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C126322002

Internal medicine

https://doi.org/10.1159/000453569

medical specialty dealing with the prevention, diagnosis, and treatment of adult diseases

PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer

Immune checkpoint inhibition represents a major recent breakthrough in the treatment of malignant diseases including breast cancer. Blocking the programmed death receptor-1 (PD-1) and its ligand, PD-L1, has shown impressive antitumor activity and may lead to durable long-term disease control, especially in the triple-negative subtypes of breast cancer (TNBC). Although immune checkpoint blockade is generally well tolerated, specific immune-related adverse events (irAEs) may occur. This review summarizes the clinical efficacy, perspectives, and future challenges of using PD-1/PD-L1-directed antibodies in the treatment of breast cancer.

C126322002

Internal medicine

https://doi.org/10.1159/000468530

medical specialty dealing with the prevention, diagnosis, and treatment of adult diseases

Magnesium Replacement Improves the Metabolic Profile in Obese and Pre-Diabetic Patients with Mild-to-Moderate Chronic Kidney Disease: A 3-Month, Randomised, Double-Blind, Placebo-Controlled Study

Epidemiological studies have associated low dietary Mg2+ intake with insulin resistance (IR) and increased risk for metabolic syndrome; however, the effect of Mg2+ supplementation on IR has not been adequately investigated. This study aimed to investigate the effects of oral Mg2+ supplementation on insulin sensitivity (IS) and serum lipids.<br />Forty-eight patients with mild uncomplicated hypertension participated in the study. Among them, 24 subjects were assigned to 600 mg of pidolate Mg2+ daily in addition to lifestyle recommendations for a 12-week period, and another 24 age- and sex-matched controls were only given lifestyle recommendations. At baseline and study-end, blood sampling for determination of fasting glucose and insulin levels, serum lipids and other standard laboratory tests, as well as an oral glucose tolerance test (OGTT) for estimation of IS indices, were performed in all subjects.<br />In the Mg2+ supplementation group the OGTT-derived IS indices of Stumvoll, Matsuda and Cedercholm in were increased between baseline baseline and study-end. In contrast, none of these parameters were changed in the control group. Reductions in total cholesterol, LDL-cholesterol and triglyceride levels, along with a parallel increase in HDL-cholesterol levels, were evident at study-end in the intervention group, but not in the control group.<br />This study suggests that oral Mg2+ supplementation improves IS and lipid profile in mildly hypertensive patients. These potential beneficial effects of Mg2+ on associated metabolic factors could be helpful for patients with hypertension in terms of overall cardiovascular risk reduction.

C126322002

Internal medicine

https://doi.org/10.1056/nejm199309303291401

medical specialty dealing with the prevention, diagnosis, and treatment of adult diseases

The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long-Term Complications in Insulin-Dependent Diabetes Mellitus

Long-term microvascular and neurologic complications cause major morbidity and mortality in patients with insulin-dependent diabetes mellitus (IDDM). We examined whether intensive treatment with the goal of maintaining blood glucose concentrations close to the normal range could decrease the frequency and severity of these complications.

C126322002

Internal medicine

https://doi.org/10.1159/000454668

medical specialty dealing with the prevention, diagnosis, and treatment of adult diseases

The “Golden Age” of Probiotics: A Systematic Review and Meta-Analysis of Randomized and Observational Studies in Preterm Infants

This review reports the beneficial effects, observed in our clinical studies, of Bifidobacterium breve for premature infants, and children with cancers undergoing chemotherapy. To investigate the protective effects of B. breve (M-16V) as a probiotic on necrotizing enterocolitis (NEC) and infection in premature infants, we carried out a clinical study in 338 very low birth weight infants over a five-year period. These patients were supplemented with B. breve starting several hours after birth (Bifido group). 226 premature infants served as controls. Infants of the Bifido group were administered B. breve in a daily dose of 1×10(9) cells/day. The incidence of NEC was significantly reduced in the Bifido group (nil) compared with that in controls (6 cases, P<0.01). Infection also decreased significantly. Thus, administration of B. breve as a probiotic looks to be a very effective treatment for preventing NEC and infection in preterm infants. Mucositis, also referred to as mucosal barrier injury, is one of the most debilitating side effects of chemotherapy treatment. To evaluate the effects of the administration of B. breve (BBG-01, another strain than that used in the study of premature infants), a clinical study was performed to ascertain whether it attenuated intestinal mucositis in children with cancers on chemotherapy. A placebo-controlled trial was performed in patients with malignancies admitted for chemotherapy (n=42), who were randomised into two groups receiving probiotic or placebo. The frequency of fever and the use of intravenous antibiotics were significantly lower in the Bifido group than the placebo group. The B. breve administration enhanced the colonisation of anaerobes. Disruption of the intestinal microbiota after chemotherapy, such as the increase in the population levels of Enterobacteriaceae, was more pronounced in the placebo group. In conclusion, these data suggest that administration of B. breve is an effective approach to attenuating chemotherapy-induced mucositis in children with cancers. The study results strongly suggest that B. breve administration as a probiotic is an effective therapy for the prevention of NEC and infection in premature infants, and also a promising treatment for attenuating chemotherapy-induced mucositis in children with cancers.

C126322002

Internal medicine

https://doi.org/10.1056/nejmoa043330

medical specialty dealing with the prevention, diagnosis, and treatment of adult diseases

Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma

Glioblastoma, the most common primary brain tumor in adults, is usually rapidly fatal. The current standard of care for newly diagnosed glioblastoma is surgical resection to the extent feasible, followed by adjuvant radiotherapy. In this trial we compared radiotherapy alone with radiotherapy plus temozolomide, given concomitantly with and after radiotherapy, in terms of efficacy and safety.Patients with newly diagnosed, histologically confirmed glioblastoma were randomly assigned to receive radiotherapy alone (fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks, for a total of 60 Gy) or radiotherapy plus continuous daily temozolomide (75 mg per square meter of body-surface area per day, 7 days per week from the first to the last day of radiotherapy), followed by six cycles of adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28-day cycle). The primary end point was overall survival.A total of 573 patients from 85 centers underwent randomization. The median age was 56 years, and 84 percent of patients had undergone debulking surgery. At a median follow-up of 28 months, the median survival was 14.6 months with radiotherapy plus temozolomide and 12.1 months with radiotherapy alone. The unadjusted hazard ratio for death in the radiotherapy-plus-temozolomide group was 0.63 (95 percent confidence interval, 0.52 to 0.75; P<0.001 by the log-rank test). The two-year survival rate was 26.5 percent with radiotherapy plus temozolomide and 10.4 percent with radiotherapy alone. Concomitant treatment with radiotherapy plus temozolomide resulted in grade 3 or 4 hematologic toxic effects in 7 percent of patients.The addition of temozolomide to radiotherapy for newly diagnosed glioblastoma resulted in a clinically meaningful and statistically significant survival benefit with minimal additional toxicity.

C126322002

Internal medicine

https://doi.org/10.1056/nejmoa012512

medical specialty dealing with the prevention, diagnosis, and treatment of adult diseases

Reduction in the Incidence of Type 2 Diabetes with Lifestyle Intervention or Metformin

Type 2 diabetes affects approximately 8 percent of adults in the United States. Some risk factors — elevated plasma glucose concentrations in the fasting state and after an oral glucose load, overweight, and a sedentary lifestyle — are potentially reversible. We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes.

C126322002

Internal medicine

https://doi.org/10.1001/jama.2020.1585

medical specialty dealing with the prevention, diagnosis, and treatment of adult diseases

Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China

<h3>Importance</h3> In December 2019, novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited. <h3>Objective</h3> To describe the epidemiological and clinical characteristics of NCIP. <h3>Design, Setting, and Participants</h3> Retrospective, single-center case series of the 138 consecutive hospitalized patients with confirmed NCIP at Zhongnan Hospital of Wuhan University in Wuhan, China, from January 1 to January 28, 2020; final date of follow-up was February 3, 2020. <h3>Exposures</h3> Documented NCIP. <h3>Main Outcomes and Measures</h3> Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Outcomes of critically ill patients and noncritically ill patients were compared. Presumed hospital-related transmission was suspected if a cluster of health professionals or hospitalized patients in the same wards became infected and a possible source of infection could be tracked. <h3>Results</h3> Of 138 hospitalized patients with NCIP, the median age was 56 years (interquartile range, 42-68; range, 22-92 years) and 75 (54.3%) were men. Hospital-associated transmission was suspected as the presumed mechanism of infection for affected health professionals (40 [29%]) and hospitalized patients (17 [12.3%]). Common symptoms included fever (136 [98.6%]), fatigue (96 [69.6%]), and dry cough (82 [59.4%]). Lymphopenia (lymphocyte count, 0.8 × 10⁹/L [interquartile range {IQR}, 0.6-1.1]) occurred in 97 patients (70.3%), prolonged prothrombin time (13.0 seconds [IQR, 12.3-13.7]) in 80 patients (58%), and elevated lactate dehydrogenase (261 U/L [IQR, 182-403]) in 55 patients (39.9%). Chest computed tomographic scans showed bilateral patchy shadows or ground glass opacity in the lungs of all patients. Most patients received antiviral therapy (oseltamivir, 124 [89.9%]), and many received antibacterial therapy (moxifloxacin, 89 [64.4%]; ceftriaxone, 34 [24.6%]; azithromycin, 25 [18.1%]) and glucocorticoid therapy (62 [44.9%]). Thirty-six patients (26.1%) were transferred to the intensive care unit (ICU) because of complications, including acute respiratory distress syndrome (22 [61.1%]), arrhythmia (16 [44.4%]), and shock (11 [30.6%]). The median time from first symptom to dyspnea was 5.0 days, to hospital admission was 7.0 days, and to ARDS was 8.0 days. Patients treated in the ICU (n = 36), compared with patients not treated in the ICU (n = 102), were older (median age, 66 years vs 51 years), were more likely to have underlying comorbidities (26 [72.2%] vs 38 [37.3%]), and were more likely to have dyspnea (23 [63.9%] vs 20 [19.6%]), and anorexia (24 [66.7%] vs 31 [30.4%]). Of the 36 cases in the ICU, 4 (11.1%) received high-flow oxygen therapy, 15 (41.7%) received noninvasive ventilation, and 17 (47.2%) received invasive ventilation (4 were switched to extracorporeal membrane oxygenation). As of February 3, 47 patients (34.1%) were discharged and 6 died (overall mortality, 4.3%), but the remaining patients are still hospitalized. Among those discharged alive (n = 47), the median hospital stay was 10 days (IQR, 7.0-14.0). <h3>Conclusions and Relevance</h3> In this single-center case series of 138 hospitalized patients with confirmed NCIP in Wuhan, China, presumed hospital-related transmission of 2019-nCoV was suspected in 41% of patients, 26% of patients received ICU care, and mortality was 4.3%.

C126322002

Internal medicine

https://doi.org/10.1001/jama.288.3.321

medical specialty dealing with the prevention, diagnosis, and treatment of adult diseases

Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women: Principal Results From the Women's Health Initiative Randomized Controlled Trial

ContextDespite decades of accumulated observational evidence, the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain.ObjectiveTo assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States.DesignEstrogen plus progestin component of the Women's Health Initiative, a randomized controlled primary prevention trial (planned duration, 8.5 years) in which 16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998.InterventionsParticipants received conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102).Main Outcomes MeasuresThe primary outcome was coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome. A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, and death due to other causes.ResultsOn May 31, 2002, after a mean of 5.2 years of follow-up, the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits. This report includes data on the major clinical outcomes through April 30, 2002. Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs]) were as follows: CHD, 1.29 (1.02-1.63) with 286 cases; breast cancer, 1.26 (1.00-1.59) with 290 cases; stroke, 1.41 (1.07-1.85) with 212 cases; PE, 2.13 (1.39-3.25) with 101 cases; colorectal cancer, 0.63 (0.43-0.92) with 112 cases; endometrial cancer, 0.83 (0.47-1.47) with 47 cases; hip fracture, 0.66 (0.45-0.98) with 106 cases; and death due to other causes, 0.92 (0.74-1.14) with 331 cases. Corresponding HRs (nominal 95% CIs) for composite outcomes were 1.22 (1.09-1.36) for total cardiovascular disease (arterial and venous disease), 1.03 (0.90-1.17) for total cancer, 0.76 (0.69-0.85) for combined fractures, 0.98 (0.82-1.18) for total mortality, and 1.15 (1.03-1.28) for the global index. Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the global index was 19 per 10 000 person-years.ConclusionsOverall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women. All-cause mortality was not affected during the trial. The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD.

C199539241

Law

https://doi.org/10.1137/070710111

system of rules and guidelines, generally backed by governmental authority

Power-Law Distributions in Empirical Data

Power-law distributions occur in many situations of scientific interest and have significant consequences for our understanding of natural and man-made phenomena. Unfortunately, the detection and characterization of power laws is complicated by the large fluctuations that occur in the tail of the distribution—the part of the distribution representing large but rare events—and by the difficulty of identifying the range over which power-law behavior holds. Commonly used methods for analyzing power-law data, such as least-squares fitting, can produce substantially inaccurate estimates of parameters for power-law distributions, and even in cases where such methods return accurate answers they are still unsatisfactory because they give no indication of whether the data obey a power law at all. Here we present a principled statistical framework for discerning and quantifying power-law behavior in empirical data. Our approach combines maximum-likelihood fitting methods with goodness-of-fit tests based on the Kolmogorov–Smirnov (KS) statistic and likelihood ratios. We evaluate the effectiveness of the approach with tests on synthetic data and give critical comparisons to previous approaches. We also apply the proposed methods to twenty-four real-world data sets from a range of different disciplines, each of which has been conjectured to follow a power-law distribution. In some cases we find these conjectures to be consistent with the data, while in others the power law is ruled out.

C199539241

Law

https://doi.org/10.1080/00107510500052444

system of rules and guidelines, generally backed by governmental authority

Power laws, Pareto distributions and Zipf's law

Abstract When the probability of measuring a particular value of some quantity varies inversely as a power of that value, the quantity is said to follow a power law, also known variously as Zipf's law or the Pareto distribution. Power laws appear widely in physics, biology, earth and planetary sciences, economics and finance, computer science, demography and the social sciences. For instance, the distributions of the sizes of cities, earthquakes, forest fires, solar flares, moon craters and people's personal fortunes all appear to follow power laws. The origin of power-law behaviour has been a topic of debate in the scientific community for more than a century. Here we review some of the empirical evidence for the existence of power-law forms and the theories proposed to explain them. Acknowledgments The author would like to thank Petter Holme, Cris Moore and Erik van Nimwegen for useful conversations, and Lada Adamic for the Web site hit data. This work was funded in part by the National Science Foundation under grant number DMS – 0405348. Notes *Power laws also occur in many situations other than the statistical distributions of quantities. For instance, Newton's famous 1/r 2 law for gravity has a power-law form with exponent α = 2. While such laws are certainly interesting in their own way, they are not the topic of this paper. Thus, for instance, there has in recent years been some discussion of the ‘allometric’ scaling laws seen in the physiognomy and physiology of biological organisms [Citation17], but since these are not statistical distributions they will not be discussed here. †http://linkage.rockefeller.edu/wli/zipf/. ‡This can be done using the so-called transformation method. If we can generate a random real number r uniformly distributed in the range 0 ⩽ r < 1, then x = xmin (1 – r)−1/α−1 is a random power-law-distributed real number in the range xmin ⩽ x < ∞ with exponent α. Note that there has to be a lower limit xmin on the range; the power-law distribution diverges as x→0—see section 2.1. *See http://www.hpl.hp.com/research/idl/papers/ranking/ for a useful discussion of these and related points. †The most common words in this case are, in order, ‘the’, ‘of’, ‘and’, ‘a’ and ‘to’, and the same is true for most written English texts. Interestingly, however, it is not true for spoken English. The most common words in spoken English are, in order, ‘I’, ‘and’, ‘the’, ‘to’ and ‘that’ [Citation22]. *Sometimes the tail is also cut off because there is, for one reason or another, a limit on the largest value that may occur. An example is the finite-size effects found in critical phenomena—see section 4.5. In this case, Equationequation (5) must be modified [Citation20]. †Significantly more tenuous claims to power-law behaviour for other quantities have appeared elsewhere in the literature, for instance in the discussion of the distribution of the sizes of electrical blackouts [Citation31,Citation32]. These however I consider insufficiently substantiated for inclusion in the present work. *Also called the Eulerian integral of the first kind. †This can be demonstrated by approximating the Γ-functions of Equationequation (19) using Sterling's formula. *This argument is sometimes called the ‘monkeys with typewriters' argument, the monkey being the traditional exemplar of a random typist. *Gambler's ruin is so called because a gambler's night of betting ends when his or her supply of money hits zero (assuming the gambling establishment declines to offer him or her a line of credit). †The enthusiastic reader can easily derive this result for him or herself by expanding using the binomial theorem. *Modern phylogenetic analysis, the quantitative comparison of species' genetic material, can provide a picture of the evolutionary tree and hence allow the accurate ‘cladistic’ assignment of species to taxa. For prehistoric species, however, whose genetic material is not usually available, determination of evolutionary ancestry is difficult, so classification into taxa is based instead on morphology, i.e. on the shapes of organisms. It is widely accepted that such classifications are subjective and that the taxonomic assignments of fossil species are probably riddled with errors. †To be fair, I consider the power law for the distribution of genus lifetimes to fall in the category of ‘tenuous’ identifications to which I alluded in the second footnote on p. 9. This theory should be taken with a pinch of salt. *Yule's analysis of the process was considerably more involved than the one presented here, essentially because the theory of stochastic processes as we now know it did not yet exist in his time. The master equation method we employ is a relatively modern innovation, introduced in this context by Simon [Citation35].

C199539241

Law

https://doi.org/10.5860/choice.44-2056

system of rules and guidelines, generally backed by governmental authority

Frontiers of justice: disability, nationality, species membership

rather "as a nexus of distinctive sensibilities, cares, and concerns that are expressed in distinctive patterns of emotional and practical response" (p.236).Drawing on Philippa Foot and Simone Weil, Wiggins draws out the moral significance of solidarity and recognition."In recognizing another person, we recognize not merely a subject of consciousness but a being who will seek to interpret us even as we seek to interpret him or her" (p.243).The priority of primitive aversions, with which Wiggins began, is then linked to acts that violate solidarity and deny recognition.What if we must violate basic deontological rules to prevent catastrophe?Wiggins responds with a fifth moral category "subsuming the ordinary passably virtuous agent's concern to preserve the very conditions under which human civilization will survive and/or ordinary morality can make its characteristic demands on normal human life" (p.259).It is a mistake, as consequentialists do, to model the whole of morality on these emergency cases.Wiggins resolutely defends a "piecemeal" approach to morality."[T]hose who despise the piecemeal . . .cut themselves off from all sorts of truths that bear closely on the questions they ask. . . .In so far as the case for morality can be stated briefly, all that can be said is that, in a way already illustrated, it is the most enterprising and durable expression that a human being will find for the benevolent dispositions he or she can discover within himself or herself " (p.265).This intriguing book is not aimed at teenage undergraduates, who will find Wiggins a very difficult and frustrating read.Ethics would certainly not be a suitable text for introductory ethics classes.Its target audience is rather those who, while beginners in philosophy, are not beginners in life.Such readers will still find Wiggins challenging (and, at times, opaque and old-fashioned), but they may also find him an intriguing and provocative guide as they seek to apply moral philosophy to moral life.

C199539241

Law

https://doi.org/10.1007/978-3-0348-8629-1

system of rules and guidelines, generally backed by governmental authority

Numerical Methods for Conservation Laws

These notes developed from a course on the numerical solution of conservation laws first taught at the University of Washington in the fall of 1988 and then at ETH during the following spring. The ove

C199539241

Law

https://doi.org/10.5124/jkma.2014.57.11.899

system of rules and guidelines, generally backed by governmental authority

World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects

Published research in English-language journals are increasingly required to carry a statement that the study has been approved and monitored by an Institutional Review Board in conformance with 45 CFR 46 standards if the study was conducted in the United States. Alternative language attesting conformity with the Helsinki Declaration is often included when the research was conducted in Europe or elsewhere. The Helsinki Declaration was created by the World Medical Association in 1964 (ten years before the Belmont Report) and has been amended several times. The Helsinki Declaration differs from its American version in several respects, the most significant of which is that it was developed by and for physicians. The term "patient" appears in many places where we would expect to see "subject." It is stated in several places that physicians must either conduct or have supervisory control of the research. The dual role of the physician-researcher is acknowledged, but it is made clear that the role of healer takes precedence over that of scientist. In the United States, the federal government developed and enforces regulations on researcher; in the rest of the world, the profession, or a significant part of it, took the initiative in defining and promoting good research practice, and governments in many countries have worked to harmonize their standards along these lines. The Helsinki Declaration is based less on key philosophical principles and more on prescriptive statements. Although there is significant overlap between the Belmont and the Helsinki guidelines, the latter extends much further into research design and publication. Elements in a research protocol, use of placebos, and obligation to enroll trials in public registries (to ensure that negative findings are not buried), and requirements to share findings with the research and professional communities are included in the Helsinki Declaration. As a practical matter, these are often part of the work of American IRBs, but not always as a formal requirement. Reflecting the socialist nature of many European counties, there is a requirement that provision be made for patients to be made whole regardless of the outcomes of the trial or if they happened to have been randomized to a control group that did not enjoy the benefits of a successful experimental intervention.

C199539241

Law

https://doi.org/10.5194/acp-15-4399-2015

system of rules and guidelines, generally backed by governmental authority

Compilation of Henry's law constants (version 4.0) for water as solvent

Abstract. Many atmospheric chemicals occur in the gas phase as well as in liquid cloud droplets and aerosol particles. Therefore, it is necessary to understand the distribution between the phases. According to Henry's law, the equilibrium ratio between the abundances in the gas phase and in the aqueous phase is constant for a dilute solution. Henry's law constants of trace gases of potential importance in environmental chemistry have been collected and converted into a uniform format. The compilation contains 17 350 values of Henry's law constants for 4632 species, collected from 689 references. It is also available at http://www.henrys-law.org.

C199539241

Law

https://doi.org/10.4135/9781483346663.n124

system of rules and guidelines, generally backed by governmental authority

Convention on the Rights of Persons with Disabilities

At this session, an esteemed panel of speakers discuss: • How has Canada committed to the equality and full social inclusion of persons with disabilities? • Are persons with disabilities enjoying the rights guaranteed by the Convention on the Rights of Persons with Disabilities? • What does the Convention mean for Nova Scotians with disabilities, and how can we ensure an inclusive and accessible Nova Scotia?

C199539241

Law

https://doi.org/10.1029/wr016i006p01016

system of rules and guidelines, generally backed by governmental authority

Validity of Cubic Law for fluid flow in a deformable rock fracture

Water Resources ResearchVolume 16, Issue 6 p. 1016-1024 Papers Validity of Cubic Law for fluid flow in a deformable rock fracture P. A. Witherspoon, P. A. WitherspoonSearch for more papers by this authorJ. S. Y. Wang, J. S. Y. WangSearch for more papers by this authorK. Iwai, K. IwaiSearch for more papers by this authorJ. E. Gale, J. E. GaleSearch for more papers by this author P. A. Witherspoon, P. A. WitherspoonSearch for more papers by this authorJ. S. Y. Wang, J. S. Y. WangSearch for more papers by this authorK. Iwai, K. IwaiSearch for more papers by this authorJ. E. Gale, J. E. GaleSearch for more papers by this author First published: December 1980 https://doi.org/10.1029/WR016i006p01016Citations: 1,519AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract The validity of the cubic law for laminar flow of fluids through open fractures consisting of parallel planar plates has been established by others over a wide range of conditions with apertures ranging down to a minimum of 0.2 µm. The law may be given in simplified form by Q/Δh = C(2b)3, where Q is the flow rate, Δh is the difference in hydraulic head, C is a constant that depends on the flow geometry and fluid properties, and 2b is the fracture aperture. The validity of this law for flow in a closed fracture where the surfaces are in contact and the aperture is being decreased under stress has been investigated at room temperature by using homogeneous samples of granite, basalt, and marble. Tension fractures were artificially induced, and the laboratory setup used radial as well as straight flow geometries. Apertures ranged from 250 down to 4µm, which was the minimum size that could be attained under a normal stress of 20 MPa. The cubic law was found to be valid whether the fracture surfaces were held open or were being closed under stress, and the results are not dependent on rock type. Permeability was uniquely defined by fracture aperture and was independent of the stress history used in these investigations. The effects of deviations from the ideal parallel plate concept only cause an apparent reduction in flow and may be incorporated into the cubic law by replacing C by C/ƒ. The factor ƒ varied from 1.04 to 1.65 in these investigations. The model of a fracture that is being closed under normal stress is visualized as being controlled by the strength of the asperities that are in contact. These contact areas are able to withstand significant stresses while maintaining space for fluids to continue to flow as the fracture aperture decreases. The controlling factor is the magnitude of the aperture, and since flow depends on (2b)3, a slight change in aperture evidently can easily dominate any other change in the geometry of the flow field. Thus one does not see any noticeable shift in the correlations of our experimental results in passing from a condition where the fracture surfaces were held open to one where the surfaces were being closed under stress. Citing Literature Volume16, Issue6December 1980Pages 1016-1024 RelatedInformation

C15708023

Humanities

https://doi.org/10.1002/andp.19083300302

academic disciplines that study human culture

Beiträge zur Optik trüber Medien, speziell kolloidaler Metallösungen

Annalen der PhysikVolume 330, Issue 3 p. 377-445 ArticleFree Access Beiträge zur Optik trüber Medien, speziell kolloidaler Metallösungen Gustav Mie, Gustav Mie Physikalisches Instiut, GreifswaldSearch for more papers by this author Gustav Mie, Gustav Mie Physikalisches Instiut, GreifswaldSearch for more papers by this author First published: 1908 https://doi.org/10.1002/andp.19083300302Citations: 8,308AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume330, Issue31908Pages 377-445 ReferencesRelatedInformation

C15708023

Humanities

https://doi.org/10.1590/s0034-75901995000300004

academic disciplines that study human culture

Pesquisa qualitativa: tipos fundamentais

The qualitative approach ollers three representatives kinds 01doing research: document study, case study and ethnography.

C15708023

Humanities

https://doi.org/10.1111/j.1558-5646.1995.tb04456.x

academic disciplines that study human culture

AN EXACT TEST FOR POPULATION DIFFERENTIATION

Journal Article AN EXACT TEST FOR POPULATION DIFFERENTIATION Get access Michel Raymond, Michel Raymond Institut des Sciences de l'Evolution, URA CNRS 327, Laboratoire de Génétique et Environnement CC 065, USTL, Place E. Bataillon 34095 Montpellier cedex 05 France Search for other works by this author on: Oxford Academic Google Scholar François Rousset François Rousset Institut des Sciences de l'Evolution, URA CNRS 327, Laboratoire de Génétique et Environnement CC 065, USTL, Place E. Bataillon 34095 Montpellier cedex 05 France Search for other works by this author on: Oxford Academic Google Scholar Evolution, Volume 49, Issue 6, 1 December 1995, Pages 1280–1283, https://doi.org/10.1111/j.1558-5646.1995.tb04456.x Published: 01 December 1995 Article history Received: 11 March 1994 Accepted: 19 September 1994 Published: 01 December 1995

C15708023

Humanities

https://doi.org/10.1097/hjh.0000000000001940

academic disciplines that study human culture

2018 ESC/ESH Guidelines for the management of arterial hypertension

Document reviewers: Guy De Backer (ESC Review Co-ordinator) (Belgium), Anthony M. Heagerty (ESH Review Co-ordinator) (UK), Stefan Agewall (Norway), Murielle Bochud (Switzerland), Claudio Borghi (Italy), Pierre Boutouyrie (France), Jana Brguljan (Slovenia), Héctor Bueno (Spain), Enrico G. Caiani (Italy), Bo Carlberg (Sweden), Neil Chapman (UK), Renata Cifkova (Czech Republic), John G. F. Cleland (UK), Jean-Philippe Collet (France), Ioan Mircea Coman (Romania), Peter W. de Leeuw (The Netherlands), Victoria Delgado (The Netherlands), Paul Dendale (Belgium), Hans-Christoph Diener (Germany), Maria Dorobantu (Romania), Robert Fagard (Belgium), Csaba Farsang (Hungary), Marc Ferrini (France), Ian M. Graham (Ireland), Guido Grassi (Italy), Hermann Haller (Germany), F. D. Richard Hobbs (UK), Bojan Jelakovic (Croatia), Catriona Jennings (UK), Hugo A. Katus (Germany), Abraham A. Kroon (The Netherlands), Christophe Leclercq (France), Dragan Lovic (Serbia), Empar Lurbe (Spain), Athanasios J. Manolis (Greece), Theresa A. McDonagh (UK), Franz Messerli (Switzerland), Maria Lorenza Muiesan (Italy), Uwe Nixdorff (Germany), Michael Hecht Olsen (Denmark), Gianfranco Parati (Italy), Joep Perk (Sweden), Massimo Francesco Piepoli (Italy), Jorge Polonia (Portugal), Piotr Ponikowski (Poland), Dimitrios J. Richter (Greece), Stefano F. Rimoldi (Switzerland), Marco Roffi (Switzerland), Naveed Sattar (UK), Petar M. Seferovic (Serbia), Iain A. Simpson (UK), Miguel Sousa-Uva (Portugal), Alice V. Stanton (Ireland), Philippe van de Borne (Belgium), Panos Vardas (Greece), Massimo Volpe (Italy), Sven Wassmann (Germany), Stephan Windecker (Switzerland), Jose Luis Zamorano (Spain). The disclosure forms of all experts involved in the development of these Guidelines are available on the ESC website www.escardio.org/guidelines

C15708023

Humanities

https://doi.org/10.30845/ijhss

academic disciplines that study human culture

International Journal of Humanities and Social Science

In Theater-Therapy, that is Stanislavskij's method linked to Positive Psychology, emotions are produced through body actions; where the body is the custodian of the actions associated with emotions.This association could improve some aspects of personality.Everyone can feel themselves in an immediate way.Hence, an increased knowledge of emotions and thoughts can improve the relationship with others.In the current study, 6 subjects took part in a research to ascertain if participation to Theater-therapy to verify if they can improve some personality aspects, according to the Big Five theory.The experiment included one three-hours weekly meeting for six months.On the first day, the BFQ was administered to each subject and re-administered on the last day of the experiment.Results showed that all factors improve after the Theater-therapy meeting.This can be explained by Theater-therapy enabling subjects to feel emotion and handle conflicts immediately through the body and the use of actions.

C15708023

Humanities

https://doi.org/10.5860/choice.48-3075

academic disciplines that study human culture

Not for profit: why democracy needs the humanities

Foreword by Ruth O'Brien ix Acknowledgments xiii Chapter I: The Silent Crisis 1 Chapter II: Education for Profit, Education for Democracy 13 Chapter III: Educating Citizens: The Moral (and Anti-Moral) Emotions 27 Chapter IV: Socratic Pedagogy: The Importance of Argument 47 Chapter V: Citizens of the World 79 Chapter VI: Cultivating Imagination: Literature and the Arts 95 Chapter VII: Democratic Education on the Ropes 121 Notes 145 Index 153

C15708023

Humanities

https://doi.org/10.1136/ip.9.1.93

academic disciplines that study human culture

World Report on Violence and Health.

The World Report on Violence and Health is a watershed publication, marking a turning point in violence prevention efforts. It offers a framework to stimulate coordinated preventive action and research across types of violence; to address social, economic, and policy factors that transcend national boundaries; and to pursue violence prevention efforts on a regional or global scale. The report presents violence as a growing, yet preventable public health problem at a time when the problem of violence is among the priority agenda items of many nations. At the United Nations (UN) meeting on UN Collaboration for the Prevention of Interpersonal Violence held in November 2001, the UN recognized the global and widespread impact of interpersonal violence on health, development, human rights, human security, and peace and acknowledged that the multiple and complex causes of interpersonal violence require a …

C15708023

Humanities

https://doi.org/10.6018/analesps.29.3.178511

academic disciplines that study human culture

Un sistema de clasificación de los diseños de investigación en psicología

In this work we devise a conceptual framework and develop some basic principles to promove a classification system for the most usual research designs in psychology based on three strategies (manipulative, associative and descriptive) from which emerge different types of studies, three for manipulative strategy (experimental, quasi-experimental and single-case), three for associative strategy (comparative, predictive and explanatory) and two for descriptive strategy (observational and selective).

C62520636

Quantum mechanics

https://doi.org/10.1103/physrev.140.a1133

fundamental theory in physics describing the properties of nature on an atomic scale

Self-Consistent Equations Including Exchange and Correlation Effects

From a theory of Hohenberg and Kohn, approximation methods for treating an inhomogeneous system of interacting electrons are developed. These methods are exact for systems of slowly varying or high density. For the ground state, they lead to self-consistent equations analogous to the Hartree and Hartree-Fock equations, respectively. In these equations the exchange and correlation portions of the chemical potential of a uniform electron gas appear as additional effective potentials. (The exchange portion of our effective potential differs from that due to Slater by a factor of $\frac{2}{3}$.) Electronic systems at finite temperatures and in magnetic fields are also treated by similar methods. An appendix deals with a further correction for systems with short-wavelength density oscillations.

C62520636

Quantum mechanics

https://doi.org/10.1119/1.1463744

fundamental theory in physics describing the properties of nature on an atomic scale

<i>Quantum Computation and Quantum Information</i>

First Page

C62520636

Quantum mechanics

https://doi.org/10.1103/physrevb.23.5048

fundamental theory in physics describing the properties of nature on an atomic scale

Self-interaction correction to density-functional approximations for many-electron systems

The exact density functional for the ground-state energy is strictly self-interaction-free (i.e., orbitals demonstrably do not self-interact), but many approximations to it, including the local-spin-density (LSD) approximation for exchange and correlation, are not. We present two related methods for the self-interaction correction (SIC) of any density functional for the energy; correction of the self-consistent one-electron potenial follows naturally from the variational principle. Both methods are sanctioned by the Hohenberg-Kohn theorem. Although the first method introduces an orbital-dependent single-particle potential, the second involves a local potential as in the Kohn-Sham scheme. We apply the first method to LSD and show that it properly conserves the number content of the exchange-correlation hole, while substantially improving the description of its shape. We apply this method to a number of physical problems, where the uncorrected LSD approach produces systematic errors. We find systematic improvements, qualitative as well as quantitative, from this simple correction. Benefits of SIC in atomic calculations include (i) improved values for the total energy and for the separate exchange and correlation pieces of it, (ii) accurate binding energies of negative ions, which are wrongly unstable in LSD, (iii) more accurate electron densities, (iv) orbital eigenvalues that closely approximate physical removal energies, including relaxation, and (v) correct longrange behavior of the potential and density. It appears that SIC can also remedy the LSD underestimate of the band gaps in insulators (as shown by numerical calculations for the rare-gas solids and CuCl), and the LSD overestimate of the cohesive energies of transition metals. The LSD spin splitting in atomic Ni and $s\ensuremath{-}d$ interconfigurational energies of transition elements are almost unchanged by SIC. We also discuss the admissibility of fractional occupation numbers, and present a parametrization of the electron-gas correlation energy at any density, based on the recent results of Ceperley and Alder.

C62520636

Quantum mechanics

https://doi.org/10.1103/physrev.46.618

fundamental theory in physics describing the properties of nature on an atomic scale

Note on an Approximation Treatment for Many-Electron Systems

A perturbation theory is developed for treating a system of $n$ electrons in which the Hartree-Fock solution appears as the zero-order approximation. It is shown by this development that the first order correction for the energy and the charge density of the system is zero. The expression for the second-order correction for the energy greatly simplifies because of the special property of the zero-order solution. It is pointed out that the development of the higher approximation involves only calculations based on a definite one-body problem.

C62520636

Quantum mechanics

https://doi.org/10.1103/physrevlett.70.1895

fundamental theory in physics describing the properties of nature on an atomic scale

Teleporting an unknown quantum state via dual classical and Einstein-Podolsky-Rosen channels

An unknown quantum state \ensuremath{\Vert}\ensuremath{\varphi}〉 can be disassembled into, then later reconstructed from, purely classical information and purely nonclassical Einstein-Podolsky-Rosen (EPR) correlations. To do so the sender, ``Alice,'' and the receiver, ``Bob,'' must prearrange the sharing of an EPR-correlated pair of particles. Alice makes a joint measurement on her EPR particle and the unknown quantum system, and sends Bob the classical result of this measurement. Knowing this, Bob can convert the state of his EPR particle into an exact replica of the unknown state \ensuremath{\Vert}\ensuremath{\varphi}〉 which Alice destroyed.

C62520636

Quantum mechanics

https://doi.org/10.1103/physrev.108.1175

fundamental theory in physics describing the properties of nature on an atomic scale

Theory of Superconductivity

A theory of superconductivity is presented, based on the fact that the interaction between electrons resulting from virtual exchange of phonons is attractive when the energy difference between the electrons states involved is less than the phonon energy, $\ensuremath{\hbar}\ensuremath{\omega}$. It is favorable to form a superconducting phase when this attractive interaction dominates the repulsive screened Coulomb interaction. The normal phase is described by the Bloch individual-particle model. The ground state of a superconductor, formed from a linear combination of normal state configurations in which electrons are virtually excited in pairs of opposite spin and momentum, is lower in energy than the normal state by amount proportional to an average ${(\ensuremath{\hbar}\ensuremath{\omega})}^{2}$, consistent with the isotope effect. A mutually orthogonal set of excited states in one-to-one correspondence with those of the normal phase is obtained by specifying occupation of certain Bloch states and by using the rest to form a linear combination of virtual pair configurations. The theory yields a second-order phase transition and a Meissner effect in the form suggested by Pippard. Calculated values of specific heats and penetration depths and their temperature variation are in good agreement with experiment. There is an energy gap for individual-particle excitations which decreases from about $3.5k{T}_{c}$ at $T=0\ifmmode^\circ\else\textdegree\fi{}$K to zero at ${T}_{c}$. Tables of matrix elements of single-particle operators between the excited-state superconducting wave functions, useful for perturbation expansions and calculations of transition probabilities, are given.

C62520636

Quantum mechanics

https://doi.org/10.1088/0953-8984/14/11/302

fundamental theory in physics describing the properties of nature on an atomic scale

The SIESTA method for<i>ab initio</i>order-<i>N</i>materials simulation

An efficient method is described to handle mesh indexes in multidimensional problems like numerical integration of partial differential equations, lattice model simulations, and determination of atomic neighbor lists. By creating an extended mesh, beyond the periodic unit cell, the stride in memory between equivalent pairs of mesh points is independent of their position within the cell. This allows to contract the mesh indexes of all dimensions into a single index, avoiding modulo and other implicit index operations.

C62520636

Quantum mechanics

https://doi.org/10.1103/revmodphys.81.865

fundamental theory in physics describing the properties of nature on an atomic scale

Quantum entanglement

All our former experience with application of quantum theory seems to say: {\it what is predicted by quantum formalism must occur in laboratory}. But the essence of quantum formalism - entanglement, recognized by Einstein, Podolsky, Rosen and Schr\"odinger - waited over 70 years to enter to laboratories as a new resource as real as energy. This holistic property of compound quantum systems, which involves nonclassical correlations between subsystems, is a potential for many quantum processes, including ``canonical'' ones: quantum cryptography, quantum teleportation and dense coding. However, it appeared that this new resource is very complex and difficult to detect. Being usually fragile to environment, it is robust against conceptual and mathematical tools, the task of which is to decipher its rich structure. This article reviews basic aspects of entanglement including its characterization, detection, distillation and quantifying. In particular, the authors discuss various manifestations of entanglement via Bell inequalities, entropic inequalities, entanglement witnesses, quantum cryptography and point out some interrelations. They also discuss a basic role of entanglement in quantum communication within distant labs paradigm and stress some peculiarities such as irreversibility of entanglement manipulations including its extremal form - bound entanglement phenomenon. A basic role of entanglement witnesses in detection of entanglement is emphasized.

C55493867

Biochemistry

https://doi.org/10.1073/pnas.76.9.4350

study of chemical processes in living organisms

Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications.

A method has been devised for the electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets. The method results in quantitative transfer of ribosomal proteins from gels containing urea. For sodium dodecyl sulfate gels, the original band pattern was obtained with no loss of resolution, but the transfer was not quantitative. The method allows detection of proteins by autoradiography and is simpler than conventional procedures. The immobilized proteins were detectable by immunological procedures. All additional binding capacity on the nitrocellulose was blocked with excess protein; then a specific antibody was bound and, finally, a second antibody directed against the first antibody. The second antibody was either radioactively labeled or conjugated to fluorescein or to peroxidase. The specific protein was then detected by either autoradiography, under UV light, or by the peroxidase reaction product, respectively. In the latter case, as little as 100 pg of protein was clearly detectable. It is anticipated that the procedure will be applicable to analysis of a wide variety of proteins with specific reactions or ligands.

C55493867

Biochemistry

https://doi.org/10.3168/jds.s0022-0302(91)78551-2

study of chemical processes in living organisms

Methods for Dietary Fiber, Neutral Detergent Fiber, and Nonstarch Polysaccharides in Relation to Animal Nutrition

There is a need to standardize the NDF procedure.Procedures have varied because of the use of different amylases in attempts to remove starch interference.'Ihe original Bacillus subtilis enzyme Type IIIA (XIA) no longer is available and has been replaced by a less effective enzyme.For fiber work, a new enzyme' has received AOAC approval and is rapidly displacing other amylases in analyt- ical work.This enzyme is available from Sigma (Number A3306, Sigma Chemical Co., St. Louis, MO).The original publications for NDF and ADF (43, 53) and the Agricultural Handbook 379 (14) are obsolete and of historical interest only.Up to date procedures should be followed.Tnethylene glycol has replaced 2-ethoxyethanol because of reported toxicity.Considerable development in regard to fiber methods has occurred over the past 5 yr because of a redefinition of dietary fiber for man and monogastric animals that includes lignin and all polysaccharides resistant to mammalian digestive enzymes.In addition to NDF, new improved methods for total dietary fiber and nonstarch polysaccharides including pectin and B-glucans now are available.The latter are also of interest in rumen fermentation.Unlike starch.

C55493867

Biochemistry

https://doi.org/10.1016/s0021-9258(19)42083-8

study of chemical processes in living organisms

Glutathione S-Transferases

The purification of homogeneous glutathione S-transferases B and C from rat liver is described. Kinetic and physical properties of these enzymes are compared with those of homogeneous transferases A and E. The letter designations for the transferases are based on the reverse order of elution from carboxymethylcellulose, the purification step in which the transferases are separated from each other. Transferase B was purified on the basis of its ability to conjugate iodomethane with glutathione, whereas transferase C was purified on the basis of conjugation with 1,2-dichloro-4-nitrobenzene. Although each of the four enzymes can be identified by its reactivity with specific substrates, all of the enzymes are active to differing degrees in the conjugation of glutathione with p-nitrobenzyl chloride. Assay conditions for a variety of substrates are included. All four glutathione transferases have a molecular weight of 45,000 and are dissociable into subunits of approximately 25,000 daltons. Despite the similar physical properties and overlapping substrate specificities of these enzymes, only transferases A and C are immunologically related.

C55493867

Biochemistry

https://doi.org/10.1016/s0021-9258(18)57021-6

study of chemical processes in living organisms

DETERMINATION OF SERUM PROTEINS BY MEANS OF THE BIURET REACTION

In the course of an investigation of the biochemical changes following experimental liver injury we felt the need of a simple, rapid, and accurate method for determining the protein fractions in small amounts of serum. Among the simpler procedures known, the biuret reaction seemed to offer the most encouraging possibilities. Variations and improvements in the application of the biuret reaction to clinical chemistry can be traced in the works of Autenrieth (l), Hiller (2), Fine (3), Kingsley (4), and Robinson and Hogden (5). Kingsley (6) simplified the technique by adding serum directly to a “one piece” reagent. Efforts have been made to increase the stability of such biuret reagents with ethylene glycol (7), tartrate (8), and citrate (9)) We began our investigation with Kingsley’s (6) method and report briefly on the two main difficulties encountered in its use. The first is that the total protein (TP) reagent and, to a lesser extent, the albumin (ALB) reagent are not sufficiently stable. The length of time they remain so depends upon the technique of their preparation. One consequence of this variable stability is a difficulty in duplicating calibration curves with different lots of reagent. Errors may arise when results with a new reagent are read from an old calibration curve. Serious errors occur if a reagent is used after the separation of any black deposit gives evidence of deterioration. A second difficulty has been that total protein estimations made with the TP reagent and read, as prescribed, from calibration curves prepared with the ALB reagent have tended to be too low. Recorded in Table I are the results of a number of analyses in which Kingsley’s biuret procedure has been compared with the Kjeldahl method2 on both normal and ab-

C55493867

Biochemistry

https://doi.org/10.1177/29.4.6166661

study of chemical processes in living organisms

Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures.

The use of avidin-biotin interaction in immunoenzymatic techniques provides a simple and sensitive method to localize antigens in formalin-fixed tissues. Among the several staining procedures available, the ABC method, which involves an application of biotin-labeled secondary antibody followed by the addition of avidin-biotin-peroxidase complex, gives a superior result when compared to the unlabeled antibody method. The availability of biotin-binding sites in the complex is created by the incubation of a relative excess of avidin with biotin-labeled peroxidase. During formation of the complex, avidin acts as a bridge between biotin-labeled peroxidase molecules; and biotin-labeled peroxidase molecules, which contains several biotin moieties, serve as a link between the avidin molecules. Consequently, a "lattice" complex containing several peroxidase molecules is likely formed. Binding of this complex to the biotin moieties associated with secondary antibody results in a high staining intensity.

C55493867

Biochemistry

https://doi.org/10.1126/science.1160809

study of chemical processes in living organisms

Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation

In contrast to normal differentiated cells, which rely primarily on mitochondrial oxidative phosphorylation to generate the energy needed for cellular processes, most cancer cells instead rely on aerobic glycolysis, a phenomenon termed "the Warburg effect." Aerobic glycolysis is an inefficient way to generate adenosine 5'-triphosphate (ATP), however, and the advantage it confers to cancer cells has been unclear. Here we propose that the metabolism of cancer cells, and indeed all proliferating cells, is adapted to facilitate the uptake and incorporation of nutrients into the biomass (e.g., nucleotides, amino acids, and lipids) needed to produce a new cell. Supporting this idea are recent studies showing that (i) several signaling pathways implicated in cell proliferation also regulate metabolic pathways that incorporate nutrients into biomass; and that (ii) certain cancer-associated mutations enable cancer cells to acquire and metabolize nutrients in a manner conducive to proliferation rather than efficient ATP production. A better understanding of the mechanistic links between cellular metabolism and growth control may ultimately lead to better treatments for human cancer.

C55493867

Biochemistry

https://doi.org/10.1152/physrev.00018.2001

study of chemical processes in living organisms

Free Radicals in the Physiological Control of Cell Function

At high concentrations, free radicals and radical-derived, nonradical reactive species are hazardous for living organisms and damage all major cellular constituents. At moderate concentrations, however, nitric oxide (NO), superoxide anion, and related reactive oxygen species (ROS) play an important role as regulatory mediators in signaling processes. Many of the ROS-mediated responses actually protect the cells against oxidative stress and reestablish “redox homeostasis.” Higher organisms, however, have evolved the use of NO and ROS also as signaling molecules for other physiological functions. These include regulation of vascular tone, monitoring of oxygen tension in the control of ventilation and erythropoietin production, and signal transduction from membrane receptors in various physiological processes. NO and ROS are typically generated in these cases by tightly regulated enzymes such as NO synthase (NOS) and NAD(P)H oxidase isoforms, respectively. In a given signaling protein, oxidative attack induces either a loss of function, a gain of function, or a switch to a different function. Excessive amounts of ROS may arise either from excessive stimulation of NAD(P)H oxidases or from less well-regulated sources such as the mitochondrial electron-transport chain. In mitochondria, ROS are generated as undesirable side products of the oxidative energy metabolism. An excessive and/or sustained increase in ROS production has been implicated in the pathogenesis of cancer, diabetes mellitus, atherosclerosis, neurodegenerative diseases, rheumatoid arthritis, ischemia/reperfusion injury, obstructive sleep apnea, and other diseases. In addition, free radicals have been implicated in the mechanism of senescence. That the process of aging may result, at least in part, from radical-mediated oxidative damage was proposed more than 40 years ago by Harman ( J Gerontol 11: 298–300, 1956). There is growing evidence that aging involves, in addition, progressive changes in free radical-mediated regulatory processes that result in altered gene expression.

C55493867

Biochemistry

https://doi.org/10.1159/000337115

study of chemical processes in living organisms

Copper-Zinc Superoxide Dismutase (SOD1) Is Released by Microglial Cells and Confers Neuroprotection against 6-OHDA Neurotoxicity

The role so far ascribed to intracellular CuZn superoxide dismutase is that of an intracellular scavenger of oxygen radicals. However, other functions of cytosolic CuZn superoxide dismutase have been hypothesized. For example, CuZn superoxide dismutase incubated with rat hepatocyte cells in culture inhibits 3-hydroxy-3methylglutaryl CoA reductase, thereby reducing cholesterol synthesis. We recently demonstrated the presence of surface membrane receptors for CuZn superoxide dismutase, suggesting possible autocrine or paracrine activities. The aim of the present study was to investigate whether cytosolic CuZn superoxide dismutase can be secreted by human hepatocarcinoma and fibroblast cells lines. Proteins in human hepatocellular carcinoma (Hep G2) cells and human fibroblasts were biosynthetically labelled with [35S]-cysteine; then cell lysates and media were immunoprecipitated with rabbit polyclonal anti-human CuZn superoxide dismutase antibodies and separated by 12% polyacrylamide gel electrophoresis. Both Hep G2 cells and human fibroblasts produce and secrete CuZn superoxide dismutase which was detectable in cells and medium as a single protein band with the same electrophoretic mobility as human erythrocyte CuZn superoxide dismutase. These data suggest that CuZn superoxide dismutase, an enzyme thus far considered to be located exclusively intracellularly is secreted by at least two cell lines. This is consistent with autocrine or paracrine roles for CuZn superoxide dismutase.

C154945302

Artificial intelligence

https://doi.org/10.1109/cvpr.2016.90

field of computer science and engineering practices for intelligence demonstrated by machines and intelligent agents

Deep Residual Learning for Image Recognition

Deeper neural networks are more difficult to train. We present a residual learning framework to ease the training of networks that are substantially deeper than those used previously. We explicitly reformulate the layers as learning residual functions with reference to the layer inputs, instead of learning unreferenced functions. We provide comprehensive empirical evidence showing that these residual networks are easier to optimize, and can gain accuracy from considerably increased depth. On the ImageNet dataset we evaluate residual nets with a depth of up to 152 layers - 8× deeper than VGG nets [40] but still having lower complexity. An ensemble of these residual nets achieves 3.57% error on the ImageNet test set. This result won the 1st place on the ILSVRC 2015 classification task. We also present analysis on CIFAR-10 with 100 and 1000 layers. The depth of representations is of central importance for many visual recognition tasks. Solely due to our extremely deep representations, we obtain a 28% relative improvement on the COCO object detection dataset. Deep residual nets are foundations of our submissions to ILSVRC & COCO 2015 competitions1, where we also won the 1st places on the tasks of ImageNet detection, ImageNet localization, COCO detection, and COCO segmentation.

C154945302

Artificial intelligence

https://doi.org/10.48550/arxiv.1201.0490

field of computer science and engineering practices for intelligence demonstrated by machines and intelligent agents

Scikit-learn: Machine Learning in Python

Scikit-learn is a Python module integrating a wide range of state-of-the-art machine learning algorithms for medium-scale supervised and unsupervised problems. This package focuses on bringing machine learning to non-specialists using a general-purpose high-level language. Emphasis is put on ease of use, performance, documentation, and API consistency. It has minimal dependencies and is distributed under the simplified BSD license, encouraging its use in both academic and commercial settings. Source code, binaries, and documentation can be downloaded from http://scikit-learn.org.

C154945302

Artificial intelligence

https://doi.org/10.48550/arxiv.1706.03762

field of computer science and engineering practices for intelligence demonstrated by machines and intelligent agents

Attention Is All You Need

The dominant sequence transduction models are based on complex recurrent or convolutional neural networks in an encoder-decoder configuration. The best performing models also connect the encoder and decoder through an attention mechanism. We propose a new simple network architecture, the Transformer, based solely on attention mechanisms, dispensing with recurrence and convolutions entirely. Experiments on two machine translation tasks show these models to be superior in quality while being more parallelizable and requiring significantly less time to train. Our model achieves 28.4 BLEU on the WMT 2014 English-to-German translation task, improving over the existing best results, including ensembles by over 2 BLEU. On the WMT 2014 English-to-French translation task, our model establishes a new single-model state-of-the-art BLEU score of 41.8 after training for 3.5 days on eight GPUs, a small fraction of the training costs of the best models from the literature. We show that the Transformer generalizes well to other tasks by applying it successfully to English constituency parsing both with large and limited training data.

C154945302

Artificial intelligence

https://doi.org/10.1109/cvpr.2015.7298594

field of computer science and engineering practices for intelligence demonstrated by machines and intelligent agents

Going deeper with convolutions

We propose a deep convolutional neural network architecture codenamed Inception that achieves the new state of the art for classification and detection in the ImageNet Large-Scale Visual Recognition Challenge 2014 (ILSVRC14). The main hallmark of this architecture is the improved utilization of the computing resources inside the network. By a carefully crafted design, we increased the depth and width of the network while keeping the computational budget constant. To optimize quality, the architectural decisions were based on the Hebbian principle and the intuition of multi-scale processing. One particular incarnation used in our submission for ILSVRC14 is called GoogLeNet, a 22 layers deep network, the quality of which is assessed in the context of classification and detection.

C154945302

Artificial intelligence

https://doi.org/10.1109/tpami.2016.2577031

field of computer science and engineering practices for intelligence demonstrated by machines and intelligent agents

Faster R-CNN: Towards Real-Time Object Detection with Region Proposal Networks

State-of-the-art object detection networks depend on region proposal algorithms to hypothesize object locations. Advances like SPPnet [1] and Fast R-CNN [2] have reduced the running time of these detection networks, exposing region proposal computation as a bottleneck. In this work, we introduce a Region Proposal Network(RPN) that shares full-image convolutional features with the detection network, thus enabling nearly cost-free region proposals. An RPN is a fully convolutional network that simultaneously predicts object bounds and objectness scores at each position. The RPN is trained end-to-end to generate high-quality region proposals, which are used by Fast R-CNN for detection. We further merge RPN and Fast R-CNN into a single network by sharing their convolutional features-using the recently popular terminology of neural networks with 'attention' mechanisms, the RPN component tells the unified network where to look. For the very deep VGG-16 model [3], our detection system has a frame rate of 5 fps (including all steps) on a GPU, while achieving state-of-the-art object detection accuracy on PASCAL VOC 2007, 2012, and MS COCO datasets with only 300 proposals per image. In ILSVRC and COCO 2015 competitions, Faster R-CNN and RPN are the foundations of the 1st-place winning entries in several tracks. Code has been made publicly available.

C154945302

Artificial intelligence

https://doi.org/10.1109/cvpr.2016.91

field of computer science and engineering practices for intelligence demonstrated by machines and intelligent agents

You Only Look Once: Unified, Real-Time Object Detection

We present YOLO, a new approach to object detection. Prior work on object detection repurposes classifiers to perform detection. Instead, we frame object detection as a regression problem to spatially separated bounding boxes and associated class probabilities. A single neural network predicts bounding boxes and class probabilities directly from full images in one evaluation. Since the whole detection pipeline is a single network, it can be optimized end-to-end directly on detection performance. Our unified architecture is extremely fast. Our base YOLO model processes images in real-time at 45 frames per second. A smaller version of the network, Fast YOLO, processes an astounding 155 frames per second while still achieving double the mAP of other real-time detectors. Compared to state-of-the-art detection systems, YOLO makes more localization errors but is less likely to predict false positives on background. Finally, YOLO learns very general representations of objects. It outperforms other detection methods, including DPM and R-CNN, when generalizing from natural images to other domains like artwork.

C154945302

Artificial intelligence

https://doi.org/10.3115/v1/d14-1162

field of computer science and engineering practices for intelligence demonstrated by machines and intelligent agents

Glove: Global Vectors for Word Representation

Recent methods for learning vector space representations of words have succeeded in capturing fine-grained semantic and syntactic regularities using vector arithmetic, but the origin of these regularities has remained opaque. We analyze and make explicit the model properties needed for such regularities to emerge in word vectors. The result is a new global logbilinear regression model that combines the advantages of the two major model families in the literature: global matrix factorization and local context window methods. Our model efficiently leverages statistical information by training only on the nonzero elements in a word-word cooccurrence matrix, rather than on the entire sparse matrix or on individual context windows in a large corpus. The model produces a vector space with meaningful substructure, as evidenced by its performance of 75% on a recent word analogy task. It also outperforms related models on similarity tasks and named entity recognition.

C154945302

Artificial intelligence

https://doi.org/10.1145/3065386

field of computer science and engineering practices for intelligence demonstrated by machines and intelligent agents

ImageNet classification with deep convolutional neural networks

We trained a large, deep convolutional neural network to classify the 1.2 million high-resolution images in the ImageNet LSVRC-2010 contest into the 1000 different classes. On the test data, we achieved top-1 and top-5 error rates of 37.5% and 17.0%, respectively, which is considerably better than the previous state-of-the-art. The neural network, which has 60 million parameters and 650,000 neurons, consists of five convolutional layers, some of which are followed by max-pooling layers, and three fully connected layers with a final 1000-way softmax. To make training faster, we used non-saturating neurons and a very efficient GPU implementation of the convolution operation. To reduce overfitting in the fully connected layers we employed a recently developed regularization method called "dropout" that proved to be very effective. We also entered a variant of this model in the ILSVRC-2012 competition and achieved a winning top-5 test error rate of 15.3%, compared to 26.2% achieved by the second-best entry.

C178790620

Organic chemistry

https://doi.org/10.1016/s0022-2275(20)40190-7

subdiscipline within chemistry involving the scientific study of carbon-based compounds, hydrocarbons, and their derivatives

Preparation of fatty acid methyl esters and dimethylacetals from lipids with boron fluoride–methanol

Fatty acid methyl esters and dimethylacetals suitable for gas chromatographic analysis were prepared by treatment of lipids with boron fluoride–methanol (140 g BF3 per liter of methanol). This reagent is stable and easy to handle. Reaction conditions were investigated for triglycerides, diglycerides, monoglycerides, free fatty acids, sterol esters, phosphatidyl ethanolamines, phosphatidyl serines, phosphatidyl cholines, monophosphoinositides, monogalactosyl glycerides, phosphatidal cholines (choline plasmalogens), digalactosyl glycerides, and sphingomyelins. The methyl esters and dimethylacetals were readily purified by thin-layer chromatography, and yields were quantitative. There were few undesirable side reactions, and they did not affect the validity of the method. The procedure developed is simple, rapid, and generally applicable to lipids.

C178790620

Organic chemistry

https://doi.org/10.1021/om100106e

subdiscipline within chemistry involving the scientific study of carbon-based compounds, hydrocarbons, and their derivatives

NMR Chemical Shifts of Trace Impurities: Common Laboratory Solvents, Organics, and Gases in Deuterated Solvents Relevant to the Organometallic Chemist

Tables of 1H and 13C NMR chemical shifts have been compiled for common organic compounds often used as reagents or found as products or contaminants in deuterated organic solvents. Building upon the work of Gottlieb, Kotlyar, and Nudelman in the Journal of Organic Chemistry, signals for common impurities are now reported in additional NMR solvents (tetrahydrofuran-d8, toluene-d8, dichloromethane-d2, chlorobenzene-d5, and 2,2,2-trifluoroethanol-d3) which are frequently used in organometallic laboratories. Chemical shifts for other organics which are often used as reagents or internal standards or are found as products in organometallic chemistry are also reported for all the listed solvents.

C178790620

Organic chemistry

https://doi.org/10.2172/15008859

subdiscipline within chemistry involving the scientific study of carbon-based compounds, hydrocarbons, and their derivatives

Top Value Added Chemicals from Biomass: Volume I -- Results of Screening for Potential Candidates from Sugars and Synthesis Gas

This report identifies twelve building block chemicals that can be produced from sugars via biological or chemical conversions. The twelve building blocks can be subsequently converted to a number of high-value bio-based chemicals or materials. Building block chemicals, as considered for this analysis, are molecules with multiple functional groups that possess the potential to be transformed into new families of useful molecules. The twelve sugar-based building blocks are 1,4-diacids (succinic, fumaric and malic), 2,5-furan dicarboxylic acid, 3-hydroxy propionic acid, aspartic acid, glucaric acid, glutamic acid, itaconic acid, levulinic acid, 3-hydroxybutyrolactone, glycerol, sorbitol, and xylitol/arabinitol.

C178790620

Organic chemistry

https://doi.org/10.1177/10.3.348

subdiscipline within chemistry involving the scientific study of carbon-based compounds, hydrocarbons, and their derivatives

FLUORESCENCE OF CATECHOL AMINES AND RELATED COMPOUNDS CONDENSED WITH FORMALDEHYDE

The reaction under mild conditions between formaldehyde and phenylalanine and phenylethylamine derivatives has been studied. When the amines included in a dried protein film were exposed to formaldehyde vapour a very intense green to yellow fluorescence was give only by those that as well as being primary amines also have hydroxyl groups at the 3 and 4 positions (3,4-dihydroxyphenylalanine, dopamine, noradrenaline). The 3-OH group seems to be esssential for the reaction. The catechol amines, which are secondary amines (adrenaline, epinine), gave a much weaker fluorescence that developed more slowly. The results obtained on further examination of the reaction favour the view that the amines primarily condense with formaldehyde to 1,2,3,4-tetrahydroisoquinolines which are involved in a secondary reaction to become highly fluorescent and at the same time insoluble. This secondary reaction may be a binding to protein, and oxidation with the formation of double bonds in the heterocyclic ring, or both.

C178790620

Organic chemistry

https://doi.org/10.1021/ar800036s

subdiscipline within chemistry involving the scientific study of carbon-based compounds, hydrocarbons, and their derivatives

Palladium-Catalyzed Suzuki−Miyaura Cross-Coupling Reactions Employing Dialkylbiaryl Phosphine Ligands

The cores of many types of polymers, ligands, natural products, and pharmaceuticals contain biaryl or substituted aromatic structures, and efficient methods of synthesizing these structures are crucial to the work of a broad spectrum of organic chemists. Recently, Pd-catalyzed carbon−carbon bond-forming processes, particularly the Suzuki−Miyaura cross-coupling reaction (SMC), have risen in popularity for this purpose. The SMC has many advantages over other methods for constructing these moieties, including mild conditions, high tolerance toward functional groups, the commercial availability and stability of its reagents, and the ease of handling and separating byproducts from its reaction mixtures. Until 1998, most catalysts for the SMC employed triarylphosphine ligands. More recently, new bulky and electron-rich phosphine ligands, which can dramatically improve the efficiency and selectivity of such cross-coupling reactions, have been introduced. In the course of our studies on carbon−nitrogen bond-forming reactions, we found that the use of electron-rich and bulky phosphines enhanced the rate of both the oxidative addition and reductive elimination processes; this was the beginning of our development of a new family of ligands, the dialkylbiarylphosphines L1−L12. These ligands can be used for a wide variety of palladium-catalyzed carbon−carbon, carbon−nitrogen, and carbon−oxygen bond-forming processes as well as serving as supporting ligands for a number of other reactions. The enhanced reactivity of these catalysts has expanded the scope of cross-coupling partners that can be employed in the SMC. With use of such dialkylbiarylphosphine ligands, the coupling of unactivated aryl chlorides, aryl tosylates, heteroaryl systems, and very hindered substrate combinations have become routine. The utility of these ligands has been successfully demonstrated in a wide number of synthetic applications, including industrially relevant processes. In this Account, we provide an overview of the use and impact of dialkylbiarylphosphine ligands in the SMC. We discuss our studies on the mechanistic framework of the reaction, which have allowed us to rationally modify the ligand structures in order to tune their properties. We also describe selected applications in the synthesis of natural products and new materials to illustrate the utility of these dialkylbiarylphosphine ligands in various "real-world" synthetic applications.

C178790620

Organic chemistry

https://doi.org/10.1016/s0022-2275(20)38861-1

subdiscipline within chemistry involving the scientific study of carbon-based compounds, hydrocarbons, and their derivatives

Direct transesterification of all classes of lipids in a one-step reaction.

Conventional techniques for the determination of fatty acid composition of lipids require solvent extraction, purification, hydrolysis, and derivatization procedures that are both lengthy and cumbersome.A 1-hr direct transesterification procedure carried out in methanol-benzene 4:l with acetyl chloride circumvented all these steps and was applicable for analysis of both simple (triglycerides) and complex lipids (cholesteryl esters, phospholipids; and sphingomyelin).Recoveries ( > 95 %) of standards unaffected by the presence of 5% water and 200 mg of silica suggested that the technique could be used for the quantitative analysis of total fatty acids as well as of fatty acids in classes of lipids separated on silica from biological samples.When compared to the Folch procedure, the technique led to a 20.1% increase in total fatty acids for plasma, 3.9% for feces, 7.4% for bile, and 9.7% for rat liver.lWetherefore conclude that this one-step direct transesterification procedure is superior to currently used methods, not only because of its simplicity and speed, but also because of its added precision.-Lepage, G., and C. C. Roy.Direct transesterification of all classes of lipids in a one-step reaction.

C178790620

Organic chemistry

https://doi.org/10.1021/acs.chemrev.6b00512

subdiscipline within chemistry involving the scientific study of carbon-based compounds, hydrocarbons, and their derivatives

Applications of Palladium-Catalyzed C–N Cross-Coupling Reactions

Pd-catalyzed cross-coupling reactions that form C–N bonds have become useful methods to synthesize anilines and aniline derivatives, an important class of compounds throughout chemical research. A key factor in the widespread adoption of these methods has been the continued development of reliable and versatile catalysts that function under operationally simple, user-friendly conditions. This review provides an overview of Pd-catalyzed N-arylation reactions found in both basic and applied chemical research from 2008 to the present. Selected examples of C–N cross-coupling reactions between nine classes of nitrogen-based coupling partners and (pseudo)aryl halides are described for the synthesis of heterocycles, medicinally relevant compounds, natural products, organic materials, and catalysts.

C178790620

Organic chemistry

https://doi.org/10.1002/anie.200604274

subdiscipline within chemistry involving the scientific study of carbon-based compounds, hydrocarbons, and their derivatives

Liquid‐Phase Catalytic Processing of Biomass‐Derived Oxygenated Hydrocarbons to Fuels and Chemicals

Abstract Biomass has the potential to serve as a sustainable source of energy and organic carbon for our industrialized society. The focus of this Review is to present an overview of chemical catalytic transformations of biomass‐derived oxygenated feedstocks (primarily sugars and sugar‐alcohols) in the liquid phase to value‐added chemicals and fuels, with specific examples emphasizing the development of catalytic processes based on an understanding of the fundamental reaction chemistry. The key reactions involved in the processing of biomass are hydrolysis, dehydration, isomerization, aldol condensation, reforming, hydrogenation, and oxidation. Further, it is discussed how ideas based on fundamental chemical and catalytic concepts lead to strategies for the control of reaction pathways and process conditions to produce H 2 /CO 2 or H 2 /CO gas mixtures by aqueous‐phase reforming, to produce furan compounds by selective dehydration of carbohydrates, and to produce liquid alkanes by the combination of aldol condensation and dehydration/hydrogenation processes.

C54355233

Genetics

https://doi.org/10.1093/nar/22.22.4673

study of genes, heredity, and variation in living organisms

CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice

The sensitivity of the commonly used progressive multiple sequence alignment method has been greatly improved for the alignment of divergent protein sequences. Firstly, individual weights are assigned to each sequence in a partial alignment in order to down-weight near-duplicate sequences and up-weight the most divergent ones. Secondly, amino acid substitution matrices are varied at different alignment stages according to the divergence of the sequences to be aligned. Thirdly, residue-specific gap penalties and locally reduced gap penalties in hydrophilic regions encourage new gaps in potential loop regions rather than regular secondary structure. Fourthly, positions in early alignments where gaps have been opened receive locally reduced gap penalties to encourage the opening up of new gaps at these positions. These modifications are incorporated into a new program, CLUSTAL W which is freely available.

C54355233

Genetics

https://doi.org/10.1093/molbev/msw054

study of genes, heredity, and variation in living organisms

MEGA7: Molecular Evolutionary Genetics Analysis Version 7.0 for Bigger Datasets

Abstract We present the latest version of the Molecular Evolutionary Genetics Analysis (M ega ) software, which contains many sophisticated methods and tools for phylogenomics and phylomedicine. In this major upgrade, M ega has been optimized for use on 64-bit computing systems for analyzing larger datasets. Researchers can now explore and analyze tens of thousands of sequences in M ega . The new version also provides an advanced wizard for building timetrees and includes a new functionality to automatically predict gene duplication events in gene family trees. The 64-bit M ega is made available in two interfaces: graphical and command line. The graphical user interface (GUI) is a native Microsoft Windows application that can also be used on Mac OS X. The command line M ega is available as native applications for Windows, Linux, and Mac OS X. They are intended for use in high-throughput and scripted analysis. Both versions are available from www.megasoftware.net free of charge.

C54355233

Genetics

https://doi.org/10.1093/genetics/155.2.945

study of genes, heredity, and variation in living organisms

Inference of Population Structure Using Multilocus Genotype Data

Abstract We describe a model-based clustering method for using multilocus genotype data to infer population structure and assign individuals to populations. We assume a model in which there are K populations (where K may be unknown), each of which is characterized by a set of allele frequencies at each locus. Individuals in the sample are assigned (probabilistically) to populations, or jointly to two or more populations if their genotypes indicate that they are admixed. Our model does not assume a particular mutation process, and it can be applied to most of the commonly used genetic markers, provided that they are not closely linked. Applications of our method include demonstrating the presence of population structure, assigning individuals to populations, studying hybrid zones, and identifying migrants and admixed individuals. We show that the method can produce highly accurate assignments using modest numbers of loci—e.g., seven microsatellite loci in an example using genotype data from an endangered bird species. The software used for this article is available from http://www.stats.ox.ac.uk/~pritch/home.html.

C54355233

Genetics

https://doi.org/10.1186/gb-2009-10-3-r25

study of genes, heredity, and variation in living organisms

Ultrafast and memory-efficient alignment of short DNA sequences to the human genome

Abstract Bowtie is an ultrafast, memory-efficient alignment program for aligning short DNA sequence reads to large genomes. For the human genome, Burrows-Wheeler indexing allows Bowtie to align more than 25 million reads per CPU hour with a memory footprint of approximately 1.3 gigabytes. Bowtie extends previous Burrows-Wheeler techniques with a novel quality-aware backtracking algorithm that permits mismatches. Multiple processor cores can be used simultaneously to achieve even greater alignment speeds. Bowtie is open source http://bowtie.cbcb.umd.edu .

C54355233

Genetics

https://doi.org/10.1186/1471-2105-12-323

study of genes, heredity, and variation in living organisms

RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome

RNA-Seq is revolutionizing the way transcript abundances are measured. A key challenge in transcript quantification from RNA-Seq data is the handling of reads that map to multiple genes or isoforms. This issue is particularly important for quantification with de novo transcriptome assemblies in the absence of sequenced genomes, as it is difficult to determine which transcripts are isoforms of the same gene. A second significant issue is the design of RNA-Seq experiments, in terms of the number of reads, read length, and whether reads come from one or both ends of cDNA fragments. We present RSEM, an user-friendly software package for quantifying gene and isoform abundances from single-end or paired-end RNA-Seq data. RSEM outputs abundance estimates, 95% credibility intervals, and visualization files and can also simulate RNA-Seq data. In contrast to other existing tools, the software does not require a reference genome. Thus, in combination with a de novo transcriptome assembler, RSEM enables accurate transcript quantification for species without sequenced genomes. On simulated and real data sets, RSEM has superior or comparable performance to quantification methods that rely on a reference genome. Taking advantage of RSEM's ability to effectively use ambiguously-mapping reads, we show that accurate gene-level abundance estimates are best obtained with large numbers of short single-end reads. On the other hand, estimates of the relative frequencies of isoforms within single genes may be improved through the use of paired-end reads, depending on the number of possible splice forms for each gene. RSEM is an accurate and user-friendly software tool for quantifying transcript abundances from RNA-Seq data. As it does not rely on the existence of a reference genome, it is particularly useful for quantification with de novo transcriptome assemblies. In addition, RSEM has enabled valuable guidance for cost-efficient design of quantification experiments with RNA-Seq, which is currently relatively expensive.

C54355233

Genetics

https://doi.org/10.1038/nature11247

study of genes, heredity, and variation in living organisms

An integrated encyclopedia of DNA elements in the human genome

The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research. This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription-factor association, chromatin structure and histone modification. In this overview, the Consortium guides the readers through the project itself, the data and their integrated analyses. Eighty per cent of the human genome now has at least one biochemical function assigned to it. In addition to expanding our understanding of how gene expression is regulated on a genome-wide scale, the newly identified functional elements should help researchers to interpret the results of genome-wide associated studies because many correspond to sites associated with human disease.

C54355233

Genetics

https://doi.org/10.1073/pnas.95.25.14863

study of genes, heredity, and variation in living organisms

Cluster analysis and display of genome-wide expression patterns

A system of cluster analysis for genome-wide expression data from DNA microarray hybridization is described that uses standard statistical algorithms to arrange genes according to similarity in pattern of gene expression. The output is displayed graphically, conveying the clustering and the underlying expression data simultaneously in a form intuitive for biologists. We have found in the budding yeast Saccharomyces cerevisiae that clustering gene expression data groups together efficiently genes of known similar function, and we find a similar tendency in human data. Thus patterns seen in genome-wide expression experiments can be interpreted as indications of the status of cellular processes. Also, coexpression of genes of known function with poorly characterized or novel genes may provide a simple means of gaining leads to the functions of many genes for which information is not available currently.

C54355233

Genetics

https://doi.org/10.1126/science.1225829

study of genes, heredity, and variation in living organisms

A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems provide bacteria and archaea with adaptive immunity against viruses and plasmids by using CRISPR RNAs (crRNAs) to guide the silencing of invading nucleic acids. We show here that in a subset of these systems, the mature crRNA that is base-paired to trans-activating crRNA (tracrRNA) forms a two-RNA structure that directs the CRISPR-associated protein Cas9 to introduce double-stranded (ds) breaks in target DNA. At sites complementary to the crRNA-guide sequence, the Cas9 HNH nuclease domain cleaves the complementary strand, whereas the Cas9 RuvC-like domain cleaves the noncomplementary strand. The dual-tracrRNA:crRNA, when engineered as a single RNA chimera, also directs sequence-specific Cas9 dsDNA cleavage. Our study reveals a family of endonucleases that use dual-RNAs for site-specific DNA cleavage and highlights the potential to exploit the system for RNA-programmable genome editing.

C18903297

Ecology

https://doi.org/10.1146/annurev.es.04.110173.000245

scientific study of the relationships between living organisms

Resilience and Stability of Ecological Systems

Individuals die, populations disappear, and species become extinct. That is one view of the world. But another view of the world concentrates not so much on presence or absence as upon the numbers of organisms and the degree of constancy of their numbers. These are two very different ways of viewing the behavior of systems and the usefulness of the view depends very much on the properties of the system concerned. If we are examining a particular device designed by the engineer to perform specific tasks under a rather narrow range of predictable external conditions, we are likely to be more concerned with consistent nonvariable performance in which slight departures from the performance goal are immediately counteracted. A quantitative view of the behavior of the system is, therefore, essential. With attention focused upon achieving constancy, the critical events seem to be the amplitude and frequency of oscillations. But if we are dealing with a system profoundly affected by changes external to it, and continually confronted by the unexpected, the constancy of its behavior becomes less important than the persistence of the relationships. Attention shifts, therefore, to the qualitative and to questions of existence or not. Our traditions of analysis in theoretical and empirical ecology have been largely inherited from developments in classical physics and its applied variants. Inevitably, there has been a tendency to emphasize the quantitative rather than the qualitative, for it is important in this tradition to know not just that a quantity is larger than another quantity, but precisely how much larger. It is similarly important, if a quantity fluctuates, to know its amplitude and period of fluctuation. But this orientation may simply reflect an analytic approach developed in one area because it was useful and then transferred to another where it may not be. Our traditional view of natural systems, therefore, might well be less a meaningful reality than a perceptual convenience. There can in some years be more owls and fewer mice and in others, the reverse. Fish populations wax and wane as a natural condition, and insect populations can range over extremes that only logarithmic

C18903297

Ecology

https://doi.org/10.1038/nature11234

scientific study of the relationships between living organisms

Structure, function and diversity of the healthy human microbiome

Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitat's signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81–99% of the genera, enzyme families and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology and translational applications of the human microbiome. The Human Microbiome Project Consortium reports the first results of their analysis of microbial communities from distinct, clinically relevant body habitats in a human cohort; the insights into the microbial communities of a healthy population lay foundations for future exploration of the epidemiology, ecology and translational applications of the human microbiome. The Human Microbiome Project (HMP), supported by the National Institutes of Health Common Fund, has the goal of characterizing the microbial communities that inhabit and interact with the human body in sickness and in health. In two Articles in this issue of Nature, the HMP Consortium presents the first population-scale details of the organismal and functional composition of the microbiota across five areas of the body. An associated News & Views discusses the initial results — which, along with those of a series of co-publications, already constitute the most extensive catalogue of organisms and genes related to the human microbiome yet published — and highlights some of the major questions that the project will tackle in the next few years.

C18903297

Ecology

https://doi.org/10.1111/j.2006.0906-7590.04596.x

scientific study of the relationships between living organisms

Novel methods improve prediction of species’ distributions from occurrence data

Prediction of species’ distributions is central to diverse applications in ecology, evolution and conservation science. There is increasing electronic access to vast sets of occurrence records in museums and herbaria, yet little effective guidance on how best to use this information in the context of numerous approaches for modelling distributions. To meet this need, we compared 16 modelling methods over 226 species from 6 regions of the world, creating the most comprehensive set of model comparisons to date. We used presence‐only data to fit models, and independent presence‐absence data to evaluate the predictions. Along with well‐established modelling methods such as generalised additive models and GARP and BIOCLIM, we explored methods that either have been developed recently or have rarely been applied to modelling species’ distributions. These include machine‐learning methods and community models, both of which have features that may make them particularly well suited to noisy or sparse information, as is typical of species’ occurrence data. Presence‐only data were effective for modelling species’ distributions for many species and regions. The novel methods consistently outperformed more established methods. The results of our analysis are promising for the use of data from museums and herbaria, especially as methods suited to the noise inherent in such data improve.

C18903297

Ecology

https://doi.org/10.1128/aem.71.12.8228-8235.2005

scientific study of the relationships between living organisms

UniFrac: a New Phylogenetic Method for Comparing Microbial Communities

ABSTRACT We introduce here a new method for computing differences between microbial communities based on phylogenetic information. This method, UniFrac, measures the phylogenetic distance between sets of taxa in a phylogenetic tree as the fraction of the branch length of the tree that leads to descendants from either one environment or the other, but not both. UniFrac can be used to determine whether communities are significantly different, to compare many communities simultaneously using clustering and ordination techniques, and to measure the relative contributions of different factors, such as chemistry and geography, to similarities between samples. We demonstrate the utility of UniFrac by applying it to published 16S rRNA gene libraries from cultured isolates and environmental clones of bacteria in marine sediment, water, and ice. Our results reveal that (i) cultured isolates from ice, water, and sediment resemble each other and environmental clone sequences from sea ice, but not environmental clone sequences from sediment and water; (ii) the geographical location does not correlate strongly with bacterial community differences in ice and sediment from the Arctic and Antarctic; and (iii) bacterial communities differ between terrestrially impacted seawater (whether polar or temperate) and warm oligotrophic seawater, whereas those in individual seawater samples are not more similar to each other than to those in sediment or ice samples. These results illustrate that UniFrac provides a new way of characterizing microbial communities, using the wealth of environmental rRNA sequences, and allows quantitative insight into the factors that underlie the distribution of lineages among environments.

C18903297

Ecology

https://doi.org/10.1086/226424

scientific study of the relationships between living organisms

The Population Ecology of Organizations

A population ecology perspective on organization-environment relations is proposed as an alternative to the dominant adaptation perspective. The strength of inertial pressures on organizational structure suggests the application of models that depend on competition and selection in populations of organizations. Several such models as well as issues that arise in attempts to apply them to the organization-environment problem are discussed.

C18903297

Ecology

https://doi.org/10.1890/04-0922

scientific study of the relationships between living organisms

EFFECTS OF BIODIVERSITY ON ECOSYSTEM FUNCTIONING: A CONSENSUS OF CURRENT KNOWLEDGE

Humans are altering the composition of biological communities through a variety of activities that increase rates of species invasions and species extinctions, at all scales, from local to global. These changes in components of the Earth's biodiversity cause concern for ethical and aesthetic reasons, but they also have a strong potential to alter ecosystem properties and the goods and services they provide to humanity. Ecological experiments, observations, and theoretical developments show that ecosystem properties depend greatly on biodiversity in terms of the functional characteristics of organisms present in the ecosystem and the distribution and abundance of those organisms over space and time. Species effects act in concert with the effects of climate, resource availability, and disturbance regimes in influencing ecosystem properties. Human activities can modify all of the above factors; here we focus on modification of these biotic controls. The scientific community has come to a broad consensus on many aspects of the relationship between biodiversity and ecosystem functioning, including many points relevant to management of ecosystems. Further progress will require integration of knowledge about biotic and abiotic controls on ecosystem properties, how ecological communities are structured, and the forces driving species extinctions and invasions. To strengthen links to policy and management, we also need to integrate our ecological knowledge with understanding of the social and economic constraints of potential management practices. Understanding this complexity, while taking strong steps to minimize current losses of species, is necessary for responsible management of Earth's ecosystems and the diverse biota they contain. Based on our review of the scientific literature, we are certain of the following conclusions: 1) Species' functional characteristics strongly influence ecosystem properties. Functional characteristics operate in a variety of contexts, including effects of dominant species, keystone species, ecological engineers, and interactions among species (e.g., competition, facilitation, mutualism, disease, and predation). Relative abundance alone is not always a good predictor of the ecosystem-level importance of a species, as even relatively rare species (e.g., a keystone predator) can strongly influence pathways of energy and material flows. 2) Alteration of biota in ecosystems via species invasions and extinctions caused by human activities has altered ecosystem goods and services in many well-documented cases. Many of these changes are difficult, expensive, or impossible to reverse or fix with technological solutions. 3) The effects of species loss or changes in composition, and the mechanisms by which the effects manifest themselves, can differ among ecosystem properties, ecosystem types, and pathways of potential community change. 4) Some ecosystem properties are initially insensitive to species loss because (a) ecosystems may have multiple species that carry out similar functional roles, (b) some species may contribute relatively little to ecosystem properties, or (c) properties may be primarily controlled by abiotic environmental conditions. 5) More species are needed to insure a stable supply of ecosystem goods and services as spatial and temporal variability increases, which typically occurs as longer time periods and larger areas are considered. We have high confidence in the following conclusions: 1) Certain combinations of species are complementary in their patterns of resource use and can increase average rates of productivity and nutrient retention. At the same time, environmental conditions can influence the importance of complementarity in structuring communities. Identification of which and how many species act in a complementary way in complex communities is just beginning. 2) Susceptibility to invasion by exotic species is strongly influenced by species composition and, under similar environmental conditions, generally decreases with increasing species richness. However, several other factors, such as propagule pressure, disturbance regime, and resource availability also strongly influence invasion success and often override effects of species richness in comparisons across different sites or ecosystems. 3) Having a range of species that respond differently to different environmental perturbations can stabilize ecosystem process rates in response to disturbances and variation in abiotic conditions. Using practices that maintain a diversity of organisms of different functional effect and functional response types will help preserve a range of management options. Uncertainties remain and further research is necessary in the following areas: 1) Further resolution of the relationships among taxonomic diversity, functional diversity, and community structure is important for identifying mechanisms of biodiversity effects. 2) Multiple trophic levels are common to ecosystems but have been understudied in biodiversity/ecosystem functioning research. The response of ecosystem properties to varying composition and diversity of consumer organisms is much more complex than responses seen in experiments that vary only the diversity of primary producers. 3) Theoretical work on stability has outpaced experimental work, especially field research. We need long-term experiments to be able to assess temporal stability, as well as experimental perturbations to assess response to and recovery from a variety of disturbances. Design and analysis of such experiments must account for several factors that covary with species diversity. 4) Because biodiversity both responds to and influences ecosystem properties, understanding the feedbacks involved is necessary to integrate results from experimental communities with patterns seen at broader scales. Likely patterns of extinction and invasion need to be linked to different drivers of global change, the forces that structure communities, and controls on ecosystem properties for the development of effective management and conservation strategies. 5) This paper focuses primarily on terrestrial systems, with some coverage of freshwater systems, because that is where most empirical and theoretical study has focused. While the fundamental principles described here should apply to marine systems, further study of that realm is necessary. Despite some uncertainties about the mechanisms and circumstances under which diversity influences ecosystem properties, incorporating diversity effects into policy and management is essential, especially in making decisions involving large temporal and spatial scales. Sacrificing those aspects of ecosystems that are difficult or impossible to reconstruct, such as diversity, simply because we are not yet certain about the extent and mechanisms by which they affect ecosystem properties, will restrict future management options even further. It is incumbent upon ecologists to communicate this need, and the values that can derive from such a perspective, to those charged with economic and policy decision-making.

C18903297

Ecology

https://doi.org/10.5751/es-00650-090205

scientific study of the relationships between living organisms

Resilience, Adaptability and Transformability in Social-ecological Systems

Walker, B., C. Holling, S. R. Carpenter and A. P. Kinzig 2004. Resilience, adaptability and transformability in social–ecological systems. Ecology and Society 9(2): 5. https://doi.org/10.5751/ES-00650-090205

C18903297

Ecology

https://doi.org/10.2307/1941447

scientific study of the relationships between living organisms

The Problem of Pattern and Scale in Ecology: The Robert H. MacArthur Award Lecture

It is argued that the problem of pattern and scale is the central problem in ecology, unifying population biology and ecosystems science, and marrying basic and applied ecology. Applied challenges, such as the prediction of the ecological causes and consequences of global climate change, require the interfacing of phenomena that occur on very different scales of space, time, and ecological organization. Furthermore, there is no single natural scale at which ecological phenomena should be studied; systems generally show characteristic variability on a range of spatial, temporal, and organizational scales. The observer imposes a perceptual bias, a filter through which the system is viewed. This has fundamental evolutionary significance, since every organism is an "observer" of the environment, and life history adaptations such as dispersal and dormancy alter the perceptual scales of the species, and the observed variability. It likewise has fundamental significance for our own study of ecological systems, since the patterns that are unique to any range of scales will have unique causes and biological consequences. The key to prediction and understanding lies in the elucidation of mechanisms underlying observed patterns. Typically, these mechanisms operate at different scales than those on which the patterns are observed; in some cases, the patterns must be understood as emerging form the collective behaviors of large ensembles of smaller scale units. In other cases, the pattern is imposed by larger scale constraints. Examination of such phenomena requires the study of how pattern and variability change with the scale of description, and the development of laws for simplification, aggregation, and scaling. Examples are given from the marine and terrestrial literatures.

C142724271

Pathology

https://doi.org/10.1007/s00401-007-0243-4

study and diagnosis of disease

The 2007 WHO Classification of Tumours of the Central Nervous System

The fourth edition of the World Health Organization (WHO) classification of tumours of the central nervous system, published in 2007, lists several new entities, including angiocentric glioma, papillary glioneuronal tumour, rosette-forming glioneuronal tumour of the fourth ventricle, papillary tumour of the pineal region, pituicytoma and spindle cell oncocytoma of the adenohypophysis. Histological variants were added if there was evidence of a different age distribution, location, genetic profile or clinical behaviour; these included pilomyxoid astrocytoma, anaplastic medulloblastoma and medulloblastoma with extensive nodularity. The WHO grading scheme and the sections on genetic profiles were updated and the rhabdoid tumour predisposition syndrome was added to the list of familial tumour syndromes typically involving the nervous system. As in the previous, 2000 edition of the WHO ‘Blue Book’, the classification is accompanied by a concise commentary on clinico-pathological characteristics of each tumour type. The 2007 WHO classification is based on the consensus of an international Working Group of 25 pathologists and geneticists, as well as contributions from more than 70 international experts overall, and is presented as the standard for the definition of brain tumours to the clinical oncology and cancer research communities world-wide.

C142724271

Pathology

https://doi.org/10.1159/000353099

study and diagnosis of disease

Evaluation of Factors Related to Late Recurrence - Later than 10 Years after the Initial Treatment - in Primary Breast Cancer

Tumors can recur years after treatment, and breast cancer is especially noted for long periods of dormancy. The status of the cancer during this period is poorly understood. As a model to study mechanisms of dormancy, we used murine D2.0R mammary carcinoma cells, which are poorly metastatic but form occasional metastases in liver and other organs after long latency. Highly metastatic D2A1 cells provided a positive, metastatic control. Our goals were to learn how the cell lines differ in survival kinetics in a secondary site and to seek evidence for the source of D2.0R dormancy. In spontaneous metastasis assays from mammary fat pad injections, we found evidence for dormancy because of a persistence of large numbers of solitary cells in the liver. To quantify the fate of cells after arrival in liver, experimental metastasis assays were used. To permit identification of cells that had not divided, cells were labeled before injection with fluorescent nanospheres, which were diluted to undetectable levels by cell division. Cancer cells were injected i.v. to target them to the liver and coinjected with reference microspheres to monitor cell survival. Dormancy was defined as retention of nanosphere fluorescence in vivo, as well as negative staining for the proliferation marker Ki67. A large proportion of D2.0R cells persisted as solitary dormant cells. No metastases formed, but viable cells could be recovered from the liver 11 weeks after injection. Large numbers of solitary, dormant, Ki67-negative D2A1 cells were also detected against a background of progressively growing metastases. Thus, this study identified a possible contributor to tumor dormancy: solitary, dormant cells that persist in tissue. If such cells are present in patients, they could contribute to tumor recurrence and would not be susceptible to current therapeutic strategies targeting proliferating cells.

C142724271

Pathology

https://doi.org/10.1038/s41598-016-0001-8

study and diagnosis of disease

Ultrastructural Characterization of the Lower Motor System in a Mouse Model of Krabbe Disease

Abstract Krabbe disease (KD) is a neurodegenerative disorder caused by the lack of β- galactosylceramidase enzymatic activity and by widespread accumulation of the cytotoxic galactosyl-sphingosine in neuronal, myelinating and endothelial cells. Despite the wide use of Twitcher mice as experimental model for KD, the ultrastructure of this model is partial and mainly addressing peripheral nerves. More details are requested to elucidate the basis of the motor defects, which are the first to appear during KD onset. Here we use transmission electron microscopy (TEM) to focus on the alterations produced by KD in the lower motor system at postnatal day 15 (P15), a nearly asymptomatic stage, and in the juvenile P30 mouse. We find mild effects on motorneuron soma, severe ones on sciatic nerves and very severe effects on nerve terminals and neuromuscular junctions at P30, with peripheral damage being already detectable at P15. Finally, we find that the gastrocnemius muscle undergoes atrophy and structural changes that are independent of denervation at P15. Our data further characterize the ultrastructural analysis of the KD mouse model, and support recent theories of a dying-back mechanism for neuronal degeneration, which is independent of demyelination.

C142724271

Pathology

https://doi.org/10.1136/jnnp.55.3.181

study and diagnosis of disease

Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases.

Few detailed clinico-pathological correlations of Parkinson9s disease have been published. The pathological findings in 100 patients diagnosed prospectively by a group of consultant neurologists as having idiopathic Parkinson9s disease are reported. Seventy six had nigral Lewy bodies, and in all of these Lewy bodies were also found in the cerebral cortex. In 24 cases without Lewy bodies, diagnoses included progressive supranuclear palsy, multiple system atrophy, Alzheimer9s disease, Alzheimer-type pathology, and basal ganglia vascular disease. The retrospective application of recommended diagnostic criteria improved the diagnostic accuracy to 82%. These observations call into question current concepts of Parkinson9s disease as a single distinct morbid entity.

C142724271

Pathology

https://doi.org/10.1172/jci39104

study and diagnosis of disease

The basics of epithelial-mesenchymal transition

The origins of the mesenchymal cells participating in tissue repair and pathological processes, notably tissue fibrosis, tumor invasiveness, and metastasis, are poorly understood. However, emerging evidence suggests that epithelial-mesenchymal transitions (EMTs) represent one important source of these cells. As we discuss here, processes similar to the EMTs associated with embryo implantation, embryogenesis, and organ development are appropriated and subverted by chronically inflamed tissues and neoplasias. The identification of the signaling pathways that lead to activation of EMT programs during these disease processes is providing new insights into the plasticity of cellular phenotypes and possible therapeutic interventions.

C142724271

Pathology

https://doi.org/10.1093/neuonc/noab106

study and diagnosis of disease

The 2021 WHO Classification of Tumors of the Central Nervous System: a summary

Abstract The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, is the sixth version of the international standard for the classification of brain and spinal cord tumors. Building on the 2016 updated fourth edition and the work of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy, the 2021 fifth edition introduces major changes that advance the role of molecular diagnostics in CNS tumor classification. At the same time, it remains wedded to other established approaches to tumor diagnosis such as histology and immunohistochemistry. In doing so, the fifth edition establishes some different approaches to both CNS tumor nomenclature and grading and it emphasizes the importance of integrated diagnoses and layered reports. New tumor types and subtypes are introduced, some based on novel diagnostic technologies such as DNA methylome profiling. The present review summarizes the major general changes in the 2021 fifth edition classification and the specific changes in each taxonomic category. It is hoped that this summary provides an overview to facilitate more in-depth exploration of the entire fifth edition of the WHO Classification of Tumors of the Central Nervous System.

C142724271

Pathology

https://doi.org/10.1002/path.1570

study and diagnosis of disease

Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis

Severe acute respiratory syndrome (SARS) is an acute infectious disease that spreads mainly via the respiratory route. A distinct coronavirus (SARS-CoV) has been identified as the aetiological agent of SARS. Recently, a metallopeptidase named angiotensin-converting enzyme 2 (ACE2) has been identified as the functional receptor for SARS-CoV. Although ACE2 mRNA is known to be present in virtually all organs, its protein expression is largely unknown. Since identifying the possible route of infection has major implications for understanding the pathogenesis and future treatment strategies for SARS, the present study investigated the localization of ACE2 protein in various human organs (oral and nasal mucosa, nasopharynx, lung, stomach, small intestine, colon, skin, lymph nodes, thymus, bone marrow, spleen, liver, kidney, and brain). The most remarkable finding was the surface expression of ACE2 protein on lung alveolar epithelial cells and enterocytes of the small intestine. Furthermore, ACE2 was present in arterial and venous endothelial cells and arterial smooth muscle cells in all organs studied. In conclusion, ACE2 is abundantly present in humans in the epithelia of the lung and small intestine, which might provide possible routes of entry for the SARS-CoV. This epithelial expression, together with the presence of ACE2 in vascular endothelium, also provides a first step in understanding the pathogenesis of the main SARS disease manifestations.

C142724271

Pathology

https://doi.org/10.1056/nejm199101033240101

study and diagnosis of disease

Tumor Angiogenesis and Metastasis — Correlation in Invasive Breast Carcinoma

Experimental evidence suggests that the growth of a tumor beyond a certain size requires angiogenesis, which may also permit metastasis. To investigate how tumor angiogenesis correlates with metastases in breast carcinoma, we counted microvessels (capillaries and venules) and graded the density of microvessels within the initial invasive carcinomas of 49 patients (30 with metastases and 19 without).

C159985019

Composite material

https://doi.org/10.1083/jcb.9.2.409

material made from a combination of two or more unlike substances

IMPROVEMENTS IN EPOXY RESIN EMBEDDING METHODS

Epoxy embedding methods of Glauert and Kushida have been modified so as to yield rapid, reproducible, and convenient embedding methods for electron microscopy. The sections are robust and tissue damage is less than with methacrylate embedding.

C159985019

Composite material

https://doi.org/10.1098/rspa.1971.0141

material made from a combination of two or more unlike substances

Surface energy and the contact of elastic solids

This paper discusses the influence of surface energy on the contact between elastic solids. Equations are derived for its effect upon the contact size and the force of adhesion between two lightly loaded spherical solid surfaces. The theory is supported by experiments carried out on the contact of rubber and gelatine spheres.

C159985019

Composite material

https://doi.org/10.1126/science.1194975

material made from a combination of two or more unlike substances

Two-Dimensional Nanosheets Produced by Liquid Exfoliation of Layered Materials

If they could be easily exfoliated, layered materials would become a diverse source of two-dimensional crystals whose properties would be useful in applications ranging from electronics to energy storage. We show that layered compounds such as MoS(2), WS(2), MoSe(2), MoTe(2), TaSe(2), NbSe(2), NiTe(2), BN, and Bi(2)Te(3) can be efficiently dispersed in common solvents and can be deposited as individual flakes or formed into films. Electron microscopy strongly suggests that the material is exfoliated into individual layers. By blending this material with suspensions of other nanomaterials or polymer solutions, we can prepare hybrid dispersions or composites, which can be cast into films. We show that WS(2) and MoS(2) effectively reinforce polymers, whereas WS(2)/carbon nanotube hybrid films have high conductivity, leading to promising thermoelectric properties.

C159985019

Composite material

https://doi.org/10.1115/1.3423688

material made from a combination of two or more unlike substances

Mechanics of Composite Materials

REVIEWSpresentation of its subject which, by having collected in one place a comprehensive assortment of methods and techniques of measurement, will be of value to any person interested in comparing the possibilities and limitations of each.It is most certainly recommended to the audience for which it is written.

C159985019

Composite material

https://doi.org/10.1016/j.polymer.2010.11.042

material made from a combination of two or more unlike substances

Graphene-based polymer nanocomposites

Graphene-based materials are single- or few-layer platelets that can be produced in bulk quantities by chemical methods. Herein, we present a survey of the literature on polymer nanocomposites with graphene-based fillers including recent work using graphite nanoplatelet fillers. A variety of routes used to produce graphene-based materials are reviewed, along with methods for dispersing these materials in various polymer matrices. We also review the rheological, electrical, mechanical, thermal, and barrier properties of these composites, and how each of these composite properties is dependent upon the intrinsic properties of graphene-based materials and their state of dispersion in the matrix. An overview of potential applications for these composites and current challenges in the field are provided for perspective and to potentially guide future progress on the development of these promising materials.

C159985019

Composite material

https://doi.org/10.1016/j.compositesa.2015.08.038

material made from a combination of two or more unlike substances

A review of recent developments in natural fibre composites and their mechanical performance

Recently, there has been a rapid growth in research and innovation in the natural fibre composite (NFC) area. Interest is warranted due to the advantages of these materials compared to others, such as synthetic fibre composites, including low environmental impact and low cost and support their potential across a wide range of applications. Much effort has gone into increasing their mechanical performance to extend the capabilities and applications of this group of materials. This review aims to provide an overview of the factors that affect the mechanical performance of NFCs and details achievements made with them.

C159985019

Composite material

https://doi.org/10.1021/nn203879f

material made from a combination of two or more unlike substances

Stretching and Breaking of Ultrathin MoS₂

We report on measurements of the stiffness and breaking strength of monolayer MoS2, a new semiconducting analogue of graphene. Single and bilayer MoS2 is exfoliated from bulk and transferred to a substrate containing an array of microfabricated circular holes. The resulting suspended, free-standing membranes are deformed and eventually broken using an atomic force microscope. We find that the in-plane stiffness of monolayer MoS2 is 180 ± 60 Nm–1, corresponding to an effective Young's modulus of 270 ± 100 GPa, which is comparable to that of steel. Breaking occurs at an effective strain between 6 and 11% with the average breaking strength of 15 ± 3 Nm–1 (23 GPa). The strength of strongest monolayer membranes is 11% of its Young's modulus, corresponding to the upper theoretical limit which indicates that the material can be highly crystalline and almost defect-free. Our results show that monolayer MoS2 could be suitable for a variety of applications such as reinforcing elements in composites and for fabrication of flexible electronic devices.

C159985019

Composite material

https://doi.org/10.1159/000363582

material made from a combination of two or more unlike substances

Matrix Metalloproteinases and Other Matrix Proteinases in Relation to Cariology: The Era of ‘Dentin Degradomics'

This review discusses current trends in the development of dentin adhesives and the possibility that some classes of currently available adhesives are too hydrophilic. Manufacturers have reformulated dentin adhesives to make them more compatible for bonding to intrinsically moist, acid-etched dentin by adding 2-hydroxyethyl methacrylate and other hydrophilic resin monomers. These 3-step adhesives work well but are more time consuming to use and more sensitive to technique than the newer, simplified adhesives. When primers are mixed with adhesives in 2-step single-bottle adhesives and self-etching primers, the adhesives are more permeable to water and hence absorb more water over time than previous generations of adhesives. The most recent single-step self-etching adhesives are even more hydrophilic and hence more permeable to water derived from the underlying bonded dentin. This permeability can lead to a wide variety of seemingly unrelated problems, including incompatibility of chemically or dual-cured composites with simplified adhesives and expedited degradation of resin-dentin bonds.

C199360897

Programming language

https://doi.org/10.1093/bioinformatics/btu638

language designed to communicate instructions to a machine

HTSeq—a Python framework to work with high-throughput sequencing data

Abstract Motivation: A large choice of tools exists for many standard tasks in the analysis of high-throughput sequencing (HTS) data. However, once a project deviates from standard workflows, custom scripts are needed. Results: We present HTSeq, a Python library to facilitate the rapid development of such scripts. HTSeq offers parsers for many common data formats in HTS projects, as well as classes to represent data, such as genomic coordinates, sequences, sequencing reads, alignments, gene model information and variant calls, and provides data structures that allow for querying via genomic coordinates. We also present htseq-count, a tool developed with HTSeq that preprocesses RNA-Seq data for differential expression analysis by counting the overlap of reads with genes. Availability and implementation: HTSeq is released as an open-source software under the GNU General Public Licence and available from http://www-huber.embl.de/HTSeq or from the Python Package Index at https://pypi.python.org/pypi/HTSeq . Contact: [email protected]

C199360897

Programming language

https://doi.org/10.1093/bioinformatics/bty560

language designed to communicate instructions to a machine

fastp: an ultra-fast all-in-one FASTQ preprocessor

Quality control and preprocessing of FASTQ files are essential to providing clean data for downstream analysis. Traditionally, a different tool is used for each operation, such as quality control, adapter trimming and quality filtering. These tools are often insufficiently fast as most are developed using high-level programming languages (e.g. Python and Java) and provide limited multi-threading support. Reading and loading data multiple times also renders preprocessing slow and I/O inefficient.We developed fastp as an ultra-fast FASTQ preprocessor with useful quality control and data-filtering features. It can perform quality control, adapter trimming, quality filtering, per-read quality pruning and many other operations with a single scan of the FASTQ data. This tool is developed in C++ and has multi-threading support. Based on our evaluation, fastp is 2-5 times faster than other FASTQ preprocessing tools such as Trimmomatic or Cutadapt despite performing far more operations than similar tools.The open-source code and corresponding instructions are available at https://github.com/OpenGene/fastp.

C199360897

Programming language

https://doi.org/10.48550/arxiv.1912.01703

language designed to communicate instructions to a machine

PyTorch: An Imperative Style, High-Performance Deep Learning Library

Deep learning frameworks have often focused on either usability or speed, but not both. PyTorch is a machine learning library that shows that these two goals are in fact compatible: it provides an imperative and Pythonic programming style that supports code as a model, makes debugging easy and is consistent with other popular scientific computing libraries, while remaining efficient and supporting hardware accelerators such as GPUs. In this paper, we detail the principles that drove the implementation of PyTorch and how they are reflected in its architecture. We emphasize that every aspect of PyTorch is a regular Python program under the full control of its user. We also explain how the careful and pragmatic implementation of the key components of its runtime enables them to work together to achieve compelling performance. We demonstrate the efficiency of individual subsystems, as well as the overall speed of PyTorch on several common benchmarks.

C199360897

Programming language

https://doi.org/10.1006/knac.1993.1008

language designed to communicate instructions to a machine

A translation approach to portable ontology specifications

To support the sharing and reuse of formally represented knowledge among AI systems, it is useful to define the common vocabulary in which shared knowledge is represented. A specification of a representational vocabulary for a shared domain of discourse—definitions of classes, relations, functions, and other objects—is called an ontology. This paper describes a mechanism for defining ontologies that are portable over representation systems. Definitions written in a standard format for predicate calculus are translated by a system called Ontolingua into specialized representations, including frame-based systems as well as relational languages. This allows researchers to share and reuse ontologies, while retaining the computational benefits of specialized implementations. We discuss how the translation approach to portability addresses several technical problems. One problem is how to accommodate the stylistic and organizational differences among representations while preserving declarative content. Another is how to translate from a very expressive language into restricted languages, remaining system-independent while preserving the computational efficiency of implemented systems. We describe how these problems are addressed by basing Ontolingua itself on an ontology of domain-independent, representational idioms.

C199360897

Programming language

https://doi.org/10.3115/v1/p14-5010

language designed to communicate instructions to a machine

The Stanford CoreNLP Natural Language Processing Toolkit

Christopher Manning, Mihai Surdeanu, John Bauer, Jenny Finkel, Steven Bethard, David McClosky. Proceedings of 52nd Annual Meeting of the Association for Computational Linguistics: System Demonstrations. 2014.

C199360897

Programming language

https://doi.org/10.1145/512950.512973

language designed to communicate instructions to a machine

Abstract interpretation

A program denotes computations in some universe of objects. Abstract interpretation of programs consists in using that denotation to describe computations in another universe of abstract objects, so that the results of abstract execution give some information on the actual computations. An intuitive example (which we borrow from Sintzoff [72]) is the rule of signs. The text -1515 * 17 may be understood to denote computations on the abstract universe {(+), (-), (±)} where the semantics of arithmetic operators is defined by the rule of signs. The abstract execution -1515 * 17 → -(+) * (+) → (-) * (+) → (-), proves that -1515 * 17 is a negative number. Abstract interpretation is concerned by a particular underlying structure of the usual universe of computations (the sign, in our example). It gives a summary of some facets of the actual executions of a program. In general this summary is simple to obtain but inaccurate (e.g. -1515 + 17 → -(+) + (+) → (-) + (+) → (±)). Despite its fundamentally incomplete results abstract interpretation allows the programmer or the compiler to answer questions which do not need full knowledge of program executions or which tolerate an imprecise answer, (e.g. partial correctness proofs of programs ignoring the termination problems, type checking, program optimizations which are not carried in the absence of certainty about their feasibility, …).

C199360897

Programming language

https://doi.org/10.1107/s0021889810022120

language designed to communicate instructions to a machine

<i>publCIF</i>: software for editing, validating and formatting crystallographic information files

publCIF is an application designed for creating, editing and validating crystallographic information files (CIFs) that are used in journal publication. It validates syntax and dictionary-defined data attributes through internal routines, and also provides a web interface to the checkCIF service of the International Union of Crystallography (IUCr), which provides a full crystallographic analysis of the structural data. The graphical interface allows users to edit the CIF either in its `raw' ASCII form (using a text editor with context-sensitive data validation and input facilities) or as a formatted representation of a structure report (using a word-processing environment), as well as via a number of convenience tools ( e.g. spreadsheet representations of looped data). Beyond file and data validation, publCIF provides access to resources to facilitate preparation of a structure report ( e.g. databases of author details, experimental data, standard references etc ., either distributed with the program or collected during its use), along with tools for reference parsing, spell checking, structure visualization and image management. publCIF was commissioned by the IUCr, both as free software for authors and as a tool for in-house journal production; the tool for authors is described here. Binary distributions for Linux, MacOS and Windows operating systems are available.

C199360897

Programming language

https://doi.org/10.1111/j.1096-0031.2008.00217.x

language designed to communicate instructions to a machine

TNT, a free program for phylogenetic analysis

Abstract The main features of the phylogeny program TNT are discussed. Windows versions have a menu interface, while Macintosh and Linux versions are command‐driven. The program can analyze data sets with discrete (additive, non‐additive, step‐matrix) as well as continuous characters (evaluated with Farris optimization). Effective analysis of large data sets can be carried out in reasonable times, and a number of methods to help identifying wildcard taxa in the case of ambiguous data sets are implemented. A variety of methods for diagnosing trees and exploring character evolution is available in TNT, and publication‐quality tree‐diagrams can be saved as metafiles. Through the use of a number of native commands and a simple but powerful scripting language, TNT allows the user an enormous flexibility in phylogenetic analyses or simulations. © The Willi Hennig Society 2008.

C166957645

Archaeology

https://doi.org/10.2458/azu_js_rc.55.16947

study of human past through material culture

IntCal13 and Marine13 Radiocarbon Age Calibration Curves 0–50,000 Years cal BP

The IntCal09 and Marine09 radiocarbon calibration curves have been revised utilizing newly available and updated data sets from 14 C measurements on tree rings, plant macrofossils, speleothems, corals, and foraminifera. The calibration curves were derived from the data using the random walk model (RWM) used to generate IntCal09 and Marine09, which has been revised to account for additional uncertainties and error structures. The new curves were ratified at the 21st International Radiocarbon conference in July 2012 and are available as Supplemental Material at www.radiocarbon.org. The database can be accessed at http://intcal.qub.ac.uk/intcal13/.

C166957645

Archaeology

https://doi.org/10.1111/j.1096-0031.1994.tb00181.x

study of human past through material culture

TESTING SIGNIFICANCE OF INCONGRUENCE

CladisticsVolume 10, Issue 3 p. 315-319 Free Access TESTING SIGNIFICANCE OF INCONGRUENCE James S. Farris, James S. Farris Naturhistoriska riksmuseet, Molekylärystematiska laboratoriet, Box 50007, S-104 05, Stockholm, Sweden Department of Entomology, American Museum of Natural History, Central Park West at 79th St., New York, New York 10024, U.S.A.Search for more papers by this authorMari Källersjö, Mari Källersjö Naturhistoriska riksmuseet, Molekylärystematiska laboratoriet, Box 50007, S-104 05, Stockholm, SwedenSearch for more papers by this authorArnold G. Kluge, Arnold G. Kluge Department of Reptiles and Amphibians, Museum of Zoology, The University of Michigan, Ann Arbor, Michigan 48109, U.S.A.Search for more papers by this authorCarol Bult, Carol Bult Institute of Genomic Research, 932 Clopper Rd., Gaithersburg, Maryland 20878, U.S.A.Search for more papers by this author James S. Farris, James S. Farris Naturhistoriska riksmuseet, Molekylärystematiska laboratoriet, Box 50007, S-104 05, Stockholm, Sweden Department of Entomology, American Museum of Natural History, Central Park West at 79th St., New York, New York 10024, U.S.A.Search for more papers by this authorMari Källersjö, Mari Källersjö Naturhistoriska riksmuseet, Molekylärystematiska laboratoriet, Box 50007, S-104 05, Stockholm, SwedenSearch for more papers by this authorArnold G. Kluge, Arnold G. Kluge Department of Reptiles and Amphibians, Museum of Zoology, The University of Michigan, Ann Arbor, Michigan 48109, U.S.A.Search for more papers by this authorCarol Bult, Carol Bult Institute of Genomic Research, 932 Clopper Rd., Gaithersburg, Maryland 20878, U.S.A.Search for more papers by this author First published: September 1994 https://doi.org/10.1111/j.1096-0031.1994.tb00181.xCitations: 2,887AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat REFERENCES Bremer, K. 1988. The limits of amino-acid sequence data in angiosperm phylogenetic reconstruction. Evolution, 42: 795– 803. Bremer, B. and L. Struwe. 1992. Phylogeny of the Rubiaceae and the Loganiaceae: congruence or conflict between morphological and molecular data Amer. Jour. Bot., 79: 1171– 1184. Bruneau, A. and E. E. Dickson. 1995. Congruence of chloroplast DNA restriction site characters with morphological and isozyme data in Solatium sect. Lasiocarpa. Can. Jour. Bot. (in press). Farris, J. S., M. Kallersjo, A. G. Kluge and C. Bult. 1994. Permutations. Cladistics, 10: 65– 76. Kluge, A. G. 1989. A concern for evidence and a phylogenetic hypothesis of relationships among Epicrates (Boidae, Serpentes). Syst. Zool., 38: 7– 25. Kallersjo, M., J. S. Farris, A. G. Kluge and C. Bult. 1992. Skewness and permutation. Cladistics, 8: 275– 287. Lindgren, B. W. 1962. Statistical Theory. MacMillan, New York . Mickevich, M. F. and J. S. Farris. 1981. The implications of congruence in Menidia. Syst. Zool., 30: 351– 370. Miyamoto, M. 1985. Consensus cladograms and general classifications. Cladistics, 1: 186– 189. Schuh, R. T. and J. S. Farris. 1981. Methods for investigating taxonomic congruence and their application to the Leptopodomorpha. Syst. Zool., 30: 331– 351. Smith, J. F. and K. J. Sytsma. 1994. Molecules and morphology: congruence of data in Columnea (Gesneriaceae). Plant Syst. Evol. (in press). Swofford, D. L. 1991. When are phylogeny estimates from molecular and morphological data incongruent? In M. M. Miyamoto and J. Cracraft, (eds), Phylogenetic Analysis of DNA Sequences. Oxford Univ. Press, New York , pp. 295– 333. Tehler, A. 1994. Cladistic analysis in ascomycete systematics: Theory and practice. In D. L. Hawksworth, (ed.), Ascomycete Systematics: Problems and Perspectives in the 90s. Plenum, New York , pp. 185– 197. Tehler, A. 1995a. Arthionales phylogeny as indicated by morphological and rDNA sequence data. Cryptogamic Botany (in press). Tehler, A. 1995b. Morphological data, molecular data, and total evidence in phylogenetic analysis. Can. Jour. Bot. (in press). Citing Literature Volume10, Issue3September 1994Pages 315-319 ReferencesRelatedInformation

C166957645

Archaeology

https://doi.org/10.15468/bxpyo3

study of human past through material culture

University of California Museum of Paleontology

The mission of the University of California Museum of Paleontology is to investigate and promote the understanding of the history of life and the diversity of the Earth's biota through research and education.

C166957645

Archaeology

https://doi.org/10.15468/c7c9qa

study of human past through material culture

Vascular Plant Specimen database of Kanagawa Prefectural Museum of Natural History

Vascular plant specimens deposited at the Kanagawa Prefectural Museum of Natural History