaea and bacteria. These defence systems are encoded by operons that have an extraordinarily diverse architecture and a high rate of evolution for both the cas genes and the unique spacer content. Here, we provide an updated analysis of the evolutionary relationships between CRISPR-Cas systems and Cas proteins. Three major types of CRISPR-Cas system are delineated, with a further division into several subtypes and a few chimeric variants. Given the complexity of the genomic architectures and the extremely dynamic evolution of the CRISPR-Cas systems, a unified classification of these systems should be based on multiple criteria. Accordingly, we propose a 'polythetic' classification that integrates the phylogenies of the most common cas genes, the sequence and organization of the CRISPR repeats and the architecture of the CRISPR-cas loci. 5. SnapShot: Class 1 CRISPR-Cas Systems. PubMed Makarova, Kira S; Zhang, Feng; Koonin, Eugene V 2017-02-23 Class 1 CRISPR-Cas systems are characterized by effector modules consisting of multiple subunits. Class 1 systems comprise about 90% of all CRISPR-Cas loci identified in bacteria and archaea and can target both DNA and RNA. 6. Evolution and classification of the CRISPR-Cas systems PubMed Central S. Makarova, Kira; H. Haft, Daniel; Barrangou, Rodolphe; J. J. Brouns, Stan; Charpentier, Emmanuelle; Horvath, Philippe; Moineau, Sylvain; J. M. Mojica, Francisco; I. Wolf, Yuri; Yakunin, Alexander F.; van der Oost, John; V. Koonin, Eugene 2012-01-01 The CRISPR–Cas (clustered regularly interspaced short palindromic repeats–CRISPR-associated proteins) modules are adaptive immunity systems that are present in many archaea and bacteria. These defence systems are encoded by operons that have an extraordinarily diverse architecture and a high rate of evolution for both the cas genes and the unique spacer content. Here, we provide an updated analysis of the evolutionary relationships between CRISPR–Cas systems and Cas proteins. Three major types of CRISPR–Cas system are delineated, with a further division into several subtypes and a few chimeric variants. Given the complexity of the genomic architectures and the extremely dynamic evolution of the CRISPR–Cas systems, a unified classification of these systems should be based on multiple criteria. Accordingly, we propose a polythetic' classification that integrates the phylogenies of the most common cas genes, the sequence and organization of the CRISPR repeats and the architecture of the CRISPR–cas loci. PMID:21552286 7. CRISPR-Cas immunity in prokaryotes. PubMed Marraffini, Luciano A 2015-10-01 Prokaryotic organisms are threatened by a large array of viruses and have developed numerous defence strategies. Among these, only clustered, regularly interspaced short palindromic repeat (CRISPR)-Cas systems provide adaptive immunity against foreign elements. Upon viral injection, a small sequence of the viral genome, known as a spacer, is integrated into the CRISPR locus to immunize the host cell. Spacers are transcribed into small RNA guides that direct the cleavage of the viral DNA by Cas nucleases. Immunization through spacer acquisition enables a unique form of evolution whereby a population not only rapidly acquires resistance to its predators but also passes this resistance mechanism vertically to its progeny. 8. Highly efficient Cas9-mediated transcriptional programming DOE PAGES Chavez, Alejandro; Scheiman, Jonathan; Vora, Suhani; ... 2015-03-02 The RNA-guided nuclease Cas9 can be reengineered as a programmable transcription factor. However, modest levels of gene activation have limited potential applications. Here we describe an improved transcriptional regulator through the rational design of a tripartite activator, VP64-p65-Rta (VPR), fused to nuclease-null Cas9. Here, we demonstrate its utility in activating endogenous coding and non-coding genes, targeting several genes simultaneously and stimulating neuronal differentiation of human induced pluripotent stem cells (iPSCs). 9. Engineered CRISPR-Cas9 nucleases with altered PAM specificities. PubMed Kleinstiver, Benjamin P; Prew, Michelle S; Tsai, Shengdar Q; Topkar, Ved V; Nguyen, Nhu T; Zheng, Zongli; Gonzales, Andrew P W; Li, Zhuyun; Peterson, Randall T; Yeh, Jing-Ruey Joanna; Aryee, Martin J; Joung, J Keith 2015-07-23 Although CRISPR-Cas9 nucleases are widely used for genome editing, the range of sequences that Cas9 can recognize is constrained by the need for a specific protospacer adjacent motif (PAM). As a result, it can often be difficult to target double-stranded breaks (DSBs) with the precision that is necessary for various genome-editing applications. The ability to engineer Cas9 derivatives with purposefully altered PAM specificities would address this limitation. Here we show that the commonly used Streptococcus pyogenes Cas9 (SpCas9) can be modified to recognize alternative PAM sequences using structural information, bacterial selection-based directed evolution, and combinatorial design. These altered PAM specificity variants enable robust editing of endogenous gene sites in zebrafish and human cells not currently targetable by wild-type SpCas9, and their genome-wide specificities are comparable to wild-type SpCas9 as judged by GUIDE-seq analysis. In addition, we identify and characterize another SpCas9 variant that exhibits improved specificity in human cells, possessing better discrimination against off-target sites with non-canonical NAG and NGA PAMs and/or mismatched spacers. We also find that two smaller-size Cas9 orthologues, Streptococcus thermophilus Cas9 (St1Cas9) and Staphylococcus aureus Cas9 (SaCas9), function efficiently in the bacterial selection systems and in human cells, suggesting that our engineering strategies could be extended to Cas9s from other species. Our findings provide broadly useful SpCas9 variants and, more importantly, establish the feasibility of engineering a wide range of Cas9s with altered and improved PAM specificities. 10. [On the role of selective silencer Freud-1 in the regulation of the brain 5-HT(1A) receptor gene expression]. PubMed Naumenko, V S; Osipova, D V; Tsybko, A S 2010-01-01 Selective 5-HT(1A) receptor silencer (Freud-1) is known to be one of the main factors for transcriptional regulation of brain serotonin 5-HT(1A) receptor. However, there is a lack of data on implication of Freud-1 in the mechanisms underlying genetically determined and experimentally altered 5-HT(1A) receptor system state in vivo. In the present study we have found a difference in the 5-HT(1A) gene expression in the midbrain of AKR and CBA inbred mouse strains. At the same time no distinction in Freud-1 expression was observed. We have revealed 90.3% of homology between mouse and rat 5-HT(1A) receptor DRE-element, whereas there was no difference in DRE-element sequence between AKR and CBA mice. This indicates the absence of differences in Freud-1 binding site in these mouse strains. In the model of 5-HT(1A) receptor desensitization produced by chronic 5-HT(1A) receptor agonist administration, a significant reduction of 5-HT(1A) receptor gene expression together with considerable increase of Freud-1 expression were found. These data allow us to conclude that the selective silencer of 5-HT(1A) receptor, Freud-1, is involved in the compensatory mechanisms that modulate the functional state of brain serotonin system, although it is not the only factor for 5-HT(1A) receptor transcriptional regulation. 11. Short-term temporal studies of the X ray emission from Cas A, Tycho and Sco X-1 NASA Technical Reports Server (NTRS) Holt, S. S.; Boldt, E. A.; Brisken, A. F.; Serlemitsos, P. J. 1972-01-01 No evidence for stable 2-10 keV periodic emission from Cas A or Tycho in the period range 1 msec to 10 sec is found. Upper limits to the pulsed fraction are presented as a function of the assumed light curve, with absolute 99% confidence upper limits of 0.089 and 0.195 for Cas A and Tycho, respectively. Previously reported transient 1-10 Hz oscillations from Sco X-1 are not observed. 12. Observation ERIC Educational Resources Information Center Helfrich, Shannon 2016-01-01 Helfrich addresses two perspectives from which to think about observation in the classroom: that of the teacher observing her classroom, her group, and its needs, and that of the outside observer coming into the classroom. Offering advice from her own experience, she encourages and defends both. Do not be afraid of the disruption of outside… 13. Observations ERIC Educational Resources Information Center Joosten, Albert Max 2016-01-01 Joosten begins his article by telling us that love and knowledge together are the foundation for our work with children. This combination is at the heart of our observation. With this as the foundation, he goes on to offer practical advice to aid our practice of observation. He offers a "List of Objects of Observation" to help guide our… 14. Quantitative autoradiographic changes in 5-[3H]HT-labeled 5-HT1 serotonin receptors in discrete regions of brain in the rat model of persistent dyskinesias induced by iminodipropionitrile (IDPN). PubMed Przedborski, S; Wright, M; Fahn, S; Cadet, J L 1990-08-14 Chronic injections of iminodipropionitrile (IDPN) to rat cause a persistent motor hyperactivity, lateral and vertical sustained twisting movement of the neck, random circling and increased startle response. These abnormalities are similar to those observed after the acute administration of serotonin (5-HT) agonists in rodents. Significant changes in 5-HT concentration and in 5-HT2 receptor density in several motor-related brain regions have been observed in IDPN-treated rats. The present quantitative autoradiographic study was undertaken to assess the possibility that IDPN may also affect 5-HT1 receptors in rat brain. IDPN caused significant increases of 5-[3H]HT binding in the oriens and pyramidal layers of the CA3 field of hippocampus. In contrast, there were significant decreases of 5-[3H]HT binding in the frontal and cingulate cortices, the olfactory tubercle, the ventromedial aspect of the caudate-putamen, the nucleus accumbens, the superior colliculus, and the lateral septal nuclei. These results provide further evidence for the involvement of the 5-HT system in the development of the IDPN-induced dyskinetic syndrome. 15. High trait aggression in men is associated with low 5-HT levels, as indexed by 5-HT4 receptor binding PubMed Central Mc Mahon, Brenda; MacDonald Fisher, Patrick; Jensen, Peter Steen; Svarer, Claus; Moos Knudsen, Gitte 2016-01-01 Impulsive aggression has commonly been associated with a dysfunction of the serotonin (5-HT) system: many, but not all, studies point to an inverse relationship between 5-HT and aggression. As cerebral 5-HT4 receptor (5-HT4R) binding has recently been recognized as a proxy for stable brain levels of 5-HT, we here test the hypothesis in healthy men and women that brain 5-HT levels, as indexed by cerebral 5-HT4R, are inversely correlated with trait aggression and impulsivity. Sixty-one individuals (47 men) underwent positron emission tomography scanning with the radioligand [11C]SB207145 for quantification of brain 5-HT4R binding. The Buss–Perry Aggression Questionnaire (BPAQ) and the Barratt Impulsiveness Scale were used for assessment of trait aggression and trait impulsivity. Among male subjects, there was a positive correlation between global 5-HT4R and BPAQ total score (P = 0.037) as well as BPAQ physical aggression (P = 0.025). No main effect of global 5-HT4R on trait aggression or impulsivity was found in the mixed gender sample, but there was evidence for sex interaction effects in the relationship between global 5-HT4R and BPAQ physical aggression. In conclusion we found that low cerebral 5-HT levels, as indexed by 5-HT4R binding were associated with high trait aggression in males, but not in females. PMID:26772668 16. 5-Hydroxytryptamine (5-HT) Cellular Sequestration during Chronic Exposure Delays 5-HT3 Receptor Resensitization due to Its Subsequent Release* PubMed Central Hothersall, J. Daniel; Alexander, Amy; Samson, Andrew J.; Moffat, Christopher; Bollan, Karen A.; Connolly, Christopher N. 2014-01-01 The serotonergic synapse is dynamically regulated by serotonin (5-hydroxytryptamine (5-HT)) with elevated levels leading to the down-regulation of the serotonin transporter and a variety of 5-HT receptors, including the 5-HT type-3 (5-HT3) receptors. We report that recombinantly expressed 5-HT3 receptor binding sites are reduced by chronic exposure to 5-HT (IC50 of 154.0 ± 45.7 μm, t½ = 28.6 min). This is confirmed for 5-HT3 receptor-induced contractions in the guinea pig ileum, which are down-regulated after chronic, but not acute, exposure to 5-HT. The loss of receptor function does not involve endocytosis, and surface receptor levels are unaltered. The rate and extent of down-regulation is potentiated by serotonin transporter function (IC50 of 2.3 ± 1.0 μm, t½ = 3.4 min). Interestingly, the level of 5-HT uptake correlates with the extent of down-regulation. Using TX-114 extraction, we find that accumulated 5-HT remains soluble and not membrane-bound. This cytoplasmically sequestered 5-HT is readily releasable from both COS-7 cells and the guinea pig ileum. Moreover, the 5-HT level released is sufficient to prevent recovery from receptor desensitization in the guinea pig ileum. Together, these findings suggest the existence of a novel mechanism of down-regulation where the chronic release of sequestered 5-HT prolongs receptor desensitization. PMID:25281748 17. Time-course of 5-HT(6) receptor mRNA expression during memory consolidation and amnesia. PubMed Huerta-Rivas, A; Pérez-García, G; González-Espinosa, C; Meneses, A 2010-01-01 Growing evidence indicates that antagonists of the 5-hydroxytryptamine (serotonin) receptor(6) (5-HT(6)) improve memory and reverse amnesia although the mechanisms involved are poorly understood. Hence, in this paper RT-PCR was used to evaluate changes in mRNA expression of 5-HT(6) receptor in trained and untrained rats treated with the 5-HT(6) receptor antagonist SB-399885 and amnesic drugs scopolamine or dizocilpine. Changes in mRNA expression of 5-HT(6) receptor were investigated at different times in prefrontal cortex, hippocampus and striatum. Data indicated that memory in the Pavlovian/instrumental autoshaping task was a progressive process associated to reduced mRNA expression of 5-HT(6) receptor in the three structures examined. SB-399885 improved long-term memory at 48h, while the muscarinic receptor antagonist scopolamine or the non-competitive NMDA receptor antagonist dizocilpine impaired it at 24h. Autoshaping training and treatment with SB-399885 increased 5-HT(6) receptor mRNA expression in (maximum increase) prefrontal cortex and striatum, 24 or 48h. The scopolamine-induced amnesia suppressed 5-HT(6) receptor mRNA expression while the dizocilpine-induced amnesia did not modify 5-HT(6) receptor mRNA expression. SB-399885 and scopolamine or dizocilpine were able to reestablish memory and 5-HT(6) receptor mRNA expression. These data confirmed previous memory evidence and of more interest is the observation that training, SB-399885 and amnesic drugs modulated 5-HT(6) receptor mRNA expression in prefrontal cortex, hippocampus and striatum. Further investigation in different memory tasks, times and amnesia models together with more complex control groups might provide further clues. 18. The selective 5-HT2A receptor antagonist M100907 enhances antidepressant-like behavioral effects of the SSRI fluoxetine. PubMed Marek, Gerard J; Martin-Ruiz, Raul; Abo, Allyson; Artigas, Francesc 2005-12-01 The addition of low doses of atypical antipsychotic drugs, which saturate 5-HT(2A) receptors, enhances the therapeutic effect of selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) in patients with major depression as well as treatment-refractory obsessive-compulsive disorder. The purpose of the present studies was to test the effects of combined treatment with a low dose of a highly selective 5-HT(2A) receptor antagonist (M100907; formerly MDL 100,907) and low doses of a SSRI using a behavioral screen in rodents (the differential-reinforcement-of low rate 72-s schedule of reinforcement; DRL 72-s) which previously has been shown to be sensitive both to 5-HT(2) antagonists and SSRIs. M100907 has a approximately 100-fold or greater selectivity at 5-HT(2A) receptors vs other 5-HT receptor subtypes, and would not be expected to appreciably occupy non-5-HT(2A) receptors at doses below 100 microg/kg. M100907 increased the reinforcement rate, decreased the response rate, and shifted the inter-response time distributions to the right in a pattern characteristic of antidepressant drugs. In addition, a positive synergistic interaction occurred when testing low doses of the 5-HT(2A) receptor antagonist (6.25-12.5 microg/kg) with clinically relevant doses of the SSRI fluoxetine (2.5-5 mg/kg), which both exerted minimal antidepressant-like effects by themselves. In vivo microdialysis study revealed that a low dose of M100907 (12.5 microg/kg) did not elevate extracellular 5-HT levels in the prefrontal cortex over those observed with fluoxetine alone (5 mg/kg). These results will be discussed in the context that the combined blockade of 5-HT(2A) receptors and serotonin transporters (SERT) may result in greater efficacy in treating neuropsychiatric syndromes than blocking either site alone. 19. Effect of selective serotonin reuptake inhibitors on expression of 5-HT1AR and neurotransmitters in rats with vascular dementia. PubMed Guo, K; Yin, G; Zi, X H; Zhu, H X; Pan, Q 2016-12-02 5-hydroxytryptamine receptor 1A (5-HT1AR) is closely associated with cognitive functions. Selective serotonin reuptake inhibitors (SSRIs) can protect individuals from brain damage following ischemia/hypoxia. To investigate the function of SSRIs in vascular dementia (VD), we established a rat model of VD, and observed the effect of SSRIs on the expression of 5-HT1AR mRNA and neurotransmitters. Male SD rats (6 months) were randomly assigned into sham, model, and SSRI groups (N = 30). VD was achieved by permanent ligation of the bilateral common carotid artery. Escitalopram, a highly selective 5-HT reabsorption inhibitor, was ip injected into the rats for three consecutive weeks. The Morris water-maze was used to test learning and memory. H&E staining for neuronal injury was conducted on cortical and hippocampal tissues. HPLC was used to determine the levels of dopamine (DA), 5-HT, and norepinephrine (NE). RT-PCR was used to determine expression of 5-HT1AR mRNA. As compared to control rats, model animals demonstrated elongated escape latency, lower platform crossing times, and significant injuries to hippocampal CA1 neurons. This was accompanied by reductions in DA, 5-HT, and NE levels in hippocampal tissues, as well as reduced cortical 5-HT and decreased 5-HT1AR mRNA expression (P < 0.05). Escitalopram treatments reduced escape latency, elevated platform crossing times, improved CA1 neuronal damage, increased DA and 5-HT levels in hippocampal and cortical neurons, as well as elevated expression of 5-HT1AR mRNA (P < 0.05). Therefore, SSRIs may improve cognitive dysfunction of VD rats, possibly by stimulating expression of neurotransmitters and protecting neurons. 20. Lack of association between the T-->C 267 serotonin 5-HT6 receptor gene (HTR6) polymorphism and prediction of response to clozapine in schizophrenia. PubMed Masellis, M; Basile, V S; Meltzer, H Y; Lieberman, J A; Sevy, S; Goldman, D A; Hamblin, M W; Macciardi, F M; Kennedy, J L 2001-01-15 The affinity of clozapine for 5-HT2A, 5-HT2C, 5-HT6, 5-HT7, and 5-HT1A receptors has been suggested to contribute to various aspects of its complex clinical actions. This study examined the hypothesis that genetic variation in 5-HT1A, 5-HT6, and 5-HT7 receptor genes is involved in the variability observed in response to clozapine. We employed a pharmacogenetic approach in a group (n=185) of schizophrenia patients that have been clinically well characterized for clozapine response. Polymorphisms in the 5-HT6 (HTR6), 5-HT1A (HTR1A) and 5-HT7 (HTR7) receptor genes were genotyped. No evidence for either an allelic or genotypic association of the T-->C 267 HTR6 polymorphism with response to clozapine was found in our sample (allele: chi(2)=0.06, 1 df, P=0.80; genotype: chi(2)=1.21, 2 df, P=0.55). The pro16leu HTR1A polymorphism was not observed in our sample; all individuals genotyped were pro/pro 16 homozygotes. With respect to the pro279leu HTR7 polymorphism, one Caucasian male responder to clozapine was observed to be heterozygous (pro/leu 279 genotype). This individual was clinically similar to the other clozapine responders. Overall, our findings do not support a role for the T-->C 267 polymorphism of the 5-HT6 receptor gene in response to clozapine, although replication is required to confirm this finding. 1. No evidence of inhibition of horizontal gene transfer by CRISPR-Cas on evolutionary timescales. PubMed Gophna, Uri; Kristensen, David M; Wolf, Yuri I; Popa, Ovidiu; Drevet, Christine; Koonin, Eugene V 2015-09-01 The CRISPR (clustered, regularly, interspaced, short, palindromic repeats)-Cas (CRISPR-associated genes) systems of archaea and bacteria provide adaptive immunity against viruses and other selfish elements and are believed to curtail horizontal gene transfer (HGT). Limiting acquisition of new genetic material could be one of the sources of the fitness cost of CRISPR-Cas maintenance and one of the causes of the patchy distribution of CRISPR-Cas among bacteria, and across environments. We sought to test the hypothesis that the activity of CRISPR-Cas in microbes is negatively correlated with the extent of recent HGT. Using three independent measures of HGT, we found no significant dependence between the length of CRISPR arrays, which reflects the activity of the immune system, and the estimated number of recent HGT events. In contrast, we observed a significant negative dependence between the estimated extent of HGT and growth temperature of microbes, which could be explained by the lower genetic diversity in hotter environments. We hypothesize that the relevant events in the evolution of resistance to mobile elements and proclivity for HGT, to which CRISPR-Cas systems seem to substantially contribute, occur on the population scale rather than on the timescale of species evolution. 2. Enhanced homology-directed human genome engineering by controlled timing of CRISPR/Cas9 delivery PubMed Central Lin, Steven; Staahl, Brett T; Alla, Ravi K; Doudna, Jennifer A 2014-01-01 The CRISPR/Cas9 system is a robust genome editing technology that works in human cells, animals and plants based on the RNA-programmed DNA cleaving activity of the Cas9 enzyme. Building on previous work (Jinek et al., 2013), we show here that new genetic information can be introduced site-specifically and with high efficiency by homology-directed repair (HDR) of Cas9-induced site-specific double-strand DNA breaks using timed delivery of Cas9-guide RNA ribonucleoprotein (RNP) complexes. Cas9 RNP-mediated HDR in HEK293T, human primary neonatal fibroblast and human embryonic stem cells was increased dramatically relative to experiments in unsynchronized cells, with rates of HDR up to 38% observed in HEK293T cells. Sequencing of on- and potential off-target sites showed that editing occurred with high fidelity, while cell mortality was minimized. This approach provides a simple and highly effective strategy for enhancing site-specific genome engineering in both transformed and primary human cells. DOI: http://dx.doi.org/10.7554/eLife.04766.001 PMID:25497837 3. CRISPR/Cas9-Derived Mutations Both Inhibit HIV-1 Replication and Accelerate Viral Escape. PubMed Wang, Zhen; Pan, Qinghua; Gendron, Patrick; Zhu, Weijun; Guo, Fei; Cen, Shan; Wainberg, Mark A; Liang, Chen 2016-04-19 Cas9 cleaves specific DNA sequences with the assistance of a programmable single guide RNA (sgRNA). Repairing this broken DNA by the cell's error-prone non-homologous end joining (NHEJ) machinery leads to insertions and deletions (indels) that often impair DNA function. Using HIV-1, we have now demonstrated that many of these indels are indeed lethal for the virus, but that others lead to the emergence of replication competent viruses that are resistant to Cas9/sgRNA. This unexpected contribution of Cas9 to the development of viral resistance is facilitated by some indels that are not deleterious for viral replication, but that are refractory to recognition by the same sgRNA as a result of changing the target DNA sequences. This observation illustrates two opposite outcomes of Cas9/sgRNA action, i.e., inactivation of HIV-1 and acceleration of viral escape, thereby potentially limiting the use of Cas9/sgRNA in HIV-1 therapy. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved. 4. Enhanced homology-directed human genome engineering by controlled timing of CRISPR/Cas9 delivery. PubMed Lin, Steven; Staahl, Brett T; Alla, Ravi K; Doudna, Jennifer A 2014-12-15 The CRISPR/Cas9 system is a robust genome editing technology that works in human cells, animals and plants based on the RNA-programmed DNA cleaving activity of the Cas9 enzyme. Building on previous work (Jinek et al., 2013), we show here that new genetic information can be introduced site-specifically and with high efficiency by homology-directed repair (HDR) of Cas9-induced site-specific double-strand DNA breaks using timed delivery of Cas9-guide RNA ribonucleoprotein (RNP) complexes. Cas9 RNP-mediated HDR in HEK293T, human primary neonatal fibroblast and human embryonic stem cells was increased dramatically relative to experiments in unsynchronized cells, with rates of HDR up to 38% observed in HEK293T cells. Sequencing of on- and potential off-target sites showed that editing occurred with high fidelity, while cell mortality was minimized. This approach provides a simple and highly effective strategy for enhancing site-specific genome engineering in both transformed and primary human cells. 5. Efficient ablation of genes in human hematopoietic stem and effector cells using CRISPR/Cas9 PubMed Central Mandal, Pankaj K.; Ferreira, Leonardo M. R.; Collins, Ryan; Meissner, Torsten B.; Boutwell, Christian L.; Friesen, Max; Vrbanac, Vladimir; Garrison, Brian S.; Stortchevoi, Alexei; Bryder, David; Musunuru, Kiran; Brand, Harrison; Tager, Andrew M.; Allen, Todd M.; Talkowski, Michael E.; Rossi, Derrick J.; Cowan, Chad A. 2014-01-01 SUMMARY Genome editing via CRISPR/Cas9 has rapidly become the tool of choice by virtue of its efficacy and ease of use. However, CRISPR/Cas9 mediated genome editing in clinically relevant human somatic cells remains untested. Here, we report CRISPR/Cas9 targeting of two clinically relevant genes, B2M and CCR5, in primary human CD4+ T cells and CD34+ hematopoietic stem and progenitor cells (HSPCs). Use of single RNA guides led to highly efficient mutagenesis in HSPCs but not in T cells. A dual guide approach improved gene deletion efficacy in both cell types. HSPCs that had undergone genome editing with CRISPR/Cas9 retained multi-lineage potential. We examined predicted on- and off-target mutations via target capture sequencing in HSPCs and observed low levels of off-target mutagenesis at only one site. These results demonstrate that CRISPR/Cas9 can efficiently ablate genes in HSPCs with minimal off-target mutagenesis, which could have broad applicability for hematopoietic cell-based therapy. PMID:25517468 6. Calculating the Flux Density Decay of Cas A with LWA1 NASA Astrophysics Data System (ADS) Erazo, Jaquelin; Schinzel, Frank; LWA Collaboration 2017-01-01 The supernova remnant Cassiopeia A (Cas A) is one of the brightest objects on the low frequency radio sky in the Northern hemisphere. Due to the expansion of the cloud of material left from the supernova, its flux density keeps decreasing at a rate of ~0.7-0.8% per year. Deviations from this steady decay were noted and a systematic monitoring of Cas A is recommended in order to better trace these fluctuations. The first station of the Long Wavelength Array, co-located with the Very Large Array in New Mexico, has been performing a systematic monitoring of the flux density ratio between the radio galaxy Cygnus A and Cas A below 100 MHz since 2013. In combination with archival observations using the VLA 74 MHz system, this dataset covers a wide range of temporal scales from days to decades. This analysis is expected to lead to a better understanding of the reliability of Cas A for low frequency flux density calibration and provide insights into the physical interaction between the expanding supernova remnant shell and the interstellar medium through light curve analysis. I will present an update on the monitoring effort and preliminary light curves that reveal a non-linear decay of the flux density of Cas A. 7. Efficient gene disruption in cultured primary human endothelial cells by CRISPR/Cas9. PubMed Abrahimi, Parwiz; Chang, William G; Kluger, Martin S; Qyang, Yibing; Tellides, George; Saltzman, W Mark; Pober, Jordan S 2015-07-03 The participation of endothelial cells (EC) in many physiological and pathological processes is widely modeled using human EC cultures, but genetic manipulation of these untransformed cells has been technically challenging. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 nuclease (Cas9) technology offers a promising new approach. However, mutagenized cultured cells require cloning to yield homogeneous populations, and the limited replicative lifespan of well-differentiated human EC presents a barrier for doing so. To create a simple but highly efficient method using CRISPR/Cas9 to generate biallelic gene disruption in untransformed human EC. To demonstrate proof-of-principle, we used CRISPR/Cas9 to disrupt the gene for the class II transactivator. We used endothelial colony forming cell-derived EC and lentiviral vectors to deliver CRISPR/Cas9 elements to ablate EC expression of class II major histocompatibility complex molecules and with it, the capacity to activate allogeneic CD4(+) T cells. We show the observed loss-of-function arises from biallelic gene disruption in class II transactivator that leaves other essential properties of the cells intact, including self-assembly into blood vessels in vivo, and that the altered phenotype can be rescued by reintroduction of class II transactivator expression. CRISPR/Cas9-modified human EC provides a powerful platform for vascular research and for regenerative medicine/tissue engineering. © 2015 American Heart Association, Inc. 8. Role of Phosphoinositide 3-Kinase in the Aggressive Tumor Growth of HT1080 Human Fibrosarcoma Cells PubMed Central Gupta, Swati; Stuffrein, Selma; Plattner, Rina; Tencati, Michael; Gray, Christa; Whang, Young E.; Stanbridge, Eric J. 2001-01-01 We have developed a model system of human fibrosarcoma cell lines that do or do not possess and express an oncogenic mutant allele of N-ras. HT1080 cells contain an endogenous mutant allele of N-ras, whereas the derivative MCH603 cell line contains only wild-type N-ras. In an earlier study (S. Gupta et al., Mol. Cell. Biol. 20:9294–9306, 2000), we had shown that HT1080 cells produce rapidly growing, aggressive tumors in athymic nude mice, whereas MCH603 cells produced more slowly growing tumors and was termed weakly tumorigenic. An extensive analysis of the Ras signaling pathways (Raf, Rac1, and RhoA) provided evidence for a potential novel pathway that was critical for the aggressive tumorigenic phenotype and could be activated by elevated levels of constitutively active MEK. In this study we examined the role of phosphoinositide 3-kinase (PI 3-kinase) in the regulation of the transformed and aggressive tumorigenic phenotypes expressed in HT1080 cells. Both HT1080 (mutant N-ras) and MCH603 (wild-type N-ras) have similar levels of constitutively active Akt, a downstream target of activated PI 3-kinase. We find that both cell lines constitutively express platelet-derived growth factor (PDGF) and PDGF receptors. Transfection with tumor suppressor PTEN cDNA into HT1080 and constitutively active PI 3-kinase–CAAX cDNA into MCH603 cells, respectively, resulted in several interesting and novel observations. Activation of the PI 3-kinase/Akt pathway, including NF-κB, is not required for the aggressive tumorigenic phenotype in HT1080 cells. Activation of NF-κB is complex: in MCH603 cells it is mediated by Akt, whereas in HT1080 cells activation also involves other pathway(s) that are activated by mutant Ras. A threshold level of activation of PI 3-kinase is required in MCH603 cells before stimulatory cross talk to the RhoA, Rac1, and Raf pathways occurs, without a corresponding activation of Ras. The increased levels of activation seen were similar to those observed 9. Role of phosphoinositide 3-kinase in the aggressive tumor growth of HT1080 human fibrosarcoma cells. PubMed Gupta, S; Stuffrein, S; Plattner, R; Tencati, M; Gray, C; Whang, Y E; Stanbridge, E J 2001-09-01 We have developed a model system of human fibrosarcoma cell lines that do or do not possess and express an oncogenic mutant allele of N-ras. HT1080 cells contain an endogenous mutant allele of N-ras, whereas the derivative MCH603 cell line contains only wild-type N-ras. In an earlier study (S. Gupta et al., Mol. Cell. Biol. 20:9294-9306, 2000), we had shown that HT1080 cells produce rapidly growing, aggressive tumors in athymic nude mice, whereas MCH603 cells produced more slowly growing tumors and was termed weakly tumorigenic. An extensive analysis of the Ras signaling pathways (Raf, Rac1, and RhoA) provided evidence for a potential novel pathway that was critical for the aggressive tumorigenic phenotype and could be activated by elevated levels of constitutively active MEK. In this study we examined the role of phosphoinositide 3-kinase (PI 3-kinase) in the regulation of the transformed and aggressive tumorigenic phenotypes expressed in HT1080 cells. Both HT1080 (mutant N-ras) and MCH603 (wild-type N-ras) have similar levels of constitutively active Akt, a downstream target of activated PI 3-kinase. We find that both cell lines constitutively express platelet-derived growth factor (PDGF) and PDGF receptors. Transfection with tumor suppressor PTEN cDNA into HT1080 and constitutively active PI 3-kinase-CAAX cDNA into MCH603 cells, respectively, resulted in several interesting and novel observations. Activation of the PI 3-kinase/Akt pathway, including NF-kappaB, is not required for the aggressive tumorigenic phenotype in HT1080 cells. Activation of NF-kappaB is complex: in MCH603 cells it is mediated by Akt, whereas in HT1080 cells activation also involves other pathway(s) that are activated by mutant Ras. A threshold level of activation of PI 3-kinase is required in MCH603 cells before stimulatory cross talk to the RhoA, Rac1, and Raf pathways occurs, without a corresponding activation of Ras. The increased levels of activation seen were similar to those observed 10. Corticosterone induced morphological changes of hippocampal and amygdaloid cell lines are dependent on 5-HT7 receptor related signal pathway. PubMed Xu, Y; Zhang, C; Wang, R; Govindarajan, S S; Barish, P A; Vernon, M M; Fu, C; Acharya, A P; Chen, L; Boykin, E; Yu, J; Pan, J; O'Donnell, J M; Ogle, W O 2011-05-19 Stress is an unavoidable life experience. It induces mood, cognitive dysfunction and plasticity changes in chronically stressed individuals. Among the various brain regions that have been studied, the hippocampus and amygdala have been observed to have different roles in controlling the limbic-hypothalamic-pituitary-adrenal axis (limbic-HPA axis). This study investigated how the stress hormone corticosterone (CORT) affects neuronal cells. The first aim is to test whether administration of CORT to hippocampal and amygdaloid cell lines induces different changes in the 5-HT receptor subtypes. The second goal is to determine whether stress induced morphological changes in these two cell lines were involved in the 5-HT receptor subtypes expression. We now show that 5-HT(7) receptor mRNA levels were significantly upregulated in HT-22 cells, but downregulated in AR-5 cells by exposure to a physiologically relevant level of CORT (50 μM) for 24 h, which was later confirmed by primary hippocampal and amygdaloid neuron cultures. Additionally, pretreatment of cells with 5-HT(7) antagonist SB-269970 or agonist LP-44 reversed CORT induced cell lesion in a dose-dependent manner. Moreover, CORT induced different changes in neurite length, number of neurites and soma size in HT-22 and AR-5 cells were also reversed by pretreatment with either SB-269970 or LP-44. The different effects of 5-HT(7) receptors on cell lines were observed in two members of the Rho family small GTPase expression: the Cdc-42 and RhoA. These observed results support the hypothesis that 5-HT may differentially modulate neuronal morphology in the hippocampus and amygdala depending on the expression levels of the 5-HT receptor subtypes during stress hormone insults. 11. Structural plasticity and in vivo activity of Cas1 from the type I-F CRISPR-Cas system. PubMed Wilkinson, Max E; Nakatani, Yoshio; Staals, Raymond H J; Kieper, Sebastian N; Opel-Reading, Helen K; McKenzie, Rebecca E; Fineran, Peter C; Krause, Kurt L 2016-04-15 CRISPR-Cas systems are adaptive immune systems in prokaryotes that provide protection against viruses and other foreign DNA. In the adaptation stage, foreign DNA is integrated into CRISPR (clustered regularly interspaced short palindromic repeat) arrays as new spacers. These spacers are used in the interference stage to guide effector CRISPR associated (Cas) protein(s) to target complementary foreign invading DNA. Cas1 is the integrase enzyme that is central to the catalysis of spacer integration. There are many diverse types of CRISPR-Cas systems, including type I-F systems, which are typified by a unique Cas1-Cas2-3 adaptation complex. In the present study we characterize the Cas1 protein of the potato phytopathogen Pectobacterium atrosepticum, an important model organism for understanding spacer acquisition in type I-F CRISPR-Cas systems. We demonstrate by mutagenesis that Cas1 is essential for adaptation in vivo and requires a conserved aspartic acid residue. By X-ray crystallography, we show that although P. atrosepticum Cas1 adopts a fold conserved among other Cas1 proteins, it possesses remarkable asymmetry as a result of structural plasticity. In particular, we resolve for the first time a flexible, asymmetric loop that may be unique to type I-F Cas1 proteins, and we discuss the implications of these structural features for DNA binding and enzymatic activity. 12. Pleiotropic behavior of 5-HT2A and 5-HT2C receptor agonists. PubMed Berg, K A; Maayani, S; Goldfarb, J; Clarke, W P 1998-12-15 There is now considerable evidence that a single receptor subtype can couple to multiple effector pathways within a cell. Recently, Kenakin proposed a new concept, termed "agonist-directed trafficking of receptor stimulus", that suggests that agonists may be able to selectively activate a subset of multiple signaling pathways coupled to a single receptor subtype. 5-HT2A and 5-HT2C receptors couple to phospholipase C-(PLC) mediated inositol phosphate (IP) accumulation and PLA2-mediated arachidonic acid (AA) release. Relative efficacies of agonists (referenced to 5-HT) differed depending upon whether IP accumulation or AA release was measured. For the 5-HT2C receptor system, some agonists (e.g. TFMPP) preferentially activated the PLC-IP pathway, whereas others (e.g. LSD) favored PLA2-AA. As expected, EC50's of agonists did not differ between pathways. For the 5-HT2A receptor system, all agonists tested had greater relative efficacy for PLA2-AA than for PLC-IP. In contrast, relative efficacies were not different for 5-HT2A agonists when sequential effects in a pathway were measured (IP accumulation vs. calcium mobilization). These data strongly support the agonist-directed trafficking hypothesis. 13. Using the CAS Standards in Assessment Projects ERIC Educational Resources Information Center Dean, Laura A. 2013-01-01 This chapter provides an overview of the use of professional standards of practice in assessment and of the Council for the Advancement of Standards in Higher Education (CAS). It outlines a model for conducting program self-studies and discusses the importance of implementing change based on assessment results. 14. Lessons Learned on Management of CAS Development. ERIC Educational Resources Information Center 1995-01-01 Computer-assisted studies (CAS) attract foreign language professionals' attention due to the reliability of personal computers, the decreasing cost of available technology, and the new generation of students for whom electronic media are a familiar habitat. This article focuses on a project of the Defense Language Institute that produced over… 15. Using the CAS Standards in Assessment Projects ERIC Educational Resources Information Center Dean, Laura A. 2013-01-01 This chapter provides an overview of the use of professional standards of practice in assessment and of the Council for the Advancement of Standards in Higher Education (CAS). It outlines a model for conducting program self-studies and discusses the importance of implementing change based on assessment results. 16. Boosting plant immunity with CRISPR/Cas. PubMed Chaparro-Garcia, Angela; Kamoun, Sophien; Nekrasov, Vladimir 2015-11-19 CRISPR/Cas has recently been transferred to plants to make them resistant to geminiviruses, a damaging family of DNA viruses. We discuss the potential and the limitations of this method.See related Research: http://www.genomebiology.com/2015/16/1/238. 17. SB 206553, a putative 5-HT2C inverse agonist, attenuates methamphetamine-seeking in rats PubMed Central 2012-01-01 Background Methamphetamine (meth) dependence presents a substantial socioeconomic burden. Despite the need, there is no FDA-approved pharmacotherapy for psychostimulant dependence. We consider 5-HT2C receptors as viable therapeutic targets. We recently revealed that the atypical antidepressant, mirtazapine, attenuates meth-seeking in a rodent model of human substance abuse. Mirtazapine historically has been considered to be an antagonist at 5-HT2C receptors, but more recently shown to exhibit inverse agonism at constitutively active 5-HT2C receptors. To help distinguish the roles for antagonism vs. inverse agonism, here we explored the ability of a more selective 5-HT2C inverse agonist, SB 206553 to attenuate meth-seeking behavior, and compared its effects to those obtained with 5-HT2C antagonists, SDZ Ser 082 and SB 242084. To do so, rats were trained to self-administer meth and tested for seeking-like behavior in cue reactivity sessions consisting of contingently presenting meth-associated cues without meth reinforcement. We also explored motor function to determine the influence of SB 206553 and SDZ Ser 082 on motor activity in the presence and absence of meth. Results Like mirtazapine, pretreatment with SB 206553 (1.0, 5.0, and 10.0 mg/kg), attenuated meth-seeking. In contrast, the antagonists, SDZ Ser 082 (0.1, 0.3, and 1.0 mg/kg) and SB 242084 (3.0 mg/kg) had no effect on cue reactivity (CR). SB 242084 (3.0 mg/kg) failed to attenuate the effects of 5.0 and 10 mg/kg SB 206553 on CR. Motor function was largely unaltered by the 5-HT2C ligands; however, SB 206553, at the highest dose tested (10.0 mg/kg), attenuated meth-induced rearing behavior. Conclusions The lack of effect by 5-HT2C antagonists suggests that meth-seeking and meth-evoked motor activity are independent of endogenous 5-HT acting at 5-HT2C receptors. While SB 206553 dramatically impacted meth-evoked behaviors it is unclear whether the observed effects were 5-HT2C receptor mediated 18. Antibodies specific for HT.sub.m4 DOEpatents Lim, Bing; Adra, Chaker N.; Lelias, Jean-Michel 1998-01-01 The invention relates to a recombinant DNA molecule which encodes a HT.sub.m4 protein, a transformed host cell which has been stably transfected with a DNA molecule which encodes a HT.sub.m4 protein and a recombinant HT.sub.m4 protein. The invention also relates to a method for detecting the presence of a hereditary atopy. 19. Recombinant HT.sub.m4 gene, protein and assays SciTech Connect Lim, Bing; Adra, Chaker N.; Lelias, Jean-Michel 1996-01-01 The invention relates to a recombinant DNA molecule which encodes a HT.sub.m4 protein, a transformed host cell which has been stably transfected with a DNA molecule which encodes a HT.sub.m4 protein and a recombinant HT.sub.m4 protein. The invention also relates to a method for detecting the presence of a hereditary atopy. 20. Aryl biphenyl-3-ylmethylpiperazines as 5-HT7 receptor antagonists. PubMed Kim, Jeeyeon; Kim, Youngjae; Tae, Jinsung; Yeom, Miyoung; Moon, Bongjin; Huang, Xi-Ping; Roth, Bryan L; Lee, Kangho; Rhim, Hyewhon; Choo, Il Han; Chong, Youhoon; Keum, Gyochang; Nam, Ghilsoo; Choo, Hyunah 2013-11-01 The 5-HT7 receptor (5-HT7 R) is a promising therapeutic target for the treatment of depression and neuropathic pain. The 5-HT7 R antagonist SB-269970 exhibited antidepressant-like activity, whereas systemic administration of the 5-HT7 R agonist AS-19 significantly inhibited mechanical hypersensitivity and thermal hyperalgesia. In our efforts to discover selective 5-HT7 R antagonists or agonists, aryl biphenyl-3-ylmethylpiperazines were designed, synthesized, and biologically evaluated against the 5-HT7 R. Among the synthesized compounds, 1-([2'-methoxy-(1,1'-biphenyl)-3-yl]methyl)-4-(2-methoxyphenyl)piperazine (28) was the best binder to the 5-HT7 R (pKi =7.83), and its antagonistic property was confirmed by functional assays. The selectivity profile of compound 28 was also recorded for the 5-HT7 R over other serotonin receptor subtypes, such as 5-HT1 R, 5-HT2 R, 5-HT3 R, and 5-HT6 R. In a molecular modeling study, the 2-methoxyphenyl moiety attached to the piperazine ring of compound 28 was proposed to be essential for the antagonistic function. 1. Conservation of 5-HT1A receptor-mediated autoinhibition of serotonin (5-HT) neurons in mice with altered 5-HT homeostasis. PubMed Araragi, Naozumi; Mlinar, Boris; Baccini, Gilda; Gutknecht, Lise; Lesch, Klaus-Peter; Corradetti, Renato 2013-01-01 Firing activity of serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) is controlled by inhibitory somatodendritic 5-HT1A autoreceptors. This autoinhibitory mechanism is implicated in the etiology of disorders of emotion regulation, such as anxiety disorders and depression, as well as in the mechanism of antidepressant action. Here, we investigated how persistent alterations in brain 5-HT availability affect autoinhibition in two genetically modified mouse models lacking critical mediators of serotonergic transmission: 5-HT transporter knockout (Sert-/-) and tryptophan hydroxylase-2 knockout (Tph2-/-) mice. The degree of autoinhibition was assessed by loose-seal cell-attached recording in DRN slices. First, application of the 5-HT1A-selective agonist R(+)-8-hydroxy-2-(di-n-propylamino)tetralin showed mild sensitization and marked desensitization of 5-HT1A receptors in Tph2-/- mice and Sert-/- mice, respectively. While 5-HT neurons from Tph2-/- mice did not display autoinhibition in response to L-tryptophan, autoinhibition of these neurons was unaltered in Sert-/- mice despite marked desensitization of their 5-HT1A autoreceptors. When the Tph2-dependent 5-HT synthesis step was bypassed by application of 5-hydroxy-L-tryptophan (5-HTP), neurons from both Tph2-/- and Sert-/- mice decreased their firing rates at significantly lower concentrations of 5-HTP compared to wildtype controls. Our findings demonstrate that, as opposed to the prevalent view, sensitivity of somatodendritic 5-HT1A receptors does not predict the magnitude of 5-HT neuron autoinhibition. Changes in 5-HT1A receptor sensitivity may rather be seen as an adaptive mechanism to keep autoinhibition functioning in response to extremely altered levels of extracellular 5-HT resulting from targeted inactivation of mediators of serotonergic signaling. 2. Heritable multiplex genetic engineering in rats using CRISPR/Cas9. PubMed Ma, Yuanwu; Shen, Bin; Zhang, Xu; Lu, Yingdong; Chen, Wei; Ma, Jing; Huang, Xingxu; Zhang, Lianfeng 2014-01-01 The CRISPR/Cas9 system has been proven to be an efficient gene-editing tool for genome modification of cells and organisms. Multiplex genetic engineering in rat holds a bright future for the study of complex disease. Here, we show that this system enables the simultaneous disruption of four genes (ApoE, B2m, Prf1, and Prkdc) in rats in one-step, by co-injection of Cas9 mRNA and sgRNAs into fertilized eggs. We further observed the gene modifications are germline transmittable, and confirmed the off-target mutagenesis and mosaicism are rarely detected by comprehensive analysis. Thus, the CRISPR/Cas9 system makes it possible to efficiently and reliably generate gene knock-out rats. 3. Rapid generation of genetic diversity by multiplex CRISPR/Cas9 genome editing in rice. PubMed Shen, Lan; Hua, Yufeng; Fu, Yaping; Li, Jian; Liu, Qing; Jiao, Xiaozhen; Xin, Gaowei; Wang, Junjie; Wang, Xingchun; Yan, Changjie; Wang, Kejian 2017-05-01 The clustered regularly interspaced short palindromic repeats (CRISPR)-associated endonuclease 9 (CRISPR/Cas9) system has emerged as a promising technology for specific genome editing in many species. Here we constructed one vector targeting eight agronomic genes in rice using the CRISPR/Cas9 multiplex genome editing system. By subsequent genetic transformation and DNA sequencing, we found that the eight target genes have high mutation efficiencies in the T0 generation. Both heterozygous and homozygous mutations of all editing genes were obtained in T0 plants. In addition, homozygous sextuple, septuple, and octuple mutants were identified. As the abundant genotypes in T0 transgenic plants, various phenotypes related to the editing genes were observed. The findings demonstrate the potential of the CRISPR/Cas9 system for rapid introduction of genetic diversity during crop breeding. 4. [Study on specificity of acupuncture effect of Shenmen (HT 7) and Daling (PC 7)]. PubMed Li, Zhen-Jing; Sun, Zhong-Ren; Sun, Chen-Yi; Tong, Xin 2012-04-01 To observe the effect of acupunture at Shenmen (HT 7) and Daling (PC 7) on different cerebral functional regions by Functional Magnetic Resonance Imaging (MRI), and discuss the relative specificity of effect of these two acupoints. Ten healthy right-handed volunteers were enrolled in this research. Under the scan of fMRI with the pattern of "rest-stimulation-rest-stimulation-rest", acupuncture stimulation was given at Shenmen (HT 7) and Daling (PC 7) on the right side, and all the data were analyzed with Matlab software and SPM5 package to observe the activated cerebral regions. The activated brodmann areas by acupuncture at Shenmen (HT 7) were mainly BA10 BA13, BA47, BA22 on the left side and BA40 BA44 on the right side, while the activated areas by acupunoture at Daling (PC7) were BA46, BA47, BA22 BA10. BA45 on the left side and BA44 BA9, BA6. BA40 on the right side. The activated cerebral functional regions of acupuncture stimulation at Shenmen (HT 7) and Daling (PC 7) are not exactly the same, which indicates that the acupuncture effects of the two acupoints are specific. With the same activated areas of language and cognitive function, the Shenmen (HT 7) specializes in emotion control while the Daling (PC 7) could active the autonomic nerve function area. 5. CasHRA (Cas9-facilitated Homologous Recombination Assembly) method of constructing megabase-sized DNA PubMed Central Zhou, Jianting; Wu, Ronghai; Xue, Xiaoli; Qin, Zhongjun 2016-01-01 Current DNA assembly methods for preparing highly purified linear subassemblies require complex and time-consuming in vitro manipulations that hinder their ability to construct megabase-sized DNAs (e.g. synthetic genomes). We have developed a new method designated ‘CasHRA (Cas9-facilitated Homologous Recombination Assembly)’ that directly uses large circular DNAs in a one-step in vivo assembly process. The large circular DNAs are co-introduced into Saccharomyces cerevisiae by protoplast fusion, and they are cleaved by RNA-guided Cas9 nuclease to release the linear DNA segments for subsequent assembly by the endogenous homologous recombination system. The CasHRA method allows efficient assembly of multiple large DNA segments in vivo; thus, this approach should be useful in the last stage of genome construction. As a proof of concept, we combined CasHRA with an upstream assembly method (Gibson procedure of genome assembly) and successfully constructed a 1.03 Mb MGE-syn1.0 (Minimal Genome of Escherichia coli) that contained 449 essential genes and 267 important growth genes. We expect that CasHRA will be widely used in megabase-sized genome constructions. PMID:27220470 6. Activation of 5-HT1A and 5-HT7 receptors in the parafascicular nucleus suppresses the affective reaction of rats to noxious stimulation. PubMed Harte, Steven E; Kender, Robert G; Borszcz, George S 2005-02-01 The antinociceptive effects of the serotonin (5-HT)1A/7 receptor agonist 8-hydroxy-dipropylaminotetralin (8-OH-DPAT) administered into the medial thalamus were evaluated. Pain behaviors organized at spinal (spinal motor reflexes, SMRs), medullary (vocalizations during shock, VDSs), and forebrain (vocalization after discharges, VADs) levels of the neuraxis were elicited by tailshock. Administration of 8-OH-DPAT (5, 10, and 20 microg/side) into nucleus parafascicularis (nPf) produced dose-dependent increases in VDS and VAD thresholds, but failed to elevate SMR threshold. The increase in VAD threshold was significantly greater than that of VDS threshold. Similar effects were observed with administration of 8-OH-DPAT (20 microg/side) into the rostral portion of the central lateral thalamic nucleus. The bilateral or unilateral administration of 8-OH-DPAT (20 microg) into other thalamic nuclei, or into sites dorsal to nPf, did not elevate vocalization thresholds. Increases in vocalization thresholds produced by nPf-administered 8-OH-DPAT were mediated by both 5-HT1A and 5-HT7 receptors. Intra-nPf administration of the 5-HT1A receptor antagonist WAY-100635 (0.05 or 0.5 microg/side), or the 5-HT7 receptor antagonist SB-269970 (1 or 2 microg/side), but not the dopamine D2 receptor antagonist raclopride (10 microg/side), reversed 8-OH-DPAT induced elevations in vocalization thresholds. These results provide the first reported evidence of behavioral antinociception following the administration of a 5-HT agonist into the medial thalamus. 7. Controlling UCAVs by JTACs in CAS missions NASA Astrophysics Data System (ADS) Kumaş, A. E. 2014-06-01 By means of evolving technology, capabilities of UAVs (Unmanned Aerial Vehicle)s are increasing rapidly. This development provides UAVs to be used in many different areas. One of these areas is CAS (Close Air Support) mission. UAVs have several advantages compared to manned aircraft, however there are also some problematic areas. The remote controlling of these vehicles from thousands of nautical miles away via satellite may lead to various problems both ethical and tactical aspects. Therefore, CAS missions require a good level of ALI (Air-Land Integration), a high SA (situational awareness) and precision engagement. In fact, there is an aware friendly element in the target area in CAS missions, unlike the other UAV operations. This element is an Airman called JTAC (Joint Terminal Attack Controller). Unlike the JTAC, UAV operators are too far away from target area and use the limited FOV (Field of View) provided by camera and some other sensor data. In this study, target area situational awareness of a UAV operator and a JTAC, in a high-risk mission for friendly ground forces and civilians such as CAS, are compared. As a result of this comparison, answer to the question who should control the UCAV (Unmanned Combat Aerial Vehicle) in which circumstances is sought. A literature review is made in UAV and CAS fields and recent air operations are examined. The control of UCAV by the JTAC is assessed by SWOT analysis and as a result it is deduced that both control methods can be used in different situations within the framework of the ROE (Rules Of Engagement) is reached. 8. Observation ERIC Educational Resources Information Center Patell, Hilla 2016-01-01 In order to achieve the goal of observation, preparation of the adult, the observer, is necessary. This preparation, says Hilla Patell, requires us to "have an appreciation of the significance of the child's spontaneous activities and a more thorough understanding of the child's needs." She discusses the growth of both the desire to… 9. Observation ERIC Educational Resources Information Center Kripalani, Lakshmi A. 2016-01-01 The adult who is inexperienced in the art of observation may, even with the best intentions, react to a child's behavior in a way that hinders instead of helping the child's development. Kripalani outlines the need for training and practice in observation in order to "understand the needs of the children and...to understand how to remove… 10. Role of 5-HT1B, 5-HT2A and 5-HT2C receptors in learning. PubMed Meneses, A; Hong, E 1997-08-01 The effects of post-training (i.p.) injection of TFMPP, mCPP, DOI or 1-NP in the autoshaping learning task was explored. Furthermore, the post-training effects of these agonists after treatment with the antagonists (+/-)-pindolol, (+/-)-propranolol, NAN-190, ketanserin, ritanserin, mesulergine, MDL-72222 or p-chloroamphetamine (5-HT depleter) were studied. Rats were individually trained with a lever-press response (conditioned response; CR) on the autoshaping task and tested 24 h later. The results showed that the injection of TFMPP (1-10 mg/kg), mCPP (1-10 mg/kg), 1-NP (0.1-1.0 mg/kg) or mesulergine (0.4 mg/kg) decreased the rate of CR, while DOI (0.01-0.1 mg/kg) and ritanserin (0.5 mg/kg) and ketanserin (0.001-0.1 mg/kg) increased it. However, the effect induced by TFMPP was reversed by (+/-)-pindolol, ketanserin, ritanserin and PCA; the mCPP-induced effect was antagonized by (+/-)-propranolol, ketanserin, ritanserin and MDL-72222; and the effect produced by 1-NP was reversed by ketanserin, ritanserin and PCA. In addition, the increment in CR provoked by DOI was enhanced by ketanserin, and reversed by ritanserin, mesulergine and PCA. These findings suggest that TFMPP, 1-NP and DOI exerted their effects via stimulation of presynaptic 5-HT receptors. The effects of mCPP most probably reflect activation of postsynaptic receptors. The present data suggest that both 5-HT1B and 5-HT2A-2C receptors play a significant role in the consolidation of learning. 11. Potentiation of RSU-1069 tumour cytotoxicity by 5-hydroxytryptamine (5-HT). PubMed Central Chaplin, D. J. 1986-01-01 It is known that many solid animal tumours have a lower oxygenation level than most normal tissues and, in addition, that this level of oxygenation can be further decreased by systemic administration of 5-hydroxytryptamine (5-HT). The present study has investigated if such selective decrease in tumour oxygenation can be exploited by using the hypoxic cell cytotoxin, RSU-1069. The results obtained show that 5-HT at a dose of 5 mg kg-1, although not cytotoxic alone, can potentiate the cytotoxic effects of RSU-1069 in the Lewis lung carcinoma over the dose range 0.01-0.15 mg g-1. Maximum potentiation occurs when 5-HT is administered after RSU-1069. Potentiation of RSU-1069 cytotoxicity was observed using both the soft agar excision assay as an endpoint as well as in situ growth delay. In addition, the study shows that potentiation of RSU-1069 (0.1 mg g-1) cytotoxicity can be seen with 5-HT doses as low as 0.5 mg kg-1. In contrast to the tumour cytotoxicity results, 5-HT at a dose of 5 mg kg-1 i.p. did not affect the systemic toxicity, as measured by LD50/7d of RSU-1069. Thus, these results indicate that 5-HT can increase the therapeutic efficiency of RSU-1069. Such a finding is consistent with the rationale that selective reduction in tumour blood flow and oxygenation induced by 5-HT can be exploited using the hypoxic cell cytotoxin RSU-1069. PMID:3801269 12. Serotonergic modulation in neuropathy induced by oxaliplatin: effect on the 5HT2C receptor. PubMed Baptista-de-Souza, Daniela; Di Cesare Mannelli, Lorenzo; Zanardelli, Matteo; Micheli, Laura; Nunes-de-Souza, Ricardo Luiz; Canto-de-Souza, Azair; Ghelardini, Carla 2014-07-15 Fluoxetine has been shown to be effective in clinical and experimental studies of neuropathic pain. Besides to increase serotonin levels in the synaptic cleft, fluoxetine is able to block the serotonergic 5-HT2C receptor subtype, which in turn has been involved in the modulation of neuropathic pain. This study investigated the effect of repeated treatments with fluoxetine on the neuropathic nociceptive response induced by oxaliplatin and the effects of both treatments on 5-HT2C receptor mRNA expression and protein levels in the rat spinal cord (SC), rostral ventral medulla (RVM), midbrain periaqueductal gray (PAG) and amygdala (Amy). Nociception was assessed by paw-pressure, cold plate and Von Frey tests. Fluoxetine prevented mechanical hypersensitivity and pain threshold alterations induced by oxaliplatin but did not prevent the impairment in weight gain induced by this anticancer drug. Ex vivo analysis revealed that oxaliplatin increased the 5-HT2C receptor mRNA expression and protein levels in the SC and PAG. Similar effects were observed in fluoxetine-treated animals but only within the PAG. While oxaliplatin decreased the 5-HT2C mRNA expression levels in the Amy, fluoxetine increased their protein levels in this area. Fluoxetine impaired the oxaliplatin effects on the 5-HT2C receptor mRNA expression in the SC and Amy and protein levels in the SC. All treatments increased of 5-HT2C receptor mRNA expression and protein levels in the PAG. These results suggest that the effects of fluoxetine on neuropathic pain induced by oxaliplatin are associated with quantitative changes in the 5-HT2C receptors located within important areas of the nociceptive system. 13. 5-HT and GABA modulate intrinsic excitability of type I interneurons in Hermissenda. PubMed Jin, Nan Ge; Tian, Lian-Ming; Crow, Terry 2009-11-01 The sensory neurons (photoreceptors) in the visual system of Hermissenda are one site of plasticity produced by Pavlovian conditioning. A second site of plasticity produced by conditioning is the type I interneurons in the cerebropleural ganglia. Both photoreceptors and statocyst hair cells of the graviceptive system form monosynaptic connections with identified type I interneurons. Two proposed neurotransmitters in the graviceptive system, serotonin (5-HT) and gamma-aminobutyric acid (GABA), have been shown to modify synaptic strength and intrinsic neuronal excitability in identified photoreceptors. However, the potential role of 5-HT and GABA in plasticity of type I interneurons has not been investigated. Here we show that 5-HT increased the peak amplitude of light-evoked complex excitatory postsynaptic potentials (EPSPs), enhanced intrinsic excitability, and increased spike activity of identified type I(e(A)) interneurons. In contrast, 5-HT decreased spike activity and intrinsic excitability of type I(e(B)) interneurons. The classification of two categories of type I(e) interneurons was also supported by the observation that 5-HT produced opposite effects on whole cell steady-state outward currents in type I(e) interneurons. Serotonin produced a reduction in the amplitude of light-evoked complex inhibitory PSPs (IPSPs), increased spontaneous spike activity, decreased intrinsic excitability, and depolarized the resting membrane potential of identified type I(i) interneurons. In contrast to the effects of 5-HT, GABA produced inhibition in both types of I(e) interneurons and type I(i) interneurons. These results show that 5-HT and GABA can modulate the intrinsic excitability of type I interneurons independent of the presynaptic effects of the same transmitters on excitability and synaptic efficacy of photoreceptors. 14. 5-HT and GABA Modulate Intrinsic Excitability of Type I Interneurons in Hermissenda PubMed Central Jin, Nan Ge; Tian, Lian-Ming 2009-01-01 The sensory neurons (photoreceptors) in the visual system of Hermissenda are one site of plasticity produced by Pavlovian conditioning. A second site of plasticity produced by conditioning is the type I interneurons in the cerebropleural ganglia. Both photoreceptors and statocyst hair cells of the graviceptive system form monosynaptic connections with identified type I interneurons. Two proposed neurotransmitters in the graviceptive system, serotonin (5-HT) and γ-aminobutyric acid (GABA), have been shown to modify synaptic strength and intrinsic neuronal excitability in identified photoreceptors. However, the potential role of 5-HT and GABA in plasticity of type I interneurons has not been investigated. Here we show that 5-HT increased the peak amplitude of light-evoked complex excitatory postsynaptic potentials (EPSPs), enhanced intrinsic excitability, and increased spike activity of identified type Ie(A) interneurons. In contrast, 5-HT decreased spike activity and intrinsic excitability of type Ie(B) interneurons. The classification of two categories of type Ie interneurons was also supported by the observation that 5-HT produced opposite effects on whole cell steady-state outward currents in type Ie interneurons. Serotonin produced a reduction in the amplitude of light-evoked complex inhibitory PSPs (IPSPs), increased spontaneous spike activity, decreased intrinsic excitability, and depolarized the resting membrane potential of identified type Ii interneurons. In contrast to the effects of 5-HT, GABA produced inhibition in both types of Ie interneurons and type Ii interneurons. These results show that 5-HT and GABA can modulate the intrinsic excitability of type I interneurons independent of the presynaptic effects of the same transmitters on excitability and synaptic efficacy of photoreceptors. PMID:19710377 15. Review: 5-Ht1, 5-Ht2, 5-Ht3, And 5-Ht7 Receptors And Their Role In The Modulation Of Pain Response In The Central Nervous System. PubMed Cortes-Altamirano, José Luis; Olmos-Hernández, Adriana; Bonilla-Jaime, Herlinda; Carrillo-Mora, Paul; Bandala, Cindy; Reyes-Long, S; Alfaro-Rodríguez, Alfonso 2017-09-11 The aim of this review was to identify the mechanisms by which serotonin receptors involved at the central level are able to modulate the nociceptive response. Pain is a defense mechanism of the body that entails physiological, anatomical, neurochemical, and psychological changes, and is defined as an unpleasant sensory and emotional experience with potential risk of tissue damage, comprising the leading cause of appointments with Physicians worldwide. Treatment for this symptom has generated several neuropharmacological lines of research, due to the different types of pain and the various drugs employed to treat this condition. Serotonin [5-HydroxyTryptamine (5-HT)] is a neurotransmitter with seven families (5-HT1–5-HT7) and approximately 15 receptor subtypes. Serotonin modulates neuronal activity; however, this neurotransmitter is related with a number of physiological processes, such as cardiovascular function, gastric motility, renal function, etc. On the other hand, several researches reported that serotonin modulates nociceptive response through 5-HT1, 5-HT2, 5-HT3, and 5-HT7 receptors in the Central Nervous System (CNS). In this review, a search was conducted on PubMed, ProQuest, EBSCO, and the Science Citation Index for studies evaluating the effects of 5-HT1, 5-HT2, 5-HT3, and 5-HT7 receptors in the CNS on the modulation of different types of pain. Conclusions We concluded that 5-HT1, 5-HT2, 5-HT3, and 5-HT7 receptors in the CNS modulate the pain, but this depends on the distribution of the receptors, dose of agonists or antagonists, administration route, pain type and duration to order to inhibit, to excite, or even maintain the nociceptive response. Copyright© Bentham Science Publishers; For any queries, please email at [email protected]. 16. Role of 5-HT6 receptors in memory formation. PubMed Meneses, A 2001-09-01 Mice lacking the 5-HT(6) receptor presented neither gross anatomical or behavioral abnormalities nor obvious changes in microscopic brain morphology, and their performance in rotarod, open field and novel object testing paradigms revealed no differences compared with wild-type animals. Nevertheless, an association between the 5-HT(6) receptor polymorphism C267T and Alzheimer's disease has been reported. Interestingly, the 5-HT(6) antisense oligonucleotide decreased 5-HT(6) gene expression and enhanced spatial learning acquisition in the water maze. Similarly, injection of the 5-HT(6) receptor antagonist Ro-04-6790 improved learning consolidation in an autoshaping task, while mCPP, scopolamine and dizocilpine decreased performance. The effect induced by scopolamine or dizocilpine, but not that induced by mCPP, was completely or partially reversed by Ro-04-6790. Ro-04-6790 did not modify the 8-OH-DPAT facilitatory effects on learning consolidation. Since Ro-04-6790 facilitatory effect was unaffected by 5-HT(1A), 5-HT(2A/2B/2C), 5-HT(3), 5-HT(4) or 5-HT(7) receptor blockade, the facilitatory effect induced by Ro-04-6790 involved specifically 5-HT6 receptors. Similarly, the 5-HT(6) receptor antagonist SB-271046 improved retention in the water maze and produced a significant performance improvement in aged rats in an operant-delayed alternation task. A series of Ro-04-6790 analogues that penetrate the brain and specifically bind to 5-HT(6) receptors reversed scopolamine-induced retention deficit in a passive avoidance learning test. Collectively, these data provide further support to the notion that 5-HT systems, via 5-HT(6) receptors, also play a significant role in memory formation under normal and dysfunctional memory conditions. 17. Structure and Engineering of Francisella novicida Cas9 PubMed Central Hirano, Hisato; Gootenberg, Jonathan S.; Horii, Takuro; Abudayyeh, Omar O.; Kimura, Mika; Hsu, Patrick D.; Nakane, Takanori; Ishitani, Ryuichiro; Hatada, Izuho; Zhang, Feng; Nishimasu, Hiroshi; Nureki, Osamu 2016-01-01 Summary The RNA-guided endonuclease Cas9 cleaves double-stranded DNA targets complementary to the guide RNA, and has been applied to programmable genome editing. Cas9-mediated cleavage requires a protospacer adjacent motif (PAM) juxtaposed with the DNA target sequence, thus constricting the range of targetable sites. Here, we report the 1.7 Å resolution crystal structures of Cas9 from Francisella novicida (FnCas9), one of the largest Cas9 orthologs, in complex with a guide RNA and its PAM-containing DNA targets. A structural comparison of FnCas9 with other Cas9 orthologs revealed striking conserved and divergent features among distantly related CRISPR-Cas9 systems. We found that FnCas9 recognizes the 5′-NGG-3′ PAM, and used the structural information to create a variant that can recognize the more relaxed 5′-YG-3′ PAM. Furthermore, we demonstrated that pre-assembled FnCas9 ribonucleoprotein complexes can be microinjected into mouse zygotes to edit endogenous sites with the 5′-YG-3′ PAMs, thus expanding the target space of the CRISPR-Cas9 toolbox. PMID:26875867 18. Naturally Occurring Off-Switches for CRISPR-Cas9. PubMed Pawluk, April; Amrani, Nadia; Zhang, Yan; Garcia, Bianca; Hidalgo-Reyes, Yurima; Lee, Jooyoung; Edraki, Alireza; Shah, Megha; Sontheimer, Erik J; Maxwell, Karen L; Davidson, Alan R 2016-12-15 CRISPR-Cas9 technology would be enhanced by the ability to inhibit Cas9 function spatially, temporally, or conditionally. Previously, we discovered small proteins encoded by bacteriophages that inhibit the CRISPR-Cas systems of their host bacteria. These "anti-CRISPRs" were specific to type I CRISPR-Cas systems that do not employ the Cas9 protein. We posited that nature would also yield Cas9 inhibitors in response to the evolutionary arms race between bacteriophages and their hosts. Here, we report the discovery of three distinct families of anti-CRISPRs that specifically inhibit the CRISPR-Cas9 system of Neisseria meningitidis. We show that these proteins bind directly to N. meningitidis Cas9 (NmeCas9) and can be used as potent inhibitors of genome editing by this system in human cells. These anti-CRISPR proteins now enable "off-switches" for CRISPR-Cas9 activity and provide a genetically encodable means to inhibit CRISPR-Cas9 genome editing in eukaryotes. VIDEO ABSTRACT. Copyright © 2016 Elsevier Inc. All rights reserved. 19. Guided crystallization of P3HT in ternary blend solar cell based on P3HT:PCPDTBT:PCBM SciTech Connect Gu, Yu; Wang, Cheng; Liu, Feng; Chen, Jihua; Dyck, Ondrej E.; Duscher, Gerd; Russell, Thomas P. 2014-01-01 In ternary blend of P3HT:PCPDTBT:PC61BM, bundles of well-defined P3HT fibrils formed a network in a matrix comprised of a mixture of P3HT, PCPDTBT and PCBM yielding a 27% improvement in device efficiency. 20. HT-2 toxin 4-glucuronide as new T-2 toxin metabolite: enzymatic synthesis, analysis, and species specific formation of T-2 and HT-2 toxin glucuronides by rat, mouse, pig, and human liver microsomes. PubMed Welsch, Tanja; Humpf, Hans-Ulrich 2012-10-10 Glucuronides of the mycotoxin T-2 toxin and its phase I metabolite HT-2 toxin are important phase II metabolites under in vivo and in vitro conditions. Since standard substances are essential for the direct quantitation of these glucuronides, a method for the enzymatic synthesis of T-2 and HT-2 toxin glucuronides employing liver microsomes was optimized. Structure elucidation by nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry revealed that besides T-2 toxin glucuronide and HT-2 toxin 3-glucuronide also the newly identified isomer HT-2 toxin 4-glucuronide was formed. Glucuronidation of T-2 and HT-2 toxin in liver microsomes of rat, mouse, pig, and human was compared and metabolites were analyzed directly by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). A distinct, species specific pattern of glucuronidation of T-2 and HT-2 toxin was observed with interesting interindividual differences. Until recently, glucuronides have frequently been analyzed indirectly by quantitation of the aglycone after enzymatic cleavage of the glucuronides by β-glucuronidase. Therefore, the hydrolysis efficiencies of T-2 and HT-2 toxin glucuronides using β-glucuronidases from Helix pomatia, bovine liver, and Escherichia coli were compared. 1. Photometric analysis of the overcontact binary CW Cas SciTech Connect Wang, J. J.; Qian, S. B.; He, J. J.; Li, L. J.; Zhao, E. G. 2014-11-01 New CCD photometric observations of overcontact binary CW Cas were carried out in 2004 and 2011. In particular, the light curve obtained in 2004 shows a remarkable O'Connell effect. Compared with light curves in different observing seasons, variations were found. These variations can be explained by dark spot activities on the surface of at least one component. Using the Wilson-Devinney code with a spot model, we find that the photometric solutions confirm CW Cas is a shallow W-subtype overcontact binary with a spotted massive component. Our new determined times of minimum light together with the others published in the literature were analyzed to find a change of orbital period. From the O – C curves, the period of the system shows a cyclic period change (P {sub 3} = 69.9 yr, A {sub 3} = 0.03196 days) superposed on the linear increase. The cyclic variation, if explained as the light-travel time effect, reveals the presence of a tertiary companion. 2. Different distributions of the 5-HT reuptake complex and the postsynaptic 5-HT(2A) receptors in Brodmann areas and brain hemispheres. PubMed Rosel, Pilar; Arranz, Belén; Urretavizcaya, Mikel; Oros, Miguel; San, Luis; Vallejo, Julio; Navarro, Miguel Angel 2002-08-30 The aim of the present study was to determine the distribution of the presynaptic 5-HT reuptake complex and the 5-HT(2A) receptors through Brodmann areas from two control subjects, together with the possible existence of laterality between both brain hemispheres. A left laterality was observed in the postsynaptic 5-HT(2A) binding sites, with significantly higher B(max) values in the left frontal and cingulate cortex. In frontal cortex, [3H]imipramine and [3H]paroxetine binding showed the highest B(max) values in areas 25, 10 and 11. In cingulate cortex, the highest [3H]imipramine and [3H]paroxetine B(max) values were noted in Brodmann area 33 followed by area 24, while postsynaptic 5-HT(2A) receptors were mainly distributed through Brodmann areas 23 and 29. In temporal cortex, the highest [3H]imipramine and [3H]paroxetine B(max) was noted in Brodmann areas 28 and 34, followed by areas 35 and 38. All Brodmann areas from parietal cortex (1, 2, 3, 4, 5, 6, 7, 39, 40 and 43) showed similar presynaptic and postsynaptic binding values. In occipital cortex no differences were observed with regard to the brain hemisphere or to the Brodmann area (17, 18 and 19). These results suggest the need to carefully define the brain hemisphere and the Brodmann areas studied, as well to avoid comparisons between studies including different Brodmann areas or brain hemispheres. 3. Selective 5HT2A and 5HT6 Receptor Antagonists Promote Sleep in Rats PubMed Central Morairty, Stephen R.; Hedley, Linda; Flores, Judith; Martin, Renee; Kilduff, Thomas S. 2008-01-01 Study Objectives: Serotonin (5-HT) has long been implicated in the control of sleep and wakefulness. This study evaluated the hypnotic efficacy of the 5-HT6 antagonist RO4368554 (RO) and the 5-HT2A receptor antagonist MDL100907 (MDL) relative to zolpidem. Design: A randomized, repeated-measures design was utilized in which Wistar rats received intraperitoneal injections of RO (1.0, 3.0, and 10 mg/kg), MDL (0.1, 1.0 and 3.0 mg/kg), zolpidem (10 mg/kg), or vehicle in the middle of the dark (active) period. Electroencephalogram, electromyogram, body temperature (Tb) and locomotor activity were analyzed for 6 hours after injection. Measurements and Results: RO, MDL, and zolpidem all produced significant increases in sleep and decreases in waking, compared with vehicle control. All 3 doses of MDL produced more consolidated sleep, increased non-rapid eye movement sleep (NREM) sleep, and increased electroencephalographic delta power during NREM sleep. The highest dose of RO (10.0 mg/kg) produced significant increases in sleep and decreases in waking during hour 2 following dosing. These increases in sleep duration were associated with greater delta power during NREM sleep. ZO Zolpidem induced sleep with the shortest latency and significantly increased NREM sleep and delta power but also suppressed rapid eye movement sleep sleep; in contrast, neither RO nor MDL affected rapid eye movement sleep. Whereas RO did not affect Tb, both zolpidem and MDL reduced Tb relative to vehicle-injected controls. Conclusions: These results support a role for 5-HT2A receptor modulation in NREM sleep and suggest a previously unrecognized role for 5-HT6 receptors in sleep-wake regulation. Citation: Morairty SR; Hedley L; Flores J; Martin R; Kilduff TS. Selective 5HT2A and 5HT6 receptor antagonists promote sleep in rats. SLEEP 2008;31(1):34-44. PMID:18220076 4. 5-HT3 and 5-HT4 antagonists inhibit peristaltic contractions in guinea-pig distal colon by mechanisms independent of endogenous 5-HT PubMed Central Sia, Tiong C.; Whiting, Malcolm; Kyloh, Melinda; Nicholas, Sarah J.; Oliver, John; Brookes, Simon J.; Dinning, Phil G.; Wattchow, David A.; Spencer, Nick J. 2013-01-01 Recent studies have shown that endogenous serotonin is not required for colonic peristalsis in vitro, nor gastrointestinal (GI) transit in vivo. However, antagonists of 5-Hydroxytryptamine (5-HT) receptors can inhibit peristalsis and GI-transit in mammals, including humans. This raises the question of how these antagonists inhibit GI-motility and transit, if depletion of endogenous 5-HT does not cause any significant inhibitory changes to either GI-motility or transit? We investigated the mechanism by which 5-HT3 and 5-HT4 antagonists inhibit distension-evoked peristaltic contractions in guinea-pig distal colon. In control animals, repetitive peristaltic contractions of the circular muscle were evoked in response to fixed fecal pellet distension. Distension-evoked peristaltic contractions were unaffected in animals with mucosa and submucosal plexus removed, that were also treated with reserpine (to deplete neuronal 5-HT). In control animals, peristaltic contractions were blocked temporarily by ondansetron (1–10 μM) and SDZ-205–557 (1–10 μM) in many animals. Interestingly, after this temporary blockade, and whilst in the continued presence of these antagonists, peristaltic contractions recovered, with characteristics no different from controls. Surprisingly, similar effects were seen in mucosa-free preparations, which had no detectable 5-HT, as detected by mass spectrometry. In summary, distension-evoked peristaltic reflex contractions of the circular muscle layer of the guinea-pig colon can be inhibited temporarily, or permanently, in the same preparation by selective 5-HT3 and 5-HT4 antagonists, depending on the concentration of the antagonists applied. These effects also occur in preparations that lack any detectable 5-HT. We suggest caution should be exercised when interpreting the effects of 5-HT3 and 5-HT4 antagonists; and the role of endogenous 5-HT, in the generation of distension-evoked colonic peristalsis. PMID:23935564 5. Estimating the dose from atmospheric releases of HT SciTech Connect Murphy, C.E. Jr. 1990-11-13 Measurements of uptake of tritium by humans and laboratory animals following exposure to tritiated hydrogen gas, HT, suggest that the radiotoxicity of HT is four orders of magnitude less than that of tritiated water, HTO. However, this analysis does not take into account the conversion of HT into HTO following release into the environment. Experimental releases of HT have demonstrated that HT release to the environment is converted to HTO by soil microorganisms. In this report two methods are used to estimate the effect of HT to HTO conversion on the inhalation dose of individuals exposed to tritium downwind of a release of HT. From this analysis it is predicted that the ratio of dose from inhalation of tritium following an atmospheric release of HT, as compared to inhalation of HTO, is closer to 0.01 than the 0.0001 attributed to simple HT inhalation. Under meteorologic conditions which keep the HT release near the surface and promote optimum soil microbial activity, the analysis suggests that the ratio of dose from an atmospheric HT release could be as high as 25% of that from an atmospheric HTO release. 6. Spinal 5-HT4 and 5-HT6 receptors contribute to the maintenance of neuropathic pain in rats. PubMed Pineda-Farias, Jorge Baruch; Barragán-Iglesias, Paulino; Valdivieso-Sánchez, Alann; Rodríguez-Silverio, Juan; Flores-Murrieta, Francisco Javier; Granados-Soto, Vinicio; Rocha-González, Héctor Isaac 2017-04-04 7. Behavioural evidence for a functional interaction between central 5-HT2 and 5-HT1A receptors. PubMed Central Backus, L. I.; Sharp, T.; Grahame-Smith, D. G. 1990-01-01 1. The possibility of 5-HT2 receptor modulation of central 5-HT1A receptor function has been examined using the 5-hydroxytryptamine (5-HT) behavioural syndrome induced by 5-HT1A receptor active drugs in rats. 2. The 5-HT2/5-HTIC antagonist ritanserin (0.1-2 mg kg-1) increased the 5-HT behavioural syndrome induced by submaximally effective doses of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) and gepirone. 3. Pretreatment with the 5-HT2/5-HT1C antagonist ICI 170,809 (0.25-5 mg kg-1) also enhanced the behavioural syndrome induced by 8-OH-DPAT or 5-MeODMT. 4. The 5-HT2/alpha 1-adrenoceptor antagonist ketanserin in a low dose (0.25 mg kg-1) significantly increased the 5-HT behavioural syndrome induced by 8-OH-DPAT or 5-MeODMT, while in a higher dose (2.5 mg kg-1) this drug decreased the response. Experiments with prazosin indicate that the higher dose of ketanserin might reduce the 5-HT behavioural syndrome through blockade of alpha 1-adrenoceptors. 5. Ritanserin and ICI 170,809 had no effect on apomorphine-induced stereotypy or hyperactivity, indicating that these drugs do not produce non-specific behavioural activation. 6. Ritanserin and ICI 170,809 inhibited quipazine-induced wet dog shakes at doses similar to those enhancing the 5-HT behavioural syndrome. 7. We suggest that ritanserin, ICI 170,809 and ketanserin enhance 5-HT1A agonist-induced behaviour through blockade of an inhibitory 5-HT2 receptor regulating or coupled to 5-HT1A receptor-mediated function. PMID:2145051 8. Role of 5-HT3 Receptors in the Antidepressant Response PubMed Central Bétry, Cécile; Etiévant, Adeline; Oosterhof, Chris; Ebert, Bjarke; Sanchez, Connie; Haddjeri, Nasser 2011-01-01 Serotonin (5-HT)3 receptors are the only ligand-gated ion channel of the 5-HT receptors family. They are present both in the peripheral and central nervous system and are localized in several areas involved in mood regulation (e.g., hippocampus or prefrontal cortex). Moreover, they are involved in regulation of neurotransmitter systems implicated in the pathophysiology of major depression (e.g., dopamine or GABA). Clinical and preclinical studies have suggested that 5-HT3 receptors may be a relevant target in the treatment of affective disorders. 5-HT3 receptor agonists seem to counteract the effects of antidepressants in non-clinical models, whereas 5-HT3 receptor antagonists, such as ondansetron, present antidepressant-like activities. In addition, several antidepressants, such as mirtazapine, also target 5-HT3 receptors. In this review, we will report major advances in the research of 5-HT3 receptor's roles in neuropsychiatric disorders, with special emphasis on mood and anxiety disorders. 9. On the role of brain 5-HT7 receptor in the mechanism of hypothermia: comparison with hypothermia mediated via 5-HT1A and 5-HT3 receptor. PubMed Naumenko, Vladimir S; Kondaurova, Elena M; Popova, Nina K 2011-12-01 Intracerebroventricular administration of selective agonist of serotonin 5-HT(7) receptor LP44 (4-[2-(methylthio)phenyl]-N-(1,2,3,4-tetrahydro-1-naphthalenyl)-1-pyperasinehexanamide hydrochloride; 10.3, 20.5 or 41.0 nmol) produced considerable hypothermic response in CBA/Lac mice. LP44-induced (20.5 nmol) hypothermia was significantly attenuated by the selective 5-HT(7) receptor antagonist SB 269970 (16.1 fmol, i.c.v.) pretreatment. At the same time, intraperitoneal administration of LP44 in a wide range of doses 1.0, 2.0 or 10.0 mg/kg (2.0, 4.0, 20.0 μmol/kg) did not cause considerable hypothermic response. These findings indicate the implication of central, rather than peripheral 5-HT(7) receptors in the regulation of hypothermia. The comparison of LP44-induced (20.5 nmol) hypothermic reaction in eight inbred mouse strains (DBA/2J, CBA/Lac, C57BL/6, BALB/c, ICR, AKR/J, C3H and Asn) was performed and a significant effect of genotype was found. In the same eight mouse strains, functional activity of 5-HT(1A) and 5-HT(3) receptors was studied. The comparison of hypothermic responses produced by 5-HT(7) receptor agonist LP44 (20.5 nmol, i.c.v.) and 5-HT(1A) receptor agonist 8-OH-DPAT 1.0 mg/kg, i.p. (3.0 μmol/kg), 5-HT(3) receptor agonist m-CPBG (40.0 nmol, i.c.v.) did not reveal considerable interstrain correlations between 5-HT(7) and 5-HT(1A) or 5-HT(3) receptor-induced hypothermia. The selective 5-HT(7) receptor antagonist SB 269970 (16.1 fmol, i.c.v.) failed to attenuate the hypothermic effect of 8-OH-DPAT 1.0 mg/kg, i.p. (3.0 μmol/kg) and m-CPBG (40.0 nmol, i.c.v.) indicating that the brain 5-HT(7) receptor is not involved in the hypothermic effects of 8-OH-DPAT or m-CPBG. The obtained results suggest that the central 5-HT(7) receptor plays an essential role in the mediation of thermoregulation independent of 5-HT(1A) and 5-HT(3) receptors. 10. Prostaglandin potentiates 5-HT responses in stomach and ileum innervating visceral afferent sensory neurons. PubMed Kim, Sojin; Jin, Zhenhua; Lee, Goeun; Park, Yong Seek; Park, Cheung-Seog; Jin, Young-Ho 2015-01-02 Gastrointestinal disorder is a common symptom induced by diverse pathophysiological conditions that include food tolerance, chemotherapy, and irradiation for therapy. Prostaglandin E2 (PGE2) level increase was often reported during gastrointestinal disorder and prostaglandin synthetase inhibitors has been used for ameliorate the symptoms. Exogenous administration of PGE2 induces gastrointestinal disorder, however, the mechanism of action is not known. Therefore, we tested PGE2 effect on visceral afferent sensory neurons of the rat. Interestingly, PGE2 itself did not evoked any response but enhanced serotonin (5-HT)-evoked currents up to 167% of the control level. The augmented 5-HT responses were completely inhibited by a 5-HT type 3 receptor antagonist, ondansetron. The PGE2-induced potentiation were blocked by a selective E-prostanoid type 4 (EP4) receptors antagonist, L-161,982, but type 1 and 2 receptor antagonist AH6809 has no effect. A membrane permeable protein kinase A (PKA) inhibitor, KT5720 also inhibited PGE2 effects. PGE2 induced 5-HT current augmentation was observed on 15% and 21% of the stomach and ileum projecting neurons, respectively. Current results suggest a synergistic signaling in visceral afferent neurons underlying gastrointestinal disorder involving PGE2 potentiation of 5-HT currents. Our findings may open a possibility for screen a new type drugs with lower side effects than currently using steroidal prostaglandin synthetase inhibitors by selectively targeting EP4 receptor/PKA pathway without interrupt prostaglandin synthesis. 11. Metabolism of the Fusarium Mycotoxins T-2 Toxin and HT-2 Toxin in Wheat PubMed Central 2015-01-01 To investigate the metabolic fate of HT-2 toxin (HT2) and T-2 toxin (T2) in wheat (Triticum aestivum L.), an untargeted metabolomics study utilizing stable isotopic labeling and liquid chromatography–high resolution mass spectrometry was performed. In total, 11 HT2 and 12 T2 derived in planta biotransformation products were annotated putatively. In addition to previously reported mono- and diglucosylated forms of HT2, evidence for the formation of HT2-malonyl-glucoside and feruloyl-T2, as well as acetylation and deacetylation products in wheat was obtained for the first time. To monitor the kinetics of metabolite formation, a time course experiment was conducted involving the Fusarium head blight susceptible variety Remus and the resistant cultivar CM-82036. Biotransformation reactions were observed already at the earliest tested time point (6 h after treatment), and formed metabolites showed different kinetic profiles. After ripening, less than 15% of the toxins added to the plants were determined to be unmetabolized. PMID:26278508 12. Distribution of T-2 and HT-2 toxins in milling fractions of durum wheat. PubMed Pascale, Michelangelo; Haidukowski, Miriam; Lattanzio, Veronica Maria Teresa; Silvestri, Marco; Ranieri, Roberto; Visconti, Angelo 2011-10-01 The effect of processing on mycotoxin content in milling fractions has been investigated in 10 samples of durum wheat contaminated with T-2 and HT-2 toxins at levels ranging from 97 to 5,954 μg/kg (sum of T-2 and HT-2 toxins). Either naturally contaminated samples or samples artificially inoculated with Fusarium sporotrichioides under field conditions were used. A method based on liquid chromatography-tandem mass spectrometry coupled with immunoaffinity column cleanup was validated in-house for the simultaneous analysis of both toxins in a variety of matrices, including uncleaned wheat, cleaned wheat, screenings, bran, red dog, fine middlings, and semolina. Mean recoveries from samples spiked with T-2 and HT-2 toxins at levels of 100 μg/kg ranged from 85 to 107%, with relative standard deviations (RSDs) lower than 14%. The milling process led to an increase of T-2 and HT-2 toxin contents up to 13- and 5-fold in screenings and bran, respectively, compared with occurrence in the uncleaned wheat; however, an overall reduction of T-2 and HT-2 toxins by 54% (RSD, 20%) and 89% (RSD, 3%) was observed in cleaned wheat and in semolina, respectively. 13. On the voltage-dependent Ca2+ block of serotonin 5-HT3 receptors: a critical role of intracellular phosphates PubMed Central Noam, Yoav; Wadman, Wytse J; van Hooft, Johannes A 2008-01-01 Natively expressed serotonin 5-HT3 receptors typically possess a negative-slope conductance region in their I–V curve, due to a voltage-dependent block by external Ca2+ ions. However, in almost all studies performed with heterologously expressed 5-HT3 receptors, this feature was not observed. Here we show that mere addition of ATP to the pipette solution is sufficient to reliably observe a voltage-dependent block in homomeric (h5-HT3A) and heteromeric (h5-HT3AB) receptors expressed in HEK293 cells. A similar block was observed with a plethora of molecules containing a phosphate moiety, thus excluding a role of phosphorylation. A substitution of three arginines in the intracellular vestibule of 5-HT3A with their counterpart residues from the 5-HT3B subunit (RRR-QDA) was previously shown to dramatically increase single channel conductance. We find this mutant to have a linear I–V curve that is unaffected by the presence of ATP, with a fractional Ca2+ current (Pf%) that is reduced (1.8 ± 0.2%) compared to that of the homomeric receptor (4.1 ± 0.2%), and similar to that of the heteromeric form (2.0 ± 0.3%). Moreover, whereas ATP decreased the Pf% of the homomeric receptor, this was not observed with the RRR-QDA mutant. Finally, ATP was found to be critical for voltage-dependent channel block also in hippocampal interneurons that natively express 5-HT3 receptors. Taken together, our results indicate a novel mechanism by which ATP, and similar molecules, modulate 5-HT3 receptors via interactions with the intracellular vestibule of the receptor. PMID:18566001 14. Discovery and development of 5-HT(₂C) receptor agonists for obesity: is there light at the end of the tunnel? PubMed Miller, Keith J; Wacker, Dean A 2010-12-01 Ever since the observation of late-onset obesity during the phenotypic characterization of the 5-HT(₂C) knock-out mouse, the serotonin 5-HT(₂C) receptor has been a drug target for obesity. Small-molecule agonists have repeatedly been shown to reduce food intake and body weight in rodent models of obesity. To date, however, only one compound, lorcaserin, has completed Phase III trials and currently awaits an US FDA decision following a negative advisory committee meeting. Agonist selectivity versus the highly homologous 5-HT(₂A) and 5-HT(₂B) receptors remains a significant hurdle. Ideally, a specific 5-HT(₂C) agonist (completely devoid of 5-HT(₂A) and 5-HT(₂B) activity) would be preferred. The requirement of a basic amine coupled with larger, often aromatic, hydrophobic domains, to gain selectivity, often leads to additional challenges associated with cationic amphiphilic molecules such as hERG-channel inhibition and phospholipidosis. The success of future 5-HT(₂C) agonists will depend on further improvements in selectivity (or attainment of complete specificity) and pharmaceutical properties to permit greater and sustained receptor stimulation, while avoiding side effects associated with the activation of other 5-HT receptors. 15. Réactions immunoallergiques graves aux antibacillaires: à propos de 10 cas PubMed Central Alami, Sabah El Machichi; Hammi, Sanae; Bourkadi, Jamal Eddine 2014-01-01 L'hypersensibilité aux antituberculeux est l'un des effets secondaires imprévisibles qui apparait chez 4 à 5 % de la population exposée et s’élève à 25% chez les sujets VIH positifs. Dans notre étude parmi 39 patients ayant présenté des réactions immunoallergiques, 10 avaient des formes graves. Le délai moyen d'apparition des signes était de 23 jours. Les réactions immunoallergiques observées étaient 5 cas de toxidermie généralisée fébrile, un cas de Dress syndrome, un cas de neutropénie, un cas de pancitopénie et 2 cas de thrombopénie. Tous nos patients avaient bien évolué cliniquement et bactériologiquement après l'adoption d'un régime thérapeutique excluant le ou les médicaments incriminés. En pratique, si l'effet indésirable imputé à un antituberculeux est grave, il est impératif de l'arrêter, de traiter l'incident et d'associer une autre molécule chez certains cas. Notre étude a montré une fréquence significative des complications graves probablement sous-estimée, surtout dans les pays fortement touchés par l'infection HIV. 16. Ezrin and BCAR1/p130Cas mediate breast cancer growth as 3-D spheroids. PubMed Konstantinovsky, Sophya; Davidson, Ben; Reich, Reuven 2012-08-01 CAS proteins and Ezrin, Radixin, Moesin (ERM) family members act as intracellular scaffolds and are involved in interactions with the cytoskeleton, respectively. Both protein families have previously been associated with metastasis and poor prognosis in cancer. Our group recently reported on the overexpression of EZR/VIL2 and BCAR1 and their protein products in breast carcinoma effusions compared to primary breast carcinoma. In the present study, the role of these two proteins was studied in semi-normal MCF10A cells and metastatic MDA-MB-231 breast carcinoma cells cultured in tri-dimensional (3-D) conditions that were hypothesized to reproduce the in vivo conditions of breast cancer metastasis. MCF10A cells formed spheroid-shaped colonies without any Matrigel invasion, while MDA-MB-231 cells displayed an invasive phenotype and showed satellite projections that bridged multiple cell colonies in 3-D culture. E-cadherin was expressed in MCF10A, but not in MDA-MB-231 cells. The temporal expression of ezrin and BCAR1/p130Cas at the mRNA and protein level differed in the two cell lines upon 3-D culturing on Matrigel. Upregulation of BCAR1/p130cas was observed in the transition of MDA-MB-231 from attached to detached culture. Silencing of Ezrin and p130Cas in MDA-MB-231 cells by short hairpin RNA resulted in decreased invasive potential, and p130Cas silencing further resulted in smaller spheroid/colony formation. Our data show that MCF10A and MDA-MB-231 cells differ in their ability to form spheroids, in expression of E-cadherin and in the expression of Ezrin and BCAR1/p130Cas in 3-D cultures on Matrigel, suggesting a role in tumor progression in breast carcinoma. 17. Substrate generation for endonucleases of CRISPR/cas systems. PubMed Zoephel, Judith; Dwarakanath, Srivatsa; Richter, Hagen; Plagens, André; Randau, Lennart 2012-09-08 The interaction of viruses and their prokaryotic hosts shaped the evolution of bacterial and archaeal life. Prokaryotes developed several strategies to evade viral attacks that include restriction modification, abortive infection and CRISPR/Cas systems. These adaptive immune systems found in many Bacteria and most Archaea consist of clustered regularly interspaced short palindromic repeat (CRISPR) sequences and a number of CRISPR associated (Cas) genes (Fig. 1) (1-3). Different sets of Cas proteins and repeats define at least three major divergent types of CRISPR/Cas systems (4). The universal proteins Cas1 and Cas2 are proposed to be involved in the uptake of viral DNA that will generate a new spacer element between two repeats at the 5' terminus of an extending CRISPR cluster (5). The entire cluster is transcribed into a precursor-crRNA containing all spacer and repeat sequences and is subsequently processed by an enzyme of the diverse Cas6 family into smaller crRNAs (6-8). These crRNAs consist of the spacer sequence flanked by a 5' terminal (8 nucleotides) and a 3' terminal tag derived from the repeat sequence (9). A repeated infection of the virus can now be blocked as the new crRNA will be directed by a Cas protein complex (Cascade) to the viral DNA and identify it as such via base complementarity(10). Finally, for CRISPR/Cas type 1 systems, the nuclease Cas3 will destroy the detected invader DNA (11,12) . These processes define CRISPR/Cas as an adaptive immune system of prokaryotes and opened a fascinating research field for the study of the involved Cas proteins. The function of many Cas proteins is still elusive and the causes for the apparent diversity of the CRISPR/Cas systems remain to be illuminated. Potential activities of most Cas proteins were predicted via detailed computational analyses. A major fraction of Cas proteins are either shown or proposed to function as endonucleases (4). Here, we present methods to generate crRNAs and precursor-cRNAs for 18. Substrate Generation for Endonucleases of CRISPR/Cas Systems PubMed Central Zoephel, Judith; Dwarakanath, Srivatsa; Richter, Hagen; Plagens, André; Randau, Lennart 2012-01-01 The interaction of viruses and their prokaryotic hosts shaped the evolution of bacterial and archaeal life. Prokaryotes developed several strategies to evade viral attacks that include restriction modification, abortive infection and CRISPR/Cas systems. These adaptive immune systems found in many Bacteria and most Archaea consist of clustered regularly interspaced short palindromic repeat (CRISPR) sequences and a number of CRISPR associated (Cas) genes (Fig. 1) 1-3. Different sets of Cas proteins and repeats define at least three major divergent types of CRISPR/Cas systems 4. The universal proteins Cas1 and Cas2 are proposed to be involved in the uptake of viral DNA that will generate a new spacer element between two repeats at the 5' terminus of an extending CRISPR cluster 5. The entire cluster is transcribed into a precursor-crRNA containing all spacer and repeat sequences and is subsequently processed by an enzyme of the diverse Cas6 family into smaller crRNAs 6-8. These crRNAs consist of the spacer sequence flanked by a 5' terminal (8 nucleotides) and a 3' terminal tag derived from the repeat sequence 9. A repeated infection of the virus can now be blocked as the new crRNA will be directed by a Cas protein complex (Cascade) to the viral DNA and identify it as such via base complementarity10. Finally, for CRISPR/Cas type 1 systems, the nuclease Cas3 will destroy the detected invader DNA 11,12 . These processes define CRISPR/Cas as an adaptive immune system of prokaryotes and opened a fascinating research field for the study of the involved Cas proteins. The function of many Cas proteins is still elusive and the causes for the apparent diversity of the CRISPR/Cas systems remain to be illuminated. Potential activities of most Cas proteins were predicted via detailed computational analyses. A major fraction of Cas proteins are either shown or proposed to function as endonucleases 4. Here, we present methods to generate crRNAs and precursor-cRNAs for the study of 19. Modulation of hippocampal excitability by 5-HT4 receptor agonists persists in a transgenic model of Alzheimer's disease. PubMed Spencer, J P; Brown, J T; Richardson, J C; Medhurst, A D; Sehmi, S S; Calver, A R; Randall, A D 2004-01-01 5-HT(4) receptors are widely distributed in both peripheral and central nervous systems where they couple, via a G-protein, to the activation of adenylate cyclase. In the brain, the highest 5-HT(4) receptor densities are found in the limbic system, including the hippocampus and frontal cortex. It has been suggested that activation of these receptors may be of therapeutic benefit in diseases that produce cognitive deficits such as Alzheimer's disease (AD). Previous electrophysiological studies have shown that the 5-HT(4) agonist, Zacopride, can increase population spike amplitude recorded in region CA1 of rat hippocampal slices in a cyclic AMP (cAMP)/cAMP-dependent protein kinase A-dependent manner. We report here that the 5-HT(4) agonist, Prucalopride, and the 5-HT(4) partial agonist, SL65.0155, produce a similar effect in rat hippocampal slices and that the specific 5-HT(4) antagonist, GR113808, blocks these effects. To investigate the potential use of 5-HT(4) agonists in the treatment of AD, Prucalopride was applied to hippocampal slices from a transgenic mouse line that overexpresses the Abeta peptide. Despite the deficit in synaptic transmission present in these mice, the percentage increase of the CA1 population spike induced by Prucalopride was the same as that observed in wild-type mice. These data support 5-HT(4) receptors as a target for cognitive enhancement and suggest that a partial agonist would be sufficient to produce benefits, while reducing potential peripheral side effects. In addition, we show that 5-HT(4) receptors remain functional in the presence of excess Abeta peptide and may therefore be a useful target in AD. 20. Gi-protein-coupled 5-HT1B/D receptor agonist sumatriptan induces type I hyperalgesic priming. PubMed Araldi, Dioneia; Ferrari, Luiz F; Levine, Jon D 2016-08-01 We have recently described a novel form of hyperalgesic priming (type II) induced by agonists at two clinically important Gi-protein-coupled receptors (Gi-GPCRs), mu-opioid and A1-adenosine. Like mu-opioids, the antimigraine triptans, which act at 5-HT1B/D Gi-GPCRs, have been implicated in pain chronification. We determined whether sumatriptan, a prototypical 5-HT1B/D agonist, produces type II priming. Characteristic of hyperalgesic priming, intradermal injection of sumatriptan (10 ng) induced a change in nociceptor function such that a subsequent injection of prostaglandin-E2 (PGE2) induces prolonged mechanical hyperalgesia. However, onset to priming was delayed 3 days, characteristic of type I priming. Also characteristic of type I priming, a protein kinase Cε, but not a protein kinase A inhibitor attenuated the prolongation phase of PGE2 hyperalgesia. The prolongation of PGE2 hyperalgesia was also permanently reversed by intradermal injection of cordycepin, a protein translation inhibitor. Also, hyperalgesic priming did not occur in animals pretreated with pertussis toxin or isolectin B4-positive nociceptor toxin, IB4-saporin. Finally, as observed for other agonists that induce type I priming, sumatriptan did not induce priming in female rats. The prolongation of PGE2 hyperalgesia induced by sumatriptan was partially prevented by coinjection of antagonists for the 5-HT1B and 5-HT1D, but not 5-HT7, serotonin receptors and completely prevented by coadministration of a combination of the 5-HT1B and 5-HT1D antagonists. Moreover, the injection of selective agonists, for 5-HT1B and 5-HT1D receptors, also induced hyperalgesic priming. Our results suggest that sumatriptan, which signals through Gi-GPCRs, induces type I hyperalgesic priming, unlike agonists at other Gi-GPCRs, which induce type II priming. 1. Long-lasting alterations in 5-HT2A receptor after a binge regimen of methamphetamine in mice. PubMed Chiu, Hong-Yi; Chan, Ming-Huan; Lee, Mei-Yi; Chen, Shao-Tsu; Zhan, Zih-Yi; Chen, Hwei-Hsien 2014-10-01 The repeated administration of methamphetamine (MA) to animals in a single-day 'binge' dosing regimen produces damage to dopamine and serotonin terminals and psychosis-like behaviours similar to those observed in MA abusers. The present study aimed to examine the effects of MA binge exposure on 5-HT2A receptors, the subtype of serotonin receptors putatively involved in psychosis. ICR male mice were treated with MA (4 × 5 mg/kg) or saline at 2 h intervals. Recognition memory and social behaviours were sequentially evaluated by a novel location recognition test, a novel object recognition test, a social interaction and a nest-building test to confirm the persistent cognitive and behavioural impairments after this dosing regimen. Subsequently, a hallucinogenic 5-HT2A/2C receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI)-induced head-twitch, molecular and electrophysiological responses were monitored. Finally, the levels of 5-HT2C, 5-HT1A, 5-HT2A and mGlu2 receptors in the medial prefrontal cortex were determined. MA binge exposure produced recognition memory impairment, reduced social behaviours, and increased DOI-induced head-twitch response, c-Fos and Egr-2 expression and field potentials in the medial prefrontal cortex. Furthermore, MA binge exposure increased 5-HT2A and decreased mGlu2 receptor expression in the medial frontal cortex, whereas 5-HT2C and 5-HT1A receptors were unaffected. These data reveal that the increased behavioural, molecular and electrophysiological responses to DOI might be associated with an up-regulation of 5-HT2A receptors in the medial prefrontal cortex after MA binge exposure. Identifying the biochemical alterations that parallel the behavioural changes in a mouse model of MA binge exposure may facilitate targeting therapies for treatment of MA-related psychiatric disorders. 2. The effects of chronic ethanol self-administration on hippocampal 5-HT1A receptors in monkeys PubMed Central Burnett, Elizabeth J.; Grant, Kathleen A.; Davenport, April T.; Hemby, Scott E.; Friedman, David P. 2014-01-01 BACKGROUND Chronic alcohol consumption reduces brain serotonin and alters the synaptic mechanisms involved in memory formation. Hippocampal 5-HT1A receptors modulate these mechanisms, but the neuroadaptive response of 5HT1A receptors to chronic alcohol self-administration is not well understood. METHODS Hippocampal tissue from monkeys that voluntarily self-administered ethanol for 12 months (n=9) and accompanying controls (n=8) were prepared for in vitro receptor autoradiography and laser capture microdissection. The 5-HT1A receptor antagonist, [3H]MPPF, and the agonist, [3H]8-OH-DPAT, were used to measure total and G-protein coupled 5-HT1A receptors respectively. The expression of the genes encoding the 5-HT1A receptor and its trafficking protein Yif1B was measured in microdissected dentate gyrus (DG) granule cells and CA1 pyramidal neurons. RESULTS An increase in G-protein coupled, but not total, receptors was observed in the posterior pyramidal cell layer of CA1 in ethanol drinkers compared to controls. Chronic ethanol self-administration was also associated with an up-regulation of total and G-protein coupled 5-HT1A receptors in the posterior DG polymorphic layer. Changes in receptor binding were not associated with concomitant changes in 5-HT1A receptor mRNA expression. Chronic ethanol self-administration was associated with a significant increase in Yif1B gene expression in posterior CA1 pyramidal neurons. CONCLUSIONS Chronic, ethanol self-administration up-regulates hippocampal 5-HT1A receptor density in a region-specific manner that does not appear to be due to alterations at the level of transcription but instead may be due to increased receptor trafficking. Further exploration of the mechanisms mediating chronic ethanol-induced 5-HT1A receptor up-regulation and how hippocampal neurotransmission is altered is warranted. PMID:24467872 3. An X-ray flare from 47 Cas SciTech Connect Pandey, Jeewan C.; Karmakar, Subhajeet 2015-02-01 Using XMM-Newton observations, we investigate properties of a flare from the very active but poorly known stellar system 47 Cas. The luminosity at the peak of the flare is found to be 3.54 × 10{sup 30} erg s{sup −1}, which is ∼2 times higher than that at a quiescent state. The quiescent state corona of 47 Cas can be represented by two temperature plasma: 3.7 and 11.0 MK. The time-resolved X-ray spectroscopy of the flare show the variable nature of the temperature, the emission measure, and the abundance. The maximum temperature during the flare is derived as 72.8 MK. We infer the length of a flaring loop to be 3.3 × 10{sup 10} cm using a hydrodynamic loop model. Using the RGS spectra, the density during the flare is estimated as 4.0 × 10{sup 10} cm{sup −3}. The loop scaling laws are also applied when deriving physical parameters of the flaring plasma. 4. Stabilization of Foxp3 expression by CRISPR-dCas9-based epigenome editing in mouse primary T cells. PubMed Okada, Masahiro; Kanamori, Mitsuhiro; Someya, Kazue; Nakatsukasa, Hiroko; Yoshimura, Akihiko 2017-01-01 Epigenome editing is expected to manipulate transcription and cell fates and to elucidate the gene expression mechanisms in various cell types. For functional epigenome editing, assessing the chromatin context-dependent activity of artificial epigenetic modifier is required. In this study, we applied clustered regularly interspaced short palindromic repeats (CRISPR)-dCas9-based epigenome editing to mouse primary T cells, focusing on the Forkhead box P3 (Foxp3) gene locus, a master transcription factor of regulatory T cells (Tregs). The Foxp3 gene locus is regulated by combinatorial epigenetic modifications, which determine the Foxp3 expression. Foxp3 expression is unstable in transforming growth factor beta (TGF-β)-induced Tregs (iTregs), while stable in thymus-derived Tregs (tTregs). To stabilize Foxp3 expression in iTregs, we introduced dCas9-TET1CD (dCas9 fused to the catalytic domain (CD) of ten-eleven translocation dioxygenase 1 (TET1), methylcytosine dioxygenase) and dCas9-p300CD (dCas9 fused to the CD of p300, histone acetyltransferase) with guide RNAs (gRNAs) targeted to the Foxp3 gene locus. Although dCas9-TET1CD induced partial demethylation in enhancer region called conserved non-coding DNA sequences 2 (CNS2), robust Foxp3 stabilization was not observed. In contrast, dCas9-p300CD targeted to the promoter locus partly maintained Foxp3 transcription in cultured and primary T cells even under inflammatory conditions in vitro. Furthermore, dCas9-p300CD promoted expression of Treg signature genes and enhanced suppression activity in vitro. Our results showed that artificial epigenome editing modified the epigenetic status and gene expression of the targeted loci, and engineered cellular functions in conjunction with endogenous epigenetic modification, suggesting effective usage of these technologies, which help elucidate the relationship between chromatin states and gene expression. 5. Protein engineering of Cas9 for enhanced function. PubMed Oakes, Benjamin L; Nadler, Dana C; Savage, David F 2014-01-01 CRISPR/Cas systems act to protect the cell from invading nucleic acids in many bacteria and archaea. The bacterial immune protein Cas9 is a component of one of these CRISPR/Cas systems and has recently been adapted as a tool for genome editing. Cas9 is easily targeted to bind and cleave a DNA sequence via a complementary RNA; this straightforward programmability has gained Cas9 rapid acceptance in the field of genetic engineering. While this technology has developed quickly, a number of challenges regarding Cas9 specificity, efficiency, fusion protein function, and spatiotemporal control within the cell remain. In this work, we develop a platform for constructing novel proteins to address these open questions. We demonstrate methods to either screen or select active Cas9 mutants and use the screening technique to isolate functional Cas9 variants with a heterologous PDZ domain inserted within the protein. As a proof of concept, these methods lay the groundwork for the future construction of diverse Cas9 proteins. Straightforward and accessible techniques for genetic editing are helping to elucidate biology in new and exciting ways; a platform to engineer new functionalities into Cas9 will help forge the next generation of genome-modifying tools. 6. CRISPR–Cas9-assisted recombineering in Lactobacillus reuteri PubMed Central Oh, Jee-Hwan; van Pijkeren, Jan-Peter 2014-01-01 Clustered regularly interspaced palindromic repeats (CRISPRs) and the CRISPR-associated (Cas) nuclease protect bacteria and archeae from foreign DNA by site-specific cleavage of incoming DNA. Type-II CRISPR–Cas systems, such as the Streptococcus pyogenes CRISPR–Cas9 system, can be adapted such that Cas9 can be guided to a user-defined site in the chromosome to introduce double-stranded breaks. Here we have developed and optimized CRISPR–Cas9 function in the lactic acid bacterium Lactobacillus reuteri ATCC PTA 6475. We established proof-of-concept showing that CRISPR–Cas9 selection combined with single-stranded DNA (ssDNA) recombineering is a realistic approach to identify at high efficiencies edited cells in a lactic acid bacterium. We show for three independent targets that subtle changes in the bacterial genome can be recovered at efficiencies ranging from 90 to 100%. By combining CRISPR–Cas9 and recombineering, we successfully applied codon saturation mutagenesis in the L. reuteri chromosome. Also, CRISPR–Cas9 selection is critical to identify low-efficiency events such as oligonucleotide-mediated chromosome deletions. This also means that CRISPR–Cas9 selection will allow identification of recombinant cells in bacteria with low recombineering efficiencies, eliminating the need for ssDNA recombineering optimization procedures. We envision that CRISPR–Cas genome editing has the potential to change the landscape of genome editing in lactic acid bacteria, and other Gram-positive bacteria. PMID:25074379 7. Costs of CRISPR-Cas-mediated resistance in Streptococcus thermophilus PubMed Central Vale, Pedro F.; Lafforgue, Guillaume; Gatchitch, Francois; Gardan, Rozenn; Moineau, Sylvain; Gandon, Sylvain 2015-01-01 CRISPR-Cas is a form of adaptive sequence-specific immunity in microbes. This system offers unique opportunities for the study of coevolution between bacteria and their viral pathogens, bacteriophages. A full understanding of the coevolutionary dynamics of CRISPR-Cas requires knowing the magnitude of the cost of resisting infection. Here, using the gram-positive bacterium Streptococcus thermophilus and its associated virulent phage 2972, a well-established model system harbouring at least two type II functional CRISPR-Cas systems, we obtained different fitness measures based on growth assays in isolation or in pairwise competition. We measured the fitness cost associated with different components of this adaptive immune system: the cost of Cas protein expression, the constitutive cost of increasing immune memory through additional spacers, and the conditional costs of immunity during phage exposure. We found that Cas protein expression is particularly costly, as Cas-deficient mutants achieved higher competitive abilities than the wild-type strain with functional Cas proteins. Increasing immune memory by acquiring up to four phage-derived spacers was not associated with fitness costs. In addition, the activation of the CRISPR-Cas system during phage exposure induces significant but small fitness costs. Together these results suggest that the costs of the CRISPR-Cas system arise mainly due to the maintenance of the defence system. We discuss the implications of these results for the evolution of CRISPR-Cas-mediated immunity. PMID:26224708 8. Inhibition of CRISPR-Cas9 with Bacteriophage Proteins. PubMed Rauch, Benjamin J; Silvis, Melanie R; Hultquist, Judd F; Waters, Christopher S; McGregor, Michael J; Krogan, Nevan J; Bondy-Denomy, Joseph 2017-01-12 Bacterial CRISPR-Cas systems utilize sequence-specific RNA-guided nucleases to defend against bacteriophage infection. As a countermeasure, numerous phages are known that produce proteins to block the function of class 1 CRISPR-Cas systems. However, currently no proteins are known to inhibit the widely used class 2 CRISPR-Cas9 system. To find these inhibitors, we searched cas9-containing bacterial genomes for the co-existence of a CRISPR spacer and its target, a potential indicator for CRISPR inhibition. This analysis led to the discovery of four unique type II-A CRISPR-Cas9 inhibitor proteins encoded by Listeria monocytogenes prophages. More than half of L. monocytogenes strains with cas9 contain at least one prophage-encoded inhibitor, suggesting widespread CRISPR-Cas9 inactivation. Two of these inhibitors also blocked the widely used Streptococcus pyogenes Cas9 when assayed in Escherichia coli and human cells. These natural Cas9-specific "anti-CRISPRs" present tools that can be used to regulate the genome engineering activities of CRISPR-Cas9. 9. Non-Mendelian Dominant Maternal Effects Caused by CRISPR/Cas9 Transgenic Components in Drosophila melanogaster PubMed Central Lin, Chun-Chieh; Potter, Christopher J. 2016-01-01 The CRISPR/Cas9 system has revolutionized genomic editing. The Cas9 endonuclease targets DNA via an experimentally determined guide RNA (gRNA). This results in a double-strand break at the target site . We generated transgenic Drosophila melanogaster in which the CRISPR/Cas9 system was used to target a GAL4 transgene in vivo. To our surprise, progeny whose genomes did not contain CRISPR/Cas9 components were still capable of mutating GAL4 sequences. We demonstrate this effect was caused by maternal deposition of Cas9 and gRNAs into the embryo, leading to extensive GAL4 mutations in both somatic and germline tissues. This serves as a cautionary observation on the effects of maternal contributions when conducting experiments using genomically encoded CRISPR/Cas9 components. These results also highlight a mode of artificial inheritance in which maternal contributions of DNA editing components lead to transmissible mutant defects even in animals whose genomes lack the editing components. We suggest calling this a dominant maternal effect to reflect it is caused by the gain of maternally contributed products. Models of CRISPR-mediated gene drive will need to incorporate dominant maternal effects in order to accurately predict the efficiency and dynamics of gene drive in a population. PMID:27638686 10. Annotation and Classification of CRISPR-Cas Systems. PubMed Makarova, Kira S; Koonin, Eugene V 2015-01-01 The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated proteins) is a prokaryotic adaptive immune system that is represented in most archaea and many bacteria. Among the currently known prokaryotic defense systems, the CRISPR-Cas genomic loci show unprecedented complexity and diversity. Classification of CRISPR-Cas variants that would capture their evolutionary relationships to the maximum possible extent is essential for comparative genomic and functional characterization of this theoretically and practically important system of adaptive immunity. To this end, a multipronged approach has been developed that combines phylogenetic analysis of the conserved Cas proteins with comparison of gene repertoires and arrangements in CRISPR-Cas loci. This approach led to the current classification of CRISPR-Cas systems into three distinct types and ten subtypes for each of which signature genes have been identified. Comparative genomic analysis of the CRISPR-Cas systems in new archaeal and bacterial genomes performed over the 3 years elapsed since the development of this classification makes it clear that new types and subtypes of CRISPR-Cas need to be introduced. Moreover, this classification system captures only part of the complexity of CRISPR-Cas organization and evolution, due to the intrinsic modularity and evolutionary mobility of these immunity systems, resulting in numerous recombinant variants. Moreover, most of the cas genes evolve rapidly, complicating the family assignment for many Cas proteins and the use of family profiles for the recognition of CRISPR-Cas subtype signatures. Further progress in the comparative analysis of CRISPR-Cas systems requires integration of the most sensitive sequence comparison tools, protein structure comparison, and refined approaches for comparison of gene neighborhoods. 11. Precision Targeted Mutagenesis via Cas9 Paired Nickases in Rice PubMed Central Mikami, Masafumi; Toki, Seiichi; Endo, Masaki 2016-01-01 Recent reports of CRISPR- (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) mediated heritable mutagenesis in plants highlight the need for accuracy of the mutagenesis directed by this system. Off-target mutations are an important issue when considering functional gene analysis, as well as the molecular breeding of crop plants with large genome size, i.e. with many duplicated genes, and where the whole-genome sequence is still lacking. In mammals, off-target mutations can be suppressed by using Cas9 paired nickases together with paired guide RNAs (gRNAs). However, the performance of Cas9 paired nickases has not yet been fully assessed in plants. Here, we analyzed on- and off-target mutation frequency in rice calli and regenerated plants using Cas9 nuclease or Cas9 nickase with paired gRNAs. When Cas9 paired nickases were used, off-target mutations were fully suppressed in rice calli and regenerated plants. However, on-target mutation frequency also decreased compared with that induced by the Cas9 paired nucleases system. Since the gRNA sequence determines specific binding of Cas9 protein–gRNA ribonucleoproteins at the targeted sequence, the on-target mutation frequency of Cas9 paired nickases depends on the design of paired gRNAs. Our results suggest that a combination of gRNAs that can induce mutations at high efficiency with Cas9 nuclease should be used together with Cas9 nickase. Furthermore, we confirmed that a combination of gRNAs containing a one nucleotide (1 nt) mismatch toward the target sequence could not induce mutations when expressed with Cas9 nickase. Our results clearly show the effectiveness of Cas9 paired nickases in delivering on-target specific mutations. PMID:26936792 12. Interactions of isamoltane (CGP 361A), an anxiolytic phenoxypropanolamine derivative, with 5-HT1 receptor subtypes in the rat brain. PubMed Waldmeier, P C; Williams, M; Baumann, P A; Bischoff, S; Sills, M A; Neale, R F 1988-06-01 Isamoltane (CGP 361A; (1-(2-(1-pyrrolyl)-phenoxy)-3-isopropylamino-2-propanol hydrochloride), a beta-adrenoceptor ligand (IC50 = 8.4 nmol/l) which has reported activity as an anxiolytic in man was found to be a reasonably active inhibitor of the binding of [125I]ICYP to 5-HT1B recognition sites in rat brain membranes with 27-fold selectivity (IC50 = 39 nmol/l) as compared to the inhibition of binding of [3H]8-OH-DPAT to 5-HT1A receptors (IC50 = 1070 nmol/l). This selectivity was considerably greater than that observed for other beta-adrenoceptor ligands including propranolol (5-HT1A/5-HT1B ratio = 2), oxpenolol (3.5) and cyanopindolol (8.7). The 5-HT1B activity of the compound resided in the (-)-enantiomer. (-)-Isamoltane had weak activity (IC50 3-10 mumol/l) at 5-HT2 and alpha 1-adrenoceptors. The compound was devoid of activity at a number of other central neurotransmitter recognition sites including the 5-HT1C site. Isamoltane increased the electrically evoked release of [3H]5-HT from prelabeled rat cortical slices in a manner similar to that of cyanopindolol. While both compounds were similar in potency to methiothepin, they had lower efficacy. Oxprenolol was less potent that both isamoltane and cyanopindolol while propranolol was essentially inactive. The effects of the compounds on 5-HT release appeared to be correlated with their 5-HT1B rather than 5-HT1A activity. In vivo, isamoltane increased 5-HTP accumulation in rat cortex following central decarboxylase inhibition at doses of 1 and 3 mg/kg i.p. At higher doses this effect was gradually diminished. Similar, but less clearcut results were obtained with cyanopindolol and oxprenolol, but propranolol was ineffective. No changes in brain tryptophan levels were associated with the isamoltane-evoked changes in brain 5-HTP levels. In reserpinized animals, isamoltane reduced 5-HTP accumulation even at doses which enhanced accumulation of this metabolite when given alone. The effects of the putative 5-HT1B agonist 13. Effect of Selective 5-HT6R Agonist on Expression of 5-HT Receptor and Neurotransmitter in Vascular Dementia Rats PubMed Central Yu, Haining; Chen, Tao; Zhou, Li; Tang, Jiyou 2017-01-01 Background 5-HT6 receptor (5-HT6R) has pluripotent roles regulating secretion of neurotransmitters. However, whether 5-HT6R is involved in the development of vascular dementia (VD) remains unclear. To evaluate the role and mechanism of 5-HT6R in VD, this study established a rat VD model to evaluate the effect of selective 5-HT6R agonist on the expression of 5-HT6R mRNA and neurotransmitter. Material/Methods Eighty healthy male SD rats (7 weeks old) were randomly assigned to sham, model, 5-HT6R agonist, and placebo groups (N=20 each). A rat VD model was generated by permeant bilateral ligation of the common carotid artery. 5-HT6R agonist, placebo, or saline were given intraperitoneally for 4 weeks. The Morris water maze was utilized to test learning and memory function. Brains were extracted to separate the cortex and hippocampal tissues, in which glutamate and γ-aminobutyric acid (GABA) levels were analyzed. mRNA and protein levels of 5-HT6R were determined by RT-PCR and immunohistochemistry (IHC), respectively. Results Model rats had longer escape latency and fewer crossing platform times. Contents of DA, Glu, GABA, and Ach were lowered in cortical and hippocampal tissues, and 5-HT6R expression was suppressed (p<0.05). The application of 5-HT6R agonist shortened escape latency and increased the number of passing through the platform. It also improved hippocampal CA1 neuronal damage and elevated DA, Glu, GABA, and Ach contents and expression of 5-HT6R. Expression of 5-HT6R was not different from the placebo group. Conclusions Selective 5-HT6R agonist can alleviate learning deficit of VD rats, possibly via improving neurotransmitter levels in brain regions. PMID:28196966 14. Detection and use of HT and DT gamma rays to diagnose mix in ICF capsules NASA Astrophysics Data System (ADS) Schmitt, M. J.; Kim, Y. H.; Herrmann, H. W.; McEvoy, A. M.; Zylstra, A.; Leatherland, A.; Gales, S. 2015-11-01 Recent results from Omega capsule implosion experiments containing HT-rich gas mixtures indicate that the 19.8 MeV gamma ray from aneutronic HT fusion can be measured using existing time-resolved gas Cherenkov detectors (GCDs). Additional dedicated experiments to characterize HT- γ emission in ICF experiments already have been planned. The concurrent temporally-resolved measurement of both HT- γs and DT- γs opens the door for in-depth exploration of interface mix in gas-filled ICF capsules. We propose a method to temporally resolve and observe the evolution of shell material into the capsule core as a function of fuel/shell interface temperature (which can be varied by varying the capsule shell thickness). Our proposed method uses a CD-lined plastic capsule filled with 50/50 HT gas and diagnosed using GCDs to temporally resolve both the HT clean'' and DT `mix'' gamma ray burn histories. It will be shown that these burn history profiles are sensitive to the depth to which shell material mixes into the gas region. An experiment to observe these differences as a function of capsule shell thickness is proposed to determine if interface mixing is consistent with thermal diffusion (λion ~Tion2 /Zion2 ρ) at the gas/shell interface. Since hydrodynamic mixing from shell perturbations, such as the mounting stalk and glue, could complicate these types of capsule-averaged temporal measurements, simulations including their effects also will be shown. This research supported by the US DOE/NNSA, performed in part at LANL, operated by LANS LLC under contract DE-AC52-06NA25396. 15. Evidence for a role of a dopamine/5-HT6 receptor interaction in cocaine reinforcement. PubMed Valentini, V; Piras, G; De Luca, M A; Perra, V; Bordi, F; Borsini, F; Frau, R; Di Chiara, G 2013-02-01 16. The GR127935-sensitive 5-HT1 receptors mediating canine internal carotid vasoconstriction: resemblance to the 5-HT1B, but not to the 5-HT1D or 5-ht1F, receptor subtype PubMed Central Centurión, David; Sánchez-López, Araceli; De Vries, Peter; Saxena, Pramod R; Villalón, Carlos M 2001-01-01 This study has further investigated the pharmacological profile of the GR127935-sensitive 5-HT1 receptors mediating vasoconstriction in the internal carotid bed of anaesthetized vagosympathectomized dogs. One-minute intracarotid infusions of the agonists 5-hydroxytryptamine (5-HT; 0.1–10 μg min−1; endogenous ligand) and sumatriptan (0.3–10 μg min−1; 5-HT1B/1D), but not PNU-142633 (1–1000 μg min−1; 5-HT1D) or LY344864 (1–1000 μg min−1; 5-ht1F), produced dose-dependent decreases in internal carotid blood flow without changing blood pressure or heart rate. The responses to 5-HT were apparently resistant to blockade by i.v. administration of the antagonists SB224289 (300 μg kg−1; 5-HT1B), BRL15572 (300 μg kg−1; 5-HT1D) or ritanserin (100 μg kg−1; 5-HT2). In contrast, the responses to sumatriptan were antagonized by SB224289, but not by BRL15572. In the animals receiving SB224289, but not those receiving BRL15572, the subsequent administration of ritanserin abolished the 5-HT-induced vasoconstriction and unmasked a vasodilator component. Similarly, in ritanserin-treated animals, the subsequent administration of SB224289, but not BRL15572, completely blocked the 5-HT-induced vasoconstriction, revealing vasodilatation. In animals receiving initially BRL15572, the subsequent administration of SB224289 did not affect (except at 10 μg min−1) the vasoconstrictor responses to 5-HT. Notably, in animals pretreated with 1000 μg kg−1 of mesulergine, a 5-HT2/7 receptor antagonist, 5-HT produced a dose-dependent vasoconstriction, which was practically abolished by SB224289. After BRL15572, no further blockade was produced and the subsequent administration of ritanserin was similarly inactive. These results suggest that the GR127935-sensitive 5-HT1 receptors mediating canine internal carotid vasoconstriction resemble the 5-HT1B but not the 5-HT1D or 5-ht1F, receptor subtype. PMID:11226129 17. The pharmacology of the 5-HT4 receptor. PubMed Costall, B; Naylor, R J 1993-11-01 Dumuis and colleagues (1988) in their investigation of a 5-HT receptor positively linked to adenylate cyclase in the central nervous system, concluded that the receptor was not 5-HT1, 5-HT2 or 5-HT3-like and suggested that it belonged to a new class of 5-HT receptor called 5-HT4. A similar, if not identical receptor was located by Craig and Clark (1990) in the guinea pig ileum and a functional role for the peripheral 5-HT4 receptor has since been established in many species to mediate muscle contraction or relaxation within the gut and positive inotropic effects in the heart. In contrast, a functional role for central 5-HT4 receptors has remained obscure. Using measurements of rodent behaviour in the mouse light and dark test box and rat social interaction, anxiolytic agents such as diazepam and putative anxiolytic agents such as the 5-HT1A and 5-HT3 receptor ligands 8-OH-DPAT and low doses of tropisetron release behaviour suppressed by the aversive situation. 5-Hydroxytryptophan has the opposite effect exacerbating the behavioural response to the aversive situation. But an anxiolytic profile is revealed by co-treatment with ritanserin plus 5-hydroxytryptophan. The drug-induced anxiolytic profiles are inhibited by SDZ205-557 and a high dose of tropisetron. Both compounds are 5-HT3/5-HT4 receptor antagonists yet the selective 5-HT3 receptor antagonist ondansetron fails to inhibit the drug-induced anxiolytic profiles.(ABSTRACT TRUNCATED AT 250 WORDS) 18. Suppression of inflammatory events associated to intestinal ischemia-reperfusion by 5-HT1A blockade in mice. PubMed Bertoni, Simona; Arcaro, Valentina; Vivo, Valentina; Rapalli, Alberto; Tognolini, Massimiliano; Cantoni, Anna Maria; Saccani, Francesca; Flammini, Lisa; Domenichini, Giuseppe; Ballabeni, Vigilio; Barocelli, Elisabetta 2014-03-01 Intestinal ischemia and reperfusion (I/R) is a potentially life-threatening disease, ensuing from various clinical conditions. Experimentally, either protective or detrimental roles have been attributed to 5-HT in the functional and morphological injury caused by mesenteric I/R. Recently, we proved the involvement of 5-HT2A receptors in the intestinal dysmotility and leukocyte recruitment induced by 45min occlusion of the superior mesenteric artery (SMA) followed by 24h reperfusion in mice. Starting from these premises, the aim of our present work was to investigate the role played by endogenous 5-HT in the same experimental model where 45min SMA clamping was followed by 5h reflow. To this end, we first observed that ischemic preconditioning before I/R injury (IPC+I/R) reverted the increase in 5-HT tissue content and in inflammatory parameters induced by I/R in mice. Second, the effects produced by intravenous administration of 5-HT1A ligands (partial agonist buspirone 10mgkg(-1), antagonist WAY100135 0.5-5mgkg(-1)), 5-HT2A antagonist sarpogrelate (10mgkg(-1)), 5-HT3 antagonist alosetron (0.1mgkg(-1)), 5-HT4 antagonist GR125487 (5mgkg(-1)) and 5-HT re-uptake inhibitor fluoxetine (10mgkg(-1)) on I/R-induced inflammatory response were investigated in I/R mice and compared to those obtained in sham-operated animals (S). Our results confirmed the significant role played by 5-HT2A receptors not only in the late but also in the early I/R-induced microcirculatory dysfunction and showed that blockade of 5-HT1A receptors protected against the intestinal leukocyte recruitment, plasma extravasation and reactive oxygen species formation triggered by SMA occlusion and reflow. The ability of α7 nicotinic receptor (α7nAchR) antagonist methyllycaconitine (5mgkg(-1)) to counteract the beneficial action provided by buspirone on I/R-induced neutrophil infiltration suggests that the anti-inflammatory effect produced by 5-HT1A receptor antagonism could be partly ascribed to the 19. Regulation of p130Cas/BCAR1 Expression in Tamoxifen-Sensitive and Tamoxifen-Resistant Breast Cancer Cells by EGR1 and NAB21 PubMed Central Kumbrink, Joerg; Kirsch, Kathrin H 2012-01-01 Elevated levels of p130Cas/BCAR1 (Crk-associated substrate/breast cancer antiestrogen resistance 1) are found in aggressive breast tumors and are associated with tamoxifen resistance of mammary cancers. p130Cas promotes the integration of protein complexes involved in multiple signaling pathways frequently deregulated in breast cancer. To elucidate mechanisms leading to p130Cas up-regulation in mammary carcinomas and during acquired tamoxifen resistance, the regulation of p130Cas/BCAR1 was studied. Because multiple putative binding motifs for the inducible transcription factor EGR1 were identified in the 5′ region of BCAR1, the p130Cas/BCAR1 regulation by EGR1 and its coregulator NAB2 was investigated. Overexpression or short interfering RNA (siRNA)-mediated down-regulation of EGR1 or NAB2, and chromatin immunoprecipitations indicated that EGR1 and NAB2 act in concert to positively regulate p130Cas/BCAR1 expression in breast cancer cells. p130Cas depletion using siRNA showed that, in tamoxifen-sensitive MCF-7 cells, p130Cas regulates EGR1 and NAB2 expression, whereas in the derivative tamoxifen-resistant TAM-R cells, only NAB2 levels were influenced. BCAR1 messenger RNA and p130Cas protein were upregulated by phorbol esters following the kinetics of late response genes in MCF-7 but not in TAM-R cells. Thus, in MCF-7 cells, we identified a positive feedback loop where p130Cas positively regulates EGR1 and NAB2, which in turn induce p130Cas expression. Importantly, compared with MCF-7, enhanced NAB2 expression and increased EGR1 binding to the BCAR1 5′ region observed in TAM-R may lead to the constitutively increased p130Cas/BCAR1 levels in TAM-R cells. The uncovered differences in this EGR1/NAB2/p130Cas network in MCF-7 versus TAM-R cells may also contribute to p130Cas up-regulation during acquired tamoxifen resistance. PMID:22431919 20. Pharmacological profile of the 5-HT-induced inhibition of cardioaccelerator sympathetic outflow in pithed rats: correlation with 5-HT1 and putative 5-ht5A/5B receptors PubMed Central Sánchez-López, Araceli; Centurión, David; Vázquez, Erika; Arulmani, Udayasankar; Saxena, Pramod R; Villalón, Carlos M 2003-01-01 Continuous infusions of 5-hydroxytryptamine (5-HT) inhibit the tachycardiac responses to preganglionic (C7-T1) sympathetic stimulation in pithed rats pretreated with desipramine. The present study identified the pharmacological profile of this inhibitory action of 5-HT. The inhibition induced by intravenous (i.v.) continuous infusions of 5-HT (5.6 μg kg−1 min−1) on sympathetically induced tachycardiac responses remained unaltered after i.v. treatment with saline or the antagonists GR 127935 (5-HT1B/1D), the combination of WAY 100635 (5-HT1A) plus GR 127935, ritanserin (5-HT2), tropisetron (5-HT3/4), LY215840 (5-HT7) or a cocktail of antagonists/inhibitors consisting of yohimbine (α2), prazosin (α1), ritanserin, GR 127935, WAY 100635 and indomethacin (cyclooxygenase), but was abolished by methiothepin (5-HT1/2/6/7 and recombinant 5-ht5A/5B). These drugs, used in doses high enough to block their respective receptors/mechanisms, did not modify the sympathetically induced tachycardiac responses per se. I.v. continuous infusions of the agonists 5-carboxamidotryptamine (5-CT; 5-HT1/7 and recombinant 5-ht5A/5B), CP 93,129 (r5-HT1B), sumatriptan (5-HT1B/1D), PNU-142633 (5-HT1D) and ergotamine (5-HT1B/1D and recombinant 5-ht5A/5B) mimicked the above sympatho-inhibition to 5-HT. In contrast, the agonists indorenate (5-HT1A) and LY344864 (5-ht1F) were inactive. Interestingly, 5-CT-induced cardiac sympatho-inhibition was abolished by methiothepin, the cocktail of antagonists/inhibitors, GR 127935 or the combination of SB224289 (5-HT1B) plus BRL15572 (5-HT1D), but remained unchanged when SB224289 or BRL15572 were given separately. Therefore, 5-HT-induced cardiac sympatho-inhibition, being unrelated to 5-HT2, 5-HT3, 5-HT4, 5-ht6, 5-HT7 receptors, α1/2-adrenoceptor or prostaglandin synthesis, seems to be primarily mediated by (i) 5-HT1 (probably 5-HT1B/1D) receptors and (ii) a novel mechanism antagonized by methiothepin that, most likely, involves putative 5-ht5A/5B 1. CRISPR/Cas9-mediated gene editing in human zygotes using Cas9 protein. PubMed Tang, Lichun; Zeng, Yanting; Du, Hongzi; Gong, Mengmeng; Peng, Jin; Zhang, Buxi; Lei, Ming; Zhao, Fang; Wang, Weihua; Li, Xiaowei; Liu, Jianqiao 2017-03-01 Previous works using human tripronuclear zygotes suggested that the clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 system could be a tool in correcting disease-causing mutations. However, whether this system was applicable in normal human (dual pronuclear, 2PN) zygotes was unclear. Here we demonstrate that CRISPR/Cas9 is also effective as a gene-editing tool in human 2PN zygotes. By injection of Cas9 protein complexed with the appropriate sgRNAs and homology donors into one-cell human embryos, we demonstrated efficient homologous recombination-mediated correction of point mutations in HBB and G6PD. However, our results also reveal limitations of this correction procedure and highlight the need for further research. 2. Harnessing CRISPR-Cas9 immunity for genetic engineering. PubMed Charpentier, Emmanuelle; Marraffini, Luciano A 2014-06-01 CRISPR-Cas encodes an adaptive immune system that defends prokaryotes against infectious viruses and plasmids. Immunity is mediated by Cas nucleases, which use small RNA guides (the crRNAs) to specify a cleavage site within the genome of invading nucleic acids. In type II CRISPR-Cas systems, the DNA-cleaving activity is performed by a single enzyme Cas9 guided by an RNA duplex. Using synthetic single RNA guides, Cas9 can be reprogrammed to create specific double-stranded DNA breaks in the genomes of a variety of organisms, ranging from human cells to bacteria, and thus constitutes a powerful tool for genetic engineering. Here we describe recent advancements in our understanding of type II CRISPR-Cas immunity and how these studies led to revolutionary genome editing applications. 3. Guide RNA functional modules direct Cas9 activity and orthogonality. PubMed Briner, Alexandra E; Donohoue, Paul D; Gomaa, Ahmed A; Selle, Kurt; Slorach, Euan M; Nye, Christopher H; Haurwitz, Rachel E; Beisel, Chase L; May, Andrew P; Barrangou, Rodolphe 2014-10-23 The RNA-guided Cas9 endonuclease specifically targets and cleaves DNA in a sequence-dependent manner and has been widely used for programmable genome editing. Cas9 activity is dependent on interactions with guide RNAs, and evolutionarily divergent Cas9 nucleases have been shown to work orthogonally. However, the molecular basis of selective Cas9:guide-RNA interactions is poorly understood. Here, we identify and characterize six conserved modules within native crRNA:tracrRNA duplexes and single guide RNAs (sgRNAs) that direct Cas9 endonuclease activity. We show the bulge and nexus are necessary for DNA cleavage and demonstrate that the nexus and hairpins are instrumental in defining orthogonality between systems. In contrast, the crRNA:tracrRNA complementary region can be modified or partially removed. Collectively, our results establish guide RNA features that drive DNA targeting by Cas9 and open new design and engineering avenues for CRISPR technologies. 4. Advances in therapeutic CRISPR/Cas9 genome editing. PubMed Savić, Nataša; Schwank, Gerald 2016-02-01 Targeted nucleases are widely used as tools for genome editing. Two years ago the clustered regularly interspaced short palindromic repeat (CRISPR)-associated Cas9 nuclease was used for the first time, and since then has largely revolutionized the field. The tremendous success of the CRISPR/Cas9 genome editing tool is powered by the ease design principle of the guide RNA that targets Cas9 to the desired DNA locus, and by the high specificity and efficiency of CRISPR/Cas9-generated DNA breaks. Several studies recently used CRISPR/Cas9 to successfully modulate disease-causing alleles in vivo in animal models and ex vivo in somatic and induced pluripotent stem cells, raising hope for therapeutic genome editing in the clinics. In this review, we will summarize and discuss such preclinical CRISPR/Cas9 gene therapy reports. Copyright © 2016 Elsevier Inc. All rights reserved. 5. Peripheral 5-HT1A and 5-HT7 Serotonergic Receptors Modulate Parasympathetic Neurotransmission in Long-Term Diabetic Rats PubMed Central Restrepo, Beatriz; Martín, María Luisa; San Román, Luis; Morán, Asunción 2010-01-01 We analyzed the modulation of serotonin on the bradycardia induced in vivo by vagal electrical stimulation in alloxan-induced long-term diabetic rats. Bolus intravenous administration of serotonin had a dual effect on the bradycardia induced either by vagal stimulation or exogenous Ach, increasing it at low doses and decreasing it at high doses of 5-hydroxytryptamine (5-HT), effect reproduced by 5-carboxamidotryptamine maleate (5-CT), a 5-HT1/7 agonist. The enhancement of the bradycardia at low doses of 5-CT was reproduced by 5-HT1A agonist 8-hydroxy-2-dipropylaminotetralin hydrobromide (8-OH-DPAT) and abolished by WAY-100,635, 5-HT1A antagonist. Pretreatment with 5-HT1 antagonist methiothepin blocked the stimulatory and inhibitory effect of 5-CT, whereas pimozide, 5-HT7 antagonist, only abolished 5-CT inhibitory action. In conclusion, long-term diabetes elicits changes in the subtype of the 5-HT receptor involved in modulation of vagally induced bradycardia. Activation of the 5-HT1A receptors induces enhancement, whereas attenuation is due to 5-HT7 receptor activation. This 5-HT dual effect occurs at pre- and postjunctional levels. PMID:21403818 6. Possible roles of 5-HT in vein graft failure due to intimal hyperplasia 5-HT, nitric oxide and vein graft. PubMed Kodama, Akio; Itoh, Takeo; Komori, Kimihiro 2014-02-01 For vascular occlusive disease, an autologous vein graft is the most suitable conduit for arterial reconstruction. Intimal hyperplasia, resulting from the migration and proliferation of vascular smooth muscle cells, is a major obstacle to patency after vein grafting. The degree to which the function of nitric oxide (NO) in the vein graft is preserved has been reported to be associated with the magnitude of intimal hyperplasia. Serotonin (5-HT) is released from platelets in the vascular system and plays physiological roles in controlling the vascular tone. The subtype receptors contributing to the 5-HT-induced mechanical responses vary by vessel type (artery and vein) and among species (dogs, rabbits, rats, and so on). Recent studies have demonstrated that 5-HT induces vasoconstriction through the activation of 5-HT2A receptors in smooth muscle cells or vasodilatation through the activation of endothelial 5-HT1B receptors in arteries from various animals. However, the effects of 5-HT have not been clarified in grafted veins. We herein demonstrate the responses to 5-HT in un-operated veins and then autogenous vein grafts. Next, we describe the effects of chronic in vivo administration of Rho-kinase inhibitors and 5-HT2A receptor antagonists, both of which reduce the 5-HT-induced contraction and intimal hyperplasia in vein grafts. Further studies targeting 5-HT are required to evaluate its possible benefits for autologous vein grafts with respect to vasospasm, function, and patency. 7. The involvement of 5-HT3 and 5-HT4 receptors in two models of gastrointestinal transit in mice. PubMed Pascual, D; Alsasua, A; Goicoechea, C; Martín, M I 2002-07-05 Our aim was to study the involvement of 5-hydroxytryptamine (5-HT)(3) and 5-HT(4) receptors in two models of gastrointestinal transit (GIT) in mice: the 5-hydroxytryptophan (5-HTP)-induced diarrhea and intestinal inflammation produced by an irritant agent, croton oil (CO). 5-HTP (10 mg/kg) produced diarrhea that was significantly inhibited after pretreatment with ondansetron (5-HT(3) antagonist) or RS 39604 (5-HT(4) antagonist) (1-5 mg/kg). The GIT speed was increased after CO and 5-HTP administration. 5-HT(3-4) antagonists decreased GIT after 5-HTP-treatment but not after CO-treatment. Our results show that 5-HT(3) and 5-HT(4) receptors are involved in 5-HTP-induced diarrhea. This may be the reason why 5-HT(3-4) antagonists could be useful in the treatment of carcinoid syndrome diarrhea. 5-HT(3-4) antagonists were not effective in the modifications of GIT; nevertheless, they could be useful in the treatment of inflammatory bowel diseases because some symptoms as abdominal pain, discomfort or abnormal bowel function are modulated via 5-HT(3). 8. High trait aggression in men is associated with low 5-HT levels, as indexed by 5-HT4 receptor binding. PubMed da Cunha-Bang, Sofi; Mc Mahon, Brenda; Fisher, Patrick MacDonald; Jensen, Peter Steen; Svarer, Claus; Knudsen, Gitte Moos 2016-04-01 Impulsive aggression has commonly been associated with a dysfunction of the serotonin (5-HT) system: many, but not all, studies point to an inverse relationship between 5-HT and aggression. As cerebral 5-HT4 receptor (5-HT4R) binding has recently been recognized as a proxy for stable brain levels of 5-HT, we here test the hypothesis in healthy men and women that brain 5-HT levels, as indexed by cerebral 5-HT4R, are inversely correlated with trait aggression and impulsivity. Sixty-one individuals (47 men) underwent positron emission tomography scanning with the radioligand [(11)C]SB207145 for quantification of brain 5-HT4R binding. The Buss-Perry Aggression Questionnaire (BPAQ) and the Barratt Impulsiveness Scale were used for assessment of trait aggression and trait impulsivity. Among male subjects, there was a positive correlation between global 5-HT4R and BPAQ total score (P = 0.037) as well as BPAQ physical aggression (P = 0.025). No main effect of global 5-HT4R on trait aggression or impulsivity was found in the mixed gender sample, but there was evidence for sex interaction effects in the relationship between global 5-HT4R and BPAQ physical aggression. In conclusion we found that low cerebral 5-HT levels, as indexed by 5-HT4R binding were associated with high trait aggression in males, but not in females. © The Author (2016). Published by Oxford University Press. For Permissions, please email: [email protected]. 9. Serotonin 5-HT2 and 5-HT1A-like receptors differentially modulate aggressive behaviors in Drosophila melanogaster PubMed Central Johnson, Oralee; Becnel, Jaime; Nichols, Charles D. 2009-01-01 Aggressive behavior is widespread throughout the animal kingdom, and is a complex social behavior influenced by both genetics and environment. Animals typically fight over resources that include food, territory, and sexual partners. Of all the neurotransmitters, serotonin has been the most implicated in modulating aggressive behaviors in mammalian systems. In the fruit fly, Drosophila melanogaster, the involvement of serotonin itself in aggressive behaviors has been recently established, however, the underlying mechanisms have largely remained elusive. Here we describe the influence of different serotonin receptor subtypes on aggressive behaviors in Drosophila. Drosophila express homologs of three mammalian serotonin receptors: the 5-HT1A, 5-HT2, and 5-HT7 receptors. Significantly, these receptors mediate important behaviors in mammalian systems ranging from feeding, aggression, and sleep, to cognition. To examine the role of the 5-HT2Dro receptor, we utilized the selective 5-HT2 receptor agonist (R)-1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI), and the 5-HT2 receptor antagonist, ketanserin. To examine the role of 5-HT1A-like receptors we used the 5-HT1A receptor agonist 8-hydroxy-2-dipropylaminotetralin hydrobromide (8-OH-DPAT), and the 5-HT1A receptor antagonist WAY100635. We find that activation of 5-HT2 receptors with (R)-DOI appears to decrease overall aggression, whereas activation of 5-HT1A-like receptors with 8-OH-DPAT increases overall aggression. Furthermore, the different serotonin receptor circuitries appear to mediate different aspects of aggression: 5-HT2 receptor manipulation primarily alters lunging and boxing, whereas 5-HT1A-like receptor manipulation primarily affects wing threats and fencing. Elucidating the effects of serotonergic systems on aggression in the fly is a significant advancement not only in establishing the fly as a system to study aggression, but as a system relevant to elucidating molecular mechanisms underlying aggression 10. The rapid recovery of 5-HT cell firing induced by the antidepressant vortioxetine involves 5-HT(3) receptor antagonism. PubMed Bétry, Cécile; Pehrson, Alan L; Etiévant, Adeline; Ebert, Bjarke; Sánchez, Connie; Haddjeri, Nasser 2013-06-01 The therapeutic effect of current antidepressant drugs appears after several weeks of treatment and a significant number of patients do not respond to treatment. Here, we report the effects of the multi-modal antidepressant vortioxetine (Lu AA21004), a 5-HT(3) and 5-HT(7) receptor antagonist, 5-HT(1B) receptor partial agonist, 5-HT(1A) receptor agonist and 5-HT transporter (SERT) inhibitor, on rat 5-HT neurotransmission. Using in vivo electrophysiological recordings in the dorsal raphe nucleus of anaesthetized rats, we assessed the acute and subchronic effects of vortioxetine and/or the selective 5-HT(3) receptor agonist, SR57227 or the selective 5-HT(1A) receptor agonist flesinoxan, on 5-HT neuronal firing activity. Using ex-vivo autoradiography, we correlated SERT occupancy and presumed 5-HT firing activity. The selective serotonin reuptake inhibitor, fluoxetine, was used as comparator. Importantly, the recovery of 5-HT neuronal firing was achieved after 1 d with vortioxetine and 14 d with fluoxetine. SR57227 delayed this recovery. In contrast, vortioxetine failed to alter the reducing action of 3 d treatment of flesinoxan. Acute dosing of vortioxetine inhibited neuronal firing activity more potently than fluoxetine. SR57227 prevented the suppressant effect of vortioxetine, but not of fluoxetine. In contrast, flesinoxan failed to modify the suppressant effect of vortioxetine acutely administered. Differently to fluoxetine, vortioxetine suppressed neuronal firing without saturating occupancy at the SERT. Vortioxetine produced a markedly faster recovery of 5-HT neuronal firing than fluoxetine. This is at least partly due to 5-HT(3) receptor antagonism of vortioxetine in association with its reduced SERT occupancy. 11. Effects of the 5-HT receptor antagonists GR127935 (5-HT1B/1D) and MDL100907 (5-HT2A) in the consolidation of learning. PubMed Meneses, A; Terrón, J A; Hong, E 1997-12-01 We have previously reported that 5-HT1B/1D and 5-HT2A/2B/2C receptors play a role in learning and memory. The present investigation was devoted to analyze further in the autoshaping learning task: (1) the effects of the 5-HT1A/1B/1D receptor agonist, GR46611, the 5-HT1B/1D receptor antagonist, GR127935, and the selective 5-HT2A receptor antagonist, MDL100907. Consistent with a role of 5-HT1B/1D receptors in learning, the post-training injection of GR46611 (1-10 mg/kg) decreased the consolidation of learning whereas GR127935 (10 mg/kg) increased it; the effects of both drugs were reversed by PCA pretreatment. GR127935 abolished the decrease induced by GR46611, TFMPP and mCPP, whereas MDL100907 (0.1-3.0 mg/kg) had no effect by itself but abolished the effects of DOI, ketanserin and TFMPP and moderately inhibited the effects elicited by mCPP, 1-NP and mesulergine. Neither did GR127935 nor MDL100907 significantly modify the increase in the consolidation of learning induced by 8-OH-DPAT. Thus, the present findings suggest that stimulation of presynaptic 5-HT1B/1D receptors impairs the consolidation of learning whilst stimulation of 5-HT2A/2C receptors enhances it; the blockade of 5-HT2A receptors has no effects. In addition, 5-HT2 receptors seem to modulate this cognitive stage. 12. Effects of serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibition plus 5-HT(2A) receptor antagonism on the firing activity of norepinephrine neurons. PubMed Szabo, Steven T; Blier, Pierre 2002-09-01 13. 5-HT(1A)-like receptor activation inhibits abstinence-induced methamphetamine withdrawal in planarians. PubMed Rawls, Scott M; Shah, Hardik; Ayoub, George; Raffa, Robert B 2010-10-29 No pharmacological therapy is approved to treat methamphetamine physical dependence, but it has been hypothesized that serotonin (5-HT)-enhancing drugs might limit the severity of withdrawal symptoms. To test this hypothesis, we used a planarian model of physical dependence that quantifies withdrawal as a reduction in planarian movement. Planarians exposed to methamphetamine (10 μM) for 60 min, and then placed (tested) into drug-free water for 5 min, displayed less movement (i.e., withdrawal) than either methamphetamine-naïve planarians tested in water or methamphetamine-exposed planarians tested in methamphetamine. A concentration-related inhibition of withdrawal was observed when methamphetamine-exposed planarians were placed into a solution containing either methamphetamine and 5-HT (0.1-100 μM) or methamphetamine and the 5-HT(1A) receptor agonist 8-hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT) (10, 20 μM). Planarians with prior methamphetamine exposure displayed enhanced withdrawal when tested in a solution of the 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide (WAY 100635) (1 μM). Methamphetamine-induced withdrawal was not affected by the 5-HT(2B/2C) receptor agonist meta-chlorophenylpiperazine (m-CPZ) (0.1-20 μM). These results provide pharmacological evidence that serotonin-enhancing drugs inhibit expression of methamphetamine physical dependence in an invertebrate model of withdrawal, possibly through a 5-HT(1A)-like receptor-dependent mechanism. 14. Differential expression of 5-HT-related genes in symptomatic pulmonary embolism patients PubMed Central Jin, Yun; Wang, Lemin; Duan, Qianglin; Gong, Zhu; Yang, Fan; Song, Yanli 2015-01-01 Objective: Whole human genome oligo microarrays were employed to systematically investigate the mRNA expression profile of 5-HT synthetase, transporter, receptor, and factors in 5-HT signaling pathway in peripheral blood karyocytes from pulmonary embolism (PE) patients. Methods: A total of 20 PE patients and 20 healthy subjects matched in gender and age were recruited. The human genome microarrays were performed to detect the mRNA expression profile of 5-HT synthetase, transporter, receptor, and factors in 5-HT signal pathway of two groups. The random variance model corrected t-test was used for analysis. Results: Our results showed (1) tryptophan hydroxylase (TPH1)-related gene expression was markedly down-regulated in PE patients (P < 0.01); (2) monoamine oxidases (MAO)-related gene (MAOB) expression was significantly up-regulated in PE patients (P < 0.01); (3) the expression of 17 genes of 7 5-HT receptors showed a down-regulated tendency in PE patients, and significant difference was observed in the expression of HTR1E, HTR3B, HTR4 and HTR5A between them (P < 0.05); (4) the expression of DalDAG-GEF I, Tubby, PKA and EPAC in 5-HT signal pathways was dramatically up-regulated in PE patients (P < 0.05); the expression of SPA1, RIAM, RAPL, Talin, PKC, PLC and Pyk2 was remarkably up-regulated in PE patients (P < 0.05); (5) the expression of integrin genes ITGA2B, ITGB1 and ITGB3 was significantly up-regulated in PE patients (P < 0.05). Conclusion: In PE patients, the expression of TPH1 and HTR4 was down-regulated as a negative feedback; the MAOB expression was up-regulated. Consistent with the expression of 5-HTR1E and 5-HTR4 and the abnormally activated Tubby, the expression of integrins in platelets was activated. PMID:25785024 15. 5-HT1A-like receptor activation inhibits abstinence-induced methamphetamine withdrawal in planarians PubMed Central Rawls, Scott M.; Shah, Hardik; Ayoub, George; Raffa, Robert B. 2010-01-01 No pharmacological therapy is approved to treat methamphetamine physical dependence, but it has been hypothesized that serotonin (5-HT)-enhancing drugs might limit the severity of withdrawal symptoms. To test this hypothesis, we used a planarian model of physical dependence that quantifies withdrawal as a reduction in planarian movement. Planarians exposed to methamphetamine (10 µM) for 60 min, and then placed (tested) into drug-free water for 5 min, displayed less movement (i.e., withdrawal) than either methamphetamine-naïve planarians tested in water or methamphetamine-exposed planarians tested in methamphetamine. A concentration-related inhibition of withdrawal was observed when methamphetamine-exposed planarians were placed into a solution containing either methamphetamine and 5-HT (0.1 – 100 µM) or methamphetamine and the 5-HT1A receptor agonist 8-Hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT) (10, 20 µM). Planarians with prior methamphetamine exposure displayed enhanced withdrawal when tested in a solution of the 5-HT1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]- N-(2-pyridyl)cyclohexanecarboxamide (WAY 100635) (1 µM). Methamphetamine-induced withdrawal was not affected by the 5-HT2B/2C receptor agonist meta-chlorophenylpiperazine (m-CPZ) (0.1 – 20 µM). These results provide pharmacological evidence that serotonin-enhancing drugs inhibit expression of methamphetamine physical dependence in an invertebrate model of withdrawal, possibly through a 5-HT1A-like receptor-dependent mechanism. PMID:20709144 16. 5-HT7 receptor activation promotes an increase in TrkB receptor expression and phosphorylation PubMed Central Samarajeewa, Anshula; Goldemann, Lolita; Vasefi, Maryam S.; Ahmed, Nawaz; Gondora, Nyasha; Khanderia, Chandni; Mielke, John G.; Beazely, Michael A. 2014-01-01 The serotonin (5-HT) type 7 receptor is expressed throughout the CNS including the cortex and hippocampus. We have previously demonstrated that the application of 5-HT7 receptor agonists to primary hippocampal neurons and SH-SY5Y cells increases platelet-derived growth factor (PDGF) receptor expression and promotes neuroprotection against N-methyl-D-aspartate-(NMDA)-induced toxicity. The tropomyosin-related kinase B (TrkB) receptor is one of the receptors for brain-derived neurotrophic factor (BDNF) and is associated with neurodevelopmental and neuroprotective effects. Application of LP 12 to primary cerebral cortical cultures, SH-SY5Y cells, as well as the retinal ganglion cell line, RGC-5, increased both the expression of full length TrkB as well as its basal phosphorylation state at tyrosine 816. The increase in TrkB expression and phosphorylation was observed as early as 30 min after 5-HT7 receptor activation. In addition to full-length TrkB, kinase domain-deficient forms may be expressed and act as dominant-negative proteins toward the full length receptor. We have identified distinct patterns of TrkB isoform expression across our cell lines and cortical cultures. Although TrkB receptor expression is regulated by cyclic AMP and Gαs-coupled GPCRs in several systems, we demonstrate that, depending on the model system, pathways downstream of both Gαs and Gα12 are involved in the regulation of TrkB expression by 5-HT7 receptors. Given the number of psychiatric and degenerative diseases associated with TrkB/BDNF deficiency and the current interest in developing 5-HT7 receptor ligands as pharmaceuticals, identifying signaling relationships between these two receptors will aid in our understanding of the potential therapeutic effects of 5-HT7 receptor ligands. PMID:25426041 17. 5-HT7 receptor activation promotes an increase in TrkB receptor expression and phosphorylation. PubMed Samarajeewa, Anshula; Goldemann, Lolita; Vasefi, Maryam S; Ahmed, Nawaz; Gondora, Nyasha; Khanderia, Chandni; Mielke, John G; Beazely, Michael A 2014-01-01 The serotonin (5-HT) type 7 receptor is expressed throughout the CNS including the cortex and hippocampus. We have previously demonstrated that the application of 5-HT7 receptor agonists to primary hippocampal neurons and SH-SY5Y cells increases platelet-derived growth factor (PDGF) receptor expression and promotes neuroprotection against N-methyl-D-aspartate-(NMDA)-induced toxicity. The tropomyosin-related kinase B (TrkB) receptor is one of the receptors for brain-derived neurotrophic factor (BDNF) and is associated with neurodevelopmental and neuroprotective effects. Application of LP 12 to primary cerebral cortical cultures, SH-SY5Y cells, as well as the retinal ganglion cell line, RGC-5, increased both the expression of full length TrkB as well as its basal phosphorylation state at tyrosine 816. The increase in TrkB expression and phosphorylation was observed as early as 30 min after 5-HT7 receptor activation. In addition to full-length TrkB, kinase domain-deficient forms may be expressed and act as dominant-negative proteins toward the full length receptor. We have identified distinct patterns of TrkB isoform expression across our cell lines and cortical cultures. Although TrkB receptor expression is regulated by cyclic AMP and Gαs-coupled GPCRs in several systems, we demonstrate that, depending on the model system, pathways downstream of both Gαs and Gα12 are involved in the regulation of TrkB expression by 5-HT7 receptors. Given the number of psychiatric and degenerative diseases associated with TrkB/BDNF deficiency and the current interest in developing 5-HT7 receptor ligands as pharmaceuticals, identifying signaling relationships between these two receptors will aid in our understanding of the potential therapeutic effects of 5-HT7 receptor ligands. 18. Cas9 as a versatile tool for engineering biology PubMed Central Mali, Prashant; Esvelt, Kevin M; Church, George M 2014-01-01 RNA-guided Cas9 nucleases derived from clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems have dramatically transformed our ability to edit the genomes of diverse organisms. We believe tools and techniques based on Cas9, a single unifying factor capable of colocalizing RNA, DNA and protein, will grant unprecedented control over cellular organization, regulation and behavior. Here we describe the Cas9 targeting methodology, detail current and prospective engineering advances and suggest potential applications ranging from basic science to the clinic. PMID:24076990 19. CRISPR-Cas9-guided Genome Engineering in C. elegans PubMed Central Kim, Hyun-Min; Colaiácovo, Monica P. 2016-01-01 The CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) system is successfully being used for efficient and targeted genome editing in various organisms including the nematode C. elegans. Recent studies developed various CRISPR-Cas9 approaches to enhance genome engineering via two major DNA double-strand break repair pathways: non-homologous end joining and homologous recombination. Here we describe a protocol for Cas9-mediated C. elegans genome editing together with single guide RNA (sgRNA) and repair template cloning and injection methods required for delivering Cas9, sgRNAs and repair template DNA into the C. elegans germline. PMID:27366893 20. Calibrated Ancillary System (CAS) user's guide, volume 1 NASA Technical Reports Server (NTRS) 1986-01-01 The Calibrated Ancillary System (CAS) provides real-time calibrated parameters from the orbiter downlink (ancillary data) to the Goddard Space Flight Center (GSFC). This user's guide contains the introduction to the equipment, operation, general procedures, and specific procedures of the CAS. Volume 1 includes a general overview of the CAS relationships with other equipment, physical design, and hardware and software subsystems. In addition, a description of the user levels and tasks, an introduction to CAS operation, and an outline of general operating procedures are included. 1. Control of gene expression by CRISPR-Cas systems. PubMed Bikard, David; Marraffini, Luciano A 2013-01-01 Clustered regularly interspaced short palindromic repeats (CRISPR) loci and their associated cas (CRISPR-associated) genes provide adaptive immunity against viruses (phages) and other mobile genetic elements in bacteria and archaea. While most of the early work has largely been dominated by examples of CRISPR-Cas systems directing the cleavage of phage or plasmid DNA, recent studies have revealed a more complex landscape where CRISPR-Cas loci might be involved in gene regulation. In this review, we summarize the role of these loci in the regulation of gene expression as well as the recent development of synthetic gene regulation using engineered CRISPR-Cas systems. 2. Ectopia cordis thoracique sporadique: description clinique d'un cas PubMed Central Lubala, Toni Kasole; Mutombo, Augustin Mulangu; Katamea, Tina; Lubala, Nina; Munkana, Arthur Ndundula; Kabuya, Maguy Sangaji; Monga, Joséphine Kalenga; Luboya, Oscar Numbi 2012-01-01 Nous décrivons un cas d'ectopia cordis, une malformation cardiaque congénitale extrêmement rare dans laquelle le coeur est partiellement ou complètement situé en dehors des limites de la cage thoracique. Dans le cas que nous décrivons, elle est thoracique et isolée. Ce cas a été diagnostiqué en salle de naissance au Katanga, au sud de la République Démocratique du Congo. Il s'agit du premier cas documenté chez un nouveau-né Congolais. PMID:23346276 3. Application of CRISPR-Cas9 in eye disease. PubMed Wu, Wenyi; Tang, Luosheng; D'Amore, Patricia A; Lei, Hetian 2017-08-01 The system of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated nuclease (Cas)9 is an effective instrument for revising the genome with great accuracy. This system has been widely employed to generate mutants in genomes from plants to human cells. Rapid improvements in Cas9 specificity in eukaryotic cells have opened great potential for the use of this technology as a therapeutic. Herein, we summarize the recent advancements of CRISPR-Cas9 use in research on human cells and animal models, and outline a basic and clinical pipeline for CRISPR-Cas9-based treatments of genetic eye diseases. Copyright © 2017 Elsevier Ltd. All rights reserved. 4. Control of gene expression by CRISPR-Cas systems PubMed Central 2013-01-01 Clustered regularly interspaced short palindromic repeats (CRISPR) loci and their associated cas (CRISPR-associated) genes provide adaptive immunity against viruses (phages) and other mobile genetic elements in bacteria and archaea. While most of the early work has largely been dominated by examples of CRISPR-Cas systems directing the cleavage of phage or plasmid DNA, recent studies have revealed a more complex landscape where CRISPR-Cas loci might be involved in gene regulation. In this review, we summarize the role of these loci in the regulation of gene expression as well as the recent development of synthetic gene regulation using engineered CRISPR-Cas systems. PMID:24273648 5. Recombinant HT{sub m4} gene, protein and assays DOEpatents Lim, B.; Adra, C.N.; Lelias, J.M. 1996-09-03 The invention relates to a recombinant DNA molecule which encodes a HT{sub m4} protein, a transformed host cell which has been stably transfected with a DNA molecule which encodes a HT{sub m4} protein and a recombinant HT{sub m4} protein. The invention also relates to a method for detecting the presence of a hereditary atopy. 2 figs. 6. Antibodies specific for HT{sub m4} DOEpatents Lim, B.; Adra, C.N.; Lelias, J.M. 1998-01-06 The invention relates to a recombinant DNA molecule which encodes a HT{sub m4} protein, a transformed host cell which has been stably transfected with a DNA molecule which encodes a HT{sub m4} protein and a recombinant HT{sub m4} protein. The invention also relates to a method for detecting the presence of a hereditary atopy. 2 figs. 7. Repeated lysergic acid diethylamide in an animal model of depression: Normalisation of learning behaviour and hippocampal serotonin 5-HT2 signalling. PubMed Buchborn, Tobias; Schröder, Helmut; Höllt, Volker; Grecksch, Gisela 2014-06-01 A re-balance of postsynaptic serotonin (5-HT) receptor signalling, with an increase in 5-HT1A and a decrease in 5-HT2A signalling, is a final common pathway multiple antidepressants share. Given that the 5-HT1A/2A agonist lysergic acid diethylamide (LSD), when repeatedly applied, selectively downregulates 5-HT2A, but not 5-HT1A receptors, one might expect LSD to similarly re-balance the postsynaptic 5-HT signalling. Challenging this idea, we use an animal model of depression specifically responding to repeated antidepressant treatment (olfactory bulbectomy), and test the antidepressant-like properties of repeated LSD treatment (0.13 mg/kg/d, 11 d). In line with former findings, we observe that bulbectomised rats show marked deficits in active avoidance learning. These deficits, similarly as we earlier noted with imipramine, are largely reversed by repeated LSD administration. Additionally, bulbectomised rats exhibit distinct anomalies of monoamine receptor signalling in hippocampus and/or frontal cortex; from these, only the hippocampal decrease in 5-HT2 related [(35)S]-GTP-gamma-S binding is normalised by LSD. Importantly, the sham-operated rats do not profit from LSD, and exhibit reduced hippocampal 5-HT2 signalling. As behavioural deficits after bulbectomy respond to agents classified as antidepressants only, we conclude that the effect of LSD in this model can be considered antidepressant-like, and discuss it in terms of a re-balance of hippocampal 5-HT2/5-HT1A signalling. © The Author(s) 2014. 8. Selective 5-HT7 Receptor Activation May Enhance Synaptic Plasticity Through N-methyl-D-aspartate (NMDA) Receptor Activity in the Visual Cortex. PubMed Xiang, Kangjian; Zhao, Xuefei; Li, Youjun; Zheng, Liang; Wang, Jue; Li, Yan-Hai 2016-01-01 Serotonin (5-hydroxytryptamine, 5-HT) is an important neurotransmitter that modulates N-methyl-D-aspartate (NMDA) receptor activity by binding to several different 5-HT receptor subtypes. In the present study, we used whole-cell patch-clamp recordings in transverse slice preparations to test the role of 5-HT receptors in modulating the NMDA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) in layer II/III pyramidal neurons of the rat visual cortex. We found that the NMDA receptor-mediated component of mEPSCs could be potentiated by exogenously applied 5-HT. Similar results were obtained by exogenously applied 5-CT or 8-OH-DPAT (the 5-HT1A and 5-HT7 receptor agonist). A specific antagonist for the 5-HT7 receptor, SB-269970, completely blocked the increase in NMDA receptor-mediated component of mEPSCs by 5-CT or 8- OH-DPAT. Moreover, the selective 5-HT1A receptor antagonist, WAY-100135, displayed no influence on the enhancement in NMDA receptor-mediated component of mEPSCs by 5-CT or 8-OHDPAT. These results indicated that the increase in NMDA receptor-mediated component of mEPSCs by 5-HT in layer II/III pyramidal neurons of the young rat visual cortex requires activation of 5-HT7 receptors, but not 5-HT1A receptors. These observations might be clinically relevant to schizophrenia and Alzheimer's disease (AD), where enhancing NMDA receptor-mediated neurotransmission is considered to be a promising strategy for treatment of these diseases. 9. Effects of the serotonin 5-HT2A and 5-HT2C receptor ligands on the discriminative stimulus effects of nicotine in rats. PubMed Zaniewska, Magdalena; McCreary, Andrew C; Przegaliński, Edmund; Filip, Malgorzata 2007-10-01 The present study tested the hypothesis that serotonergic (5-HT) 5-HT2A or 5-HT2C receptors or their pharmacological stimulation modulated the discriminative stimulus effects of nicotine in male Wistar rats. To this end the selective 5-HT2A receptor antagonist R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol (M100,907; 0.5-1 mg/kg, i.p.), the functional 5-HT2A receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI; 0.1-1 mg/kg, s.c.), the selective 5-HT2C receptor antagonist 6-chloro-5-methyl-1-{[2-(2-methylpyrid-3-yloxy)pyrid-5-yl]carbamoyl}indoline (SB 242,084; 0.25-1 mg/kg, i.p.) and the 5-HT2C receptor agonists (S)-2-chloro-5-fluoro-indol-1-yl)-1-methylethylamine fumarate (Ro 60-0175; 0.3-1 mg/kg, s.c.) and (7bR, 10aR)-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta-[b][1,4]diazepino[6,7,1hi]indole (WAY 163,909; 0.75-1.5 mg/kg, i.p.) were used. Additionally, the effects of the selective alpha4beta2 nicotinic acetylcholine receptor subtype agonist 5-iodo-3-(2(S)-azetidinylmethoxy)pyridine (5-IA; 0.01 mg/kg, s.c.) were investigated. In rats trained to discriminate (-)-nicotine (0.4 mg/kg, s.c.) from saline in a two-lever, water-reinforced fixed ratio 10 task, substitutions were not observed with 5-HT2 receptor ligands (<32% nicotine-lever responding), conversely 5-IA induced a full substitution (100% nicotine-lever responding). In combination studies, fixed doses of M100,907 (0.5-1 mg/kg) or SB 242,084 (0.25-1 mg/kg) did not alter the dose-response curve of nicotine, while DOI (0.3 mg/kg), Ro 60-0175 (1 mg/kg) and WAY 163,909 (1 and 1.5 mg/kg) attenuated the discriminative stimulus effects of nicotine. The decrease in the expression of the discriminative stimulus effects of nicotine produced by DOI was blocked by M100,907 (1 mg/kg), but not by SB 242,084 (1 mg/kg), while that evoked by Ro 60-0175 or WAY 163,909 was blocked by SB 242,084 (1 mg/kg), but not by M100,907 (1 mg/kg). Further studies showed that 10. The serotonin 5-HT3 receptor: a novel neurodevelopmental target. PubMed Engel, Mareen; Smidt, Marten P; van Hooft, Johannes A 2013-01-01 Serotonin (5-hydroxytryptamine, 5-HT), next to being an important neurotransmitter, recently gained attention as a key-regulator of pre- and postnatal development in the mammalian central nervous system (CNS). Several receptors for 5-HT are expressed in the developing brain including a ligand-gated ion channel, the 5-HT3 receptor. Over the past years, evidence has been accumulating that 5-HT3 receptors are involved in the regulation of neurodevelopment by serotonin. Here, we review the spatial and temporal expression patterns of 5-HT3 receptors in the pre- and early postnatal rodent brain and its functional implications. First, 5-HT3 receptors are expressed on GABAergic interneurons in neocortex and limbic structures derived from the caudal ganglionic eminence. Mature inhibitory GABAergic interneurons fine-tune neuronal excitability and thus are crucial for the physiological function of the brain. Second, 5-HT3 receptors are expressed on specific glutamatergic neurons, Cajal-Retzius cells in the cortex and granule cells in the cerebellum, where they regulate morphology, positioning, and connectivity of the local microcircuitry. Taken together, the 5-HT3 receptor emerges as a potential key-regulator of network formation and function in the CNS, which could have a major impact on our understanding of neurodevelopmental disorders in which 5-HT plays a role. 11. A dual function of the CRISPR-Cas system in bacterial antivirus immunity and DNA repair. PubMed Babu, Mohan; Beloglazova, Natalia; Flick, Robert; Graham, Chris; Skarina, Tatiana; Nocek, Boguslaw; Gagarinova, Alla; Pogoutse, Oxana; Brown, Greg; Binkowski, Andrew; Phanse, Sadhna; Joachimiak, Andrzej; Koonin, Eugene V; Savchenko, Alexei; Emili, Andrew; Greenblatt, Jack; Edwards, Aled M; Yakunin, Alexander F 2011-01-01 Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) and the associated proteins (Cas) comprise a system of adaptive immunity against viruses and plasmids in prokaryotes. Cas1 is a CRISPR-associated protein that is common to all CRISPR-containing prokaryotes but its function remains obscure. Here we show that the purified Cas1 protein of Escherichia coli (YgbT) exhibits nuclease activity against single-stranded and branched DNAs including Holliday junctions, replication forks and 5'-flaps. The crystal structure of YgbT and site-directed mutagenesis have revealed the potential active site. Genome-wide screens show that YgbT physically and genetically interacts with key components of DNA repair systems, including recB, recC and ruvB. Consistent with these findings, the ygbT deletion strain showed increased sensitivity to DNA damage and impaired chromosomal segregation. Similar phenotypes were observed in strains with deletion of CRISPR clusters, suggesting that the function of YgbT in repair involves interaction with the CRISPRs. These results show that YgbT belongs to a novel, structurally distinct family of nucleases acting on branched DNAs and suggest that, in addition to antiviral immunity, at least some components of the CRISPR-Cas system have a function in DNA repair. 12. CRISPR/Cas9-mediated efficient targeted mutagenesis in Chardonnay (Vitis vinifera L.) PubMed Central Ren, Chong; Liu, Xianju; Zhang, Zhan; Wang, Yi; Duan, Wei; Li, Shaohua; Liang, Zhenchang 2016-01-01 The type II clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 system (CRISPR/Cas9) has been successfully applied to edit target genes in multiple plant species. However, it remains unknown whether this system can be used for genome editing in grape. In this study, we described genome editing and targeted gene mutation in ‘Chardonnay’ suspension cells and plants via the CRISPR/Cas9 system. Two single guide RNAs (sgRNAs) were designed to target distinct sites of the L-idonate dehydrogenase gene (IdnDH). CEL I endonuclease assay and sequencing results revealed the expected indel mutations at the target site, and a mutation frequency of 100% was observed in the transgenic cell mass (CM) as well as corresponding regenerated plants with expression of sgRNA1/Cas9. The majority of the detected mutations in transgenic CM were 1-bp insertions, followed by 1- to 3-nucleotide deletions. Off-target activities were also evaluated by sequencing the potential off-target sites, and no obvious off-target events were detected. Our results demonstrated that the CRISPR/Cas9 system is an efficient and specific tool for precise genome editing in grape. PMID:27576893 13. Landscape of target:guide homology effects on Cas9-mediated cleavage. PubMed Fu, Becky Xu Hua; Hansen, Loren L; Artiles, Karen L; Nonet, Michael L; Fire, Andrew Z 2014-12-16 To study target sequence specificity, selectivity, and reaction kinetics of Streptococcus pyogenes Cas9 activity, we challenged libraries of random variant targets with purified Cas9::guide RNA complexes in vitro. Cleavage kinetics were nonlinear, with a burst of initial activity followed by slower sustained cleavage. Consistent with other recent analyses of Cas9 sequence specificity, we observe considerable (albeit incomplete) impairment of cleavage for targets mutated in the PAM sequence or in 'seed' sequences matching the proximal 8 bp of the guide. A second target region requiring close homology was located at the other end of the guide::target duplex (positions 13-18 relative to the PAM). Sequences flanking the guide+PAM region had measurable (albeit modest) effects on cleavage. In addition, the first-base Guanine constraint commonly imposed by gRNA expression systems has little effect on overall cleavage efficiency. Taken together, these studies provide an in vitro understanding of the complexities of Cas9-gRNA interaction and cleavage beyond the general paradigm of site determination based on the 'seed' sequence and PAM. 14. A dual function of the CRISPR-Cas system in bacterial antivirus immunity and DNA repair PubMed Central Babu, Mohan; Beloglazova, Natalia; Flick, Robert; Graham, Chris; Skarina, Tatiana; Nocek, Boguslaw; Gagarinova, Alla; Pogoutse, Oxana; Brown, Greg; Binkowski, Andrew; Phanse, Sadhna; Joachimiak, Andrzej; Koonin, Eugene V.; Savchenko, Alexei; Emili, Andrew; Greenblatt, Jack; Edwards, Aled M.; Yakunin, Alexander F. 2011-01-01 Summary Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) and the associated proteins (Cas) comprise a system of adaptive immunity against viruses and plasmids in prokaryotes. Cas1 is a CRISPR-associated protein that is common to all CRISPR-containing prokaryotes but its function remains obscure. Here we show that the purified Cas1 protein of Escherichia coli (YgbT) exhibits nuclease activity against single-stranded and branched DNAs including Holliday junctions, replication forks, and 5′-flaps. The crystal structure of YgbT and site-directed mutagenesis have revealed the potential active site. Genome-wide screens show that YgbT physically and genetically interacts with key components of DNA repair systems, including recB, recC and ruvB. Consistent with these findings, the ygbT deletion strain showed increased sensitivity to DNA damage and impaired chromosomal segregation. Similar phenotypes were observed in strains with deletion of CRISPR clusters, suggesting that the function of YgbT in repair involves interaction with the CRISPRs. These results show that YgbT belongs to a novel, structurally distinct family of nucleases acting on branched DNAs and suggest that, in addition to antiviral immunity, at least some components of the CRISPR-Cas system have a function in DNA repair. PMID:21219465 15. CRISPR-Cas9 Mediated Telomere Removal Leads to Mitochondrial Stress and Protein Aggregation. PubMed Kim, Hyojung; Ham, Sangwoo; Jo, Minkyung; Lee, Gum Hwa; Lee, Yun-Song; Shin, Joo-Ho; Lee, Yunjong 2017-10-03 Aging is considered the major risk factor for neurodegenerative diseases including Parkinson's disease (PD). Telomere shortening is associated with cellular senescence. In this regard, pharmacological or genetic inhibition of telomerase activity has been used to model cellular aging. Here, we employed CRISPR-Cas9 technology to instantly remove the telomere to induce aging in a neuroblastoma cell line. Expression of both Cas9 and guide RNA targeting telomere repeats ablated the telomere, leading to retardation of cell proliferation. Instant deletion of telomere in SH-SY5Y cells impaired mitochondrial function with diminished mitochondrial respiration and cell viability. Supporting the pathological relevance of cell aging by CRISPR-Cas9 mediated telomere removal, alterations were observed in the levels of PD-associated proteins including PTEN-induced putative kinase 1, peroxisome proliferator-activated receptor γ coactivator 1-α, nuclear respiratory factor 1, parkin, and aminoacyl tRNA synthetase complex interacting multifunctional protein 2. Significantly, α-synuclein expression in the background of telomere removal led to the enhancement of protein aggregation, suggesting positive feed-forward interaction between aging and PD pathogenesis. Collectively, our results demonstrate that CRISPR-Cas9 can be used to efficiently model cellular aging and PD. 16. Efficient biallelic mutation in porcine parthenotes using a CRISPR-Cas9 system. PubMed Tao, Li; Yang, Mingyao; Wang, Xiaodong; Zhang, Zhenni; Wu, Zhonghong; Tian, Jianhui; An, Lei; Wang, Shumin 2016-08-05 The parthenotes represent ideal models mimicking the embryonic development and characterizing the function of maternal genomes as well as an alternative source of pluripotent cell lines. Besides, parthenogenetically activated (PA) embryos serve as a rapid assay system to maximize the efficiency of generating genetically modified pig CRISPR/Cas9 system, an efficient and multiplex gene editing tool, has been utilized to modify the genome of porcine parthenotes. However, lower biallelic mutation rate and high mosaicism frequency were observed. Here, we aimed to enhance the biallelic mutation rate with reduced mosaicism by optimization of the concentration and injection time of the Cas9/sgRNA mixture in porcine parthenotes. The results showed that the efficient biallelic mutation (93%) and low mosaicism (33%) could be achieved in porcine parthenotes by cytoplasmic injection of Cas9 mRNA/sgRNA (125/12.5 ng/μl) after 8 h of parthenogenetical activation. Thus, our study provides an effective strategy for increasing the biallelic mutation rate and population homogeneity of genetically modified parthenotes, which will strengthen the role of parthenotes in uncovering early embryonic development and assessing the mutation efficiency due to the simplicity and adaptability of CRISPR/Cas9. Copyright © 2016 Elsevier Inc. All rights reserved. 17. Efficient and Heritable Gene Targeting in Tilapia by CRISPR/Cas9 PubMed Central Li, Minghui; Yang, Huihui; Zhao, Jiue; Fang, Lingling; Shi, Hongjuan; Li, Mengru; Sun, Yunlv; Zhang, Xianbo; Jiang, Dongneng; Zhou, Linyan; Wang, Deshou 2014-01-01 Studies of gene function in non-model animals have been limited by the approaches available for eliminating gene function. The CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR associated) system has recently become a powerful tool for targeted genome editing. Here, we report the use of the CRISPR/Cas9 system to disrupt selected genes, including nanos2, nanos3, dmrt1, and foxl2, with efficiencies as high as 95%. In addition, mutations in dmrt1 and foxl2 induced by CRISPR/Cas9 were efficiently transmitted through the germline to F1. Obvious phenotypes were observed in the G0 generation after mutation of germ cell or somatic cell-specific genes. For example, loss of Nanos2 and Nanos3 in XY and XX fish resulted in germ cell-deficient gonads as demonstrated by GFP labeling and Vasa staining, respectively, while masculinization of somatic cells in both XY and XX gonads was demonstrated by Dmrt1 and Cyp11b2 immunohistochemistry and by up-regulation of serum androgen levels. Our data demonstrate that targeted, heritable gene editing can be achieved in tilapia, providing a convenient and effective approach for generating loss-of-function mutants. Furthermore, our study shows the utility of the CRISPR/Cas9 system for genetic engineering in non-model species like tilapia and potentially in many other teleost species. PMID:24709635 18. Harnessing the CRISPR/Cas9 system to disrupt latent HIV-1 provirus. PubMed Ebina, Hirotaka; Misawa, Naoko; Kanemura, Yuka; Koyanagi, Yoshio 2013-01-01 Even though highly active anti-retroviral therapy is able to keep HIV-1 replication under control, the virus can lie in a dormant state within the host genome, known as a latent reservoir, and poses a threat to re-emerge at any time. However, novel technologies aimed at disrupting HIV-1 provirus may be capable of eradicating viral genomes from infected individuals. In this study, we showed the potential of the CRISPR/Cas9 system to edit the HIV-1 genome and block its expression. When LTR-targeting CRISPR/Cas9 components were transfected into HIV-1 LTR expression-dormant and -inducible T cells, a significant loss of LTR-driven expression was observed after stimulation. Sequence analysis confirmed that this CRISPR/Cas9 system efficiently cleaved and mutated LTR target sites. More importantly, this system was also able to remove internal viral genes from the host cell chromosome. Our results suggest that the CRISPR/Cas9 system may be a useful tool for curing HIV-1 infection. 19. Deletion of a target gene in Indica rice via CRISPR/Cas9. PubMed Wang, Ying; Geng, Lizhao; Yuan, Menglong; Wei, Juan; Jin, Chen; Li, Min; Yu, Kun; Zhang, Ya; Jin, Huaibing; Wang, Eric; Chai, Zhijian; Fu, Xiangdong; Li, Xianggan 2017-08-01 Using CRISPR/Cas9, we successfully deleted large fragments of the yield-related gene DENSE AND ERECT PANICLE1 in Indica rice at relatively high frequency and generated gain-of-function dep1 mutants. CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 is a rapidly developing technology used to produce gene-specific modifications in both mammalian and plant systems. Most CRISPR-induced modifications in plants reported to date have been small insertions or deletions. Few large target gene deletions have thus far been reported, especially for Indica rice. In this study, we designed multiple CRISPR sgRNAs and successfully deleted DNA fragments in the gene DENSE AND ERECT PANICLE1 (DEP1) in the elite Indica rice line IR58025B. We achieved deletion frequencies of up to 21% for a 430 bp target and 9% for a 10 kb target among T0 events. Constructs with four sgRNAs did not generate higher full-length deletion frequencies than constructs with two sgRNAs. The multiple mutagenesis frequency reached 93% for four targets, and the homozygous mutation frequency reached 21% at the T0 stage. Important yield-related trait characteristics, such as dense and erect panicles and reduced plant height, were observed in dep1 homozygous T0 mutant plants produced by CRISPR/Cas9. Therefore, we successfully obtained deletions in DEP1 in the Indica background using the CRISPR/Cas9 editing tool at relatively high frequency. 20. Simple and Efficient Targeting of Multiple Genes Through CRISPR-Cas9 in Physcomitrella patens PubMed Central Lopez-Obando, Mauricio; Hoffmann, Beate; Géry, Carine; Guyon-Debast, Anouchka; Téoulé, Evelyne; Rameau, Catherine; Bonhomme, Sandrine; Nogué, Fabien 2016-01-01 Powerful genome editing technologies are needed for efficient gene function analysis. The CRISPR-Cas9 system has been adapted as an efficient gene-knock-out technology in a variety of species. However, in a number of situations, knocking out or modifying a single gene is not sufficient; this is particularly true for genes belonging to a common family, or for genes showing redundant functions. Like many plants, the model organism Physcomitrella patens has experienced multiple events of polyploidization during evolution that has resulted in a number of families of duplicated genes. Here, we report a robust CRISPR-Cas9 system, based on the codelivery of a CAS9 expressing cassette, multiple sgRNA vectors, and a cassette for transient transformation selection, for gene knock-out in multiple gene families. We demonstrate that CRISPR-Cas9-mediated targeting of five different genes allows the selection of a quintuple mutant, and all possible subcombinations of mutants, in one experiment, with no mutations detected in potential off-target sequences. Furthermore, we confirmed the observation that the presence of repeats in the vicinity of the cutting region favors deletion due to the alternative end joining pathway, for which induced frameshift mutations can be potentially predicted. Because the number of multiple gene families in Physcomitrella is substantial, this tool opens new perspectives to study the role of expanded gene families in the colonization of land by plants. PMID:27613750 1. Serotonin 1A receptor (5-HT1A) of the sea lamprey: cDNA cloning and expression in the central nervous system. PubMed Cornide-Petronio, María Eugenia; Anadón, Ramón; Barreiro-Iglesias, Antón; Rodicio, María Celina 2013-09-01 Serotonergic cells are among the earliest neurons to be born in the developing central nervous system and serotonin is known to regulate the development of the nervous system. One of the major targets of the activity of serotonergic cells is the serotonin 1A receptor (5-HT1A), an ancestral archetypical serotonin receptor. In this study, we cloned and characterized the 3D structure of the sea lamprey 5-HT1A, and studied the expression of its transcript in the central nervous system by means of in situ hybridization. In phylogenetic analyses, the sea lamprey 5-HT1A sequence clustered together with 5-HT1A sequences of vertebrates and emerged as an outgroup to all gnathostome sequences. In situ hybridization analysis during prolarval, larval and adult stages showed a widespread expression of the lamprey 5-ht1a transcript. In P1 prolarvae 5-ht1a mRNA expression was observed in diencephalic nuclei, the rhombencephalon and rostral spinal cord. At P2 prolarval stage the 5-ht1a expression extended to other brain areas including telencephalic regions. 5-ht1a expression in larvae was observed throughout almost all the main brain regions with the strongest expression in the olfactory bulbs, lateral pallium, striatum, preoptic region, habenula, prethalamus, thalamus, pretectum, hypothalamus, rhombencephalic reticular area, dorsal column nucleus and rostral spinal cord. In adults, the 5-ht1a transcript was also observed in cells of the subcommissural organ. Comparison of the expression of 5-ht1a between the sea lamprey and other vertebrates reveals a conserved pattern in most of the brain regions, likely reflecting the ancestral vertebrate condition. 2. The serotonergic hallucinogen 5-methoxy-N,N-dimethyltryptamine disrupts cortical activity in a regionally-selective manner via 5-HT(1A) and 5-HT(2A) receptors. PubMed Riga, Maurizio S; Bortolozzi, Analia; Campa, Letizia; Artigas, Francesc; Celada, Pau 2016-02-01 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a natural hallucinogen, acting as a non-selective serotonin 5-HT(1A)/5-HT(2A)-R agonist. Psychotomimetic agents such as the non-competitive NMDA-R antagonist phencyclidine and serotonergic hallucinogens (DOI and 5-MeO-DMT) disrupt cortical synchrony in the low frequency range (<4 Hz) in rat prefrontal cortex (PFC), an effect reversed by antipsychotic drugs. Here we extend these observations by examining the effect of 5-MeO-DMT on low frequency cortical oscillations (LFCO, <4 Hz) in PFC, visual (V1), somatosensory (S1) and auditory (Au1) cortices, as well as the dependence of these effects on 5-HT(1A)-R and 5-HT(2A)-R, using wild type (WT) and 5-HT(2A)-R knockout (KO2A) anesthetized mice. 5-MeO-DMT reduced LFCO in the PFC of WT and KO2A mice. The effect in KO2A mice was fully prevented by the 5-HT(1A)-R antagonist WAY-100635. Systemic and local 5-MeO-DMT reduced 5-HT release in PFC mainly via 5-HT(1A)-R. Moreover, 5-MeO-DMT reduced LFCO in S1, Au1 and V1 of WT mice and only in V1 of KO2A mice, suggesting the involvement of 5-HT(1A)-R activation in the 5-MeO-DMT-induced disruption of V1 activity. In addition, antipsychotic drugs reversed 5-MeO-DMT effects in WT mice. The present results suggest that the hallucinogen action of 5-MeO-DMT is mediated by simultaneous alterations of the activity of sensory (S1, Au1, V1) and associative (PFC) cortical areas, also supporting a role of 5-HT(1A)-R stimulation in V1 and PFC, in addition to the well-known action on 5-HT(2A)-R. Moreover, the reversal by antipsychotic drugs of 5-MeO-DMT effects adds to previous literature supporting the usefulness of the present model in antipsychotic drug development. 3. SeisRockHT - Seismic Rockfall Monitoring in the Hohe Tauern region NASA Astrophysics Data System (ADS) Binder, Daniel; Hartmeyer, Ingo; Keuschnig, Markus; Mertl, Stefan; Lenhardt, Wolfgang 2016-04-01 SeisRockHT focuses on open hardware and free software applied for scientific long-term monitoring strategies in harsh environments. In detail, SeisRockHT aims at the establishment of two seismic networks to quantitatively observe seismicity and rockfall events at high alpine north faces. Due to the rare character of rockfall events, a continuous and long-term observation strategy is targeted. The long-term perspective is assured through the project partner of the Austrian seismic service who will include SeisRockHT networks when the project is completed. Two study sites were selected for monitoring: the Kitzsteinhorn and the Hohe Sonnblick exhibiting two different scales of monitoring networks. The smaller scaled Kitzsteinhorn investigation site is closely related to bedrock permafrost processes, whereas the larger-scaled Sonnblick investigation site aims a classic alpine north face. SeisRockHT will develop a suite of optimum methods for characterization, detection and localization of the seismic events recorded at the two sites. Beside analysis of discrete seismic events, ambient seismic noise analysis promises a closer insight into rockfall precursory seismic characteristics.Based on the high quality complementary data delivered by already established long-term monitoring projects at the two sites, potential rockfall triggers will be suggested. 4. Structural and electrical characteristics of solution processed P3HT-carbon nanotube composite NASA Astrophysics Data System (ADS) Mahakul, Prakash Chandra; Mahanandia, Pitamber 2017-02-01 Organic semiconductors have been identified as a fascinating class of low cost and flexible novel semiconductor materials that have the electrical and optical properties which can be easily processed. Due to their interesting physical properties, organic semiconductors have attracted tremendous research attention for next generation electronics and optoelectronics. Multiwalled carbon nanotubes (MWCNT) incorporated Poly[3-hexylthiophene-2,5-diyl] (P3HT) hybrid nano-composite film have been fabricated by solution processing technique followed by spin coating method using 1,2-dichlorobenzene as an intermediate solvent. Structural and morphological characteristics of the composite film have been studied by x-ray diffraction (XRD) and scanning electron microscope (SEM). The MWCNTs were observed to be well dispersed in the polymer matrix. Crystallites were found to be more ordered barely affecting the lamellar structure of P3HT in the nano-composite film. Structural and functional characteristics of P3HT and its hybrid nano-composite have been studied by UV-Visible (UV-Vis), Fourier transform infrared (FTIR) and Raman spectroscopic characterization. Excellent electrical properties have been observed from I-V and cyclic-voltammetric characterization of the well dispersed MWCNT in the P3HT composite. Improvement in electrical properties can be attributed to the higher carrier mobility of MWCNTs in the composites. 5. Tenth anniversary of CAS ONLINE service : What CAS services should be in the new era of chemical information NASA Astrophysics Data System (ADS) Kostakos, Charles N. Chemical Abstracts Service celebrated 10th anniversary of CAS online information service in 1990. A speech given on the occasion reviewed history of the CAS ONLINE, in relation to its most important benefits for scientists and engineers. The development of STN international, the network through which CAS ONLINE is accessible around the world, was also discussed in the speech. The CAS ONLINE now contains a wide variety of files relating to chemical field including CA file, Registry file. CA previews,. CASREACT, CIN. MARPAT, etc for supplying chemical information worldwide. 6. Prostaglandin potentiates 5-HT responses in stomach and ileum innervating visceral afferent sensory neurons SciTech Connect Kim, Sojin; Jin, Zhenhua; Lee, Goeun; Park, Yong Seek; Park, Cheung-Seog; Jin, Young-Ho 2015-01-02 Highlights: • Prostaglandin E2 (PGE{sub 2}) effect was tested on visceral afferent neurons. • PGE{sub 2} did not evoke response but potentiated serotonin (5-HT) currents up to 167%. • PGE{sub 2}-induced potentiation was blocked by E-prostanoid type 4 receptors antagonist. • PGE{sub 2} effect on 5-HT response was also blocked by protein kinase A inhibitor KT5720. • Thus, PGE{sub 2} modulate visceral afferent neurons via synergistic signaling with 5-HT. - Abstract: Gastrointestinal disorder is a common symptom induced by diverse pathophysiological conditions that include food tolerance, chemotherapy, and irradiation for therapy. Prostaglandin E{sub 2} (PGE{sub 2}) level increase was often reported during gastrointestinal disorder and prostaglandin synthetase inhibitors has been used for ameliorate the symptoms. Exogenous administration of PGE{sub 2} induces gastrointestinal disorder, however, the mechanism of action is not known. Therefore, we tested PGE{sub 2} effect on visceral afferent sensory neurons of the rat. Interestingly, PGE{sub 2} itself did not evoked any response but enhanced serotonin (5-HT)-evoked currents up to 167% of the control level. The augmented 5-HT responses were completely inhibited by a 5-HT type 3 receptor antagonist, ondansetron. The PGE{sub 2}-induced potentiation were blocked by a selective E-prostanoid type4 (EP{sub 4}) receptors antagonist, L-161,982, but type1 and 2 receptor antagonist AH6809 has no effect. A membrane permeable protein kinase A (PKA) inhibitor, KT5720 also inhibited PGE{sub 2} effects. PGE{sub 2} induced 5-HT current augmentation was observed on 15% and 21% of the stomach and ileum projecting neurons, respectively. Current results suggest a synergistic signaling in visceral afferent neurons underlying gastrointestinal disorder involving PGE{sub 2} potentiation of 5-HT currents. Our findings may open a possibility for screen a new type drugs with lower side effects than currently using steroidal prostaglandin 7. Shuyu Capsules Relieve Premenstrual Syndrome Depression by Reducing 5-HT3AR and 5-HT3BR Expression in the Rat Brain PubMed Central Li, Fang; Feng, Jizhen; Gao, Dongmei; Wang, Jieqiong; Song, Chunhong; Wei, Sheng 2016-01-01 The effects of the Shuyu capsule on 5-HT3AR and 5-HT3BR expression in a rat model of premenstrual syndrome (PMS) depression and on 5-HT3AR and 5-HT3BR expression and hippocampal neuron 5-HT3 channel current were investigated, to elucidate its mechanism of action against PMS depression. PMS depression model rats were divided into depression and Shuyu- and fluoxetine-treated groups, which were compared to control rats for frontal lobe and hippocampal 5-HT3AR and 5-HT3BR expression and behavior. The depressed model rats displayed symptoms of depression, which were reduced in treated and normal control rats. Frontal lobe and hippocampal 5-HT3AR and 5-HT3BR levels were significantly higher in the model versus the control group and were significantly lower in the Shuyu group. As compared to control rats, the 5-HT3R channel current in the model group was significantly higher; the 5-HT3R channel current in hippocampal neurons treated with serum from Shuyu group rats was significantly lower than that in those treated with model group serum. Thus, PMS depression may be related to 5-HT3AR and 5-HT3BR expression and increased 5-HT3 channel current. Shuyu capsules rectified abnormal 5-HT3AR and 5-HT3BR expression and 5-HT3 channel current changes in a rat model; this finding may provide insight into treating PMS depression. PMID:27725889 8. Multiscale analysis of the effect of micro-phase separation on the charge transfer at the PEDOT:PSS and P3HT:PCBM layer interface NASA Astrophysics Data System (ADS) Huang, Min 2015-09-01 The influence of micro phase behavior on the charge transfer at the interface between PEDOT:PSS and P3HT:PCBM layers was studied using multiscale analysis. Calculated Flory- Huggins parameters indicated that the PEDOT attracts P3HT and repulses PCBM that agrees well with the experimental observation of the development of P3HT rich interface during the BHJ layer formation. Based on the calculated Flory-Huggins parameters, mesoscale DPD simulations were conducted for PEDOT:PSS and P3HT:PCBM layers. Results were mapped to the CG (coarse grained) and then atomistic scales where atomistic details of the interface were studied. The density of nonbonding close contacts including that from reorientation between PEDOT and P3HT was quantified, vibronic coupling and carrier transfer efficiency were discussed. 9. Leiomyoblastome gastrique: à propos de trois cas PubMed Central Moujahid, Mountassir; Ennafaa, Issam; EL Rhari, Ahmed; Serghini, Issam; Chekoura, Khalid; Tahiri, Moulay Hassan 2015-01-01 Le leiomyoblastome gastrique est une tumeur musculaire rare qui touche essentiellement l'adulte. Son développement est souvent exogastrique. Le diagnostic positif repose sur l'histologie et le traitement est basé sur la chirurgie. Nous rapportons trois cas de leiomyoblastome gastrique colligés dans le service de chirurgie générale au 5ème Hôpital Militaire. L’âge moyen des patients est de 47 ans; le motif de consultation était représenté par une hémorragie digestive et l'imagerie médicale a posé le diagnostic de masse tumorale dans tous les cas. Le traitement chirurgical consistait en une gastrectomie partielle et le compte rendu anatomopathologique a confirmé le leiomyoblastome gastrique dans les trois cas. Le siège de la tumeur a été posé par la fibroscopie oeso gastroduodénale, le traitement était chirurgical et les suites post opératoires étaient simples avec un contrôle par des fibroscopies répétitives sans aucun signe de récidive. Le leiomyoblastome gastrique est une tumeur rare. L’écho endoscopie joue un rôle primordial dans le diagnostic positif ainsi que dans l’évaluation de l'extension pariétale de ces tumeurs. Le traitement est essentiellement chirurgical. PMID:26090000 10. Neonatal DSP-4 treatment impairs 5-HT(1B) receptor reactivity in adult rats. Behavioral and biochemical studies. PubMed Ferdyn-Drosik, Marzena; Nowak, Przemysław; Bojanek, Kamila; Bałasz, Michał; Kasperski, Jacek; Skaba, Dariusz; Muchacki, Rafał; Kostrzewa, Richard M 2010-01-01 To examine the effect of a central noradrenergic lesion on the reactivity of the 5-HT(1B) receptor we compared intact male rats with rats in which noradrenergic nerve terminals were largely destroyed with the neurotoxin DSP-4 (50 mg/kg x 2, on the 1st and 3rd days of postnatal life). When rats attained 10 weeks of age, control and DSP-4 rats were divided into two subgroups receiving either saline or the serotonin (5-HT) synthesis inhibitor (p-chlorophenylalanine; p-CPA; 100 mg/kg). Employing an elevated plus maze test, we demonstrated that CP 94,253 (5-propoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-pyrrolo[3,2-b]pyridine hydrochloride) (4.0 mg/kg; 5-HT(1B) agonist) induced an anxiogenic-like action in control rats; however, it failed to elicit this effect in the DSP-4 group. Surprisingly, in p-CPA pretreated rats anxiogenic-like activity was observed both in control and DSP-4 treated rats. CP 94,253 significantly attenuated 5-HT synthesis in the medial prefrontal cortex (mPFC) of control rats, and SB 216641 (N-{3-[3-(dimethylamino)ethoxy]-4-methoxyphenyl}-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-[1,1'-biphenyl]-4-carboxamide hydrochloride) (4.0 mg/kg; 5-HT(1B) antagonist) was able to antagonize this effect. Conversely, CP 94,253 failed to significantly inhibit the 5-HT synthesis rate in DSP-4-treated rats. In the microdialysis study CP 94,253 induced long-lasting attenuation of 5-HT release in the mPFC of control rats but had no effect in DSP-4 rats. These data lead to the proposal that presynaptic 5-HT(1B) autoreceptors underwent desensitization in DSP-4 treated rats. 11. Safety evaluation of Astragalus extract mixture HT042 and its constituent herbs in Sprague-Dawley rats. PubMed Song, Jungbin; Lee, Donghun; Min, Byoungjae; Bae, Jin-Sook; Chang, Gyu Tae; Kim, Hocheol 2017-08-15 Astragalus extract mixture HT042 is a combination of three standardized extracts from Astragalus membranaceus root, Eleutherococcus senticosus stem, and Phlomis umbrosa root, which has proven to stimulate children's height growth. The aim of this study was to demonstrate the safety of HT042 and its three constituent herbs when administered orally. Acute and sub-chronic oral toxicity studies were conducted using male and female Sprague-Dawley rats. In the acute toxicity study, HT042 and each of the herbs was administered at single doses of up to 5000 mg/kg. In the 13-week sub-chronic toxicity study, HT042 was administered at repeated doses of up to 4000 mg/kg/day. In the acute toxicity study of HT042 and each of the herbs, no deaths occurred and there was no indication of toxicity, on the basis of clinical signs, body weight, and necropsy findings. In the sub-chronic toxicity study of HT042, there were no deaths and no changes in clinical signs or the findings of ophthalmic examinations. Although there were some treatment-related changes in other findings, these alterations were not considered toxicologically significant because they remained within normal ranges or recovered during the recovery period. The oral approximate lethal doses of HT042 and each of the herbs were > 5000 mg/kg, and the no-observed-adverse-effect level of HT042 was 4000 mg/kg/day in male and female rats. Copyright © 2017 Elsevier GmbH. All rights reserved. 12. 5-HT2A receptors are concentrated in regions of the human infant medulla involved in respiratory and autonomic control. PubMed Paterson, David S; Darnall, Ryan 2009-05-11 The serotonergic (5-HT) system in the human medulla oblongata is well-recognized to play an important role in the regulation of respiratory and autonomic function. In this study, using both immunocytochemistry (n=5) and tissue section autoradiography with the radioligand (125)I-1-(2,5-dimethoxy-4-iodo-phenyl)2-aminopropane (n=7), we examine the normative development and distribution of the 5-HT(2A) receptor in the human medulla during the last part of gestation and first postnatal year when dramatic changes are known to occur in respiratory and autonomic control, in part mediated by the 5-HT(2A) receptor. High 5-HT(2A) receptor binding was observed in the dorsal motor nucleus of the vagus (preganglionic parasympathetic output) and hypoglossal nucleus (airway patency); intermediate binding was present in the nucleus of the solitary tract (visceral sensory input), gigantocellularis, intermediate reticular zone, and paragigantocellularis lateralis. Negligible binding was present in the raphé obscurus and arcuate nucleus. The pattern of 5-HT(2A) immunoreactivity paralleled that of binding density. By 15 gestational weeks, the relative distribution of the 5-HT(2A) receptor was similar to that in infancy. In all nuclei sampled, 5-HT(2A) receptor binding increased with age, with significant increases in the hypoglossal nucleus (p=0.027), principal inferior olive (p=0.044), and medial accessory olive (0.038). Thus, 5-HT(2A) receptors are concentrated in regions involved in autonomic and respiratory control in the human infant medulla, and their developmental profile changes over the first year of life in the hypoglossal nucleus critical to airway patency and the inferior olivary complex essential to cerebellar function. 13. Is the potent 5-HT1A receptor agonist, alnespirone (S-20499), affecting dopaminergic systems in the rat brain? PubMed Dugast, C; Soulière, F; Schmitt, P; Casanovas, J M; Fattaccini, C M; Mocaër, E; Lesourd, M; Renaud, B; Artigas, F; Hamon, M; Chouvet, G 1998-06-05 The effects of the new methoxy-chroman 5-HT1A receptor agonist, alnespirone (S-20499), on the dopamine systems in the rat brain were assessed in vivo by means of electrophysiological and neurochemical techniques. Cumulative doses of alnespirone (0.032-4.1 mg kg(-1), i.v.) did not modify the spontaneous firing rate of dopamine neurons in the substantia nigra as well as in the ventral tegmental area. The local application of alnespirone (0.1-10 microM) by reverse microdialysis into the dorsal striatum did not affect the dopamine output but induced a moderate, although dose-independent, increase of 5-HT (5-hydroxytryptamine, serotonin) concentrations in the dialysate. As expected of a 5-HT1A receptor agonist, intraperitoneal (i.p.) administration of alnespirone at 2-32 mg kg(-1) markedly decreased 5-HT turnover in the striatum. Parallel measurements of dopamine turnover showed that alnespirone exerted no effect except at the highest dose (32 mg kg(-1), i.p.) for which a significant increase was observed. Interestingly, both alnespirone-induced reduction in 5-HT turnover and increase in dopamine turnover could be prevented by pretreatment with the selective 5-HT1A receptor antagonist WAY-100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexa ne carboxamide). Altogether, these data indicate that alnespirone does not exert any direct influence on central dopamine systems. The enhanced dopamine turnover due to alnespirone at high dose appeared to result from 5-HT1A receptor stimulation, further supporting the idea that this receptor type may play a key role in 5-HT-dopamine interactions in brain. 14. New CRISPR–Cas systems from uncultivated microbes SciTech Connect Burstein, David; Harrington, Lucas B.; Strutt, Steven C.; Probst, Alexander J.; Anantharaman, Karthik; Thomas, Brian C.; Doudna, Jennifer A.; Banfield, Jillian F. 2016-12-22 We present that CRISPR-Cas systems provide microbes with adaptive immunity by employing short DNA sequences, termed spacers, that guide Cas proteins to cleave foreign DNA. Class 2 CRISPR-Cas systems are streamlined versions, in which a single RNA-bound Cas protein recognizes and cleaves target sequences. The programmable nature of these minimal systems has enabled researchers to repurpose them into a versatile technology that is broadly revolutionizing biological and clinical research. However, current CRISPR-Cas technologies are based solely on systems from isolated bacteria, leaving the vast majority of enzymes from organisms that have not been cultured untapped. Metagenomics, the sequencing of DNA extracted directly from natural microbial communities, provides access to the genetic material of a huge array of uncultivated organisms. Here, using genome-resolved metagenomics, we identify a number of CRISPR-Cas systems, including the first reported Cas9 in the archaeal domain of life, to our knowledge. This divergent Cas9 protein was found in little-studied nanoarchaea as part of an active CRISPR-Cas system. In bacteria, we discovered two previously unknown systems, CRISPR-CasX and CRISPR-CasY, which are among the most compact systems yet discovered. Notably, all required functional components were identified by metagenomics, enabling validation of robust in vivo RNA-guided DNA interference activity in Escherichia coli. Lastly, interrogation of environmental microbial communities combined with in vivo experiments allows us to access an unprecedented diversity of genomes, the content of which will expand the repertoire of microbe-based biotechnologies. 15. New CRISPR-Cas systems from uncultivated microbes NASA Astrophysics Data System (ADS) Burstein, David; Harrington, Lucas B.; Strutt, Steven C.; Probst, Alexander J.; Anantharaman, Karthik; Thomas, Brian C.; Doudna, Jennifer A.; Banfield, Jillian F. 2017-02-01 CRISPR-Cas systems provide microbes with adaptive immunity by employing short DNA sequences, termed spacers, that guide Cas proteins to cleave foreign DNA. Class 2 CRISPR-Cas systems are streamlined versions, in which a single RNA-bound Cas protein recognizes and cleaves target sequences. The programmable nature of these minimal systems has enabled researchers to repurpose them into a versatile technology that is broadly revolutionizing biological and clinical research. However, current CRISPR-Cas technologies are based solely on systems from isolated bacteria, leaving the vast majority of enzymes from organisms that have not been cultured untapped. Metagenomics, the sequencing of DNA extracted directly from natural microbial communities, provides access to the genetic material of a huge array of uncultivated organisms. Here, using genome-resolved metagenomics, we identify a number of CRISPR-Cas systems, including the first reported Cas9 in the archaeal domain of life, to our knowledge. This divergent Cas9 protein was found in little-studied nanoarchaea as part of an active CRISPR-Cas system. In bacteria, we discovered two previously unknown systems, CRISPR-CasX and CRISPR-CasY, which are among the most compact systems yet discovered. Notably, all required functional components were identified by metagenomics, enabling validation of robust in vivo RNA-guided DNA interference activity in Escherichia coli. Interrogation of environmental microbial communities combined with in vivo experiments allows us to access an unprecedented diversity of genomes, the content of which will expand the repertoire of microbe-based biotechnologies. 16. New CRISPR-Cas systems from uncultivated microbes. PubMed Burstein, David; Harrington, Lucas B; Strutt, Steven C; Probst, Alexander J; Anantharaman, Karthik; Thomas, Brian C; Doudna, Jennifer A; Banfield, Jillian F 2017-02-09 CRISPR-Cas systems provide microbes with adaptive immunity by employing short DNA sequences, termed spacers, that guide Cas proteins to cleave foreign DNA. Class 2 CRISPR-Cas systems are streamlined versions, in which a single RNA-bound Cas protein recognizes and cleaves target sequences. The programmable nature of these minimal systems has enabled researchers to repurpose them into a versatile technology that is broadly revolutionizing biological and clinical research. However, current CRISPR-Cas technologies are based solely on systems from isolated bacteria, leaving the vast majority of enzymes from organisms that have not been cultured untapped. Metagenomics, the sequencing of DNA extracted directly from natural microbial communities, provides access to the genetic material of a huge array of uncultivated organisms. Here, using genome-resolved metagenomics, we identify a number of CRISPR-Cas systems, including the first reported Cas9 in the archaeal domain of life, to our knowledge. This divergent Cas9 protein was found in little-studied nanoarchaea as part of an active CRISPR-Cas system. In bacteria, we discovered two previously unknown systems, CRISPR-CasX and CRISPR-CasY, which are among the most compact systems yet discovered. Notably, all required functional components were identified by metagenomics, enabling validation of robust in vivo RNA-guided DNA interference activity in Escherichia coli. Interrogation of environmental microbial communities combined with in vivo experiments allows us to access an unprecedented diversity of genomes, the content of which will expand the repertoire of microbe-based biotechnologies. 17. New CRISPR–Cas systems from uncultivated microbes NASA Astrophysics Data System (ADS) Burstein, David; Harrington, Lucas B.; Strutt, Steven C.; Probst, Alexander J.; Anantharaman, Karthik; Thomas, Brian C.; Doudna, Jennifer A.; Banfield, Jillian F. 2016-12-01 CRISPR–Cas systems provide microbes with adaptive immunity by employing short DNA sequences, termed spacers, that guide Cas proteins to cleave foreign DNA. Class 2 CRISPR–Cas systems are streamlined versions, in which a single RNA-bound Cas protein recognizes and cleaves target sequences. The programmable nature of these minimal systems has enabled researchers to repurpose them into a versatile technology that is broadly revolutionizing biological and clinical research. However, current CRISPR–Cas technologies are based solely on systems from isolated bacteria, leaving the vast majority of enzymes from organisms that have not been cultured untapped. Metagenomics, the sequencing of DNA extracted directly from natural microbial communities, provides access to the genetic material of a huge array of uncultivated organisms. Here, using genome-resolved metagenomics, we identify a number of CRISPR–Cas systems, including the first reported Cas9 in the archaeal domain of life, to our knowledge. This divergent Cas9 protein was found in little-studied nanoarchaea as part of an active CRISPR–Cas system. In bacteria, we discovered two previously unknown systems, CRISPR–CasX and CRISPR–CasY, which are among the most compact systems yet discovered. Notably, all required functional components were identified by metagenomics, enabling validation of robust in vivo RNA-guided DNA interference activity in Escherichia coli. Interrogation of environmental microbial communities combined with in vivo experiments allows us to access an unprecedented diversity of genomes, the content of which will expand the repertoire of microbe-based biotechnologies. 18. Recent Advances in Genome Editing Using CRISPR/Cas9 PubMed Central Ding, Yuduan; Li, Hong; Chen, Ling-Ling; Xie, Kabin 2016-01-01 The CRISPR (clustered regularly interspaced short palindromic repeat)-Cas9 (CRISPR-associated nuclease 9) system is a versatile tool for genome engineering that uses a guide RNA (gRNA) to target Cas9 to a specific sequence. This simple RNA-guided genome-editing technology has become a revolutionary tool in biology and has many innovative applications in different fields. In this review, we briefly introduce the Cas9-mediated genome-editing method, summarize the recent advances in CRISPR/Cas9 technology, and discuss their implications for plant research. To date, targeted gene knockout using the Cas9/gRNA system has been established in many plant species, and the targeting efficiency and capacity of Cas9 has been improved by optimizing its expression and that of its gRNA. The CRISPR/Cas9 system can also be used for sequence-specific mutagenesis/integration and transcriptional control of target genes. We also discuss off-target effects and the constraint that the protospacer-adjacent motif (PAM) puts on CRISPR/Cas9 genome engineering. To address these problems, a number of bioinformatic tools are available to help design specific gRNAs, and new Cas9 variants and orthologs with high fidelity and alternative PAM specificities have been engineered. Owing to these recent efforts, the CRISPR/Cas9 system is becoming a revolutionary and flexible tool for genome engineering. Adoption of the CRISPR/Cas9 technology in plant research would enable the investigation of plant biology at an unprecedented depth and create innovative applications in precise crop breeding. PMID:27252719 19. New CRISPR–Cas systems from uncultivated microbes DOE PAGES Burstein, David; Harrington, Lucas B.; Strutt, Steven C.; ... 2016-12-22 We present that CRISPR-Cas systems provide microbes with adaptive immunity by employing short DNA sequences, termed spacers, that guide Cas proteins to cleave foreign DNA. Class 2 CRISPR-Cas systems are streamlined versions, in which a single RNA-bound Cas protein recognizes and cleaves target sequences. The programmable nature of these minimal systems has enabled researchers to repurpose them into a versatile technology that is broadly revolutionizing biological and clinical research. However, current CRISPR-Cas technologies are based solely on systems from isolated bacteria, leaving the vast majority of enzymes from organisms that have not been cultured untapped. Metagenomics, the sequencing of DNAmore » extracted directly from natural microbial communities, provides access to the genetic material of a huge array of uncultivated organisms. Here, using genome-resolved metagenomics, we identify a number of CRISPR-Cas systems, including the first reported Cas9 in the archaeal domain of life, to our knowledge. This divergent Cas9 protein was found in little-studied nanoarchaea as part of an active CRISPR-Cas system. In bacteria, we discovered two previously unknown systems, CRISPR-CasX and CRISPR-CasY, which are among the most compact systems yet discovered. Notably, all required functional components were identified by metagenomics, enabling validation of robust in vivo RNA-guided DNA interference activity in Escherichia coli. Lastly, interrogation of environmental microbial communities combined with in vivo experiments allows us to access an unprecedented diversity of genomes, the content of which will expand the repertoire of microbe-based biotechnologies.« less 20. 5-HT2A receptor antagonists improve motor impairments in the MPTP mouse model of Parkinson's disease. PubMed Ferguson, Marcus C; Nayyar, Tultul; Deutch, Ariel Y; Ansah, Twum A 2010-01-01 Clinical observations have suggested that ritanserin, a 5-HT(2A/C) receptor antagonist may reduce motor deficits in persons with Parkinson's Disease (PD). To better understand the potential antiparkinsonian actions of ritanserin, we compared the effects of ritanserin with the selective 5-HT(2A) receptor antagonist M100907 and the selective 5-HT(2C) receptor antagonist SB 206553 on motor impairments in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP-treated mice exhibited decreased performance on the beam-walking apparatus. These motor deficits were reversed by acute treatment with L-3,4-dihydroxyphenylalanine (levodopa). Both the mixed 5-HT(2A/C) antagonist ritanserin and the selective 5-HT(2A) antagonist M100907 improved motor performance on the beam-walking apparatus. In contrast, SB 206553 was ineffective in improving the motor deficits in MPTP-treated mice. These data suggest that 5-HT(2A) receptor antagonists may represent a novel approach to ameliorate motor symptoms of Parkinson's disease. 1. Matrix metalloproteinase-9 silencing by RNA interference promotes the adhesive-invasive switch in HT1080 human fibrosarcoma cells. PubMed Zhu, Xishan; Tai, Weiping; Shi, Wei; Song, Yuguang; Zhang, Hongmei; An, Guangyu 2012-01-01 A high level of matrix metalloproteinase-9 (MMP-9) is associated with human tumor invasion and/or metastasis. The HT1080 human fibrosarcoma cell line is highly invasive and metastatic which constitutively express MMP-9. HT1080 cells transfected with a double stranded RNA that targeted the MMP-9 mRNA and the cellular characteristics were examined before and after interference. The inhibition effects of MMP-9 interference on the tumor growth of HT1080 cells in nude mice was also tested by xenograft assay. MMP-9 extinction in HT1080 resulted in the following: (1) inhibited cell mobility; (2) increased cell adhesion, and (3) attenuated tumor cell migration. In addition, MMP-9 knockdown concomitantly resulted in decreased levels of soluble ICAM-1, leading to an adhesion defect and tumor metastasis. Moreover, in vivo assay further demonstrated MMP-9 interference affecting the tumorigenesis of HT1080 cells in mice as follows (1) inhibition of tumor growth; (2) reduced tumor volume, and (3) prolonged survival time. Our observations defined a novel critical role for MMP-9 in the progression of HT1080 fibrosarcoma by changing the inter-cellular adhesion molecular-1 from membrane-anchored state to a soluble one which provides a target for promising tumor therapy in clinics. 2. Alcohol interactions with channel activation and desensitization at 5-HT[sub 3] and GABA[sub A] receptors SciTech Connect Lovinger, D.M.; Zhou, O. ) 1992-01-01 Ethanol (EtOH) and trichloroethanol (TCEt) potentiate 5-HT[sub 3] receptor-mediated ion current in NCB-20 neuroblastoma cells and nodose ganglion neurons. TCEt potentiates GABA[sub A] receptor-mediated current in dorsal root ganglion neurons. Whole-cell patch-clamp recording was used to examine the interactions of alcohols with current activation and receptor desensitization. Alcohols increased the potency of 5-HT, consistent with an increase in channel activation rate. Current decay rate increased in the presence of alcohols such that potentiation decreased with time following in onset of agonist + alcohol treatment. Potentiation of 5-HT-activated current by EtOH was 61 [plus minus] 17% above control at the start of application but was absent 10 sec after current onset. Agonist pretreatment decreased potentiation by subsequent agonist + alcohol application. Potentiation by TCEt of 5-HT-activated current decreased from 96% above control with simultaneous application of 5-HT + TCEt to 44% after a 30 sec 5-HT treatment. This agonist- and time-dependent loss of potentiation was observed prior to the onset of current decay when low agonist concentrations were used. Agonist pretreatment appears to drive the channel into an alcohol-insensitive. Current activated by GABA + TCEt recovers from desensitization produced by GABA alone more slowly than recovery tested in the absence of TCEt. 3. S100B interacts with the serotonin 5-HT7 receptor to regulate a depressive-like behavior. PubMed Stroth, Nikolas; Svenningsson, Per 2015-12-01 The serotonin 5-HT7 receptor (5-HT7) is an emerging target for psychiatric pharmacotherapy. Recent observations in rodent models and humans suggest that its blockade mediates antidepressant efficacy. In the present study, we identify the Ca(2+)-binding protein S100B as an interacting partner of 5-HT7 and show that S100B negatively regulates inducible cyclic AMP (cAMP) accumulation in transfected HeLa cells and mouse cortical astrocytes. Overexpression of S100B causes brain region-specific dysregulation of the cAMP pathway in vivo, such that concentrations of cAMP in the frontal cortex are higher in S100B transgenic female mice compared to wild-types. Finally, S100B transgenic female mice show depressive-like behavior in the forced swim test (FST) and pharmacological blockade of 5-HT7 with SB269970 normalizes FST behavior. Taken together, our results show that S100B affects behavioral despair in female mice through functional interaction with the 5-HT7 receptor. Furthermore, we identify S100B as a cAMP-regulatory protein in cultured astrocytes and the murine frontal cortex. Future experiments will clarify whether there is a direct link between the 5-HT7-associated and cAMP-regulatory actions of S100B. 4. Spatio-temporal Spectral Variability in Cas A NASA Astrophysics Data System (ADS) Nambiar, Yamini; Kashyap, V.; Patnaude, D. 2014-01-01 We have analyzed Chandra archival data of Cas A Supernova Remnant to identify regions with large spectral abnormalities and variability over the last decade. We use 8 ACIS-S observations spanning the years 2000 to 2012. We compute spectral hardness ratios in the soft/medium and medium/hard CSC bands over spatial scales corresponding to binning by 4, 8, 16, 32, and 64. We reduce the data and apply the latest calibration using the CIAO tool chandra_repro. We account for exposure variations using exposure maps and compute photon fluxes using the CIAO tool fluximage. We then renormalize the color light curves at each pixel and flag large departures from the norm by comparing with the observed spread in the renormalized color light curves. This allows regions with different intrinsic spectral properties to be compared. We flag deviations of >3σ from the renormalized mean at each epoch, and combine all such pixels to form a map of interesting regions in the remnant. We also identify pixels which have intrinsically abnormal hardness ratios at each epoch. We show that there exist many sites on Cas A where abnormal variations in the spectrum exist. Specifically, we find that many of the identified regions coincide with prominent features of the SNR, such as the edge of the remnant, the central compact object, and numerous knots. In addition, we find various other locations 1000) where there is indication of an atypical spectral signature. The full region lists, along with analysis scripts and the figures and tables shown in this poster, are stored on the Harvard Dataverse Network, at http://dx.doi.org/10.7910/DVN1/22634 YN thanks ABRHS and Young Einsteins Science Club for support and guidance. VK and DP acknowledge support during this project from the Chandra X-Ray Center. 5. 5-HT2A and 5-HT2C receptors as hypothalamic targets of developmental programming in male rats. PubMed Martin-Gronert, Malgorzata S; Stocker, Claire J; Wargent, Edward T; Cripps, Roselle L; Garfield, Alastair S; Jovanovic, Zorica; D'Agostino, Giuseppe; Yeo, Giles S H; Cawthorne, Michael A; Arch, Jonathan R S; Heisler, Lora K; Ozanne, Susan E 2016-04-01 Although obesity is a global epidemic, the physiological mechanisms involved are not well understood. Recent advances reveal that susceptibility to obesity can be programmed by maternal and neonatal nutrition. Specifically, a maternal low-protein diet during pregnancy causes decreased intrauterine growth, rapid postnatal catch-up growth and an increased risk for diet-induced obesity. Given that the synthesis of the neurotransmitter 5-hydroxytryptamine (5-HT) is nutritionally regulated and 5-HT is a trophic factor, we hypothesised that maternal diet influences fetal 5-HT exposure, which then influences development of the central appetite network and the subsequent efficacy of 5-HT to control energy balance in later life. Consistent with our hypothesis, pregnant rats fed a low-protein diet exhibited elevated serum levels of 5-HT, which was also evident in the placenta and fetal brains at embryonic day 16.5. This increase was associated with reduced levels of 5-HT2CR, the primary 5-HT receptor influencing appetite, in the fetal, neonatal and adult hypothalamus. As expected, a reduction of 5-HT2CR was associated with impaired sensitivity to 5-HT-mediated appetite suppression in adulthood. 5-HT primarily achieves effects on appetite by 5-HT2CR stimulation of pro-opiomelanocortin (POMC) peptides within the arcuate nucleus of the hypothalamus (ARC). We show that 5-HT2ARs are also anatomically positioned to influence the activity of ARC POMC neurons and that mRNA encoding 5-HT2AR is increased in the hypothalamus ofin uterogrowth-restricted offspring that underwent rapid postnatal catch-up growth. Furthermore, these animals at 3 months of age are more sensitive to appetite suppression induced by 5-HT2AR agonists. These findings not only reveal a 5-HT-mediated mechanism underlying the programming of susceptibility to obesity, but also provide a promising means to correct it, by treatment with a 5-HT2AR agonist. © 2016. Published by The Company of Biologists Ltd. 6. P3HT-b-PS Copolymers as P3HT/PCBM Interfacial Compatibilizers for High Efficiency Photovoltaics SciTech Connect Sun, Zhenzhong; Xiao, Kai; Yu, Xiang; Hong, Kunlun; Keum, Jong Kahk; Browning, Jim; Ivanov, Ilia N; Chen, Jihua; Alonzo Calderon, Jose E; Sumpter, Bobby G; Payzant, E Andrew; Rouleau, Christopher M; Geohegan, David B 2011-01-01 To control the donor-acceptor phase separation for more efficient organic bulk heterojunction photovoltaic cells, poly(3-hexylthiophene)-block-polystyrene (P3HT-b-PS) diblock copolymer was added to serve as a compatibilizer in a P3HT/ [6,6]-phenyl-C61-butyric acid methyl ester fullerene derivative (PCBM) blend. An addition of 5 wt% of P3HT-b-PS copolymer in the P3HT/PCBM blend improved the power-conversion efficiency from 3.3% to 4.1% due to an enhancement of both the short-circuit current density and fill factor compared to that of a pristine P3HT/PCBM solar cell. Grazing incidence x-ray scattering (GIXS), absorption spectroscopy and carrier mobility studies reveal that the crystallinity and orientation of P3HT were improved, thereby enhancing hole transport in the P3HT polymer, and leading to a better balance between the electron and hole mobilities in the P3HT/PCBM active layer. Neutron reflectometry (NR) experiments demonstrate that a distinct scattering length density profile shows the highest PCBM concentration in the middle layer region and a more compact and homogeneous layer, presumably due to an increase in miscibility of P3HT and PCBM driven by the copolymer compatibilizer, while adding 5 wt% of P3HT-b-PS copolymer in the P3HT/PCBM blend. Quantum density functional theory calculations show that the P3HT-b-PS additive tends to promote microphase segregation, with the PCBM attracted to the PS block, and the P3HT stacking onto the P3HT block, which presumably leads to improvements in long-range crystallinity , consistent with the GIXS findings. Overall, the results for P3HT-b-PS copolymer in a P3HT/PCBM blend demonstrate that tailored block copolymers can act as an effective compatibilizer in blended systems to further improve solar cell performance 7. Antihyperalgesic effect of 5-HT7 receptor activation on the midbrain periaqueductal gray in a rat model of neuropathic pain. PubMed Li, Shu-Fa; Zhang, Yuan-Yuan; Li, You-Yan; Wen, Song; Xiao, Zhi 2014-12-01 The 5-HT7 receptor is the most recently discovered receptor for 5-hydroxytryptamine (5-HT), and only little is known about the analgesic potential of this receptor. Adenosine triphosphate (ATP) modulates pain transmission by activating P2X/P2Y receptors, in which the P2X3 subtype is an important target for this effect. This study examined the antihyperalgesic effect of the 5-HT7 receptors in the ventrolateral midbrain periaqueductal gray (vlPAG), a crucial site for endogenous pain inhibition. This study also explored the importance of the interactions between the 5-HT7 and P2X3 receptors in this effect. To address this issue, neuropathic pain was induced through chronic constriction injury (CCI) of the sciatic nerve in Sprague-Dawley (SD) rats. The expression level and distribution of the 5-HT7 receptor were evaluated through Western blot and immunohistochemistry. The mechanical withdrawal threshold (MWT) was measured by using an electronic pressure meter test. Different doses (3, 6, and 12μmol) of AS-19, a selective agonist of the 5-HT7 receptor, were administered in the vlPAG of CCI rats. The effects of pretreatment with the selective 5-HT7 receptor antagonist SB-269970 or the selective P2X3 receptor antagonist A-317491 on the analgesic effect of AS-19 were observed. Results showed that CCI decreased the MWT values of the rats. The injury also increased the protein level of the 5-HT7 receptor in the vlPAG of neuropathic pain rats. AS-19 microinjection significantly elevated the MWT values in a dose-dependent manner, but SB-269970 pretreatment attenuated the antihyperalgesic effect of AS-19. Furthermore, the antihyperalgesic effect of the 5-HT7 receptor was partially but significantly blocked by A-317491 pretreatment. These data indicate that the 5-HT7 receptor in the vlPAG exerts an antihyperalgesic effect on rats with neuropathic pain. The 5-HT7 and P2X3 receptors interact in the vlPAG and exhibit an analgesic action through the enhanced function of the 8. Acupuncture stimulation at HT7 alleviates depression-induced behavioral changes via regulation of the serotonin system in the prefrontal cortex of maternally-separated rat pups. PubMed Park, Hyemee; Yoo, Doyoung; Kwon, Sunoh; Yoo, Tae-Won; Park, Hi-Joon; Hahm, Dae-Hyun; Lee, Hyejung; Kim, Seung-Tae 2012-07-01 A possible application of acupuncture in alleviating depression-like behavioral changes and regulating serotonin signaling in the prefrontal cortex (PFC) of maternally-separated rat pups was investigated in this study. On postnatal day 15, rat pups were maternally-separated and received acupuncture stimulation at acupoint HT7 or ST36 once a day for 7 days. On postnatal day 21, the tail suspension test was performed and the PFC was harvested. Tissue levels of serotonin (5-HT) and 5-hydroxyindole-3-acetic acid (5-HIAA) were then measured by high-performance liquid chromatography and expression of serotonin transporter (5-HTT) and brain-derived neurotrophic factor (BDNF) were assessed by western blotting. Levels of 5-HT and 5-HIAA were not significantly changed, but the 5-HIAA/5-HT ratio was significantly increased by maternal separation. The immobility time of maternally-separated rat pups was increased, and increased 5-HTT expression and reduced BDNF level were observed in the PFC. But acupuncture stimulation at HT7 alleviated the behavioral change and regulated the changes of 5-HIAA/5-HT ratio, 5-HTT, and BDNF. In conclusion, acupuncture stimulation at HT7 can relieve maternal separation-induced changes, and we propose that regulation of the 5-HIAA/5-HT ratio and of 5-HTT expression by acupuncture stimulation are important acupuncture-induced benefits in this animal model of depression. 9. Activation of the serotonergic 5-HT1A receptor in the paraventricular nucleus of the hypothalamus inhibits water intake and increases urinary excretion in water-deprived rats. PubMed de Souza Villa, Patrícia; Menani, José Vanderlei; de Arruda Camargo, Gabriela Maria Pavan; de Arruda Camargo, Luiz Antônio; Saad, Wilson Abrão 2008-10-09 The paraventricular nucleus (PVN) may be considered as a dynamic mosaic of chemically-specified subgroups of neurons. 5-HT(1A) is one of the prime receptors identified and there is expressed throughout all magnocellular regions of the PVN. Several reports have demonstrated that a subpopulation of the magnocellular neurons expressing 5-HT(1A) receptors are oxytocin (OT) neurons and activation of 5-HT(1A) receptors in the PVN increases the plasma OT. Increasing evidence shows that OT inhibits water intake and increases urinary excretion in rats. The aim of this study was to investigate the role of serotonergic 5-HT(1A) receptors in the lateral-medial posterior magnocellular region of the PVN in the water intake and diuresis induced by 24 h of water deprivation. Cannulae were implanted in the PVN of rats. 5-HT injections in the PVN reduced water intake and increased urinary excretion. 8-OH-DPAT (a 5-HT(1A) agonist) injections blocked the water intake and increased urinary output in all the periods of the observation. pMPPF (a 5-HT(1A) antagonist) injected bilaterally before the 8-OH-DPAT blocked its inhibitory effect on water intake and its diuretic effect. We suggest that antidipsogenic and diuretic responses seem to be mediated via 5-HT(1A) receptors of the lateral-medial posterior magnocellular region of the PVN in water-deprived rats. 10. Inhibition of K+-stimulated [3H]dopamine and [14C]acetylcholine release by the putative dopamine autoreceptor agonist, B-HT 920. PubMed Schmidt, C J; Lobur, A; Lovenberg, W 1986-12-01 The inhibition of K+-stimulated [3H]dopamine and [14C]acetylcholine release from preloaded rat striatal slices was used to examine the presynaptic selectivity of the putative dopamine autoreceptor agonist, B-HT 920. In the micromolar range, B-HT 920 caused a concentration-dependent inhibition of the release of both labeled neurotransmitters as evoked by 20 mM K+. The effect of B-HT 920 on both [3H]dopamine and [14C]acetylcholine release was completely blocked by (+) butaclamol but not by (-) butaclamol. Sulpiride, a selective D2 antagonist, similarly blocked the inhibitory effect of B-HT 920 on the release of both labeled neurotransmitters indicating both responses were mediated by D2 receptors. (+) Butaclamol alone elevated stimulated [3H]dopamine release suggesting a significant amount of autoreceptor occupancy by endogenously released dopamine. Experiments with tolazoline and the alpha 2 agonist, B-HT 933, did not suggest any involvement of alpha-adrenoceptor activity in the inhibitory effects of B-HT 920 on the release of either transmitter. Inhibition of release was a selective effect of B-HT 920 as the drug was without effect on the K+-stimulated release of [3H]serotonin. The results indicate that in vitro B-HT 920 is active of both pre- and postsynaptic dopamine receptors in contrast to the pattern of effects observed after its in vivo administration. 11. 48 CFR 9903.201-2 - Types of CAS coverage. Code of Federal Regulations, 2010 CFR 2010-10-01 ...) Receive a single CAS-covered contract award of $50 million or more; or (2) Received$50 million or more in... business unit receives a single CAS-covered contract award of \$50 million or more, that contract must be... institution that operate as independent organizational entities under the auspices of the parent... 12. 48 CFR 970.3002-1 - CAS applicability. Code of Federal Regulations, 2011 CFR 2011-10-01 ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false CAS applicability. 970.3002-1 Section 970.3002-1 Federal Acquisition Regulations System DEPARTMENT OF ENERGY AGENCY....3002-1 CAS applicability. The provisions of 48 CFR part 30 and 48 CFR chapter 99 (FAR Appendix) shall... 13. Reaction to Indispensable Manual Calculation Skills in a CAS Environment. ERIC Educational Resources Information Center Monaghan, John 2001-01-01 Reacts to an article published in a previous issue of this journal on the effects of graphing calculators and computer algebra systems (CAS) on students' manual calculation and algebraic manipulation skills. Considers the contribution made by Jean-Baptiste Lagrange to thinking about the role of CAS in teaching algebra. (ASK) 14. Recent Progress in CRISPR/Cas9 Technology. PubMed Mei, Yue; Wang, Yan; Chen, Huiqian; Sun, Zhong Sheng; Ju, Xing-Da 2016-02-20 15. Calibrated Ancillary System (CAS) user's guide, volume 2 NASA Technical Reports Server (NTRS) 1986-01-01 The Calibrated Ancillary System (CAS) provides real-time calibrated parameters from the orbiter downlink (ancillary data) to the Goddard Space Flight Center (GSFC). This user's guide contains the introduction to the equipment, operation, general procedures, and specific procedures of CAS. Volume 2 describes the central status and control (CSAC) procedures, supervisor procedures, and logging procedures. 16. Calibrated Ancillary System (CAS) user's guide, volume 3 NASA Technical Reports Server (NTRS) 1986-01-01 The Calibrated Ancillary System (CAS) provides real-time calibrated parameters from the orbiter downlink (ancillary data) to the Goddard Space Flight Center (GSFC). This user's guide contains the introduction to the equipment, operation, general procedures, and specific procedures of the CAS. Volume 3 describes logging and delogging procedures, real-time procedures, and error messages. 17. Calibrated Ancillary System (CAS) user's guide, volume 8 NASA Technical Reports Server (NTRS) 1986-01-01 The Calibrated Ancillary System (CAS) provides real-time calibrated parameters from the orbiter downlink (ancillary data) to the Goddard Space Flight Center (GSFC). This user's guide contains the introduction to the equipment, operation, general procedures, and specific procedures of CAS. Volume 8 describes procedures for invoking checkout software, file maintenance procedures, system manager procedures. 18. Expanding the CRISPR Toolbox: Targeting RNA with Cas13b. PubMed Barrangou, Rodolphe; Gersbach, Charles A 2017-02-16 In this issue of Molecular Cell, Smargon et al. (2017) unearth Cas13b from type VI-B CRISPR-Cas immune systems and characterize its RNA-guided, RNA-targeting activity, including regulation by the novel co-factors Csx27 and Csx28, as well as non-specific collateral RNA damage. 19. Teaching Undergraduate Mathematics Using CAS Technology: Issues and Prospects ERIC Educational Resources Information Center Tobin, Patrick C.; Weiss, Vida 2016-01-01 The use of handheld CAS technology in undergraduate mathematics courses in Australia is paradoxically shrinking under sustained disapproval or disdain from the professional mathematics community. Mathematics education specialists argue with their mathematics colleagues over a range of issues in course development and this use of CAS or even… 20. Transformation of OODT CAS to Perform Larger Tasks NASA Technical Reports Server (NTRS) Mattmann, Chris; Freeborn, Dana; Crichton, Daniel; Hughes, John; Ramirez, Paul; Hardman, Sean; Woollard, David; Kelly, Sean 2008-01-01 A computer program denoted OODT CAS has been transformed to enable performance of larger tasks that involve greatly increased data volumes and increasingly intensive processing of data on heterogeneous, geographically dispersed computers. Prior to the transformation, OODT CAS (also alternatively denoted, simply, 'CAS') [wherein 'OODT' signifies 'Object-Oriented Data Technology' and 'CAS' signifies 'Catalog and Archive Service'] was a proven software component used to manage scientific data from spaceflight missions. In the transformation, CAS was split into two separate components representing its canonical capabilities: file management and workflow management. In addition, CAS was augmented by addition of a resource-management component. This third component enables CAS to manage heterogeneous computing by use of diverse resources, including high-performance clusters of computers, commodity computing hardware, and grid computing infrastructures. CAS is now more easily maintainable, evolvable, and reusable. These components can be used separately or, taking advantage of synergies, can be used together. Other elements of the transformation included addition of a separate Web presentation layer that supports distribution of data products via Really Simple Syndication (RSS) feeds, and provision for full Resource Description Framework (RDF) exports of metadata. 1. Interacting Parallel Constructions of Knowledge in a CAS Context ERIC Educational Resources Information Center Kidron, Ivy; Dreyfus, Tommy 2010-01-01 We consider the influence of a CAS context on a learner's process of constructing a justification for the bifurcations in a logistic dynamical process. We describe how instrumentation led to cognitive constructions and how the roles of the learner and the CAS intertwine, especially close to the branching and combining of constructing actions. The… 2. Using CAS to Solve a Mathematics Task: A Deconstruction ERIC Educational Resources Information Center Berger, Margot 2010-01-01 I investigate how and whether a heterogeneous group of first-year university mathematics students in South Africa harness the potential power of a computer algebra system (CAS) when doing a specific mathematics task. In order to do this, I develop a framework for deconstructing a mathematics task requiring the use of CAS, into its primary… 3. Teaching Undergraduate Mathematics Using CAS Technology: Issues and Prospects ERIC Educational Resources Information Center Tobin, Patrick C.; Weiss, Vida 2016-01-01 The use of handheld CAS technology in undergraduate mathematics courses in Australia is paradoxically shrinking under sustained disapproval or disdain from the professional mathematics community. Mathematics education specialists argue with their mathematics colleagues over a range of issues in course development and this use of CAS or even… 4. From Calculus to Dynamical Systems through DGS and CAS ERIC Educational Resources Information Center García, Jeanett López; Zamudio, Jorge Javier Jiménez 2015-01-01 Several factors have motivated the use of CAS or DGS in the teaching-learning process, such as: the development of new technologies, the availability of computers, and the widespread use of the Internet, among others. Even more, the trend to include CAS and DGS in the curricula of some undergraduate studies has resulted in the instruction of the… 5. From Calculus to Dynamical Systems through DGS and CAS ERIC Educational Resources Information Center García, Jeanett López; Zamudio, Jorge Javier Jiménez 2015-01-01 Several factors have motivated the use of CAS or DGS in the teaching-learning process, such as: the development of new technologies, the availability of computers, and the widespread use of the Internet, among others. Even more, the trend to include CAS and DGS in the curricula of some undergraduate studies has resulted in the instruction of the… 6. Optimization of genome editing through CRISPR-Cas9 engineering. PubMed Zhang, Jian-Hua; Adikaram, Poorni; Pandey, Mritunjay; Genis, Allison; Simonds, William F 2016-04-01 CRISPR (Clustered Regularly-Interspaced Short Palindromic Repeats)-Cas9 (CRISPR associated protein 9) has rapidly become the most promising genome editing tool with great potential to revolutionize medicine. Through guidance of a 20 nucleotide RNA (gRNA), CRISPR-Cas9 finds and cuts target protospacer DNA precisely 3 base pairs upstream of a PAM (Protospacer Adjacent Motif). The broken DNA ends are repaired by either NHEJ (Non-Homologous End Joining) resulting in small indels, or by HDR (Homology Directed Repair) for precise gene or nucleotide replacement. Theoretically, CRISPR-Cas9 could be used to modify any genomic sequences, thereby providing a simple, easy, and cost effective means of genome wide gene editing. However, the off-target activity of CRISPR-Cas9 that cuts DNA sites with imperfect matches with gRNA have been of significant concern because clinical applications require 100% accuracy. Additionally, CRISPR-Cas9 has unpredictable efficiency among different DNA target sites and the PAM requirements greatly restrict its genome editing frequency. A large number of efforts have been made to address these impeding issues, but much more is needed to fully realize the medical potential of CRISPR-Cas9. In this article, we summarize the existing problems and current advances of the CRISPR-Cas9 technology and provide perspectives for the ultimate perfection of Cas9-mediated genome editing. 7. Tuberculose pelvi-péritoneale pseudotumorale: à propos de quatre cas PubMed Central Saadi, Hanane; Mamouni, Nissrine; Errarhay, Sanaa; Bouchikhi, Chahrazed; Banani, Abdelaziz; Ammor, Hicham; Sqalli, Nadia; Tizniti, Siham; Benmajdoube, Karim; Maazaze, Khalid; Fatmi, Hind; Amarti, Afaf 2012-01-01 La tuberculose pelvienne pseudo tumorale est une maladie infectieuse curable. Son tableau clinique est souvent trompeur simulant une tumeur ovarienne ou tubaire. Le but de notre travail est de préciser les caractéristiques cliniques, biologiques et radiologiques de cette pathologie et sa prise en charge. Nous rapportons une étude rétrospective à propos de quatre observations. L’âge moyen de nos patientes est de 24 ans (16 ans, 40 ans), trois parmi elles étaient célibataires. Le motif de consultation est dominé par les douleurs abdominopelviennes chroniques. Les résultats des explorations radiologiques (échographie pelvienne associé à la TDM ou IRM pelvienne) ont été en faveur d'une tumeur ovarienne dans trois cas et d'un hydrosapinx bilatéral pour un cas. L'ascite a été présente dans tous les cas. Le dosage de la Ca 125 a été élevé. La prise en charge a été l'exploration chirurgicale soit par c'lioscopie ou laparotomie. Deux cas ont bénéficié seulement des biopsies et deux patientes ont eu une salpingectomie bilatérale devant l'aspect pseudo tumoral très suspect. L’étude histologique a confirmé des lésions graulomateuses avec nécrose caséeuse. Le traitement par les antibacillaires a été instauré selon le protocole 2ERHZ/ 4RH. La tuberculose pelvienne pseudo tumorale est l'apanage de la femme jeune. Son pronostic est lié à l'infertilité séquellaire. PMID:23330043 8. Tianeptine: 5-HT uptake sites and 5-HT(1-7) receptors modulate memory formation in an autoshaping Pavlovian/instrumental task. PubMed Meneses, Alfredo 2002-05-01 Recent studies using invertebrate and mammal species have revealed that, endogenous serotonin (5-hydroxytryptamine, 5-HT) modulates cognitive processes, particularly learning and memory, though, at present, it is unclear the manner, where, and how long 5-HT systems are involved. Hence in this work, an attempt was made to study the effects of 5-HT endogenous on memory formation, using a 5-HT uptake facilitator (tianeptine) and, selective 5-HT(1-7) receptor antagonists to determine whether 5-HT uptake sites and which 5-HT receptors are involved, respectively. Results showed that post-training tianeptine injection enhanced memory consolidation in an autoshaping Pavlovian/instrumental learning task, which has been useful to detect changes on memory formation elicited by drugs or aging. On interaction experiments, ketanserin (5-HT(1D/2A/2C) antagonist) slightly enhanced tianeptine effects, while WAY 100635 (5-HT(1A) antagonist), SB-224289 (5-HT(1B) inverse agonist), SB-200646 (5-HT(2B/2C) antagonist), ondansetron (5-HT(3) antagonist), GR 127487 (5-HT(4) antagonist), Ro 04-6790 (5-HT(6) antagonist), DR 4004 (5-HT(7) antagonist), or fluoxetine (an inhibitor of 5-HT reuptake) blocked the facilitatory tianeptine effect. Notably, together tianeptine and Ro 04-6790 impaired learning consolidation. Moreover, 5-HT depletion completely reversed the tianeptine effect. Tianeptine also normalized an impaired memory elicited by scopolamine (an antimuscarinic) or dizocilpine (non-competitive glutamatergic antagonist), while partially reversed that induced by TFMPP (5-HT(1B/1D/2A-2C/7) agonist/antagonist). Finally, tianeptine-fluoxetine coadministration had no effect on learning consolidation; nevertheless, administration of an acetylcholinesterase inhibitor, phenserine, potentiated subeffective tianeptine or fluoxetine doses. Collectively, these data confirmed that endogenously 5-HT modulates, via uptake sites and 5-HT(1-7) receptors, memory consolidation, and are consistent with the 9. Spinal 5-HT1A, not the 5-HT1B or 5-HT3 receptors, mediates descending serotonergic inhibition for late-phase mechanical allodynia of carrageenan-induced peripheral inflammation. PubMed Kim, Joung Min; Jeong, Seong Wook; Yang, Jihoon; Lee, Seong Heon; Kim, Woon Mo; Jeong, Seongtae; Bae, Hong Beom; Yoon, Myung Ha; Choi, Jeong Il 2015-07-23 Previous electrophysiological studies demonstrated a limited role of 5-hydroxytryptamine 3 receptor (5-HT3R), but facilitatory role of 5-HT1AR and 5-HT1BR in spinal nociceptive processing of carrageenan-induced inflammatory pain. The release of spinal 5-HT was shown to peak in early-phase and return to baseline in late-phase of carrageenan inflammation. We examined the role of the descending serotonergic projections involving 5-HT1AR, 5-HT1BR, and 5-HT3R in mechanical allodynia of early- (first 4h) and late-phase (24h after) carrageenan-induced inflammation. Intrathecal administration of 5-HT produced a significant anti-allodynic effect in late-phase, but not in early-phase. Similarly, intrathecal 5-HT1AR agonist (8-OH-DPAT) attenuated the intensity of late-phase allodynia in a dose dependent fashion which was antagonized by 5-HT1AR antagonist (WAY-100635), but produced no effect on the early-phase allodynia. However, other agonists or antagonists of 5-HT1BR (CP-93129, SB-224289) and 5-HT3R (m-CPBG, ondansetron) did not produce any anti- or pro-allodynic effect in both early- and late- phase allodynia. These results suggest that spinal 5-HT1A, but not 5-HT1B or 5-HT3 receptors mediate descending serotonergic inhibition on nociceptive processing of late-phase mechanical allodynia in carrageenan-induced inflammation. 10. 5-HT(1A) and 5-HT(7) receptors differently modulate AMPA receptor-mediated hippocampal synaptic transmission. PubMed Costa, L; Trovato, C; Musumeci, S A; Catania, M V; Ciranna, L 2012-04-01 We have studied the effects of 5-HT(1A) and 5-HT(7) serotonin receptor activation in hippocampal CA3-CA1 synaptic transmission using patch clamp on mouse brain slices. Application of either 5-HT or 8-OH DPAT, a mixed 5-HT(1A)/5-HT(7) receptor agonist, inhibited AMPA receptor-mediated excitatory post synaptic currents (EPSCs); this effect was mimicked by the 5-HT(1A) receptor agonist 8-OH PIPAT and blocked by the 5-HT(1A) antagonist NAN-190. 8-OH DPAT increased paired-pulse facilitation and reduced the frequency of mEPSCs, indicating a presynaptic reduction of glutamate release probability. In another group of neurons, 8-OH DPAT enhanced EPSC amplitude but did not alter paired-pulse facilitation, suggesting a postsynaptic action; this effect persisted in the presence of NAN-190 and was blocked by the 5-HT(7) receptor antagonist SB-269970. To confirm that EPSC enhancement was mediated by 5-HT(7) receptors, we used the compound LP-44, which is considered a selective 5-HT(7) agonist. However, LP-44 reduced EPSC amplitude in most cells and instead increased EPSC amplitude in a subset of neurons, similarly to 8-OH DPAT. These effects were respectively antagonized by NAN-190 and by SB-269970, indicating that under our experimental condition LP-44 behaved as a mixed agonist. 8-OH DPAT also modulated the current evoked by exogenously applied AMPA, inducing either a reduction or an increase of amplitude in distinct neurons; these effects were respectively blocked by 5-HT(1A) and 5-HT(7) receptor antagonists, indicating that both receptors exert a postsynaptic action. Our results show that 5-HT(1A) receptors inhibit CA3-CA1 synaptic transmission acting both pre- and postsynaptically, whereas 5-HT(7) receptors enhance CA3-CA1 synaptic transmission acting exclusively at a postsynaptic site. We suggest that a selective pharmacological targeting of either subtype may be envisaged in pathological loss of hippocampal-dependent cognitive functions. In this respect, we underline the 11. Agonist properties of N,N-dimethyltryptamine at serotonin 5-HT2A and 5-HT2C receptors. PubMed Smith, R L; Canton, H; Barrett, R J; Sanders-Bush, E 1998-11-01 Extensive behavioral and biochemical evidence suggests an agonist role at the 5-HT2A receptor, and perhaps the 5-HT2C receptor, in the mechanism of action of hallucinogenic drugs. However the published in vitro pharmacological properties of N,N-dimethyltryptamine (DMT), an hallucinogenic tryptamine analog, are not consistent with this hypothesis. We, therefore, undertook an extensive investigation into the properties of DMT at 5-HT2A and 5-HT2C receptors. In fibroblasts transfected with the 5-HT2A receptor or the 5-HT2C receptor, DMT activated the major intracellular signaling pathway (phosphoinositide hydrolysis) to an extent comparable to that produced by serotonin. Because drug efficacy changes with receptor density and cellular microenvironment, we also examined the properties of DMT in native preparations using a behavioral and biochemical approach. Rats were trained to discriminate an antagonist ketanserin from an agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) in a two-lever choice paradigm. Pharmacological studies showed that responding on the DOI and ketanserin lever reflected agonist and antagonist activity at 5-HT2A receptors, and hence, was a suitable model for evaluating the in vivo functional properties of DMT. Like other 5-HT2A receptor agonists, DMT substituted fully for DOI. Intact choroid plexus was used to evaluate the agonist properties at endogenous 5-HT2C receptors; DMT was a partial agonist at 5-HT2C receptors in this native preparation. Thus, we conclude that DMT behaves as an agonist at both 5-HT2A and 5-HT2A receptors. One difference was evident in that the 5-HT2C, but not the 5-HT2A, receptor showed a profound desensitization to DMT over time. This difference is interesting in light of the recent report that the hallucinogenic activity of DMT does not tolerate in humans and suggests the 5-HT2C receptor plays a less prominent role in the action of DMT. 12. Effects of MDMA and related analogs on plasma 5-HT: relevance to 5-HT transporters in blood and brain. PubMed Yubero-Lahoz, Samanta; Ayestas, Mario A; Blough, Bruce E; Partilla, John S; Rothman, Richard B; de la Torre, Rafael; Baumann, Michael H 2012-01-15 (±)-3,4-Methylenedioxymethamphetamine (MDMA) is an illicit drug that evokes transporter-mediated release of serotonin (5-HT) in the brain. 5-HT transporter (SERT) proteins are also expressed in non-neural tissues (e.g., blood), and evidence suggests that MDMA targets platelet SERT to increase plasma 5-HT. Here we tested two hypotheses related to the effects of MDMA on circulating 5-HT. First, to determine if MDMA metabolites might contribute to actions of the drug in vivo, we used in vitro microdialysis in rat blood specimens to examine the effects of MDMA and its metabolites on plasma 5-HT. Second, to determine whether effects of MDMA on plasma 5-HT might be used as an index of central SERT activity, we carried out in vivo microdialysis in blood and brain after intravenous MDMA administration. The in vitro results show that test drugs evoke dose-related increases in plasma 5-HT ranging from two- to sevenfold above baseline, with MDMA and its metabolite, (±)-3,4-methylenedioxyamphetamine (MDA), producing the largest effects. The ability of MDMA and related analogs to elevate plasma 5-HT is correlated with their potency as SERT substrates in rat brain synaptosomes. The in vivo results reveal that MDMA causes concurrent increases in extracellular 5-HT in blood and brain, but there are substantial individual differences in responsiveness to the drug. Collectively, our findings indicate that MDMA and its metabolites increase plasma 5-HT by a SERT-dependent mechanism, and suggest the possibility that measures of evoked 5-HT release in blood may reflect central SERT activity. 13. Human 5–HT4 and 5–HT7 Receptor Splice Variants: Are they Important? PubMed Central Coupar, Ian M; Desmond, Paul V; Irving, Helen R 2007-01-01 G-protein-coupled receptors (GPCRs), which are encoded by >300 genes in the human genome, are by far the largest class of targets for modern drugs. These macromolecules display inherent adaptability of function, which is partly due to the production of different forms of the receptor protein. These are commonly called ‘isoforms’ or ‘splice variants’ denoting the molecular process of their production/assembly. Not all GPCRs are expressed as splice variants, but certain subclasses of 5–HT receptors are for example, the 5–HT4 and 5–HT7 receptors. There are at least 11 human 5–HT4 and three h5–HT7 receptor splice variants. This review describestheir discoveries, nomenclature and structures. The discovery that particular splice variants are tissue specific (or prominent) has highlighted their potential as future drug targets. In particular, this review examines the functional relevance of different 5–HT4 and 5–HT7 receptor splice variants. Examples are given to illustrate that splice variants have differential modulatory influences on signalling processes. Differences in agonist potency and efficacies and also differences in desensitisation rates to 5–HT occur with both 5–HT4 and 5–HT7 receptor splice variants. The known and candidate signalling systems that allow for splice variant specific responses include GPCR interacting proteins (GIPs) and GPCR receptor kinases (GRKs) which are examined.Finally, the relevance of 5–HT receptor splice variants to clinical medicine and to the pharmaceutical industry is discussed. PMID:19305739 14. Possible involvement of 5-HT and 5-HT2 receptors in acceleration of gastrointestinal transit by escin Ib in mice. PubMed Matsuda, H; Li, Y; Yoshikawa, M 2000-01-01 We have reported previously that escin Ib accelerated gastrointestinal transit (GIT) in mice, and that its effect may be mediated by the release of endogenous prostaglandins (PGs) and nitric oxide (NO). In this study, the possible involvement of 5-HT and 5-HT receptors in the GIT acceleration of escin Ib was investigated in mice. The acceleration of GIT by escin Ib (25 or 50 mg/kg, p.o.) was attenuated by pretreatment with ritanserin (0.5-5 mg/kg, s.c., a 5-HT(2A/2C/2B) receptor antagonist), but not with MDL 72222 (1 and 5 mg/kg, s.c.) and metoclopramide (10 mg/kg, s.c.) (5-HT3 receptor antagonists) or tropisetron (1 and 10 mg/kg, s.c., a 5-HT(3/4) receptor antagonist). Furthermore, pretreatment with ketanserin (0.05-5 mg/kg, s.c.), haloperidol (1-5 mg/kg, s.c.) and spiperone (0.5-5 mg/kg, s.c.) (5-HT2A receptor antagonists), as well as a bolus of dl-p-chlorophenylalanine methyl ester (PCPA, 1000 mg/kg, p.o., 1, 6 or 24 h before administration of the sample) (an inhibitor of 5-HT synthesizing enzyme tryptophan hydroxylase) and reserpine (5 mg/kg, p.o.) (a 5-HT depletor), but not 6-hydroxydopamine (80 mg/kg, i.p., a dopamine depletor) or repeated PCPA (300 mg/kg x2, p.o., 72 and 48 h before administration of the sample), also attenuated the effects of escin Ib. It is postulated that escin Ib accelerates GIT, at least in part, by stimulating the synthesis of 5-HT to act through 5-HT2, possibly 5-HT2A receptors, which in turn causes the release of NO and PGs. 15. Guide RNA engineering for versatile Cas9 functionality PubMed Central Nowak, Chance M.; Lawson, Seth; Zerez, Megan; Bleris, Leonidas 2016-01-01 The Clustered Regularly Interspaced Short Palindromic Repeats system allows a single guide RNA (sgRNA) to direct a protein with combined helicase and nuclease activity to the DNA. Streptococcus pyogenes Cas9 (SpCas9), a CRISPR-associated protein, has revolutionized our ability to probe and edit the human genome in vitro and in vivo. Arguably, the true modularity of the Cas9 platform is conferred through the ease of sgRNA programmability as well as the degree of modifications the sgRNA can tolerate without compromising its association with SpCas9 and function. In this review, we focus on the properties and recent engineering advances of the sgRNA component in Cas9-mediated genome targeting. PMID:27733506 16. Diversity and evolution of class 2 CRISPR-Cas systems. PubMed Shmakov, Sergey; Smargon, Aaron; Scott, David; Cox, David; Pyzocha, Neena; Yan, Winston; Abudayyeh, Omar O; Gootenberg, Jonathan S; Makarova, Kira S; Wolf, Yuri I; Severinov, Konstantin; Zhang, Feng; Koonin, Eugene V 2017-03-01 Class 2 CRISPR-Cas systems are characterized by effector modules that consist of a single multidomain protein, such as Cas9 or Cpf1. We designed a computational pipeline for the discovery of novel class 2 variants and used it to identify six new CRISPR-Cas subtypes. The diverse properties of these new systems provide potential for the development of versatile tools for genome editing and regulation. In this Analysis article, we present a comprehensive census of class 2 types and class 2 subtypes in complete and draft bacterial and archaeal genomes, outline evolutionary scenarios for the independent origin of different class 2 CRISPR-Cas systems from mobile genetic elements, and propose an amended classification and nomenclature of CRISPR-Cas. 17. CRISPR-Cas Technologies and Applications in Food Bacteria. PubMed Stout, Emily; Klaenhammer, Todd; Barrangou, Rodolphe 2017-02-28 Clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins form adaptive immune systems that occur in many bacteria and most archaea. In addition to protecting bacteria from phages and other invasive mobile genetic elements, CRISPR-Cas molecular machines can be repurposed as tool kits for applications relevant to the food industry. A primary concern of the food industry has long been the proper management of food-related bacteria, with a focus on both enhancing the outcomes of beneficial microorganisms such as starter cultures and probiotics and limiting the presence of detrimental organisms such as pathogens and spoilage microorganisms. This review introduces CRISPR-Cas as a novel set of technologies to manage food bacteria and offers insights into CRISPR-Cas biology. It primarily focuses on the applications of CRISPR-Cas systems and tools in starter cultures and probiotics, encompassing strain-typing, phage resistance, plasmid vaccination, genome editing, and antimicrobial activity. 18. Cas9-mediated targeting of viral RNA in eukaryotic cells. PubMed Price, Aryn A; Sampson, Timothy R; Ratner, Hannah K; Grakoui, Arash; Weiss, David S 2015-05-12 Clustered, regularly interspaced, short palindromic repeats-CRISPR associated (CRISPR-Cas) systems are prokaryotic RNA-directed endonuclease machineries that act as an adaptive immune system against foreign genetic elements. Using small CRISPR RNAs that provide specificity, Cas proteins recognize and degrade nucleic acids. Our previous work demonstrated that the Cas9 endonuclease from Francisella novicida (FnCas9) is capable of targeting endogenous bacterial RNA. Here, we show that FnCas9 can be directed by an engineered RNA-targeting guide RNA to target and inhibit a human +ssRNA virus, hepatitis C virus, within eukaryotic cells. This work reveals a versatile and portable RNA-targeting system that can effectively function in eukaryotic cells and be programmed as an antiviral defense. 19. Cas9-mediated targeting of viral RNA in eukaryotic cells PubMed Central Price, Aryn A.; Sampson, Timothy R.; Ratner, Hannah K.; Grakoui, Arash; Weiss, David S. 2015-01-01 Clustered, regularly interspaced, short palindromic repeats–CRISPR associated (CRISPR-Cas) systems are prokaryotic RNA-directed endonuclease machineries that act as an adaptive immune system against foreign genetic elements. Using small CRISPR RNAs that provide specificity, Cas proteins recognize and degrade nucleic acids. Our previous work demonstrated that the Cas9 endonuclease from Francisella novicida (FnCas9) is capable of targeting endogenous bacterial RNA. Here, we show that FnCas9 can be directed by an engineered RNA-targeting guide RNA to target and inhibit a human +ssRNA virus, hepatitis C virus, within eukaryotic cells. This work reveals a versatile and portable RNA-targeting system that can effectively function in eukaryotic cells and be programmed as an antiviral defense. PMID:25918406 20. Application of CRISPR/Cas9 in plant biology. PubMed Liu, Xuan; Wu, Surui; Xu, Jiao; Sui, Chun; Wei, Jianhe 2017-05-01 The CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins) system was first identified in bacteria and archaea and can degrade exogenous substrates. It was developed as a gene editing technology in 2013. Over the subsequent years, it has received extensive attention owing to its easy manipulation, high efficiency, and wide application in gene mutation and transcriptional regulation in mammals and plants. The process of CRISPR/Cas is optimized constantly and its application has also expanded dramatically. Therefore, CRISPR/Cas is considered a revolutionary technology in plant biology. Here, we introduce the mechanism of the type II CRISPR/Cas called CRISPR/Cas9, update its recent advances in various applications in plants, and discuss its future prospects to provide an argument for its use in the study of medicinal plants. 1. Nano-confinement induced chain alignment in ordered P3HT nanostructures defined by nanoimprint lithography. PubMed Aryal, Mukti; Trivedi, Krutarth; Hu, Wenchuang Walter 2009-10-27 Control of polymer morphology and chain orientation is of great importance in organic solar cells and field effect transistors (OFETs). Here we report the use of nanoimprint lithography to fabricate large-area, high-density, and ordered nanostructures in conjugated polymer poly(3-hexylthiophene) or P3HT, and also to simultaneously control 3D chain alignment within these P3HT nanostructures. Out-of-plane and in-plane grazing incident X-ray diffraction were used to determine the chain orientation in the imprinted P3HT nanostructures, which shows a strong dependence on their geometry (gratings or pillars). Vertical chain alignment was observed in both nanogratings and nanopillars, indicating strong potential to improve charge transport and optical properties for solar cells in comparison to bulk heterojunction structure. For P3HT nanogratings, pi-pi stacking along the grating direction with an angular distribution of +/-20 degrees was found, which is favorable for OFETs. We propose the chain alignment is induced by the nanoconfinement during nanoimprinting via pi-pi interaction and hydrophobic interaction between polymer chain and mold surfaces. 2. The Contact Activation System (CAS) in cord blood: Measurement of CAS components and comparison with mother's blood. A pilot study. PubMed Uszyński, Mieczysław; Kuczyński, Jarosław; Żekanowska, Ewa; Uszyński, Waldemar 2015-11-01 Classical reference data concerning the coagulation system and fibrinolysis in fetuses and newborns date back to the 1990 s. Since that time a number of methodological or other improvements have been implemented, which may cast some doubt on timeliness of the data. The study objective was to measure the levels of Contact Activation System (CAS) components by antigen, i.e. factors XII and XI (FXII, FXI), prekallikrein (PK) and high molecular weight kininogen (HMWK) in cord blood and maternal blood. The study group consisted of 35 healthy parturient women with an uneventful pregnancy and birth. The samples of cord blood and maternal blood were obtained immediately after delivery, before clumping the umbilical cord. The CAS components were measured by immunoenzymatic method (ELISA). The median concentrations of CAS components in cord blood plasma and mother's plasma were as follow: FXII: 1.02 (0.60- 2.58) ng/mg protein vs. 0.94 (0.66-1.86) ng/mg protein (p>0.05); FXI: 2.71(0.03-8.0) ng/mg protein vs. 0.92 (0.03-10.44) ng/mg protein (p>0.05); PK: 168.78 (104.28-261.16) pg/mg protein vs. 113.44 (79.94-146.70) pg/mg protein (p>0.05); HMWK: 2169.45 (1530.64- 2539.83) ng/mg protein vs. 2857.96 (2541.52-3161.04) ng/mg protein (p<0.001). 1. The antigen levels of the three contact factors, i.e. FXII, FXI and PK in the cord blood of full-term and healthy fetuses were similar to those observed in mother's blood immediately after delivery. Only high molecular weight kininogen was found to be lower (accounting for 84% of the values noted in mothers). 2. Based on our measurements, we claim that the cited reference data concerning the contact factors in full-term and healthy newborns are underestimated; hence, new reference values need to be determined for each antigen and activity contact factor level. Copyright © 2015. Published by Elsevier Ltd. 3. Photodynamic action of palmatine hydrochloride on colon adenocarcinoma HT-29 cells. PubMed Wu, Juan; Xiao, Qicai; Zhang, Na; Xue, Changhu; Leung, Albert Wingnang; Zhang, Hongwei; Xu, Chuanshan; Tang, Qing-Juan 2016-09-01 Palmatine hydrochloride (PaH) is a natural active compound from a traditional Chinese medicine (TCM). The present study aims to evaluate the effect of PaH as a new photosensitizer on colon adenocarcinoma HT-29 cells upon light irradiation. Firstly, the absorption and fluorescence spectra of PaH were measured using a UV-vis spectrophotometer and RF-1500PC spectrophotometer, respectively. Singlet oxygen ((1)O2) production of PaH was determined using 1, 3-diphenylisobenzofuran (DPBF). Dark toxicity of PaH was estimated using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Cellular uptake of PaH in HT-29 cells was detected at different time intervals. Subellular localization of PaH in HT-29 cells was observed using confocal laser fluorescence microscopy. For photodynamic treatment, HT-29 cells were incubated with PaH and then irradiated by visible light (470nm) from a LED light source. Photocytotoxicity was investigated 24h after photodynamic treatment using MTT assay. Cell apoptosis was observed 18h after photodynamic treatment using a flow cytometry with Annexin V/PI staining. Results showed that PaH has an absorption peak in the visible region from 400nm to 500nm and a fluorescence emission peak at 406nm with an excitation wavelength of 365nm. PaH was activated by the 470nm visible light from a LED light source to produce (1)O2. Dark toxicity showed that PaH alone treatment had no cytotoxicity to HT-29 cancer cells and NIH-3T3 normal cells after incubation for 24h. After incubation for 40min, the cellular uptake of PaH reached to the maximum and PaH was located in mitochondria. Photodynamic treatment of PaH demonstrated a significant photocytotoxicity on HT-29 cells. The rate of cell death increased significantly in a PaH concentration-dependent and light dose-dependent manner. Further evaluation revealed that the early and late apoptotic rate of HT-29 cells increased remarkably up to 21.54% and 5.39% after photodynamic treatment of 4. Evidence that mCPP may have behavioural effects mediated by central 5-HT1C receptors. PubMed Central Kennett, G. A.; Curzon, G. 1988-01-01 1. The effects of 1-(3-chlorophenyl)piperazine (mCPP) and 1-[3-(trifluoromethyl)phenyl] piperazine (TFMPP) on activity of rats in a novel cage, and on the rotorod and elevated bar co-ordination tests was examined. 2. Peripherally administered mCPP and TFMPP dose-dependently reduced locomotion, rearing, and feeding scores but not grooming of freely fed rats placed in a novel observation cage. Yawning behaviour was increased. Similar effects were also observed after injection of mCPP into the 3rd ventricle. 3. Co-ordination on a rotating drum of both untrained and trained rats was impaired following mCPP but co-ordination on an elevated bar was not. 4. The hypoactivity induced by mCPP was opposed by three antagonists with high affinity for the 5-hydroxytryptamine (5-HT1C) site; metergoline, mianserin, cyproheptadine and possibly also by a fourth antagonist mesulergine. Metergoline, mianserin and cyproheptadine also opposed the reduction in feeding scores. However, neither effect of mCPP was antagonized by the 5-HT2-receptor antagonists ketanserin or ritanserin, the 5-HT3-receptor antagonist ICS 205-930, the 5-HT1A and 5-HT1B-receptor antagonists (-)-pindolol, (-)-propranolol and (+/-)-cyanopindolol or the 5-HT1A-, 5-HT2- and dopamine receptor antagonist spiperone. The specific alpha 2-adrenoceptor antagonist idazoxan was also without effect. 5. Hypoactivity induced by TFMPP was similarly antagonized by mianserin but unaffected by (+/-)-cyanopindolol. 6. These results suggest that the hypoactivity is mediated by central 5-HT1C-receptors and that mCPP and possibly TFMPP may be 5-HT1C-receptor agonists. 7. As mianserin, cyproheptadine and mesulergine in the absence of mCPP did not increase locomotion but increased the number of feeding scores, the activation of 5-HT1C-receptors may be of physiological importance in the control of appetite. The possible relevance of these results to the therapeutic and side-effects of clinically used antidepressants (particularly 5. Interstellar and ejecta dust in the cas a supernova remnant SciTech Connect Arendt, Richard G.; Dwek, Eli; Kober, Gladys; Rho, Jeonghee; Hwang, Una 2014-05-01 Infrared continuum observations provide a means of investigating the physical composition of the dust in the ejecta and swept up medium of the Cas A supernova remnant (SNR). Using low-resolution Spitzer IRS spectra (5-35 μm), and broad-band Herschel PACS imaging (70, 100, and 160 μm), we identify characteristic dust spectra, associated with ejecta layers that underwent distinct nuclear burning histories. The most luminous spectrum exhibits strong emission features at ∼9 and 21 μm and is closely associated with ejecta knots with strong Ar emission lines. The dust features can be reproduced by magnesium silicate grains with relatively low Mg to Si ratios. Another dust spectrum is associated with ejecta having strong Ne emission lines. It has no indication of any silicate features and is best fit by Al{sub 2}O{sub 3} dust. A third characteristic dust spectrum shows features that are best matched by magnesium silicates with a relatively high Mg to Si ratio. This dust is primarily associated with the X-ray-emitting shocked ejecta, but it is also evident in regions where shocked interstellar or circumstellar material is expected. However, the identification of dust composition is not unique, and each spectrum includes an additional featureless dust component of unknown composition. Colder dust of indeterminate composition is associated with emission from the interior of the SNR, where the reverse shock has not yet swept up and heated the ejecta. Most of the dust mass in Cas A is associated with this unidentified cold component, which is ≲ 0.1 M {sub ☉}. The mass of warmer dust is only ∼0.04 M {sub ☉}. 6. Interstellar and Ejecta Dust in the Cas A Supernova Remnant NASA Astrophysics Data System (ADS) Arendt, Richard G.; Dwek, Eli; Kober, Gladys; Rho, Jeonghee; Hwang, Una 2014-05-01 Infrared continuum observations provide a means of investigating the physical composition of the dust in the ejecta and swept up medium of the Cas A supernova remnant (SNR). Using low-resolution Spitzer IRS spectra (5-35 μm), and broad-band Herschel PACS imaging (70, 100, and 160 μm), we identify characteristic dust spectra, associated with ejecta layers that underwent distinct nuclear burning histories. The most luminous spectrum exhibits strong emission features at ~9 and 21 μm and is closely associated with ejecta knots with strong Ar emission lines. The dust features can be reproduced by magnesium silicate grains with relatively low Mg to Si ratios. Another dust spectrum is associated with ejecta having strong Ne emission lines. It has no indication of any silicate features and is best fit by Al2O3 dust. A third characteristic dust spectrum shows features that are best matched by magnesium silicates with a relatively high Mg to Si ratio. This dust is primarily associated with the X-ray-emitting shocked ejecta, but it is also evident in regions where shocked interstellar or circumstellar material is expected. However, the identification of dust composition is not unique, and each spectrum includes an additional featureless dust component of unknown composition. Colder dust of indeterminate composition is associated with emission from the interior of the SNR, where the reverse shock has not yet swept up and heated the ejecta. Most of the dust mass in Cas A is associated with this unidentified cold component, which is <~ 0.1 M ⊙. The mass of warmer dust is only ~0.04 M ⊙. 7. Bivalent Ligands for the Serotonin 5-HT3 Receptor PubMed Central 2011-01-01 The serotonin 5-HT3 receptor is a ligand-gated ion channel, which by virtue of its pentameric architecture, can be considered to be an intriguing example of intrinsically multivalent biological receptors. This paper describes a general design approach to the study of multivalency in this multimeric ion channel. Bivalent ligands for 5-HT3 receptor have been designed by linking an arylpiperazine moiety to probes showing different functional features. Both homobivalent and heterobivalent ligands have shown 5-HT3 receptor affinity in the nanomolar range, providing evidence for the viability of our design approach. Moreover, the high affinity shown by homobivalent ligands suggests that bivalency is a promising approach in 5-HT3 receptor modulation and provides the rational basis for applying the concepts of multivalency to the study of 5-HT3 receptor function. PMID:24900351 8. Probing the structural dynamics of the CRISPR-Cas9 RNA-guided DNA-cleavage system by coarse-grained modeling. PubMed Zheng, Wenjun 2017-02-01 In the adaptive immune systems of many bacteria and archaea, the Cas9 endonuclease forms a complex with specific guide/scaffold RNA to identify and cleave complementary target sequences in foreign DNA. This DNA targeting machinery has been exploited in numerous applications of genome editing and transcription control. However, the molecular mechanism of the Cas9 system is still obscure. Recently, high-resolution structures have been solved for Cas9 in different structural forms (e.g., unbound forms, RNA-bound binary complexes, and RNA-DNA-bound tertiary complexes, corresponding to an inactive state, a pre-target-bound state, and a cleavage-competent or product state), which offered key structural insights to the Cas9 mechanism. To further probe the structural dynamics of Cas9 interacting with RNA and DNA at the amino-acid level of details, we have performed systematic coarse-grained modeling using an elastic network model and related analyses. Our normal mode analysis predicted a few key modes of collective motions that capture the observed conformational changes featuring large domain motions triggered by binding of RNA and DNA. Our flexibility analysis identified specific regions with high or low flexibility that coincide with key functional sites (such as DNA/RNA-binding sites, nuclease cleavage sites, and key hinges). We also identified a small set of hotspot residues that control the energetics of functional motions, which overlap with known functional sites and offer promising targets for future mutagenesis efforts to improve the specificity of Cas9. Finally, we modeled the conformational transitions of Cas9 from the unbound form to the binary complex and then the tertiary complex, and predicted a distinct sequence of domain motions. In sum, our findings have offered rich structural and dynamic details relevant to the Cas9 machinery, and will guide future investigation and engineering of the Cas9 systems. Proteins 2017; 85:342-353. © 2016 Wiley Periodicals 9. Manipulating the Biosynthesis of Bioactive Compound Alkaloids for Next-Generation Metabolic Engineering in Opium Poppy Using CRISPR-Cas 9 Genome Editing Technology PubMed Central Alagoz, Yagiz; Gurkok, Tugba; Zhang, Baohong; Unver, Turgay 2016-01-01 Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated9 (Cas9) endonuclease system is a powerful RNA-guided genome editing tool. CRISPR/Cas9 has been well studied in model plant species for targeted genome editing. However, few studies have been reported on plant species without whole genome sequence information. Currently, no study has been performed to manipulate metabolic pathways using CRISPR/Cas9. In this study, the type II CRISPR/SpCas9 system was used to knock out, via nonhomologous end-joining genome repair, the 4′OMT2 in opium poppy (Papaver somniferum L.), a gene which regulates the biosythesis of benzylisoquinoline alkaloids (BIAs). For sgRNA transcription, viral-based TRV and synthetic binary plasmids were designed and delivered into plant cells with a Cas9 encoding-synthetic vector by Agrobacterium-mediated transformation. InDels formed by CRISPR/Cas9 were detected by sequence analysis. Our results showed that the biosynthesis of BIAs (e.g. morphine, thebaine) was significantly reduced in the transgenic plants suggesting that 4′OMT2 was efficiently knocked-out by our CRISPR-Cas9 genome editing approach. In addition, a novel uncharacterized alkaloid was observed only in CRISPR/Cas9 edited plants. Thus, the applicabilitiy of the CRISPR/Cas9 system was demonstrated for the first time for medicinal aromatic plants by sgRNAs transcribed from both synthetic and viral vectors to regulate BIA metabolism and biosynthesis. PMID:27483984 10. Object-Oriented Version of Glenn-HT Code Released: Glenn-HT2000 NASA Technical Reports Server (NTRS) Heidmann, James D.; Ameri, Ali A.; Rigby, David I.; Garg, Vijay K.; Fabian, John C.; Lucci, Barbara L.; Steinthorsson, Erlendur 2005-01-01 NASA Glenn Research Center s General Multi-Block Navier-Stokes Convective Heat Transfer Code (Glenn-HT) has been used extensively to predict heat transfer and fluid flow for a variety of steady gas turbine engine problems. Efforts have focused on turbine heat transfer, where computations have modeled tip clearance, internal coolant, and film cooling flows. Excellent agreement has been achieved for a variety of experimental test cases, and results have been published in over 40 technical publications. The code is available to U.S. industry and has been used by several domestic gas turbine engine companies. The following figure shows a typical flow solution from the Glenn-HT code for a film-cooled turbine blade. 11. Ex vivo study of 5-HT(1A) and 5-HT(7) receptor agonists and antagonists on cAMP accumulation during memory formation and amnesia. PubMed Perez-García, G; Meneses, A 2008-12-16 The cyclic adenosine monophosphate (cAMP) is a second messenger and a central component of intracellular signaling pathways that regulate a wide range of biological functions, including memory. Hence, in this work, firstly the time-course of memory formation was determined in an autoshaping learning task, which had allowed the identification of testing times for increases or decreases in performance. Next, untrained, trained and overtrained groups were compared in cAMP production. Moreover, selective stimulation and antagonism of 5-HT(1A) and 5-HT(7) receptors during memory formation and cAMP production were determined. Finally, since there is scarce information about how pharmacological models of amnesia affect cAMP production, the cholinergic or glutamatergic antagonists, scopolamine and dizocilpine, were tested. The major findings of this work showed that when the time-course was determined inasmuch as training and testing sessions occurred, memory performance was graduate and progressive. Notably, for the fourth to seventh (i.e., 48-120 h following autoshaping training session) testing session performance was significantly higher from the previous ones. When animals received 5-HT(1A) and 5-HT(7) receptor agonists and antagonists or amnesic drugs significant increases or decrements in memory performance were observed at 24 and 48 h. Moreover, when ex vivo cAMP production from trained and overtrained groups were compared to untrained ones, significant differences were observed among groups and brain areas. Trained animals treated with 8-OHDPAT, AS19, 8-OHDPAT plus AS19, WAY100635, SB-269970, scopolamine or dizocilpine were compared to similar untrained groups, and eightfold-reduced cAMP production was evident, showing the importance of cAMP production in the signaling case in mammalian memory formation. 12. Cloning and immunoreactivity of the 5-HT1Mac and 5-HT2Mac receptors in the central nervous system of the freshwater prawn Macrobrachium rosenbergii PubMed Central Vázquez-Acevedo, Nietzell; Reyes-Colón, Dalynés; Ruíz-Rodríguez, Eduardo A.; Rivera, Nilsa M.; Rosenthal, Joshua; Kohn, Andrea B.; Moroz, Leonid L.; Sosa, María A. 2009-01-01 Biogenic amines are implicated in several mental disorders, many of which involve social interactions. Simple model systems, such as crustaceans, are often more amenable than vertebrates for studying mechanisms underlying behaviors. Although various cellular responses of biogenic amines have been characterized in crustaceans, the mechanisms linking these molecules to behavior remain largely unknown. Observed effects of serotonin receptor agonists and antagonists in abdomen posture, escape responses, and fighting	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 1, "mathjax_display_tex": 0, "mathjax_asciimath": 1, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.6272903084754944, "perplexity": 20600.649780896605}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.3, "absolute_threshold": 10, "end_threshold": 15, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2018-05/segments/1516084886758.34/warc/CC-MAIN-20180116224019-20180117004019-00235.warc.gz"}
https://ask.sagemath.org/answers/15457/revisions/	# Revision history [back] I ran across another way that's posted here where the author, John D Cook mentions the nsimplify command in SymPy (which you can can access in Sage). As the post indicates, you can suggest constants (eg pi) that should be considered and "...can also give nsimplify a tolerance, asking it to find a simple representation within a neighborhood of the number". Here's a screenshot of it recognizing 1.3333333333333 in a Sage Cell Server.	{"extraction_info": {"found_math": true, "script_math_tex": 0, "script_math_asciimath": 0, "math_annotations": 0, "math_alttext": 0, "mathml": 0, "mathjax_tag": 0, "mathjax_inline_tex": 0, "mathjax_display_tex": 0, "mathjax_asciimath": 1, "img_math": 0, "codecogs_latex": 0, "wp_latex": 0, "mimetex.cgi": 0, "/images/math/codecogs": 0, "mathtex.cgi": 0, "katex": 0, "math-container": 0, "wp-katex-eq": 0, "align": 0, "equation": 0, "x-ck12": 0, "texerror": 0, "math_score": 0.7536749243736267, "perplexity": 2729.9835956480665}, "config": {"markdown_headings": true, "markdown_code": true, "boilerplate_config": {"ratio_threshold": 0.18, "absolute_threshold": 20, "end_threshold": 5, "enable": true}, "remove_buttons": true, "remove_image_figures": true, "remove_link_clusters": true, "table_config": {"min_rows": 2, "min_cols": 3, "format": "plain"}, "remove_chinese": true, "remove_edit_buttons": true, "extract_latex": true}, "warc_path": "s3://commoncrawl/crawl-data/CC-MAIN-2019-26/segments/1560627999263.6/warc/CC-MAIN-20190620165805-20190620191805-00222.warc.gz"}

Subsets and Splits

No community queries yet

The top public SQL queries from the community will appear here once available.