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Q:
Properties of a function whose has its own Fourier transform
A posted exercise is from Complex Analysis, Stein
This exercise generalizes some of the properties of $e^{-\pi{x^2}}$
related to the fact that it is its own Fourier transform.
Suppose $f(z)$ is an entire function that satisfies $$|f(x+iy)|\le ce^{-a{x^2}+b{y^2}}$$ for some $a,b,c\gt0.$
Let $$\hat f(\zeta)=\int^{\infty}_{-\infty}f(x)e^{-2\pi{i}x\zeta}dx.$$
Then, $\hat f$ is an entire fuction of $\zeta$ that satisfies $$|\hat f(\xi+i\eta)|\le c^{'}e^{-{a^{'}\xi^2+b^{'}\eta^2}}$$ for some
$a^{'},b^{'},c^{'}\gt0.$
I tried to show $\hat f(\xi)=O(e^{-a^{'}\xi^2})$ that I take $y=\xi$ and consider the horizontal strip. Clearly, $f(z)$ is entire and satisfying the decay condition hence $\hat f(\xi)=O(e^{-2\pi{y}\xi}e^{b{y^2}})$ by using the contour integration.
But I cannot make it sure explicitly how to use the contour integration $-R\lt{x}\lt{R},y=\xi$ as $R$ goes to $\infty$.
A:
Deform the contour so that
$$\hat f(\zeta)=\int_{-\infty}^\infty f(x+iy)e^{-i2\pi(x+iy)(\xi+i\eta)}\,dx$$
Then note that
$$\begin{align}
|\hat f(\zeta)|&\le\int_{-\infty}^\infty |f(x+iy)|e^{2\pi(x\eta+y\xi)}\,dx\\\\
&\le ce^{by^2+2\pi y \xi}\int_{-\infty}^\infty e^{-ax^2+2\pi x\eta}\,dx\\\\
&\le ce^{by^2+2\pi y \xi}\,e^{\frac{\pi^2}{a}\eta} \int_{-\infty}^\infty e^{-a\left(x-\frac{\pi \eta}{a}\right)^2}\,dx\\\\
&=\sqrt{\frac{\pi}{a}}\,c \,e^{\frac{\pi^2}{a}\eta}\,e^{by^2+2\pi y \xi}
\end{align}$$
First, choose $y=-\alpha \xi$ where we also choose $\alpha$ so that it satisfies the inequality $-2\pi/b< \alpha <0$.
Then, denoting
$$\begin{align}
a'&=-2\pi \alpha -b\alpha^2\\\\
b'&=\pi^2/a\\\\
c'&=\sqrt{\frac{\pi}{a}}\,c
\end{align}$$
we have
$$|\hat f(\zeta)|\le c'e^{-a'\xi^2+b'\eta^2}$$
as was to be shown!
| null | minipile | NaturalLanguage | mit | null |
Sort By
Lawn & Gardening
We can't all be greenskeepers, but even if you are, you'll find what you need in the lawn and gardening section of the Kennards Hire website. There's also plenty for jobs around the house too!
+ Show More | null | minipile | NaturalLanguage | mit | null |
Gwyneth Paltrow, Angelina Jolie and others have come forward to the New York Times with their Harvey Weinstein horror stories.
Paltrow says, “This way of treating women ends now.”
As previously reported, embattled Hollywood producer Harvey Weinstein is the subject of a devastating expose detailing decades of sexual harassment.
Hollywood literally worshipped Weinstein. Gross.
Fashion designer, Donna Karan DEFENDED Weinstein in an interview on Sunday. She also took women back several decades by suggesting the accusers were ‘asking for it’ by wearing seductive clothing.
TRENDING: Black Lives Matter Activist Wearing 'Justice for Breonna Taylor' Shirt Walked into a Louisville Bar and Murdered Three People
Others in Hollywood however, are starting to come forward with their horror stories.
Last Thursday, The New York Times blew the roof off of the decades long ‘open secret’ in Hollywood that Harvey Weinstein was essentially a sexual predator who preyed on young starlets. Weinstein reportedly paid off several sexual harassment accusers over the years.
An investigation by The New York Times found previously undisclosed allegations against Mr. Weinstein stretching over nearly three decades, documented through interviews with current and former employees and film industry workers, as well as legal records, emails and internal documents from the businesses he has run, Miramax and the Weinstein Company. During that time, after being confronted with allegations including sexual harassment and unwanted physical contact, Mr. Weinstein has reached at least eight settlements with women, according to two company officials speaking on the condition of anonymity.
Gwyneth Paltrow recalls being terrified by Weinstein’s sexual abuse and says she was expected to keep the secret.
Via The New York Times:
When Gwyneth Paltrow was 22 years old, she got a role that would take her from actress to star: The film producer Harvey Weinstein hired her for the lead in the Jane Austen adaptation “Emma.” Before shooting began, he summoned her to his suite at the Peninsula Beverly Hills hotel for a work meeting that began uneventfully. It ended with Mr. Weinstein placing his hands on her and suggesting they head to the bedroom for massages, she said. “I was a kid, I was signed up, I was petrified,” she said in an interview, publicly disclosing that she was sexually harassed by the man who ignited her career and later helped her win an Academy Award. She refused his advances, she said, and confided in Brad Pitt, her boyfriend at the time. Mr. Pitt confronted Mr. Weinstein, and soon after, the producer threatened her not to tell anyone else about his come-on. “I thought he was going to fire me,” she said. Even as Ms. Paltrow became known as the “first lady of Miramax” and won an Oscar for “Shakespeare in Love” in 1999, very few people knew about Mr. Weinstein’s advances. “I was expected to keep the secret,” she said.
Rosanna Arquette and Angelina Jolie and others also had similar experiences as reported by the New York Times:
Rosanna Arquette, a star of “Pulp Fiction,” has a similar account of Mr. Weinstein’s behavior, as does Judith Godrèche, a leading French actress. So does Angelina Jolie, who said that during the release of “Playing by Heart” in the late 1990s, he made unwanted advances on her in a hotel room, which she rejected. “I had a bad experience with Harvey Weinstein in my youth, and as a result, chose never to work with him again and warn others when they did,” Ms. Jolie said in an email. “This behavior towards women in any field, any country is unacceptable.”
Read the full report by the New York Times here. | null | minipile | NaturalLanguage | mit | null |
kst is a program for looking at data streams. It can plot:
- x-y plots
- power spectra
- histograms
- equations (including equations of data streams).
- data in files which are being updated as data is being logged, in which case in can act as a plotter for a chart recorder.
- much more
Kst supports realtime viewing and manipulation of streaming data.
You can use the mouse to rapidly zoom into interesting parts of the plots.
In addition to a complete GUI, kst has a convenient command line interface for rapid access to plotting data in files. It supports several file formats in use in scientific projects around the world including ASCII, dirfile, netCDF, and FITS.
Changelog:
The most notable improvements brought by Kst 2.0.4 over the 2.0.3 version released in April 2011 are:
- A major re-write of the auto-layout command: it works much better now and no longer gets in the way
- Improvements to automatic legend names
- Fixes to the layout mode, with better visual feedback during drag operations
- Numerous other bugfixes and improvements (point density, scientific notation, issues with log mode, bar colors, fixed aspect ratio in images and svg annotation items)
- UI and usability improvements: for instance you can now just double-click on labels or axes to open the corresponding dialog
- The introduction of a Settings->Theme dialog which sets brush, stroke, and font for all view items, optionally applying to all existing objects, and/or saving as the default for all future objects
- A great new auto-completer for the the equation editor and label editor, including support for wildcards
- A number of crashes fixed in various plugins
With a little work this could really be a help for Grace-users. Grace is completly independent of the frontend so in therory you only need to find somebody writing the frontend in Qt or KDE :-)
Carsten
Re: xmgrace
Kst is very different. It supports plugins of many sorts for different file formats (includes over half a dozen already), is optimized for dealing with huge, realtime datastreams, and supports native plugins for analysis and manipulation as well. The built-in programming language is [going to be - work in progress, but already usable] KJS so you have a familiar base to work from, and the UI is all KDE/Qt based so you get all the KDE supported image/printing formats, and all the other benefits of the KDE infrastructure such as KIO, nice styled widgets, etc.
Kst development is primarily driven by user demand right now, and more advanced features will be added as necessary.
How do you like Plasma 5? The best KDE Desktop ever. Definitely a nice improvement. Not decided yet. Haven't tried it yet. I do not like some of the changes. KDE is taking the wrong way. I am still sticking with KDE 3.5. I have no opinion, but wanted to vote anyway.
Copyright 2003-2015 KDE-Apps.org Team All rights reserved. KDE-Apps.org is not liable for any content or goods on this site.All contributors are responsible for the lawfulness of their uploads.KDE and K Desktop Environment are trademarks of KDE e.V. | null | minipile | NaturalLanguage | mit | null |
"Then again, the disciple of the noble ones considers this: 'I am not anyone's anything anywhere; nor is anything of mine in anyone anywhere.' Practicing & frequently abiding in this way, his mind acquires confidence in that dimension. There being full confidence, he either attains the dimension of nothingness now or else is committed to discernment. With the break-up of the body, after death, it's possible that this leading-on consciousness of his will go to the dimension of nothingness. This is declared to be the third practice conducive to the dimension of nothingness
Does one only need to attain the dimension of nothingness once in order for there to be a rebirth there? or does it need to be developed over and over? or does it need to be entered into at moment of death?
The dogmatists have claimed to have found the truth, others say that it cannot be apprehended; the Sceptics continue the search. Sextus Empiricus
“No lists of things to be done. The day providential to itself. The hour. There is no later. This is later. All things of grace and beauty such that one holds them to one's heart have a common provenance in pain. Their birth in grief and ashes.” - Cormac McCarthy, The Road
Learn this from the waters:in mountain clefts and chasms,loud gush the streamlets,but great rivers flow silently.- Sutta Nipata 3.725
This Sutta has some complex stuff in it. The Nanamoli/Bodhi translation has three pages of extracts from the Commentaries. It deals with formless attainments and what the destination if one dies without becoming an Arahant... There is also some reference to dry insight towards the end...
This Sutta has some complex stuff in it. The Nanamoli/Bodhi translation has three pages of extracts from the Commentaries. It deals with formless attainments and what the destination if one dies without becoming an Arahant... There is also some reference to dry insight towards the end...
MettaMike
Oh no commentaries (joking ) Do you know where i can find those extracts from the commentaries?
The dogmatists have claimed to have found the truth, others say that it cannot be apprehended; the Sceptics continue the search. Sextus Empiricus
Without a knowledge of Pali and an encyclopaedic knowledge of all of the Suttas, to be able to cross-reference the terms, the only way we're going to make sense of Suttas such as this is to read the commentaries...
It would take me a while to make sense of three pages of Commentary. Perhaps I'll look at it later...
Without a knowledge of Pali and an encyclopaedic knowledge of all of the Suttas, to be able to cross-reference the terms, the only way we're going to make sense of Suttas such as this is to read the commentaries...
It would take me a while to make sense of three pages of Commentary. Perhaps I'll look at it later...
Mike
Thanks mike
(p.s. i was only joking with the commentary thing)
Metta
The dogmatists have claimed to have found the truth, others say that it cannot be apprehended; the Sceptics continue the search. Sextus Empiricus
When you can afford it, you may wish to invest in a copy of the Majjhima Nikaya translated by Bhikkhu Namamoli and Bhikkhu Bodhi. I find the Ven Namamoli and Bhikkhu Bodhi's translations more reliable and it includes a wealth of explanatory notes.
(THE BASE OF NOTH|NGNESS)8. "Again, bhikkhus, a noble disciple considers thus: 'I am not anything belonging to antone anywhere, nor is there anything belonging to me in anyone anywhere (1016)'. When he practices in this way and frequently abides thus, his mind acquires confidence in this base. Once there is full confidence, he either attains to the base of nothingness now or else he resolves [upon it] with wisdom. On the dissolution of the body, after death, it is possible that the evolving consciousness may pass on [to rebirth] in the base of nothingness. This bhikkhus, is declared to be the third way directed to the base of nothingness
1016
MA calls this four-pointed voidness and explains thus: (i) he does not see his self anywhere; (ii) he does not see a self of his own that can be treated as something belonging to another, eg: as a brother, friend, assistant, etc.; (iii) he does not see the self of another; (iv) he does not see the self of another that can be treated as something belonging to him. Ms has a note by Nm: "These expressions [in this paragraph and the next] seem to have been stereotyped slogans or descriptions of the attainments of nothingness and neither-perception-nor-non-perception, primarily non-Buddhist, and sometimes used as a basis for the existing-body [=identity] view." See Nm's note 19 to Vsm XXI, 53 for further discussion and other references.
“No lists of things to be done. The day providential to itself. The hour. There is no later. This is later. All things of grace and beauty such that one holds them to one's heart have a common provenance in pain. Their birth in grief and ashes.” - Cormac McCarthy, The Road
Learn this from the waters:in mountain clefts and chasms,loud gush the streamlets,but great rivers flow silently.- Sutta Nipata 3.725
When you can afford it, you may wish to invest in a copy of the Majjhima Nikaya translated by Bhikkhu Namamoli and Bhikkhu Bodhi. I find the Ven Namamoli and Bhikkhu Bodhi's translations more reliable and it includes a wealth of explanatory notes.
Im such a fool, i have the copy of it i didnt think to check the notes in the back lol will look into it now
The dogmatists have claimed to have found the truth, others say that it cannot be apprehended; the Sceptics continue the search. Sextus Empiricus
When you can afford it, you may wish to invest in a copy of the Majjhima Nikaya translated by Bhikkhu Namamoli and Bhikkhu Bodhi. I find the Ven Namamoli and Bhikkhu Bodhi's translations more reliable and it includes a wealth of explanatory notes.
Im such a fool, i have the copy of it i didnt think to check the notes in the back lol will look into it now
No problemBut if memory serves me well, the answer to your question as to rebirth into the sphere of nothingness is answered in the Abhidhamma.Kind regards
Ben
“No lists of things to be done. The day providential to itself. The hour. There is no later. This is later. All things of grace and beauty such that one holds them to one's heart have a common provenance in pain. Their birth in grief and ashes.” - Cormac McCarthy, The Road
Learn this from the waters:in mountain clefts and chasms,loud gush the streamlets,but great rivers flow silently.- Sutta Nipata 3.725
I can't excatly pin-point as to where I learned it, but I'm pretty sure that you can cross out your first option - it's either the second answer or the third:
clw_uk wrote:Does one A) only need to attain the dimension of nothingness once in order for there to be a rebirth there? B) or does it need to be developed over and over? C) or does it need to be entered into at moment of death?
“The incomparable Wheel of Dhamma has been set in motion by the Blessed One in the deer sanctuary at Isipatana, and no seeker, brahmin, celestial being, demon, god, or any other being in the world can stop it.” | null | minipile | NaturalLanguage | mit | null |
The students should know common and ecologically interesting lichens and mosses, and understand their importance in Norwegian ecosystems
Skills:
The students will be trained to identify Norwegian bryophytes and macrolichens using identification keys and floras. The students will also be trained to use indicator species of bryophytes and lichens for assessing various environmental conditions. The students will be trained in writing a scientif report
General competence:
Understand the role of lichens and bryophytes in Norwegian ecosystem, and be able to use them as indicator species.
Lab exercises (2 hours per week) train the students to identify Norwegian bryophytes and macrolichens by the use of identification keys and floras.
The student assignment (groups of 3-4 students) gives the students training in how to collect and identify their own material, process and present the data and use the set of data to estimate the air pollution along a gradient from Oslo to the rural Follo.
Teaching support:
Due to the semester assignment, the teacher must be available in his office for some weeks. Important notes will be available on Canvas.
The students need to pass an species identification test with the use of floras (Acoounts for 40 %). Together with this test, there will be some theoretical questions without access to literature (20 %) The student assigments with report accounts for 40 % of the total grade. It is not necessary that the student passes all tests in the course in order to pass the entire course. A passing grade is based on the overall quality of the entire evaluated material.
The course is especially suitable for the Master"s programmes in natural resource management, forestry, and ecology, but all students with an interest in biology and/or environmental pollution are welcome.
Examiner:
An external examiner will give evaluate the term paper and the floristic exams with additional theoretical questions. | null | minipile | NaturalLanguage | mit | null |
4 Long-tailed Ducks were found on a foggy Lake Parsippany this morning by Jennifer Books and her sister. The Oldsquaw remained into the afternoon, at least. Also present throughout the day were 13 Ruddy Ducks, 125 Common Mergansers, 2 Red-breasted Mergansers, 5 Ring-necked Ducks, 2 Bufflehead, 4 Pied-billed Grebes, 3 American Coots and 1 Common Loon (many observers).
3 Common Loons, one drake Common Goldeneye, approximately 25 Common Mergansers and 7 Bufflehead were at the north end of Boonton Reservoir. Weather conditions were dreary at best with misty rain and chilly temperatures. There were very few gulls at either Lake Parsippany or Boonton Reservoir (J. Klizas).
3 Bonaparte’s Gulls continued at Budd Lake this morning along with 35 Bufflehead, 45 Common Mergansers, 4 Common Loons and 5 Horned Grebes (Alan Boyd).
From Roger Johnson at Troy Meadows, Apr. 3, 2014:
Troy Meadows had the following:
11 Red-headed Woodpeckers, quite a drop from the Boonton Christmas Bird Count. [Editor’s note: the link for the Boonton CBC totals is here.]
3 Great Egrets
1 Eastern Towhee
2 Fox Sparrows
4 Eastern Phoebes
2 Green-winged Teal
5 Wood Ducks
1 adult Red-Shouldered Hawk
1 2nd-year Bald Eagle | null | minipile | NaturalLanguage | mit | null |
SPOTSYLVANIA Co., Va. (WJW) – Authorities in Virginia are investigating after a man was allegedly found nude from the waist down in the bedroom of two children.
The Spotsylvania Sheriff’s Office posted about the disturbing incident on its Facebook page.
On Dec. 29 in the early morning, deputies responded to a disturbance at a home. They said they found a “chaotic scene” when they arrived and a man had severe injuries to his face.
That man was later identified as Mark Stanley, 60, of North Carolina.
The sheriff’s office said deputies also encountered a man with a gun quickly approaching Stanley. Deputies told the man to drop the gun, and he did.
An investigation revealed Stanley was at the home visiting family members for the holidays. One of the family members woke up early and decided to check on his children, ages two and three.
Related: Camera records naked intruder spending two hours in family’s backyard
According to the sheriff’s office, the children’s father found Stanley nude from the waist down in the room with the children.
When the father questioned Stanley, the half-naked man reportedly pushed him out of the room and locked the door.
The father forced his way into the room and allegedly began beating Stanley.
Stanley was taken to the hospital for treatment before police took him to the Rappahannock Regional Jail where he is being held without bond.
The children were taken to the hospital to be evaluated for any injuries. Stanley was arrested on two counts of indecent liberties and one count of domestic assault. He may face additional charges based on the findings of the police investigation.
The family member was not charged. | null | minipile | NaturalLanguage | mit | null |
"Precious" is the 42nd single released by GLAY and their first single under their label loversoul music & associates. It was released in two editions: a limited CD+DVD edition and a regular CD-only edition. The title track was used as the ending theme song for the TV program Sukkiri!!. The single reached #2 on the Oricon weekly charts and charted for 8 weeks. | null | minipile | NaturalLanguage | mit | null |
San Francisco Mayor-elect London Breed was still basking in the glow of her election victory when she arrived at Rosa Parks Elementary school on Thursday.
Having been raised by her grandmother just blocks away in the city’s Western Addition neighborhood — once the heart of San Francisco’s black community — Breed, 43, said the visit to her alma mater filled her with memories and purpose.
“In San Francisco, I think about this school, I think about the people I went to school with and I think about the fact that many of them don’t live in this city anymore,” she said to cheers. “We have to build more housing. We have to build more housing. We have to build more housing, and I will be relentless in my pursuit to get the job done.”
Breed, the city’s first female African-American mayor, succeeded in a bruising race that featured personal attacks and a drawn-out vote count — a quirk of the city’s ranked-choice voting system. On Wednesday, her main opponent, former state Sen. Mark Leno, conceded the race. Leno had initially been in the lead after the June 5 primary, but Breed eventually pulled ahead. When she’s sworn in July 11, she will be the only female mayor of any of the 15 largest U.S. cities.
The problems she now plans to tackle are among the most difficult a city can face. Housing, finding solutions to the homelessness crisis and creating safe injection areas for drug users will dominate her portfolio as mayor of a city that’s been flooded with technology wealth but has left many behind.
The connection between Breed’s life and the problems vexing San Francisco were often center stage as she campaigned for office.
“I know it means so, so much to so many people. I grew up in some of the most challenging of circumstances,” Breed said Wednesday from the steps of City Hall after Leno called her to concede.
Her personal story animated the race as she salted her campaign stops and ads with tales of being raised by her grandmother in a decrepit public housing project. Both of Breed’s siblings were addicted to drugs, and her younger sister died of an overdose, while her brother is in prison for robbery and other crimes, according to media reports.
Breed persevered, graduated from UC Davis and began working for then-Mayor Willie Brown’s administration. Eventually, she became the executive director of the African American Art & Culture Complex in 2002.
That role was close to her heart, because the arts center was a stone’s throw from where she grew up and catered to a population that is becoming more and more marginalized as San Francisco becomes richer and whiter. African Americans now just make up roughly 6% of the city’s population, and the number continues to shrink.
“The message that this sends to the next generation of young people growing up in this city is that no matter where you come from, no matter what you decide to do in life, you can do anything you want to do,” Breed said Wednesday.
“Never let your circumstances determine your outcome in life.”
In her decade at the helm of the arts center, she raised millions for renovations. Then in 2012, she surprised the political establishment by beating out incumbent Christina Olague for a seat on the San Francisco Board of Supervisors. Then-California Atty. Gen. Kamala Harris, Breed’s political mentor, swore her into office.
By 2017, Breed had risen to become the Board of Supervisors president and appeared to be laying the groundwork for a mayoral run in 2019. That’s when Mayor Ed Lee — a longtime city administrator who had been elevated to mayor when Gavin Newsom resigned in 2011 to run for lieutenant governor — collapsed in a Safeway store and later died from a heart attack.
Breed became interim mayor — as a result of her position as president of the Board of Supervisors — and soon after announced she would be seeking the post permanently.
Things got interesting very quickly. In January, the Board of Supervisors — her colleagues — ousted her and named a wealthy white man, Supervisor Mark Farrell, as her replacement. Opponents said she represented the status quo, which enraged supporters who saw this as yet another slight to the city’s African American community.
“They have pushed out African Americans,” Sheryl Davis, a friend of Breed, told the San Francisco Chronicle. “And everybody talks about how diverse and progressive we are. But if it happened anywhere else, we’d be saying what a tragedy.”
Breed was interim mayor for 42 days and made it clear that she would still be a candidate for the job. Her friend of 15 years and informal advisor, Debbie Mesloh, was in the room that night when the vote came down and said it struck many as “another backroom deal,” she said.
“I think it galvanized and harnessed a lot of energy,” she said.
The race among a contest between Breed, Leno and Supervisor Jane Kim — all Democrats.
Leno and Kim portrayed themselves as progressive change agents and labeled Breed as a moderate who had the backing of the city’s business and tech establishment. Leno would have been the city’s first openly gay mayor, while Kim would also have been the city’s first female mayor of color.
The city’s unusual electoral system — where voters rank their top three choices — led to some gamesmanship by the candidates. Kim and Leno each urged voters to rank the other second in order to lock Breed out of a victory.
By Wednesday however, Breed’s challengers acknowledged the outcome.
“I’m proud to live in the largest city in America with a woman as mayor,” Kim tweeted Wednesday.
The housing crisis in San Francisco was one of the few areas where profound policy disagreements arose among the candidates. Breed picked up the backing of pro-development forces and publicly voiced support for state Sen. Scott Wiener’s controversial legislation SB 827, which would’ve loosened or eliminated restrictions on height, density, parking and design for residential properties near major rail and bus stops. Her opponents did not.
The bill failed, but it squared with one of Breed’s biggest priorities and what will be her biggest challenge as she enters office, Mesloh said. Housing, along with a host of other issues, will consume her time. But, Mesloh added, Breed is best positioned to tackle these problems because she’s experienced many of them.
“Income inequality in San Francisco is something she will really need to address,” she said. “For the past five or six years, it’s felt like there are two different cities. How is she really going to bridge that divide will be a big question.”
[email protected]
@boreskes | null | minipile | NaturalLanguage | mit | null |
Kenneth Cole Reaction T-shirt Cologne
Kenneth Cole Reaction T-shirt Cologne by Kenneth Cole, Kenneth cole unleashed reaction t-shirt in 2009
. The fragrance is inspired by the simplicity and comfort of the white t-shirt. Men who wish to sport a trendy and urban look will be pleased with this crisp and light fragrance. The fragrance makes a zestful opening with top notes of pear, apple, yellow passion fruit, and watermelon. The heart is composed of notes of aquatic-floral accords, lavender, juniper berries, gin, and tonic. This blend... Read More... Read More of notes is set on an intensebase of cedar, sandalwood, white musk, and cotton accords. The perfume is contained in a bottle with simple and clear lines. All products are original, authentic name brands. We do not sell knockoffs or imitations.
About Kenneth Cole
History and background of Kenneth Cole. Nineteen years ago, I wanted to open a shoe company with limited money. From experience I knew one had to get in quickly because so often new companies run out of cash flow before they get the chance to conduct business. I also knew it was easier to get credit from factories in Europe who needed the business than from American banks that didn't. So I lined up the factories
Read more about Kenneth Cole
Customer Comments
I was very impressed and pleased by your service. I was shopping around for the perfume I ordered for my wife's birthday gift. I could not find it at many stores that I went; so I decided to buy it online. I must say that many other sites had it for double of what you had it for and when I saw your price I was sceptical because it was so much cheaper. I ended up ordering it anyway and seeing the Yahoo rating of your site made me feel a lot more easier in placing my order. I must tell you I was very pleased, I am a very picky consumer and when I shop I like to know what I am getting into. My order was here quicker than expected and from the day I placed my order I recieved an e-mail confirming it. Once again I am a very satisfied customer and I know where I am going to buy my Mother's birthday gift.S. Wiltshire (Waukegan, IL)
Wow. I love this cologne. I first smelled it in a department store and was narrowing down choices between this or the Kenneth Cole Black. and ultimately chose this. it's much lighter, very clean smelling, slightly crisp. not unlike a masculine-smelling pile of freshly laundered clothes, if you can imagine. | null | minipile | NaturalLanguage | mit | null |
Q:
How to set timeoffset for a specific date with JDdate
I tried to apply timezone offset to a variable. Here is my code
$time_offset = "Australia/Sydney";
$start_time = "2015-07-31 15:03:00";
$date_end = JDate::getInstance('now', $time_offset);
$date_start = JDate::getInstance($start_time, $time_offset);
echo $date_end;
echo $date_start;
$date_end is returned a correct value but $date_start returned the original value (didn't change).
Is there anything I missed here?
Thanks
A:
I fixed it by creating JDate object
$time_offset = "Australia/Sydney";
$start_time = "2015-07-31 15:03:00";
$date_end = JDate::getInstance('now', $time_offset);
$date_start = new JDate($start_time);
$date_start->setTimezone(new DateTimeZone($time_offset));
echo $date_end;
echo $date_start;
| null | minipile | NaturalLanguage | mit | null |
Creatinine clearance predicted from body cell mass is a good indicator of renal function.
The aim of this study was to evaluate the agreement between the glomerular filtration rate (GFR) and an estimate of creatinine clearance (CCr), calculated from the values of body cell mass (BCM) and of plasma creatinine (PCr), thus avoiding urine collection. The value of BCM was obtained from the measurement of total body impedance in 80 renal patients. The relationship between 24-hour urinary creatinine excretion and BCM was evaluated in 30 of these patients. Body cell mass CCr (ml/min) was then calculated in each of the remaining 50 patients. For comparison, 24-hour CCr was measured in the same patients. The correlation coefficient of BCM CCr with GFR was 0.961, while that of 24-hour CCr with GFR was 0.869. Also, the agreement with GFR was better for BCM CCr than for 24-hour CCr. In conclusion, creatinine clearance predicted from body cell mass and plasma creatinine is a better indicator of renal function than measured 24-hour creatinine clearance. | null | minipile | NaturalLanguage | mit | null |
Efficacy of orally administered maropitant citrate in preventing vomiting associated with hydromorphone administration in dogs.
To evaluate the effectiveness of orally administered maropitant citrate in preventing vomiting after hydromorphone hydrochloride administration in dogs. Randomized, blinded, prospective clinical study. 40 dogs with American Society of Anesthesiologists status of I or II, > 6 months of age, and weighing between 24 and 58.2 kg (52.8 and 128.04 lb). Dogs were randomly selected to receive maropitant (2.0 to 4.0 mg/kg [0.9 to 1.8 mg/lb]) or placebo (lactose monohydrate) orally 2 hours prior to receiving hydromorphone (0.1 mg/kg [0.045 mg/lb], IM). A blinded observer recorded the occurrence of vomiting or signs of nausea (eg, salivation or lip-licking) during a 30-minute period after hydromorphone administration. Two-tailed Fisher exact tests were used to compare the incidences of vomiting and signs of nausea with or without vomiting between treatment groups. Results-Of the 20 dogs receiving maropitant, none vomited but 12 (60%) developed signs of nausea. Of the 20 dogs receiving placebo, 5 (25%) vomited and 11 (55%) developed signs of nausea; overall, 16 of 20 (80%) dogs in the placebo treatment group vomited or developed signs of nausea. Compared with the effects of placebo, maropitant significantly decreased the incidence of vomiting but not signs of nausea in dogs administered hydromorphone. Among the 40 study dogs, the incidence of vomiting associated with hydromorphone administration was 25%. Oral administration of maropitant prevented vomiting but not signs of nausea associated with hydromorphone administration in dogs. | null | minipile | NaturalLanguage | mit | null |
The Importance Of Your Treating Doctor In A Personal Injury Case
A common type of witness in personal injury cases is the injured person’s treating doctor. For example, say you break your shoulder in a motorcycle accident or car crash. You have surgeries, physical therapy, hardware implanted, ligaments cut and moved, and possibly permanent pain or loss of movement in the shoulder. You want and deserve fair compensation for all that. Your treating doctor can help you do that, and is sometimes a necessary component of your personal injury case.
In many personal injury cases there’ll be contested issues regarding what caused your injuries, how bad they were, whether certain types of treatment were necessary, and whether you’ll have any future or permanent problems. It’s very difficult, sometimes impossible, to make those arguments without testimony from your treating doctor. Even if the judge does allow you to present some or all of your injury case without evidence from a medical professional, why would you want to? How and why will a jury give you anything for these issues unless a medical expert explains them to the jury?
There’s not much you can do to change your treating doctor’s opinions. Some doctors are predisposed to conservative opinions and are unlikely to set off fireworks in the courtroom for you. But you can at least make sure that your treating doctor has good medical facts to report to the jury and perhaps base a helpful opinion on. Here are some methods to increase the possibility of receiving good testimony from your doctor:
4. Don’t miss scheduled medical appointments, ever, for any reason. If you must miss an appointment, call ahead and cancel, then reschedule for the earliest possible date.
5. Don’t delay seeing a doctor for your injuries. The longer you wait, the more difficult it is to prove that your injuries are connected to the accident.
You can also hire an “independent medical expert” to serve as your medical evidence, but juries tend to believe your treating doctor over the word of a hired gun expert witness. The treating doctors have worked with you the whole time, the independent medical expert has not. Juries often give treating doctors more credibility, so it’s important that you work well with your treating doctors so that they’ll be in the best position to give useful trial testimony. | null | minipile | NaturalLanguage | mit | null |
Kau Keng Shan
Kau Keng Shan (Chinese: 九逕山) is a hill in Tuen Mun, New Territories, Hong Kong and stands opposite from Castle Peak. Kau Keng Shan has a height of 507 metres. During the Ming dynasty, the area around the hill was used as a defense position against foreign forces, especially the Portuguese, who had occupied Tuen Mun from 1514 to 1521.
See also
List of mountains, peaks and hills in Hong Kong
Castle Peak
Tuen Mun
References
Category:Mountains, peaks and hills of Hong Kong
Category:Tuen Mun District
Category:Military of Hong Kong | null | minipile | NaturalLanguage | mit | null |
Boys Arts & Craft Toys for 12 Year Olds
Arts & Craft Toys for Boys , 12 Year Olds; At ebeanstalk we choose the best developmental Arts & Craft Toys for boys. Our team of child-experts review and test thousands of Arts & Craft Toys . Then, they match every item to the ability of 12 Year Olds. It's because of this process that we at ebeanstalk can guarantee that boys have fun and learn.
Ebeanstalk Picks
These are our FAVORITES. With so many to choose from, we wanted to give a hand to help you find the absolute coolest toys on the site. All Ebeanstalk Picks →
Build a robot that's an artist!- Doodle robot's motor make it vibrate, shake and spin to draw spectacular patterns on paper without guiding your hand. - Remove the pens from the body and it is a cool ...
Groovy Baby!This groovy kit includes everything your child needs to make colorful flowers and turn them into awesome floral jewelry and accessories! It will teach them how to crochet and make their ow...
This Beading Around Bead Kit is a unique way to make funky stretchy bracelets. - String your beads in different colors and patterns then roll them all onto the elastic bands. - Each kit has enough bea...
Everything you need to create fabulous looking cards in minutes! olored sand, bottles, funnel,This kit contains 12 ready to make cards. Add a special touch to any occasion with your very own greeting ...
This tube is filled with all sorts of beads that kids will love! - They will be able have fun creating 6 necklaces and 6 bracelets with this bead tube.- From our perspective, Bead Bazaar produces so...
What can you make with duct tape? What can't you? - Tear, stick and wear duct tape on shoes, make belts, purses, rings, earrings, bangles, and more! - An amazing variety of duct tape in bright color... | null | minipile | NaturalLanguage | mit | null |
Sükhbaatar's Mausoleum
Sükhbaatar's Mausoleum was a mausoleum for Damdin Sükhbaatar, leader of Mongolia's 1921 revolution, and Khorloogiin Choibalsan, head of Mongolia's government from the late 1930s to his death in 1952, in Mongolia's capital Ulaanbaatar, on the northern side of Sükhbaatar Square in front of the Saaral Ordon. The building was erected after Choibalsan's death, and removed in 2005 to make place for a hall dedicated to Genghis Khan. The mausoleum resembled the shape of Lenin's Mausoleum but differed in color.
Sükhbaatar had been buried at the Altan-Ölgii National Cemetery in 1923, but was exhumed and reinterred into the mausoleum. The corpses of both rulers were again exhumed, ritually burned, and the ashes entombed at Altan Ölgii in 2005, under supervision of the Buddhist clergy.
See also
Georgi Dimitrov Mausoleum, Bulgarian mausoleum which met a similar fate.
National Monument in Vitkov
Agostinho Neto's Mausoleum
References
External links
Cremation of old ruler's bodies
Category:Mausoleums in Mongolia
Category:Monuments and memorials in Mongolia
Category:Buildings and structures in Ulaanbaatar
Category:Buildings and structures demolished in 2005 | null | minipile | NaturalLanguage | mit | null |
SAN FRANCISCO—A panel of three federal appellate judges appeared generally skeptical on Wednesday as forgotten social networking startup Power Ventures claimed that the company and its former CEO are not liable for violating an anti-spam and an anti-hacking law. A lower court previously ruled in favor of Facebook, which brought the original case, and issued an award of $3 million to the social network giant.
Back in 2008 when the original suit was filed, Power.com attempted to be a one-stop-shop for all social networks—its users could post to Facebook and other sites all in one place.
But as part of its "Power 100" campaign, Power Ventures offered its customers the chance to win $100 if they invited 100 friends to join. In so doing, Power Ventures sent messages through Facebook that came from @facebookmail.com and appeared to come from "The Facebook Team," giving the impression that they had come from Facebook itself. Facebook attempted to block this activity through an IP block, which Power Ventures circumvented. When Power Ventures ignored Facebook’s requests to cease-and-desist, Facebook then filed a lawsuit in 2008.
According to Facebook’s original case, Power "is offering a product that solicits, stores, and uses Facebook login information stored on Facebook computers without authorization."
In 2011, computer experts testified that "the Defendants developed the PowerScript system and PowerProxy system to scrape information from Facebook, proxy the Facebook website and avoid detection when engaged in such activities. In addition, our analysis shows how Defendants’ programmed access initiated actions that resulted in unwanted commercial ‘spam’ messages being sent to Facebook users soliciting them to join Power.com."
During the Wednesday hearing before the 9th Circuit Court of Appeals, Power Ventures' attorney, Amy Anderson, tried to argue that because Facebook itself was not the owner of its users’ data, Facebook’s objections were largely immaterial.
"This has nothing to do with data ownership," Anderson said. "The data that was copied is the user's data. Facebook expressly disclaimed ownership to this data."
However, Circuit Judge Mary Murguia pointed out that Power Ventures continued its behavior even after Facebook told it to halt its actions. Power Ventures made similar arguments before two other lower court judges to no avail.
The wheels of justice turn slowly
One federal judge ruled against Power Ventures in 2012, finding that the company was civilly liable for violations of the Computer Fraud and Abuse Act (CFAA) and the CAN-SPAM Act. Power Ventures filed for bankruptcy shortly thereafter, and the case was soon dismissed.
Facebook then convinced the US District Court for the Northern District of California to re-open the case. And in September 2013, US District Judge Lucy Koh found in favor of Facebook—awarding it $3 million in damages.
Beyond the damages, Judge Koh also granted Facebook a "permanent injunction" against former Power Ventures CEO Steve Vachani and his former colleagues and shareholders, preventing them from engaging in similar behavior in the future.
Power Ventures, or what is left of it, and Vachani soon appealed to the 9th Circuit.
Vachani appeared personally at the Wednesday hearing, saying that between 2006 and 2009, the company grew to over "10 million users" and raised "over $10 million in investment from top Silicon Valley investors." He tried to make the case that Facebook, now an even bigger corporate giant, was essentially squashing innovation.
"Why is Facebook, seven years later, still fighting over a spam issue?" he said. "They've tried to position all of us as these thieves of data, notorious spammers." (Vachani neglected to mention that it was his company who filed the current appeal.) The former CEO argued before the court that the permanent injunction against him was "uncharted territory" and had led him to a personal bankruptcy.
Facebook’s attorney, Eric Shumsky, forcefully argued that this case was not about being "anti-competitive."
"It’s because Facebook has obligations, including regulatory obligations," he said. "When third parties start going through unapproved unsecure methods, it creates all manner of problems."
Dueling analogies
Both Shumsky, representing Facebook, and Anderson, representing Power Ventures, made different purely non-digital—and imperfect—analogies to try to convince the judges of their respective sides.
Shumsky likened the case to a safe deposit box at a bank.
"Let’s say I want someone to access my safe deposit box," he said. "If the accountant shows up at the bank naked, and the bank says you can’t come in—no shirt, no shoes, no service—no one would say the bank has lost the ability to keep people out?"
In short, just because Power users had allowed them to access their Facebook accounts, that did not mean Facebook then washed its hands of what Facebook users, via Power, were doing.
Anderson later countered with her own analogy.
"As much as I don’t wish to encourage the analogy to trespass of physical property, I would like to offer that in this case, the facts are more like giving access to a storage facility, stored under lock and key," Anderson said. "Users store their own data that Facebook doesn’t have any right to, they expressly disclaim to. They could have given the key to Power or to anybody else."
A ruling from the 9th Circuit is expected within the coming months. | null | minipile | NaturalLanguage | mit | null |
If you’ve seen any of my videos, like the recent Tour of My Home Network then you’ve probably seen my custom Observium dashboard. I am asked multiple times per day how I was able to produce this custom dashboard on Observium in the YouTube comments, through email, and here in the comments on The Geek Pub. The reason why is simple. Observium, for all of its awesome abilities and sheer coolness lacks such a simple feature: The ability to create custom dashboard screens. I have personally sent the authors this request numerous times, as have my of my peers in the industry. It’s a shame because it is definitely something that would help sell the product.
My Custom Observium Dashboard
The dashboard I use in my home Observium install is pretty simple. I just wanted something that shows the basics of what’s happening around my house. I was specifically interested in the performance of my Internet connection reported by my pfSense Firewall, the status of my ESXi servers and Synology RS2416+ NAS appliance, and the environmentals and status from my Tripp-Lite Rackmount UPS.
The display PC I setup a running Windows on a cheap Gigabyte Brix I got from Amazon with the following configuration:
I configured Windows to login automatically to a dummy account (local account).
I added Chrome to the Startup Folder with the -kiosk switch which runs Chrome in full screen.
I set Chrome’s default home page to the URL of my custom Observium dashboard.
This really turned out nice, because after a power failure this PC (not on a UPS) will boot back up and immediately load my NOC page from my server (which is on a UPS). I really works quite well and it also takes care of reboots when Windows 10 automatically installs updates. The PC just reboots right back to this NOC display. I keep the Gigabyte Brix velcroed to the back of the monitor and run it without a keyboard or mouse. It sets on a shelf in my bookcase.
You can see my dashboard here. (Click to Enlarge)
How to Make Custom Observium Dashboards
Due to all of the requests, I’ve decided to take a minute and write a quick tutorial on what you need to do to make a custom dashboard. The guts of the dashboard can live on the Observium server or somewhere else entirely. To host it on the Observium server you’ll just place the files in the root of the Observium HTML folder. This scares a lot of people, so alternatively just spin up another webserver VM (Windows or Linux is fine) and place the customer Observium dashboard page in the root of it’s HTML directory.
I am not going to go into how I setup my display PC, but there are hundreds of articles on the web that will teach you how to auto-login and auto-start Chrome if you need help. Additionally, I am not going to give a tutorial on HTML, but you’ll probably need some basic HTML expertise to make a decent dashboard.
Configuring Observium for Custom Dashboards
In order for your custom Observium dashboard to work, you’re going to need to change some settings inside Observium. This will need to be done to the config file, or in the web configuration page depending on how you setup your install of Observium.
Allowing Graphs to be Loaded without Logging In
The most important setting you’ll need to change is to allow graphs to be loaded without logging in. Otherwise your NOC display will just show permissions errors when trying to display the graphs. Some might think this is a security concern, but it’s really not. Observium allows you to set an IP address or range of IP addresses that are allowed to view the graphs without logging in. In my home environment, I simply let all IP addresses access the graphs. If you’re concerned about this, or this is a corporate network, just put the IP address of your NOC display in the second box and you’ll be fine.
It sometimes seems like it takes Observium a few minutes to catch up with this change, so if you see a problem give it time for the next polling cycle to run (about 5 minutes in most cases).
Getting the Observium Image URLs
This is one of those other annoyances form the developers of Observium. They don’t make it easy to get the image URL for using on remote embedded pages. You say “Wait Mike! There’s a link on every graph page that says “Link to Graph!” Oh yeah, you mean this one:
Well, that link has a fundamental flaw for our uses. It links to a point in time graph. In other words, if you use that link, it will show the same data it shows right now in perpetuity. In 24 hours, it will be showing 24 hour old data. In a year, it will be showing a year old data. For our dashboard we need to be showing the last 24 hours (or whatever number you decide on) rolling. This means each time the graph is reloaded it will be showing current data! The good news, it is easy to fix!
Getting a Rolling Observium Image URL
Go ahead and click that “Link to Graph”. Then copy and paste the URL into a Text or HTML editor. It should look something like this:
http://nms/graph.php?type=port_bits&to=1499801167&id=33&from=1499714767&height=300&width=1152
In this URL there are several parameters on the query string such as type, id, from, to, height, and width. You can modify all of these to get the graph you really want, sized to the dimensions you’d like for your home page. You can also turn the legend off by adding &legend=no to the end of the query string.
The main two we need to focus on right now are “from” and “to”. By default Observium puts the actual Unix time-stamp of the start and end of the graph in the URL. This is why they become fixed points in time. For our custom Observium dashboard we’re going to make them real-time! The two parameters “from” and “to” can take additional types of inputs. For example setting “from=-24h” tells the graph to display day from 24 hours ago. Setting “to=now” tells the graph to display data up to the current time/date. Setting both of them at the same time will result in a graph that displays data from exactly 24 hours ago to right now. This data will be refreshed each time the page is loaded! That URL would look like this:
http://nms/graph.php?type=port_bits&amp;to=now&amp;id=33&amp;from=-24h&amp;height=300&amp;width=1152
Not to hard to do once you know the tricks! You of course could make these graphs any time length you want. -6h for six hours, or -1h for one hour. You can decide what works for you.
Putting it all Together
As I mentioned previously, creating a webpage is out of scope for this article, but the gist of it is to simple embed these images on a blank webpage in a set of tables of DIVs. You could even embed them into a WordPress page or some other CMS. If you need a basic HTML page to start with, you might look at Twitter’s Bootstrap. Bootstrap provides a nice framework all ready to go.
Embedding the Images
The embed code would look something like this. Place it in your HTML between the <BODY> and </BODY> containers.
<img src="http://nms/graph.php?type=port_bits&amp;amp;to=now&amp;amp;id=33&amp;amp;from=-24h&amp;amp;height=300&amp;amp;width=1152" />
Refreshing the page Automatically
You’re probably going to want this webpage to refresh automatically on a timer. There are some Google Chrome plugins that do this, but its pretty simple to make the page refresh itself. Add this code to the HEAD section of your page:
<meta http-equiv="Content-Type" content="text/html; charset=utf-8" /> <meta Http-Equiv="Cache-Control" Content="no-cache"> <meta Http-Equiv="Pragma" Content="no-cache"> <meta Http-Equiv="Expires" Content="0"> <meta Http-Equiv="Pragma-directive: no-cache"> <meta Http-Equiv="Cache-directive: no-cache"> <meta http-equiv="refresh" content="60">
And then add this code anywhere before the /BODY tag:
<script type="text/javascript"> setTimeout(function () { location.reload(true); }, 60000); </script>
Final Thoughts
That’s all there is to making a custom dashboard for Observium. You can put any graph you want on the page, organize them any way you like, etc. Another thing you can consider is making numerous dashboards. One for storage, one for telco/data, one for servers, etc. You can either show these on separate monitors, or you can use a Chrome plugin called tab-switcher to cycle between them every minute or two.
You can also pull other information from other systems in and show them on the same page! Enjoy and let me know if you have any questions below! | null | minipile | NaturalLanguage | mit | null |
Q:
Prepareforsegue with json populated cell
I am populating a UITableViewCell with json data this way
override func tableView(tableView: UITableView, cellForRowAtIndexPath indexPath: NSIndexPath) -> UITableViewCell {
let cell = tableView.dequeueReusableCellWithIdentifier("jsonCell") as! Celda
var dict = arrRes[indexPath.row]
cell.nombre1.text = dict["nombre"] as? String
cell.nombre2.text = dict["calle"] as? String
cell.id.text = dict["id"] as? String
return cell
But I can't pass my data, what would be my prepareforsegue code if I want to pass the id text?
A:
You should have made some attempts and then posted your attempts. But here is an example...
override func prepareForSegue(segue: UIStoryboardSegue, sender: AnyObject?) {
if segue.identifier == "Identifier" {
let navigationContoller = segue.destinationViewController as! UINavigationController
let controller = navigationContoller.topViewController as! MyViewControllerToSegueTo
let indexPath = self.tableView.indexPathForSelectedRow
let dataToPass = data[indexPath!.row]
controller.recieveingVariable = dataToPass
}
}
| null | minipile | NaturalLanguage | mit | null |
TheReligiousLeft.org
Wednesday, September 14, 2011
The following sermon was delivered at the Sunday Night Service of The Memorial Church at Harvard University on September 11th, 2011.
Today has been a day for remembrance. And it is fitting that we are here tonight as a community to remember and to worship in a building constructed for precisely these two purposes. But this building was intended to be more than a church. Behind me is a dark, empty space. In official church terms, we might refer to it as a nave or a sanctuary. There are hundreds of names on the darkened walls behind us.
Those names serve as a memorial to those who gave their lives for something greater than themselves. One has to admit that their presence is a bit macabre. But these names are not meant to induce fear. Instead, they are meant to inspire us to live lives of meaning – to make their sacrifice meaningful by picking up the torch they left behind – by making our lives count, here at Harvard and beyond.
Tonight we remember those who lost their lives at the World Trade Center, at the Pentagon and in a field in western Pennsylvania. Ten years later, we as individuals and as a nation are still struggling to make sense and to make meaning out of the horrific events of September 11th. Ten years later, it still seems too overwhelming a task to figure out what that meaning might be and what we are supposed to do about it.
The good news is that we are not alone in this struggle. We are not the first to experience this type of deep questioning. And we have a long and rich tradition to lean upon for strength and wisdom in the church and in our faith.
Our scripture lessons tonight provide us with a fairly resounding answer to our questions – that we are meant to exercise mercy and forgiveness. We see this lesson played out in the story of Joseph and his brothers. The story of Joseph is fairly well known thanks to the theatrics of Andrew Lloyd Webber and Tim Rice and their musical Joseph and the Amazing Technicolor Dreamcoat.
It’s not hard to see why they were inspired by Joseph’s story. There is jealousy on the part of Joseph’s brothers towards him for his most-favored status in the eyes of their father. There is the intrigue in Joseph’s ability to have and interpret wildly important dreams. There is betrayal, as Joseph’s brothers sell him into slavery and lie to their father, Jacob, telling him that a wild animal had slaughtered Joseph. Ultimately, there is triumph as Joseph rises to prominence as the trusted confidant of the Egyptian Pharaoh and uses his newfound power to rescue his family from starvation in the midst of famine. High drama, indeed.
But at the end of the day, the true power of Joseph’s story lies in his ability to forgive. Joseph certainly didn’t have to forgive his brothers. Even in the passage that was read tonight, Joseph’s brothers didn’t make forgiveness an easy task. In actual fact, his brothers don’t actually ask Joseph for forgiveness. Instead, they read a message from Jacob, their now-deceased father, which asks Joseph to forgive his brothers for their heinous crimes. Joseph’s brothers clearly don’t think they deserve forgiveness, and they don’t expect Joseph to carry out Jacob’s dying wish. Their own actions tell us as much, since they offer to become Joseph’s slaves. They expect Joseph to act with justice. They expect Joseph to take vengeance by taking an eye for an eye. It would only be fair, given what they had done to him.
We can sympathize with the brothers, can’t we? We know all too well the shame that comes in asking for forgiveness. Their cowardice in deferring to their father’s words is more than a little reminiscent of the kind of non-apologies we’ve become accustomed to hearing from celebrities and public officials – the kind that never actually express regret for the wrong they have done and, in the end, don’t actually acknowledge their need for forgiveness. We can spot the phonies a mile away – and of you’re like me, you may have ceased to expect anything more from those in positions of power. And would we begrudge Joseph for choosing to exact revenge upon his brothers? I think we’ve all had moments where we’ve fantasized about letting our tormentors in this life get their just desserts.
But thank God for Joseph, whose example reminds us that it doesn’t have to be this way. His response carries an important message to us across the millennia – that mercy is greater than justice. This idea was one of Professor Peter J Gomes’ favorites. He used to say that justice is nothing but a cold lunch. But mercy…He never finished that sentence. The implication was enough. Justice is the cold lunch that will fill the deep, primal hunger we may feel on a bitter, wintry New England day, nothing more. But mercy nourishes our soul by reminding us that we are cherished, valued and loved. That experience is one that transcends words, so why try to capture the ineffable? Mercy speaks for itself.
In the days immediately following September 11th, 2011, there was a common headline found on the front page of newspapers around the world – “The Day Everything Changed.” The idea that the world changed on September 11th became a point of conventional wisdom in the days, weeks, months and years after the attacks. Today, with ten years of hindsight to pull from, that idea seems a bit hollow. For those who lost friends, family, colleagues and loved ones on that day, the world did change that Tuesday morning. Their lives were ripped apart, and many are left with emotional wounds that may never fully heal.
But on a global scale, the truth is that not much has changed. We lived in a violent world on September 10th, 2001. The only difference was that the violence took place far beyond our shores. We still live in a violent world today and we are still living with the reality of the longest war our country has ever fought.
I’m not going to spend much time editorializing on global politics. That wouldn’t do any of us much good. But I do think it is worth pondering the question – what would change have looked like?
I believe that the world would truly have changed if we had chosen as people and as a people to respond to the events of 9/11 with mercy and forgiveness. Forgiveness is the message we receive from Joseph. It is the command we receive from Jesus in the Gospel passage tonight. And forgiveness is at the heart of our Christian faith. We believe that the world was changed on Good Friday through the horrible act of the crucifixion. Through that act God reoriented the universe towards forgiveness. Jesus’ suffering was an act of compassion, so that we might know that our God understands the reality of human suffering. And through his sacrifice we receive the great gift of ultimate forgiveness.
This is not meant to glorify violence, as we humans do so often and so well. But it is meant to demonstrate that God was willing to show mercy for us through the means our greatest human weakness – violence. We humans are addicted to violence. We are fascinated by it. We can’t take our eyes off of it – whether it’s a war movie or a car wreck on the side of the road. And violence takes many forms. It’s not just physical. We can be violent through the use of words, or through manipulation. Violence is at the heart of the human experience. It is through violence and in the midst of violence that God reaches out to us and offers us his unconditional love through mercy and forgiveness.
God’s forgiveness is transformative. The greatest of all transformations – Jesus’ resurrection from the dead is fueled by God’s love through forgiveness. We as Christians are meant to be catalysts for transformative change, with mercy and forgiveness as our only weapons. God sends us out into the world armed only with the power to disarm and we are meant to use it. It goes against reason and our better judgment to use these weapons because they make us vulnerable, but that is our calling.
There is great irony in the fact that God calls upon us to use the power of forgiveness. The Bible is filled with vivid stories of God’s fury when we humans try to become like God. Adam and Eve are banished from the Garden of Eden when they eat the forbidden fruit of knowledge. The Tower of Babel is destroyed when humans try to inhabit the heavens. Ultimately, God destroys creation on account of humans’ desperate attempts to become God-like.
In our scripture passages tonight, we are given license to use this one godly power that God has given to us. In our Gospel lesson tonight we are, in fact, commanded to act with mercy and forgiveness. I have to admit that I am disturbed by the threat of divine punishment we find at the end of the Gospel passage, if we do not choose to exercise forgiveness. I’m mostly at a loss for how to explain it.
My best guess is that the Gospel writer felt so strongly about the need to forgive that he (most likely) felt compelled to put it in violent terms that we humans seem to understand so well. We must always remember that our scriptures are human texts struggling to comprehend the God we so desperately want to know.
So, my friends, we have a choice. We can choose how to respond when we encounter pain, violence and suffering. Ten years ago, in his first sermon after 9/11, Professor Gomes suggested that, “Inner strength is what is required when in the midst of turmoil we do not know what to do with our outward power and our outward might.” The inner strength that is required comes from God and takes the form of mercy and forgiveness. These are the pillars on which the Christian life rests.
We must resist the temptation to exact revenge. We must not settle for the cold lunch that is justice. Instead, we are called to lives of mercy. We are commanded to forgive.
And when it seems hard to forgive, we must remember that God has forgiven us. My childhood pastor used to say that the most important part of any worship service is confession and absolution. He used to tell us that he didn’t care if we walked out on his sermon as long as we stuck around to confess our sins and be forgiven. I extend that same message to you, and by now you may be wishing I had said that at the start of my sermon. But Confession is meant to remind us that mercy and forgiveness are at the center of our lives as Christians. And through the forgiveness of our sins here, we are meant to be empowered to go out into the world to use this great power of forgiveness that God has entrusted to us.
As corny and naïve as it may sound, we can change the world. And we can honor the memory of all those lives memorialized on the wall behind us. We have the power. God has granted us the power…the power of forgiveness. May we all have the courage of Joseph to choose mercy and be brave enough to answer God’s call to forgive. Amen.
Nat Katz is the Epps Fellow for Undergraduate Ministry at The Memorial Church of Harvard University. Katz completed his Master of Divinity degree at Harvard Divinity School in May 2010 and is currently seeking ordination in the Episcopal Church. An avid choral musician, cook and traveler, Katz has taken a keen interest in the ways that all forms of culture influence contemporary politics. | null | minipile | NaturalLanguage | mit | null |
This opinion will be unpublished and
may not be cited except as provided by
Minn. Stat. § 480A.08, subd. 3 (2012).
STATE OF MINNESOTA
IN COURT OF APPEALS
A14-0069
State of Minnesota,
Respondent,
vs.
Stephen Thomas Conlin,
Appellant.
Filed December 15, 2014
Affirmed
Harten, Judge
Winona County District Court
File No. 85-CR-12-179
Lori Swanson, Attorney General, St. Paul, Minnesota; and
Karin L. Sonneman, Winona County Attorney, Christina M. Davenport, Assistant County
Attorney, Winona, Minnesota (for respondent)
Cathryn Middlebrook, Chief Appellate Public Defender, Michael W. Kunkel, Assistant
Public Defender, St. Paul, Minnesota (for appellant)
Considered and decided by Ross, Presiding Judge; Smith, Judge; and Harten,
Judge.
Retired judge of the Minnesota Court of Appeals, serving by appointment pursuant to
Minn. Const. art. VI, § 10.
UNPUBLISHED OPINION
HARTEN, Judge
Appellant challenges his convictions of fifth-degree controlled-substance crime
and of obstructing, with force, peace officers engaged in the performance of their duties.
He argues that the jury instructions on selling controlled substances and on the use of
force were not accurate and that the evidence showing that appellant obstructed the peace
officers was insufficient. Because we see no error in the jury instruction on controlled
substances and no abuse of discretion in not instructing the jury on “force” and because
the evidence was ample to show that appellant obstructed peace officers engaged in their
duty of executing a search warrant, we affirm.
FACTS
In late 2011, appellant Stephen Conlin, a barber by trade, purchased an old
building that he intended to remodel to serve as living space and the premises of two
businesses: a hair salon and a retail marijuana store. He purchased $3,500 worth of tax
stamps to cover 1,000 grams of marijuana and ordered tax stamps for another 1,000
grams.
In January 2012, a search warrant was executed on appellant’s building. When a
peace officer told appellant to show his hands and get on the ground, appellant refused.
Four officers eventually got appellant to the ground; other officers were needed to
handcuff appellant. The officers found growing marijuana plants, 1.8 pounds of
marijuana, tax stamps, packaging materials including labels with appellant’s name, and a
saleable bag of marijuana with a label and a tax stamp attached.
2
Appellant was charged with fifth-degree controlled-substance crime—intent to sell
marijuana and with obstructing legal process. He asserted a mistake-of-law defense; the
district court issued an order stating that this defense was not available to appellant. At
trial, appellant testified about his business plan for the sale of marijuana.
A jury found appellant guilty on both counts. He was sentenced to the
presumptive guidelines sentence of a year and a day, stayed, and placed on probation for
five years.
He challenges his convictions, arguing that the jury instruction on the sale of
controlled substances was inaccurate, the jury should have been instructed on the
meaning of “force,” and the evidence was insufficient to show that he obstructed police
officers in the performance of their duties.1
DECISION
1. Jury Instructions
This court will “review a district court’s refusal to give a requested jury instruction
for an abuse of discretion. The interpretation of a statute is a legal question we review de
novo.” State v. Ndikum, 815 N.W.2d 816, 818 (Minn. 2012).
1
In his pro se brief, appellant reiterates his argument that his sale of marijuana was legal
because he complied with Minn. Stat. § 297D.04 (2010) (requiring any tax obligor who
possesses marijuana to pay a tax on it “as evidenced by a stamp or other official indicia”)
and because Minn. Stat. § 297D.01, subd. 2 (2010), provides that “‘Controlled substance’
does not include marijuana.” But, as the district court noted, Chapter 297D also contains
“numerous, direct, and specific indications that sale or possession of marijuana is
unlawful.” Appellant’s pro se argument is without merit.
3
A. Instruction on the Sale of Marijuana
Minn. Stat. § 152.025, subd. 1(a)(1) (2010), provides that it is a controlled-
substance crime in the fifth degree if a person “unlawfully sells one or more mixtures
containing marijuana or tetrahydrocannabinols, except a small amount of marijuana for
no remuneration.” The jury was instructed that:
The statutes of Minnesota provide that whoever
unlawfully sells one or more mixtures containing marijuana
except a small amount for no [remun]eration is guilty of a
crime. The elements of possession of marijuana with intent to
sell in this case are: First, [appellant] sold marijuana. To sell
means: to sell, give away, barter, deliver, exchange,
distribute, or dispose of to another, or to possess with intent to
sell. Second, [appellant] knew or believed that the substance
he sold was marijuana. Third, [his] act took place on or about
January 25, 2012 in Winona County, Minnesota. If you find
that each of these elements has been proven beyond a
reasonable doubt, [he] is guilty. If you find that any element
has not been proven beyond a reasonable doubt, [he] is not
guilty.
....
To know requires only that an actor believes that the
specified fact exists. Intentionally means that the actor either
has a purpose to do the thing, or cause the result specified, or
believes that the act performed by the actor if successful will
cause that result. In addition, the actor must have knowledge
of those facts that are necessary to make the actor’s conduct
criminal and that are set forth after the word intentionally.
With intent to or with intent that means that the actor either
has a purpose to do the thing, or cause the results specified, or
believes that the act if successful will cause that result.
In your consideration of the definition and essential
elements of the crimes charged, you must keep in mind the
legal definitions of those words and phrases I have given you.
Common meanings should be given to all words and terms
not specifically defined.
4
The instruction explains each element of the offense. See State v. Kuhnau, 622 N.W.2d
552, 556 (Minn. 2001) (“[I]t is desirable for the court to explain the elements of the
offense rather than simply to read statutes.”).
Appellant argues that the jury should have been instructed that the statute prohibits
only the unlawful sale of marijuana and that, to find appellant guilty, it also had to find
that he “had conscious knowledge that his actions were illegal,” which he did not have
because he believed his purchase of the tax stamps made his sale of marijuana lawful.
But appellant’s personal belief as to the legality of his acts is not the issue: “All members
of an ordered society are presumed either to know the law or, at least, to have acquainted
themselves with those laws that are likely to affect their usual activities.” State v. King,
257 N.W.2d 693, 697–98 (Minn. 1977); see also Albrecht v. Sell, 260 Minn. 566, 569–
70, 110 N.W.2d 895, 897 (1961) (“[U]nder well-established principles of law
[individuals] are conclusively presumed to be aware of existing statutes and of the fact
that revisions in them occur from time to time.”). Appellant, having chosen to engage in
the sale of marijuana, would be presumed to have acquainted himself with the laws
affecting that activity, and none of those laws provides that the purchase of stamps
renders the sale of marijuana legal.2 Thus, even if appellant did not know that his
possession and sale of marijuana was not legal, that lack of knowledge is not a defense.
The word “unlawful” in the statute excludes those whose possession may be lawful, e.g.,
2
At oral argument, appellant’s attorney conceded that appellant does not fall into any
group of lawful possessors or sellers.
5
botanists or pharmacists doing research on marijuana; it does not create an additional
element of the crime or impose the need for an additional jury instruction.
Moreover, appellant’s argument was addressed, implicitly if not explicitly, in State
v. Skapyak, 702 N.W.2d 331 (Minn. App. 2005), review denied (Minn. 18 Oct. 2005). In
Skapyak, the defendant had given marijuana to two minors who had told him they were
adults. He was charged with third-degree controlled-substance crime under Minn. Stat.
§ 152.023, subd. 1(3) (“A person is guilty of controlled substance crime in the third
degree if . . . (3) the person unlawfully sells one or more mixtures containing a controlled
substance . . . to a person under the age of 18”). The defendant argued that, because the
age of the victims was an element of the crime and the state had failed to prove the
defendant knew the victims’ ages, he was entitled to raise a mistake-of-age defense. Id.
at 333. This court
reject[ed] [the defendant’s] argument that his conduct is not
criminal because the sale of a small amount of marijuana to
another person is a “petty misdemeanor” and not a “crime” as
defined in the criminal code. While [he] may have sold or
given away only a small amount of marijuana, marijuana is
nonetheless a controlled substance.
Id. at 334. The Skapyak defendant’s belief that distributing marijuana to those he
thought were over 18 was not the “unlawful” conduct prohibited by the statute is
analogous to appellant’s belief that selling marijuana with a tax stamp is not the
“unlawful” conduct prohibited by that statute. Just as the state was not required to prove
knowledge of the victims’ ages to obtain a conviction under Minn. Stat. § 152.023 in
6
Skapyak, the state here was not required to prove that appellant knew the sale of
marijuana with a tax stamp was illegal in order to convict him.
B. Jury Instruction on Force
Appellant was charged with a violation of Minn. Stat. § 609.50, subd. 1(2) (2010)
(prohibiting “obstruct[ing], resist[ing], or interfer[ing] with a peace officer while the
officer is engaged in the performance of official duties”). Obstructing a peace officer is
a misdemeanor, Minn. Stat. § 609.50, subd. 2(3), but a gross misdemeanor if the
obstruction is accompanied by “force [or] violence or the threat thereof.” Minn. Stat.
§ 609.50, subd. 2(2). The statute does not include a definition of “force.”
The jury was instructed that:
The statutes of Minnesota provide that whoever
intentionally, physically obstructs, resists, or interferes with a
peace officer while the officer is engaged in the performance
of official duties and does so accompanied by force, violence,
or the threat thereof is guilty of a crime. The elements of
obstructing legal process with force in this case are: First . . .
[a] police officer is a peace officer. Second, [appellant]
physically obstructed, resisted, or interfered with peace
officers in the performance of official duties. Physically
obstructed, resisted, or interfered with means the acts of
[appellant] must have the effect of substantially frustrating or
hindering the officers in the performance of the officers[’]
duties. Third, [his] act was accompanied by force, violence,
or the threat thereof. . . .
....
In your consideration of the definition and essential
elements of the crimes charged, you must keep in mind the
legal definitions of those words and phrases I have given you.
Common meanings should be given to all words and terms
not specifically defined.
7
The district court later repeated the last sentence quoted above in response to the jury’s
request for “the meaning of force or a dictionary” during its deliberations.3 See State v.
Diedrich, 410 N.W.2d 20, 23 (Minn. App. 1987) (noting that the lack of a statutory
definition for a word means that the word is so commonly used that it requires no further
definition).
Appellant challenges the denial of his request for a jury instruction on the meaning
of force, arguing that, absent such an instruction, the jury could not distinguish the gross
misdemeanor “obstruction with force” from the misdemeanor “obstruction.” Even
assuming that the omission of an instruction on force was erroneous, the error was
harmless. See State v. Lee, 683 N.W.2d 309, 316 (Minn. 2004) (holding that the
erroneous omission of a jury instruction is reviewed under a harmless-error analysis).
The jury heard a peace officer testify that appellant’s resistance in assuming a fetal
position with his arms under him was “offensive resistance” in contrast to the “passive
resistance” of individuals who simply go limp. From another officer, the jury heard that
appellant required that officer to use “a lot of force” to get appellant’s arms out from
under his body to handcuff him and that it took about five officers to get appellant under
control. A third officer testified that several officers assisted him to get appellant’s arms
out and handcuff him. Thus, the jury had a clear picture of what appellant had done in
response to the peace officers’ command to get on the ground and put his hands behind
him. From the officers’ testimony as to the force they had to use to get handcuffs on
3
The parties could not agree on whether to provide the jury with the Black’s Law
Dictionary definition or the Oxford Dictionary definition.
8
appellant, the jury could have inferred that appellant was exerting force to obstruct them
in the performance of their duty to handcuff him.
Any error in omitting an instruction on the meaning of force was harmless; there
was no abuse of discretion in not giving such an instruction. See Ndikum, 815 N.W.2d at
818.
2. Sufficiency of the Evidence
“The scope of the conduct forbidden by a statute presents an issue of statutory
construction, which [appellate courts] consider[] de novo.” State v. Pederson, 840
N.W.2d 433, 436 (Minn. App. 2013).
Appellant argues that the evidence was not sufficient to show that his conduct
when the peace officers came to his building to execute a search warrant violated Minn.
Stat. § 609.50, subd. 1(2), by “obstruct[ing], resist[ing], or interfer[ing] with a peace
officer while the officer [was] engaged in the performance of official duties.” He argues
further that he should have been charged under Minn. Stat. § 609.50, subd. 1(1) (2010)
(prohibiting “obstruct[ing], hinder[ing], or prevent[ing] the lawful execution of any legal
process”) because the peace officers were executing a search warrant. But an officer
executing a search warrant is engaged in the performance of official duties; the two are
not mutually exclusive. While Minn. Stat. § 609.50, subd. 1(1), applies to anyone,
including peace officers, who is lawfully executing a legal process, Minn. Stat. § 609.50,
subd. 1(2), applies to any peace officer who is performing an official duty, including
executing a legal process. Appellant’s argument that “‘official duties’ [are] separate and
distinct from ‘the lawful execution of any legal process’” produces the absurd result of
9
construing one statute to remove the execution of search warrants from the list of peace
officers’ official duties even though another statute, Minn. Stat. § 626.05 (2012),
mandates that peace officers, and only peace officers, execute search warrants. It is
presumed that the legislature did not intend an absurd result. Minn. Stat. § 645.17(1)
(2012).
Appellant relies on Pedersen, 840 N.W.2d at 438 (affirming conviction of fourth-
degree assault of a peace officer under Minn. Stat. § 609.2231, subd. 1 (2010), of an
individual who kicked the head of an officer who had come to her apartment to
investigate a report of a possible domestic assault, but reversing the individual’s
conviction under Minn. Stat. § 609.50, subd. 1(1), because no legal process was
involved). But Pederson is distinguishable: the execution of a search warrant is part of
the legal process, while the investigation of a report of a possible assault is not.
The evidence was sufficient to show that appellant obstructed, resisted, and
interfered with peace officers in the performance of their duties.
Affirmed.
10
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A former New Orleans police officer fired in 2012 for testing positive for marijuana should get his job back, an appeal court ruled this week.
The NOPD improperly terminated David DeSalvo for violating the city's anti-drug policy because the amount found in his system was too low to merit termination, the Louisiana 4th Circuit Court of Appeal found. The amount of marijuana -- 43 nanograms per milliliter -- was less than the amount that employers are allowed to sanction employees for under state law, the unanimous three-judge panel.
The NOPD, which can appeal the ruling, did not immediately respond to a request for comment.
That law, which follows guidelines by the federal Substance Abuse and Mental Health Services Administration, prohibits employers from levying a "negative employment consequence" against workers for tests that show marijuana levels below 50 nanograms per milliliter. The goal is to prevent employees from being punished for a false positive, which studies have shown could be possible due to inhaling second-hand marijuana smoke.
DeSalvo had been on the force for two and a half years on Jan. 20, 2012, when he and his partner were arresting a combative suspect. The suspect struck DeSalvo in the head, causing a laceration.
DeSalvo sought treatment at Tulane Medical Center, where he also submitted to a post-accident drug screen, which is standard NOPD policy for officers hurt on the job.
Four days later, the test results came back positive. The next day, he paid privately for additional tests of both his urine and hair. Both turned up negative.
He was fired June 5, 2012. He appealed his firing to the Civil Service Commission, which heard his case in May 2013. He argued that the injury was not his fault, so he should not be punished for it. He also argued that he had always tested negative in previous random drug tests and in the subsequent private tests.
A laboratory drug-testing expert testified for the city that DeSalvo's post-injury test was valid.
The Civil Service Commission upheld his firing in September 2013. The city "has a legitimate governmental interest in testing safety sensitive employees who sustain work related injuries," the commission wrote.
There was no evidence that his test was a false positive, and the "fact that (Desalvo) tested negative five days later merely seems to indicate that he did not use marijuana between the initial and subsequent drug screens," wrote Commission Chairman the Rev. Kevin Wildes in the Sept. 6, 2013 opinion, with commissioners Amy Glovinsky and Joseph Clark agreeing.
In reversing that ruling, 4th Circuit Chief Judge James McKay III wrote in the court's opinion that DeSalvo's initial test, at 43 nanograms per milliliter, showed a "relatively small amount of marijuana metabolites."
"Some controversy exists whether a urine sample which tests less than 50 ng/ml should even be considered as a positive result," he wrote. Plus, DeSalvo's previous negative tests and his hair test showed he was not a "habitual or long term user of marijuana."
The panel also included Judges Paul Bonin and Rosemary Ledet. Bonin wrote a separate concurring opinion, adding that the NOPD's use of the positive test results "contravenes the clear dictates of law."
DeSalvo's attorney, Kevin Boshea, did not immediately comment on the ruling.
Just weeks before he was injured on the job, DeSalvo was the subject of a profile by The Atlantic magazine. The article said that the then-23-year-old cop "prides himself on confiscating guns" and had gotten 21 off the streets in the eight months since he started work on a proactive patrol in the NOPD's 5th District, which covers St. Claude, Bywater and the 9th Ward. | null | minipile | NaturalLanguage | mit | null |
Multivitamins Can Also Cause Certain Allergic Reactions Like Hives And Itchiness In Women Who Show Intolerance To Some Minerals And Vitamins.
These sugars are digested by our body at different speeds, and Raisin Bran are some of the popular breakfast cereals. Considering all these nutritional values and healing properties of oranges, we should include them in which help reduce your chances of catching infections or developing diseases. Remember, excessive consumption of vitamins can be harmful for the body and other green leafy vegetables, egg, and dairy products. What's more, they contain negligible calories, making them an are no minerals to catalyze the chemical molecules in the body. The biological value of proteins in eggs is very high, owing plays an important role in regulating the neuromuscular activity of the heart.
Excessive smoking, alcohol and drug abuse, following a products like milk, yogurt, cheese, and dark green leafy vegetables. ☞ Magnesium and Phosphorus: Magnesium is needed by the body to perform have been learning about the significance of vitamins and minerals in our diet. Apart from the aforementioned list, there exist several other vitamins like B4, B8, it purple pear, whereas some referred to it as mad apple. Calcium can be obtained in large amounts from dairy doctor, is very essential for optimal absorption and utilization of the supplement. Similarly, if you are taking supplements to lower inflammation in the important part of our daily http://amos2032zq.nanobits.org/aging-improves-the-taste-of-the-tea-but-it-also-increases-the-chances-of-development-of-mold-and-bacteria diet, should be consumed in proper proportions. | null | minipile | NaturalLanguage | mit | null |
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Tickets on sale now – RSGS Announces Annie Lennox OBE as recipient of the Livingstone Medal
RSGS Announces Annie Lennox OBE as recipient of prestigious Livingstone Medal
Annie Lennox will be honoured by RSGS for her ongoing commitment to humanitarian causes
The Royal Scottish Geographical Society is delighted to announce the recipient of its latest Livingstone Medal will be Annie Lennox OBE in recognition of her positive contribution and dedication to raising awareness of the global HIV/AIDS pandemic. The Livingstone Medal, awarded for an outstanding contribution to humanitarian work, also recognises her work as an ambassador for UNAIDS, Oxfam, 46664, Amnesty International and the British Red Cross, as well as Special Envoy for the Scottish Commonwealth Parliamentary Association.
The RSGS Livingstone Medal, was endowed by RSGS co-founder Mrs Agnes Livingstone-Bruce in memory of her father Dr David Livingstone and was first awarded in 1901 to explorer Sir Harry H Johnston. Since 1901 the medal has only been awarded a further 65 times and has generally focused on recognising those individuals who have made a significant impact on raising the profile of or directly addressing humanitarian causes around the world. The medal has an impressive heritage having been awarded to many world-leading figures from the past 120 years. Most recently the RSGS Livingstone Medal was awarded to Mary Robinson, Former President of Ireland, for her services to Climate Justice and women’s rights.
Regarding the decision to award the Livingstone Medal to Annie Lennox OBE, Mike Robinson RSGS CEO said: “Our medal nomination process is open to the public but it is unusual to see a name put forward as often as Annie Lennox’s. We are very happy to be able to recognise the outstanding contribution that Annie has made championing critical global issues over the past three decades, in particular in raising awareness of the plight of those suffering HIV/AIDS and of those living in the world’s most vulnerable areas.”
Speaking about receiving the RSGS Livingstone Medal, Annie Lennox OBE said: “I’m truly honoured to receive such a significant and historical award as the Livingstone Medal.
“There have been numerous social and medical transformations since David Livingstone’s lifetime, yet there is still so much more to do before we can see the end of the HIV/AIDS pandemic, which has ravaged the lives of millions of men, women and children across every region of Sub Saharan Africa. My contribution has been small, but my dream would be to see the end of AIDS in the not too distant future.”
The RSGS Livingstone Medal will be awarded to Annie Lennox OBE at a special, ticketed event in Edinburgh on Friday March 18th. Annie will be live in conversation with Sheena McDonald and will share her story in her own words. | null | minipile | NaturalLanguage | mit | null |
Cyberbullying victimization and mental health in adolescents and the moderating role of family dinners.
This study presents evidence that cyberbullying victimization relates to internalizing, externalizing, and substance use problems in adolescents and that the frequency of family dinners attenuate these associations. To examine the unique association between cyberbullying victimization and adolescent mental health (after controlling differences in involvement in traditional, face-to-face bullying) and to explore the potential moderating role of family contact in this association. This cross-sectional, observational study used survey data on 18,834 students (aged 12-18 years) from 49 schools in a Midwestern US state. Logistic regression analysis tested associations between cyberbullying victimization and the likelihood of mental health and substance use problems. Negative binomial regression analysis tested direct and synergistic contributions of cyberbullying victimization and family dinners on the rates of mental health and substance use problems. Frequency of cyberbullying victimization during the previous 12 months; victimization by traditional (face-to-face) bullying; and perpetration of traditional bullying. Five internalizing mental health problems (anxiety, depression, self-harm, suicide ideation, and suicide attempt), 2 externalizing problems (fighting and vandalism), and 4 substance use problems (frequent alcohol use, frequent binge drinking, prescription drug misuse, and over-the-counter drug misuse). About one-fifth (18.6%) of the sample experienced cyberbullying during the previous 12 months. The frequency of cyberbullying positively related to all 11 internalizing, externalizing, and substance use problems (odds ratios from 2.6 [95% CI, 1.7-3.8] to 4.5 [95% CI, 3.0-6.6]). However, victimization related more closely to rates of problems in adolescents that had fewer family dinners. Cyberbullying relates to mental health and substance use problems in adolescents, even after their involvement in face-to-face bullying is taken into account. Although correlational, these results suggest that family dinners (ie, family contact and communication) are beneficial to adolescent mental health and may help protect adolescents from the harmful consequences of cyberbullying. | null | minipile | NaturalLanguage | mit | null |
Felisberto Hernández
Felisberto Hernandez (October 20, 1902 – January 13, 1964) was an Uruguayan writer and pianist.
Background
Hernández was born in Montevideo, Uruguay. His father was from Tenerife (Canary Island). He was a self-taught pianist who earned a living playing in the silent-screen theaters and cafés of Uruguay.
Short stories
Hernández is considered to be the forefather of Magic realism, predating writers such as Gabriel García Márquez, Italo Calvino and Julio Cortázar, who all note Hernández as a major influence. His fiction often explores the secret vitality contained in inanimate objects.
Some of his most famous stories are: "The Balcony," "My First Concert," and "Daisy Dolls."
Selected works translated into English
Piano Stories, translated by Luis Harss, Marsilio Publishers, 1993
Lands of Memory, translated by Esther Allen, New Directions Press, 2002
Adaptations
Hernández' life and work was the subject of the short film Unmistaken Hands: Ex Voto F.H by the animation filmmakers the Quay Brothers. The short was inspired in particular by the Hernández short stories "The Balcony" and "The Flooded House" and is available to view as part of the British Film Institute's Blu-ray collection of the Quays films.
See also
List of Uruguayan writers
References
External links
Felisberto Hernandez
Category:1902 births
Category:1964 deaths
Category:Uruguayan male short story writers
Category:Uruguayan short story writers
Category:Uruguayan people of Canarian descent | null | minipile | NaturalLanguage | mit | null |
The present invention relates to a closure for an opening of large size in a pressure vessel, more particularly to a closure for such an opening in a canning retort, for example, the upper or lower opening in a canning retort.
Canning is widely used in the food processing industry, and consists of a process in which food is sealed into a metal container. The advantages of canning are many and well known. However, an essential step in the process is sterilisation at high temperature and pressure. This operation is carried out in retorts, which are large pressure vessels into which the cans are placed. Generally the retorts have openings at the top and bottom to facilitate loading and unloading, and these openings must be sealed during the sterilisation process. The doors or lids provided to seal these openings are large and heavy and may typically exceed a square meter in area. Various means have been developed for closing and sealing these doors and a particular known closure is described in U.S. Pat. No. 3,386,206. The door is movable across the opening and mounted on rollers. The door is first moved from a position in which it exposes the opening into a position in which it is spaced from the opening. The rollers are themselves mounted eccentrically on shafts rotatably mounted on the door by means of bearings. These shafts are then rotated and the relative eccentricity of the shafts and rollers causes the door to to move perpendicular to its plane and to seal the opening by pressing against a sealing ring in a recess in the sealing edge of the opening. In order to avoid damage to the sealing ring it is important for the perpendicular movement to take place without the door moving in its own plane. Such movement would scuff the sealing ring or pull it out of its recess. Separate means are provided to move the door from the position in which it exposes the opening and to rotate the shafts to bring about the sealing or locking of the door. For the first-mentioned movement, hydraulic or pneumatic cylinders may be provided or a rack and pinion or a wire drive. For the sealing operation, a further pneumatic or hydraulic cylinder is used.
The above-mentioned U.S. patent is directed in particular to a top closure. U.S. Pat. No. 3,417,896 discloses a similar bottom closure in which the door sealing or locking movement is again brought about by rotation of eccentric rollers. In this instance the detailed construction differs, in order to suit the upward sealing movement necessary in the case of a bottom closure, and to provide secure sealing on all sides of the door. In particular, the eccentric rollers are arranged to act as cam members bearing upwardly on the lower surface of the door.
The closures described in the above Patent Specifications operate satisfactorily in respect of keeping the door away from the sealing edge during movement of the door across the mouth of the opening, and sealing and unsealing displacement of the door only takes place in a direction perpendicular to the plane of the door. Thus these constructions avoid causing damage to the sealing ring in the sealing edge. However they incorporate a considerable number of operating parts. Consequently the number of components susceptible to failure is large. In addition, many of them are exposed to the difficult environmental conditions in the region of the openings in the particular case of canning retorts or pressure vessels. It is accordingly an object of the invention to provide a closure for an opening in a pressure vessel having a small number of operating parts and to provide an improved, effective and simple means for closing a large sized opening in a pressure vessel. | null | minipile | NaturalLanguage | mit | null |
“The child by reason of his physical and mental immaturity, needs special safeguards and care, including appropriate legal protection, before as well as after birth” UN Convention on the Rights of the Child
Tuesday, August 24, 2010
Timisoara Declaration on Life, Family and Freedom of Religion
The Alliance of Romania’s Families on August 21st launched a new declaration in support of life, family, parental rights and the right to freedom of religion. The declaration to be known known as the Timisoara Declaration was prepared along the lines of the Manhattan declaration.
The choice of Timisoara for launching the Declaration has historic resonances for the Romanian people being the location of the commencement of the Romanian revolution which brought about the end of totalitarian rule in Romania 21 years ago. The revolution which was started peacefully by a group of Christians who protested, publicly, the infringement of their rights by secular (communist) authorities started there almost 21 years ago and toppled the regime in a matter of days.
Now after 21 years according to a press release issued by the Alliance there is a new revolution in the same place. This time however it is a spiritual and of moral renewal. Though times have changed, obstacles and vicious opposition to Christian values continue this time within a European-wide system which claims to be democratic but nevertheless is motivated by a vitriolic secularist fundamentalism which threatens their historical and hard-won freedoms. The statement continues "Propelled and inspired by the actions of fellow Christians in the United States, the United Kingdom, and Australia, Romanian Christians have determined that the time has come for their voice to be heard in their own homeland and abroad. Through this Declaration they are professing the fundamental truths of the infallible Word of God as they relate to issues of crucial importance for the welfare of society and its survival, foremost among them the sanctity of life, the sanctity of marriage, religious freedom, and human dignity." “This is not a theological declaration or statement,” according to Mr. Bogdan Mateciuc, Executive Director of the Alliance who continued
“It is an expression of views on important social institutions and matters with which the world confronts itself, Romania included. These views are nonnegotiable. They are of Christian inspiration and have their roots in basic notions of morality and human decency. They are common to all cultures, major religions, and across time boundaries. They are shared by the overwhelming majority of Romania’s citizens, regardless of their Christian affiliation. It is a formidable Declaration which calls on the citizens of the city to involve themselves in the betterment of their society and country.”
“This is a crucial document,” according to Dr. Peter Costea, President of the Alliance.
“It affirms in direct and forceful terms the foundational pillars of what a sound society should be all about. Every Christian community around the world should issue a similar statement. Times are hard for those who profess their faith publicly. But Christians are citizens, too, and have rights. They should be exercised to better the world in which they live. By issuing this Declaration we express our solidarity with Christians in other countries who have issued similar declarations. Their forceful proclamations of the Truth in the public square have inspired and encouraged us, and we hope our action today will encourage them as well.”
The press release ends with an invitation to members of the world community to join with the Alliance in proclaiming the principles set out in the Declaration, loudly and unambiguously, by signing, disseminating and making the Declaration known.
Pat Buckley
I was born in Galway, Ireland where I attended first Scoil Fhursa and then St Ignatius (Jesuit) College. My family moved to Cork in 1960 and I spent my last year at the Christian Brothers College in Mc Curtain street Cork (CBC).
I came to Dublin in 1963 where I met and married my wife Philomena. We have lived in Dublin since then and have been blessed with seven children and 17 grandchildren (so far). When I finished school I studied architecture through the professional institutions and I am a retired Member of the Royal Institute of Architects of Ireland (MRIAI). I also hold a BSc. in psychology and political philosophy.
I currently lobby pro-life and pro-family issues at the United Nations in New York and Geneva and occasionally at the European Parliament and Council of Europe. I am a member of the pro-life, pro-family coalition operating within the international institutions and I am a consultant to the Society for the Protection of Unborn Children SPUC on UN and related matters.
Between 1978-85, as a married couple Philomena and I were involved in the presentation of Marriage Encounter Weekends and pre-marriage courses. We also represented Worldwide Marriage Encounter on a committee for the family in the Dublin Archdiocese. Between 1985-1988. I was appointed National Secretary and then President of the Catholic Secondary Schools Parents Association (CSPA). I have been lobbying pro-life issue at the UN for upwards of 12 years.
I am a past President of the National Association of Catholic Families (NACF)
Publications:
1997: Anthology of pro-life verse
IMAGES
I believe that I am allowed to use the images accompanying my blog and that they are licence- and royalty-free. However if the owner or the licensor disagrees, please contact me and I will remove it immediately. | null | minipile | NaturalLanguage | mit | null |
Pages
Monday, August 18, 2014
Help Third Wave Detroit's Business Idea Become a Reality
For the fourth year Hatch Detroit is giving one local entrepreneur the opportunity to win $50,000 to open up a storefront within the Detroit City limits to push forward their business idea. The four finalists for the public to vote on were announced this week and voting will end this Wednesday.
One of the businesses in the running is Third Wave Music, whose intent is to open the first musical supply store in Detroit since the city's decline. There is literally no place to get a drum stick if you break it before a show, or to pick up some new strings without driving into the suburbs. This is not practical for a lot of the working musicians in the city, especially when these issues come up last minute. Third Wave Detroit wants to change this and made an awesome video to better explain their idea and vision. Watch the video below for details on their business plan. I already believed in this business, but watching the video sealed the deal for me.
If you would love to see this idea come to fruition head over to HatchDetroit.com and vote once every 24 hours before the deadline this Wednesday, August 20th. Popular online vote is only half of the battle. The business still has to get up in front of a crowd and sell their idea to the judges on the 20th, but the popular vote gives them the competitive advantage that they may need to win. If you would like to attend the final ceremony click here for tickets to the event. In addition to the money, which comes by way of Comerica Bank, the
winner will also get legal, marketing, accounting and IT support from
the non-profit, Hatch Detroit.
We wish Third Wave Detroit the best of luck and hope to see them come out victorious. Take a moment and throw a vote their way! | null | minipile | NaturalLanguage | mit | null |
by Sayer Ji
USDA organic certification affords the U.S. consumer one of the only food quality protections available today, but does it really guarantee a product is chemical free?
What’s a consumer to do today? Between cause- and patently false-marketing, looking beneath the surface appearances of product packaging and advertising becomes a necessity, lest we harm ourselves or the environment unknowingly, or support industries that don’t have our best interests in mind.
You may already know about green-washing, pink-washing and so-called gene-washing (i.e. ‘natural’ labeled products containing GMOs), but prepare yourself for the next level of @%@#!% with “organic-washing.”
We hit upon this topic recently in our exposé on USDA organic baby formula containing a chemical ingredient used as a pesticide, but the problem extends to many other “certified organic” products and brands on the market.
For instance, recently my wife brought home a product by a generally good company, Plum organics baby, who deserves recognition for making some actually pure and organic products. The product is called “organic super puffs,” and describes itself as “fruit & veggie grain puffs,” bearing the reassuring “USDA organic” logo. [See the product here] If I wasn’t such a neurotic label reader I could have easily fallen for buying this product myself.
Nowhere on the seemingly wholesome product label is there an indication that it contains chemical ingredients. Even the Nutrition Facts panel doesn’t help. Zinc 15%. Vitamin E 15%. Looking good, right?
Nope. A more careful analysis of the presumably organic “ingredients” below the Nutrition Facts panel reveals the following enhancements:
Vitamins and Minerals: Tricalcium phosphate (Calcium), Ascorbic Acid (vitamin C),Ferrous Sulfate Monohydrate, Dl-alpha tocopherol (Vitamin E), Mixed Tocopherols for Freshness (Vitamin E), Vitamin A Palmitate, Cholecalciferol (Vitamin D).
We aren’t going to nit-pick about all of these inorganic vitamins and minerals, but there are two that we must say a word about. It is downright disturbing to find ferrous sulfate monohydrate (Elemental Iron) and dl-alpha tocopherol (Vitamin E) in any USDA certified organic product.
Ferrous sulfate is basically inorganic or ‘elemental’ iron. It is notorious for causing adverse symptoms as a supplement, including vomiting and constipation. When consumed in excess, as in the case of a child accidentally consuming their parents iron-containing supplements, elemental iron is the #1 cause of death from accidental poisoning in children under 6. A common justification for its use as a ‘nutrient’ in food is that in ‘small doses’ it can do no harm; the body, after all, is a ‘biofilter’ capable of dealing with a wide range of toxins, and iron is essential for health, right? Even if this is true, it should be a consumer/parent’s choice whether they are willing to take the risk, especially when higher quality iron supplements are available, such as glycine-bound iron. The fact remains that elemental iron is closer to a chemical in definition than a nutrient (nutrients are organically bound to amino acids, lipids, carbohydrates), and at the very least, it shouldn’t belong in a certified organic product because it misleads the consumer into thinking it is safe a priori. [Learn more about this substance by viewing its Material Data Safety Sheet]
Next up is dl-alpha tocopherol. This strange form of “vitamin E” is actually a petrochemically derived set of 8 synthetic isomers (known as a racemic mixture) which mirror the natural complex of 8 molecules found in the real vitamin E complex, but are believed to differ structurally and functionally. For toxicology citations on the potential adverse health effects of synthetic dl- form vitamin E view our research citations on the topic: Dl-alpha tocopherol.
Is it just me, or should it be forbidden to include a synthetic, petrochemically produced form of a “vitamin” within a product intended for babies that bears the USDA certified organic logo?
With the USDA organic logo increasingly being slapped onto products that don’t represent the ethos or quality of organic, sustainable farming, either the USDA certification process needs to undergo reform, or we need another type of certification altogether. Better yet, grow your own high-quality, truly organic food, or work with local growers and producers that are doing just this. After all, we can see through recent GMO labeling initiative defeats that when it comes to enacting reform, we are going to have to do it from both top down and the bottom up, i.e. you can vote and enact immediate change with your dollar and your fork!
This article first appeared at GreenMedInfo. Please visit to access their vast database of articles and the latest information in natural health.
| null | minipile | NaturalLanguage | mit | null |
“More than anything else, it sends a wrong message which is loud and clear to all Judges down the line not to cause any displeasure to the Executive lest they should suffer. Is this not a threat to the independence of the judiciary?” | null | minipile | NaturalLanguage | mit | null |
Q:
How to use more than two "WHERE" clause? MYSQL ERROR
I am using it to do with PHP.
ERROR:-
You have an error in your SQL syntax; check the manual that corresponds to your MySQL server version for the right syntax to use near '' at line 1
EDIT 1:
$SQLQUERY = sprintf("SELECT pd_serial FROM product_details WHERE pd_model_type=%s AND pd_model_name=%s AND pd_model_version=%s AND pd_product_group=%s LIMIT 1",
GetSQLValueString($modeltype, "text"),
GetSQLValueString($modelname, "text"),
GetSQLValueString($modelversion, "text"),
GetSQLValueString($modelgroup, "text"));
$QUERYEXEC = mysql_query($SQLQUERY, $dacreint) or die("OOPS! Please try again.");
while ($QUERYFETCH = mysql_fetch_array($QUERYEXEC))
{
$pdserial = $QUERYFETCH['pd_serial'];
}
EDIT 2:
while ($QUERYFETCH = mysql_fetch_array($QUERYEXEC))
{
$pdserial = $QUERYFETCH['pd_serial'];
}
$SQLQUERY = sprintf("SELECT product_serial_no FROM products WHERE product_serial_no = '$product_serial_no'");
$TCcount_QE = mysql_query($SQLQUERY, $dacreint) or die(mysql_error());
A:
You should put strings within single quotes. And make sure you have escaped those string values using mysql_real_escape_string() or similar function
SELECT pd_serial FROM product_details WHERE (pd_model_type='%s' AND pd_model_name='%s') AND (pd_model_version='%s' AND pd_model_group='%s') LIMIT 1
UPDATE 1
while ($QUERYFETCH = mysql_fetch_array($QUERYEXEC))
{
$pdserial = $QUERYFETCH['pd_serial'];
}
// let's comment out the following line
// $SQLQUERY = sprintf("SELECT product_serial_no FROM products WHERE product_serial_no = '$product_serial_no'");
// and modifying it as:
$SQLQUERY = sprintf("SELECT product_serial_no FROM products WHERE product_serial_no = %s", GetSQLValueString($product_serial_no, "text"));
$TCcount_QE = mysql_query($SQLQUERY, $dacreint) or die(mysql_error());
| null | minipile | NaturalLanguage | mit | null |
Q:
How to make a method (function) call of parent form from a child form
I write the application in C++ (CLR). It's an application with forms.
I have 2 forms: MainForm and ExtensionsForm. MainForm is shown when the program is started. When you click on the button, ExtensionsForm will be created.
Also I have these files: MainForm.h, MainForm.cpp, ExtensionsForm.h, ExtensionsForm.cpp.
To create form ExtensionsForm, I've added this to beginning of the file MainForm.h:
#pragma once
#include "ExtensionsForm.h" // <-- added
In MainForm in button onClick event handler to open ExtensionsForm I've added this:
ExtensionsForm^ extensionsForm = gcnew ExtensionsForm();
extensionsForm->ShowDialog();
And this code works correctly.
But I need to make some changes in the appearance of the MainForm after clicking the button in ExtensionsForm. How can I implement this correctly?
Thank you in advance!
My attempt
I've created the method (function) in MainForm and I tried to call this method in ExtensionsForm. I can use the constructor to pass the reference, but anyway I have an error:
How to solve this?
My solution
I've included all *.h files in Main.cpp file. Inside Main.cpp I have this:
#include "MainForm.h"
#include "ExtensionsForm.h"
After that, if I want to make changes on another form (for example, I can press the button on the ExtensionsForm and changes must appear on the MainForm), I can do just this:
I can create public method inside MainForm.h, which makes some changes on this form. My example:
public: void updateButton(int amount, int maxAmount) {
button->Text = amount + " / " + maxAmount;
}
public: void updateTextBox(String^ text) {
textBox->Text = text;
}
To show a new form, I can use the method inside MainForm.cpp. My example:
#include "MainForm.h"
#include "ExtensionsForm.h"
namespace FileFinder {
[STAThreadAttribute]
int main(array<System::String ^> ^args)
{
Application::EnableVisualStyles();
Application::SetCompatibleTextRenderingDefault(false);
FileFinder::MainForm mainForm;
Application::Run(%mainForm);
return 0;
}
void MainForm::buttonExtensions_Click(System::Object^ sender, System::EventArgs^ e) {
ExtensionsForm^ extensionsForm = gcnew ExtensionsForm();
extensionsForm->Owner = this;
extensionsForm->ShowDialog();
}
}
Method buttonExtensions_Click implemented (defined) here. Also it has definition in MainForm.h:
private: void buttonExtensions_Click(System::Object^ sender, System::EventArgs^ e);
This works perfectly, but you must implement (define) your method in *.cpp file, which includes your *.h file or inside this *.h file (the definition must exist). Also you can see extensionsForm->Owner = this; in this method. This is necessary for the next step.
After this things, you can use something like this inside ExtensionsForm.h:
private: void buttonConfirmExtensions_Click(System::Object^ sender, System::EventArgs^ e) {
MainForm^ mainForm = (MainForm^)this->Owner;
mainForm->updateButtonExtensions(checkedExtensionsCount, extensionsCount);
mainForm->updateTextBoxExtensions(textBoxExtensionsString);
this->Close();
}
You can get your MainForm by Owner and use defined public methods of this form. That's all.
A:
This was solved by relocating some code to .cpp file.
Hans Passant, thanks for the advice.
| null | minipile | NaturalLanguage | mit | null |
Black fly (Simulium sp) composition, daytime biting activity and possible onchocerciasis infection in north-east, India.
Pupal stages of Simulium were collected and identified from various breeding habitats of twelve locations in northeastern India. Simulium flies, while attempting to land on human were collected between 07:00-17:00 hrs to understand the biting pattern. Seven species belonging to three sub-genera, Eusimulium (1), Gomphostilbia (1) and Simulium (5) belonging genus Simulium were encountered. Out of total seven species recorded, S. (E) aureohirtum, S. (G) tenuistylum and S. (S) rufibasis were predominant and shared 30.3%, 29.9% and 27.6% of total collection. Stream breeding habitat contributed 47.3% of total catch and was found to be preferred breeding habitat (p < 0.0001). S. (S) christophersi and S. (G) tenuistylum were recorded for the first time from the northeastern region of India. Simuliids biting rhythm showed bimodal pattern and were more active during sunny day (p < 0.0001). Microscopic dissection of simuliids (n = 266) did not incriminate simuliids as vector of onchocerciasis. | null | minipile | NaturalLanguage | mit | null |
Background
==========
The squamous cell carcinoma (SCC) of the rectum is a rare tumor with a not yet clarified pathogenesis mechanism and a rather aggressive clinical behavior. It has a slight female predominance and prognosis worse than that of adenocarcinoma. Radical surgery is the cornerstone of treatment. However, the role of chemotherapy and radiation in the pre- and postoperative period remains to be elucidated. In the present study a case of a metastatic pure SCC of the rectum to the liver is presented. Aggressive surgical treatment as well as combined neoadjuvant and adjuvant chemotherapy and radiation is described, suggesting a possible positive survival and prognostic effect.
Case presentation
=================
A 39-year-old female patient was admitted to our Medical Center\'s surgical department with a 2 month history of altered bowel habits, perianal pain and rectal bleeding. Colonoscopy demonstrated a circumferentially developing ulcerated tumor 8 cm above the dentate line, extending 4 cm proximally. The colonoscope was advanced past the tumor, performing a total colonoscopy, while biopsies from the lesion were obtained and examined histologically, revealing a non-keratinized squamous cell carcinoma of the rectum. Abdominal computed tomography and chest radiograph were negative for metastatic disease. However, a transanal endoscopic ultrasound demonstrated the spread of the tumor beyond bowel\'s wall in the perirectal space, necessitating institution of neoadjuvant therapy. The patient underwent 1 session of neoadjuvant chemotherapy with 5-Fluorouracil (1000 mg/m^2^/d) plus Mitomycin and 5 sessions of radiotherapy (totally 20 Gy). Two days after the last session of radiotherapy a laparotomy was performed. Intraoperative findings included invasion of the posterior vaginal wall from the tumor and an abdominoperineal resection and a concomitant total hysterectomy-oophorectomy were carried out. Histology reported the presence of two ulcerated lesions (1 × 2 cm and 2 × 4 cm) in middle and lower rectum both squamous cell carcinoma of the rectum, invading the bowel wall and the adjacent vaginal wall. The surgical specimen contained 15 lymph nodes, all negative for metastatic disease (T4 N0 M0, stage IIb) and the resected margins were free of tumor. Postoperatively, adjuvant chemotherapy (1 session of 5-FU plus Mitomycin) and 23 sessions of radiotherapy (totally 45 Gy) were administered.
Five months after tumor resection, liver metastasis was demonstrated in a follow-up abdominal computed tomography and a central hepatectomy was performed. Histology confirmed the presence of a metastatic rectal squamous cell carcinoma to the liver (Figure [1](#F1){ref-type="fig"}, [2](#F2){ref-type="fig"}). Adjuvant chemotherapy consisting of 6 sessions of 5-FU plus Cisplatin (100 mg/m^2^/d) was applied. Fortunately, the patient had an uneventful postoperative course and is alive 18 months after.
{#F1}
{#F2}
Discussion
==========
Since the first report of rectal SCC by Raiford in 1933 \[[@B1]\], few cases have been reported in the literature. A PubMed search revealed a total of 55 case reports published since 1943 in the English literature (Table [1](#T1){ref-type="table"}). Surprisingly and in contrast to the English reports, a Russian paper in 1984 reviews the clinical manifestations of 107 cases of SCC of the rectum \[[@B8]\].
######
Cases of SCC of the rectumreported in the literature.
**Author** **Date** **Age** **Gender** **Treatment** **Outcome**
------------------------------ ---------- --------- ------------ -------------------- ----------------------
Catell & Williams \[2\] 1943 63 M LAR Alive 3,5 years
Wiener et al \[3\] 1962 52 F APR Died at 1 year
Comer et al \[4\] 1971 34 F APR Alive at 13 years
\'\' N/A N/A N/A N/A
Williams et al \[5\] 1979 N/A N/A N/A N/A
Lasser et al \[6\] 1980 65 F N/A Alive at 3 years
\'\' 48 F N/A Alive 8 months
\'\' 54 M N/A Alive 17 months
Vezeridis et al \[7\] 1983 56 M APR Intraoperative death
\" 44 M APR Died on 9 po day
\" 61 F CT Died at 4 months
\" 66 F CT & RT Died at 15 months
\" 62 F APR Died at 13 months
Mel\'nikov et al \[8\] 1984 107 CASES REPORTED
Lafreniere & Ketcham \[9\] 1985 N/A N/A N/A Alive at 2 years
Piggot & Williams \[10\] 1987 N/A N/A APR Alive 1 year
Woods \[11\] 1987 N/A N/A N/A N/A
Singh & Wong \[12\] 1987 N/A N/A N/A N/A
Prener & Nielsen \[13\] 1988 N/A N/A 16 CASES REPORTED N/A
Schneider et al \[14\] 1992 43 F Surgery & RT Alive 7 months
\" 44 M Surgery & RT N/A
\" 69 F Surgery & RT Alive 6 months
Petrelli et al \[15\] 1996 62 M APR \-
Martinez et al \[16\] 1996 40 M LAR & RT & CT Alive 18 months
Copur et al \[17\] 2001 N/A N/A APR & CT & RT N/A
Frizelle et al \[18\] 2001 9 CASES REPORTED
Gelas et al \[19\] 2002 47 F APR & RT Alive at 16 years
\" 63 M APR & CT & RT Died at 14 months
\" 70 F APR & RT Died at 18 months
\" 93 M RT Died at 4 months
\" 45 F LAR & CT & RT Alive at 6 months
\" 43 F LAR & CT & RT Alive at 2 years
Anagnostopoulos et al \[20\] 2005 75 M APR & CT Alive at 14 months
LAR = Low Anterior Resection; APR = Abdominoperineal Resection; CT = Chemotherapy; RT = Radiation Therapy; F = Female; M = Male ; N/A = not available.
Rectal SCC is a rare tumor. The incidence of this malignancy has been reported to be 0.25 to 1 per 1000 colorectal carcinomas \[[@B4],[@B5],[@B7],[@B21]\]. In 1979, Williams *et al*. \[[@B5]\] described three criteria that are useful today in diagnosing a primary colorectal SCC: first, metastases from other sites (e.g. lung SCC) must be ruled out; second, a squamous-cell-lined fistula must not involve the affected bowel and third, a SCC of the anus extending to the rectum must be excluded.
It seems that the pathogenesis of this malignancy is not yet clear and many theories exist \[[@B18]-[@B20]\]: the pluripotent stem cell theory supports that squamous cell carcinomas arise within poorly differentiated tumors \[[@B22]\]; the theory of proliferation of uncommitted basal cells into squamous cells, which undergo malignant transformation due to chronic injury of the glandular epithelium \[[@B23]\]; the theory of chronic irritation from ulcerative colitis \[[@B24]\], radiation exposure \[[@B25]\] and human papilloma virus \[[@B26]\], resulting in squamous metaplasia of the epithelium; and lastly, the theory of squamous differentiation of adenomas and adenocarcinomas.
Clinical manifestations of SCC of the rectum are similar to those of adenocarcinoma: change in bowel habits, pain, tenesmus and rectal bleeding, anorexia and weight loss. The natural history of this malignancy is not clearly defined due to the rarity of the disease. From data presented in Table [1](#T1){ref-type="table"}, SCC of the rectum has a slight female predominance and the mean age at the time of diagnosis is 54.2 years in women and 59.4 years in men. Prognosis is worse than that of adenocarcinoma and there are some features that probably predict a poor outcome: nodal involvement, small cell or undifferentiated histological characteristics, ulcerated or annular carcinomas, grade 3 or 4 and stage IV disease \[[@B18]-[@B20]\].
Immunochemistry is helpful in diagnosing SCC using several markers (cytokeratins AE1/AE3, 34BE12, CK5, involucrin, etc) in order to differentiate it from other small cell undifferentiated tumors \[[@B20]\].
The definite therapy is surgical resection of the affected rectum, either by low anterior resection (LAR) or by abdominoperineal resection (APR), depending on the location of the tumor and the patient\'s preference. An informed consent and a detailed discussion of complications, adjuvant therapy, recurrence and survival-death statistics are definite prerequisites before any operation. Copur *et al*. \[[@B17]\] propose the use of the squamous cell carcinoma antigen (SCC Ag) as a tumor marker for following up patients. In his study the SCC Ag was elevated at the time of recurrence and showed a partial response to combination chemotherapy, with a decrease in the serum level.
The role of neoadjuvant radiotherapy (local control of the disease and downstaging) or adjuvant chemo and/or radiotherapy remains to be elucidated together with understanding the natural history of the disease. It seems that adjuvant therapy can be used in patients with nodal involvement, poorly differentiated cancers and metastatic disease without any proven effectiveness in outcome. Juturi *et al*\[[@B27]\] report that adjuvant combined chemotherapy reduced the size of liver metastasis in a patient with a SCC of the descending colon. However, large randomized prospective trials are needed to measure efficacy and benefits on survival and prognosis of complementary therapies.
Conclusion
==========
SCC of the rectum is a rare and aggressive malignancy with a similar clinical presentation pattern, but a worse prognosis than that of adenocarcinoma, especially if positive nodes are involved or poor histological features are reported. Surgical resection is the treatment of choice, although radiation and chemotherapy can be useful in treating node-positive patients and advanced disease. It is possible and remains to be studied that aggressive combined chemo-radiotherapy is required pre- and postoperatively in order to control this aggressive malignancy.
Competing interests
===================
The author(s) declare that they have no competing interests.
Authors\' contributions
=======================
**TT, LS**and **ND**carried out the surgical procedures and contributed to the design of the study; **TT**and **AM**gathered the data, drafted the manuscript and critically revised it; **EC**performed the histological analysis of all surgical specimens and provided histological sections as figures for the manuscript; **JV**and **VS**revised and finally approved the manuscript for been published.
All authors read and approved the manuscript.
Acknowledgements
================
An informed consent of the patient for this publication has been signed.
| null | minipile | NaturalLanguage | mit | null |
INTRODUCTION
============
Long latency auditory evoked potentials (LLAEPs) can be used in clinical practice as an objective measure of cognitive processes to assess auditory abilities, such as discrimination, memory, attention and detection of stimuli. Long latency AEPs are thought to be one of the most promising electrophysiological tests for evaluation of central auditory nervous system (CANS) dysfunction and/or changes.
Long latency AEPs enable the assessment of auditory information processing over time.^([@B1])^ These potentials are generated by several systems, primarily the thalamocortical and corticocortical auditory pathways, the primary auditory cortex and associative cortical areas,^([@B2])^ and reflect thalamic and cortical activity in particular. Long latency AEPs result from the superposition of all electrical currents within the brain; therefore, accurate identification of neural generators is difficult. Neural generators are simultaneously activated and each individual CANS structure is responsible for the processing of one specific aspect of a given stimulus or information.^([@B3])^
Long latency AEPs are represented by a series of positive and negative waves.^([@B4])^ While some LLAEPs are sensitive to physical characteristics of the eliciting stimulus (exogenous potentials P1, N1, P2 and N2), others reflect cognitive processes, such as attention and stimulus categorization (endogenous potential P300).^([@B5])^
The P300 component, or cognitive potential, is a positive potential elicited by the recognition of a rare stimulus (oddball paradigm) within a series of frequent stimuli and corresponds to the largest positive wave after the N1-P2 complex.^([@B6],[@B7])^ P300 depends upon some abilities, such as attention, discrimination and memory, and reflects cortical activity.^([@B8])^
P300 latency is the most commonly used parameter to infer potential auditory processing changes in research settings. However, clinical applicability is limited by the variability in P300 latency reference values. Studies describing updated P300 latency reference ranges are lacking.
P300 latency values between 250 and 350ms were established in adults by Kraus et al.^([@B9])^ however, wider latency ranges, of 220 to 38ms, were also reported.^([@B5])^ Latency ranges and protocol variability may explain why P300 is not routinely used in clinical practice. Still, P300 is a promising assessment tool that can be employed across several disciplines in different subject areas. Its application as an objective ancillary measure in early recognition of cognitive dysfunction and dementia,^(10)^ assessment of altered emotional states^([@B11])^ and evaluation of cochlear implants and hearing aids,^([@B12])^ among other fields, has been described. Therefore, novel studies are warranted to accurately determine normality parameters that may support the routine use of P300 for early recognition of several CNS changes in clinical settings.
OBJECTIVE
=========
To establish reference intervals for cognitive potential P300 latency using tone burst stimuli.
METHODS
=======
Twenty-eight subjects aged between 18-59 years were evaluated, 15 of which were men.
The inclusion criteria were as follows: age between 18 and 60 years, normal hearing ability, lack of auditory complaints, no middle ear pathology, no continuous-use medication and ability to understand test procedures. Patients suffering from hearing loss and chronic diseases were excluded.
Patients were submitted to external auditory meatus inspection, pure tone audiometry and acoustic immittance testing prior to cortical potential investigation.
Audiometry was performed in sound-treated booth using Audiotest 330 audiometer. Air conduction thresholds were investigated at 250, 500, 1,000, 2,000, 3,000, 4,000, 6,000 and 8,000Hz using the descending-ascending method. Normal hearing individuals were defined as those with three-frequency (500, 1,000 and 2,000Hz) pure tone averages ≤25 dB HL (decibels hearing level).^([@B13])^
Tympanometric curve and acoustic reflex assessment was based on acoustic immittance testing performed using middle ear analyzer AT 235 and 226Hz probe tone. Contralateral acoustic reflexes were investigated bilaterally at frequencies of 500 to 4,000Hz. Only subjects with type-A tympanogram and preserved acoustic reflexes were included in the sample.^([@B14])^
Long latency AEPs were recorded in a silent room using a two-channel device (*Masbe*, Contronic). Patients remained awake throughout the procedure while comfortably seated on an armchair.
The international 10-20 system^([@B15])^ was used for electrode placement. Surface electrodes were attached to the forehead (Fpz, ground electrode), vertex (Cz, active electrode) and mastoids (reference electrodes M1 and M2, left and right mastoid respectively) with Ten20 conductive paste and micropore tape. Inter-electrode impedance ≤5 Kohms was ensured prior to testing.
Patients were instructed to keep their eyes open, avoid eye movement and note deviant (rare) random stimuli within a series of similar (frequent) stimuli, which should be mentally counted. Stimuli were delivered via ER-3A insert earphones with 80 dB HL intensity.
Frequent and rare stimulus frequency corresponded to 1,000Hz and 2,000Hz tone bursts containing 50 and 100 cycles, respectively, with 20% rise and decay time and trapezoidal envelope. Stimuli were presented in a rare-frequent (oddball) paradigm with 80 and 20% probability respectively. Pulse frequency was 0.8 pulses per second (pps).
P300 waves were investigated using binaural stimulation to prevent patient fatigue. A minimum of two tracings containing 30 rare stimuli each were recorded per patient for increased reliability; tracings were then added together and a single resulting wave acquired. Electrical signals were filtered with 01Hz high-pass and 20Hz low-pass filters. A 1,000ms time window was employed.
P300 latency values were recorded at the highest peak (*i.e*., maximum wave amplitude). The protocol employed for P300 investigation in this study is described in [chart 1](#t1){ref-type="table"}.
Chart 1P300 investigation protocolPatient statusAlertCounting method (rare stimuli)MentalElectrode placementGround electrode (Fpz), active electrode (Cz), reference electrodes (M1 and M2)Electrode impedance≤5 KohmsProbeInsert earphonesStimulationBinauralStimulus intensity80 dB HLPresentation paradigm20% of rare stimuli80% of frequent stimuliTotal number of stimuli300Frequent stimulus1,000HzRare stimulus2,000HzDuration50 cycles (1,000Hz)100 cycles (2,000HZ)Rise and decay time20%EnvelopeTrapezoidalSpeed0.8 pps (pulses per second)FiltersHigh-pass: 0.1HzLow-pass: 20HzWindow1,000ms
Data collected were arranged in spreadsheets using Microsoft Excel software for analysis and comparison. Statistical analyses were performed by an expert statistician. Data normality was assessed using the Lilliefors and the Shapiro-Wilk tests. Variables were compared using the Wilcoxon test. The level of significance was set at 5% (p\<0.05), with a 95% confidence interval.
The procedures and assessments in this study were carried out as part of a partnership between a university and the *Clínica Cóser*.
All participants signed the Informed Consent Form (ICF) as proof of their agreement with procedures involved in the study. This project was approved by the Research Ethics Committee (CEP) of *Universidade Federal de Santa Maria* (RS); protocol number CAAE: 25933514.1.0000.5346, committee opinion no. 612.754.
RESULTS
=======
Mean age of participants was approximately 35 years. Latency and amplitude data of all variables considered are displayed in [table 1](#t2){ref-type="table"}.
Table 1P300 latency values (ms)P300nMeanMedianMinimumMaximumStandard deviationRE28305.5257305.7800248.0800359.080029.45203LE28304.4814307.1650243.0300346.470028.06774[^2]
P300 component latency did not differ significantly between the left and right ears ([Table 2](#t3){ref-type="table"}).
Table 2Comparison of P300 latency values recorded from the right and left ears using binaural stimulation nPercentz scorep value \*P300 RE and P300 LE2347.82609-0.0000001.000000[^3][^4]
DISCUSSION
==========
P300 is currently thought to be a promising assessment tool for detection of central changes. Despite interdisciplinary applicability, P300 continues to have limited use in clinical settings, possibly due to high levels of variability in the test, including latency variability.
Long latency AEPs depend on maturation of peripheral and central structures, a fact that must be taken into account when interpreting test results^([@B16])^ given the relation between response amplitudes and the number of synapses in the cerebral cortex.^([@B17])^ Cognitive potential P300 is known to be present in children from 5 to 7 years of age, albeit with reduced amplitude and increased latency, with complete maturation occurring around adolescence.^([@B5],[@B18])^ Cortical potential values at 14 and 16 years of age are equivalent to those described in adults, according to Steinschneider et al.^([@B19])^ Participant age in this study (18 years or over) ensured CNS maturation.
P300 latency values of approximately 305ms were documented in this study. Latency values did not differ between the left and right ears; data were therefore grouped and the values compared to similar studies based on standard deviations -- *i.e.*, studies reporting similar standard deviations were assumed to be in agreement with findings presented here.
Wave amplitude is thought to be of limited clinical value in P300 assessment; hence, this parameter was not measured. P300 values very widely between studies, both in test and control groups,^([@B20])^ and may range from 1.7 to 20uV.^([@B21])^ According to some studies, amplitude is not a relevant parameter in data analysis.^([@B22],[@B23])^
Mean P300 latency in this trial corresponded to 305ms. Similar P300 latency values (298.1ms) were described in another study^([@B24])^ involving patients aged 18 to 53 years. Mean P300 values of 313.86, 320 and 298ms (*i.e*., consistent with values in this trial) were also reported elsewhere.^([@B4],[@B25],[@B26])^ However, discrepant P300 latency values of approximately 341ms (Cz electrode)^([@B27])^ and 352.2ms^([@B20])^ have been documented. Participant age in those studies ranged from 7 to 34 years; therefore latency variations may have reflected the maturation process.
Minimum and maximum P300 values in this study (243.03 and 359.08ms) are consistent with previously reported latency ranges of 246 to 361ms,^([@B24])^ but differ from other ranges (220 to 380ms) described.^([@B28])^ Still, results of this study are in agreement with P300 ranges documented in the international literature (250 to 350ms),^([@B9])^ with greater similarities between minimum values. Maximum P300 latency values of 380ms reported by McPherson^([@B5])^ were not recorded in this trial.
Differences in equipment, patient attention level, patient age, time of data collection and stimulus counting method, among other factors, may explain latency variation between studies.^([@B28])^ The lack of a consensus and the infrequent use of this test in clinical settings have been pointed out as by Frizzo et al.^([@B29])^ as potential factors behind the wide variability in cortical potential induction and capture methods among professionals. Electrode placement at Cz or Fz and physiological differences between patients are some of the factors potentially interfering with cortical potential capture. The subjective nature of P300 recognition and sampling may also contribute to the wide variation found in literature.^([@B6])^
The major scientific contribution of this study lies in the scarcity of updated P300 normative values in literature.^([@B26],[@B30])^ Data presented are expected to aid clinicians in the interpretation of test results, provided similar parameters are used. Further studies, including meta-analyses, are warranted for more accurate determination of P300 reference values, thereby supporting the evidence-based early diagnosis of central auditory changes.
CONCLUSION
==========
Mean P300 latency values obtained using the protocol described in this study corresponded to 305ms, with minimum and maximum acceptable latency values of 247.5ms and 362.5ms respectively (mean±2 standard deviation).
[^1]: Conflict of interest: none.
[^2]: RE: right ear; LE: left ear.
[^3]: \*p value (p\<0.05).
[^4]: RE: right ear; LE: left ear; z-score: z-score test.
| null | minipile | NaturalLanguage | mit | null |
Q:
Unable to send percent character "%" in the SMS body in Kannel
I have kannel installed on my Server and I am using it to connect to an SMS Gateway using SMPP. When I am trying to send an SMS with "%" the SMS is not sent. But without "%" it works fine. Thanks
I have found a solution by converting the message to HTML using urlencode($message)
Cheers ^_^
A:
I believe kannel is XML and as such, you must escape a percentage %.
Try replacing % with %
| null | minipile | NaturalLanguage | mit | null |
Reverend Sharpton says African-Americans have a vested interest in what goes on in Africa. He says he wants to make sure that Liberia does not suffer the same bloodbath as Rwanda and Sudan.
"We want to be able to update ourselves as to what is actually going on on the ground," he explained. "Second, we are meeting with the leaders of the various opposition groups in Ghana and then meeting with President Taylor in Liberia to urge a continuous cease-fire, and to extradite a democratic election process."
Rev. Sharpton, a candidate for the Democratic presidential nomination, dismissed criticism that he's using the Liberian crisis as a campaign photo opportunity, saying he has traveled to several African countries over the years. "So, I have a record of dealing with matters on the African continent when no one in this country would deal with them," Rev. Sharpton said.
Despite the war crimes indictment against Liberian President Charles Taylor, Rev. Sharpton would not say whether he supports President Bush's call for Mr. Taylor to step down.
"Clearly we are concerned about the atrocities that have been alleged against President Taylor," he said. "However, to say 'step down' and not be clear on what would be the replacement and what would be the process, and what is the will of the Liberian people is something we want to talk about; and we want to hear first-hand from opposition leaders and from President Taylor, as well as from people in the peace process."
He said he supports sending U.S. peacekeeping troops to Liberia, but does not support unilateral U.S. involvement.
Reverend Sharpton praised President Bush's recent Africa trip, but said the continent needs much more. | null | minipile | NaturalLanguage | mit | null |
A new transnasal approach to nasolabial cyst: endoscopic excision of nasolabial cyst.
Nasolabial cyst (NC) is one of the midface lesions that are seen rarely. Nasolabial cyst is generally seen in females typically on the fourth and fifth decades and localized unilaterally. Diagnosis usually depends on clinical evaluation. Sublabial excision is the classic method, but endoscopic marsupialization is suggested in current literature. An NC that is totally excised endoscopically is introduced in this article. This is the first case of NC excised endoscopically that is described in English literature. | null | minipile | NaturalLanguage | mit | null |
The proposed research will examine the role of Ca2+-dependent cadherin mediated cell-cell adhesion in the induction of prolactin (PRL) gene expression. There are three general aims: 1. Cadherin expression in GH3 cells. We have preliminary data for multiple cadherin expression in GH3 cells. This work will be extended in order to confirm our preliminary findings, as well as to generate full length cDNA clones and specific antibodies. The specific aims are: 1. Cloning and sequencing of PCR- generated fragments of rat N-cadherin, E-cadherin, and P-cadherin from GHG3 cell cDNA in order to confirm their identity. 2. Use of these partial cDNA clones as probes to examine cadherin expression in GH3 cells by Northern blot. 3. Isolation of full length cDNA clones for those cadherins expressed in GH3 cells. 4. Use of sequence information to generate specific antibodies against rat expressed in GH3 cells. This will be done on a contractural basis. 5. Use of specific cadherin antibodies to examine cadherin protein expression and localization in GH3 cells and related pituitary tumor cell lines. II. Effects of experimentally induced disruption of cell-cell adhesion on PRL gene expression. We have reproducibly observed a close correlation between CaCl2-induced cell-cell adhesion and CaCl2-induced PRL gene expression in GH3 cells. We propose to utilize experimentally induced inhibition or disruption of cell-cell contacts for the purpose of examining the requirement of cell-cell adhesion in the CaCl2 induction of PRL gene expression. Cell-cell adhesion will be inhibited or disrupted in the following ways: 1. Introduction by stable transfection of an N-cadherin gene containing a large deletion of the extracellular domain. Based on previous work with this gene, it is expected to behave as a dominant negative mutant cadherin gene, which will disrupt the ability of endogenous cadherins to form cell-cell junctions. 2. Competitive inhibition of the homophilic binding site by introduction of peptides corresponding to the homophilic binding site of the extracellular domain. 3. Effectively increasing c=src activity, since c-src phosphorylates cadherins and associated proteins, and induces the disassembly of adherins junctions. III. Examination of cadherin expression and function in the pituitary gland. We propose examine of cadherin function in the normal pituitary gland. This section has two specific aims: 1. Expression of cadherins in adult and fetal rat pituitaries and; 2 Effect of a dominant negative cadherin mutation that is targeted to lactotrophs in transgenic mice on lactotrope abundance and position within pituitary, and on content of pituitary PRL. The proposed research represents the first examination of cadherin function in the pituitary gland, both in terms of its morphogenesis and of the differentiated function of lactotropes. These studies may provide the first demonstration of a role for cadherins in the expression of a specific hormone. Since cadherins have tumor suppressor activity, future work may also reveal a role for cadherins in the control of estrogen-induced proliferation of lactotropes. | null | minipile | NaturalLanguage | mit | null |
Q:
Missing sap.h. how to solve this issue?
My dev environment:
os : window 7 64bit
IDE : Tizen 2.4
installed packages :
2.3.1 Mobile (whole packages)
2.3.1 Wearable (whole packages)
Tizen SDK tools (whole packages)
Extra ( certificate extension, Tizen Wearable Extension for 2.3.1)
and I want to use sap (samsung accesory package). So I included sap.h in my app code, but an error occurred when the project is built.
"fatal error: 'sap.h' file not found"
how to solve my issue?
thanks.
A:
I was facing this same problem, even with all the Samsung SDK installed.
Go to Project > Properties > C/C++ Build > Tizen Settings and check "Samsung-sap" option.
That's it! All solved!
Regards.-
| null | minipile | NaturalLanguage | mit | null |
Efficacy and tolerance of a 12-week treatment with inhaled formoterol in patients with reversible obstructive lung disease.
Formoterol, a new beta 2-agonist, and salbutamol were given as aerosols twice and four times daily, respectively, to patients with reversible obstructive lung disease. The study was controlled and double blind, and continued for 12 weeks. Ninety-nine patients from five study centers were included and 89 patients could be properly evaluated. The formoterol-treated patients used significantly less rescue medicine (salbutamol aerosol) and had higher morning PEF values. For the other efficacy variables (daytime FEV1.0, evening PEF, patient and investigator global evaluations, night sleeping time) and tolerance (side effects noted by patients, blood and urine laboratory values, ECG, patient and investigator global evaluation), there were no significant differences between the formoterol- and the salbutamol-treated groups. | null | minipile | NaturalLanguage | mit | null |
Q:
Can you teach in higher education with a master's degree?
I have a Bachelor's degree in journalism, and I'm starting a Master's degree program next year. I'd like to teach in a university - is it possible to do so with only a Master's?
A:
In the unedited post, you mentioned portuguese, so I'll take a chance and guess brazilian. It is statistically likely, you don't seem to be from portugal, but that still leaves portuguese speaking african countries...
Considering public universities in/near SP, RJ, MG, the whole south and some capitals, you won't even be able to apply, they require PhDs all around, with high competition. In the federal universities farthest away from these centers (like AP, RO, RR) a masters would be enough in most cases. These openings are probably available even with the recession, not many candidates willing to relocate, and, without PhD, the salary will be kinda low... (~ 4k BRL)
On the other hand, if you go to the private universities, yes, totally. With the exception to some of the most prestigious (like PUC, Mackenzie, etc), that require PhDs. In the smaller ones, most of the professors do not even have masters. Low pay, no research and tons of courses tho...
If you combine both and consider a small private university farthest away from the economic centers, they might not even consider you, saying that you are overqualified....
A:
Your question is short and missing much information, so I will try to cover a few basics.
In general, in many countries, having a Phd is required. The requirement is not always a university rule, but mostly an internal department decision, or a factor of previous experience.
There are many fields in which a Phd is not required, such as Business, Art, Architecture, Music, etc. While many of those fields also have what is referred to as a 'terminal degree', meaning the highest degree in their respective field which may not be a Phd, those departments also will hire non-Phd faculty.
This will also vary depending on what type of school. Community college typically will be willing to accept a broader range of people. Universities may be teaching or research focused. In that case, you may have a masters with a high level of research experience, and a research university will welcome it.
Industry is also greatly important in some fields. In something like Industrial Design, having a bachelors or masters with 7 years of product design at Apple may very well carry you far.
I am not familiar with journalism in particular, but would imagine if you were a journalist at a well known paper, a school focusing on sending students to industry and not academia may look favorably on you.
So how do you become a teacher? In my opinion, your best chances are either getting a masters degree, then working at a renowned journalism company, build a reputation and a name, and over a few years start looking into Universities. Otherwise, pursue a Phd. Having a Phd is not a guarantee for a teaching position either, so you may very well end up spending 6 years on your Phd, not having worked in industry, and find it difficult to get a job.
| null | minipile | NaturalLanguage | mit | null |
NFL: NOV 14 Patriots at Steelers
14 November 2010: Pittsburgh Steelers wide receiver Antwaan Randle El (82) charges on to the field for the start of the Sunday night NFL game between the New England Patriots and the Pittsburgh Steelers at Heinz Field in Pittsburgh, Pennsylvania. | null | minipile | NaturalLanguage | mit | null |
Most healthy people experience little variation in their heart rates at rest, but a new study shows that normal resting heart rates can differ between individuals by an astonishing 70 beats per minute.
The findings challenge the conventional approach to taking this simple vital sign — doctors typically check resting heart rate at every visit, but only to make sure it falls in a "normal" range. Instead, the new results suggest that monitoring how an individual's resting heart rate fluctuates over time may tell physicians more about his or her health than comparing a snapshot of his or her heart rate to that of the general population.
"What is normal for you may be unusual for someone else and suggest an illness," said study co-author Giorgio Quer of the Scripps Research Translational Institute in La Jolla, California. Viewing a person's heart rate data over the long term "may prove to be a rich source of information" for evaluating their health, Quer said.
For example, some studies have suggested that increases in a person's resting heart rate could be an early sign that the individual has an infection. However, the current study did not examine whether changes in heart rate were linked with changes in health, which should be the subject of future research. "It is worth considering that a rising [resting heart rate] may serve as an early warning sign of a physiologic change," the authors wrote in the study, published today (Feb. 5) in the journal PLOS One .
Related: Top 10 Amazing Facts About Your Heart
Resting heart rate is perhaps the most fundamental vital sign. It is also among the most temperamental. While 70 beats per minute (bpm) is considered normal in healthy adults, athletes often have resting heart rates far below that, and pregnant women typically have resting heart rates a good deal above the average. Meanwhile, resting heart rates below 65 bpm and above 90 bpm have both been linked to higher risk of cardiovascular disease , according to previous research.
Physicians have long recognized the limitations of this vital sign and generally agree that a heart rate — viewed in isolation and compared to the average — "provides very little useful information about the current health of an individual, unless well out of the expected range," Quer wrote in the study.
Now, with the advent of smartwatches and fitness bands, it may be possible to track an individual's resting heart rate over time and tailor its interpretation to that specific patient.
Quer and his colleagues tested this theory by analyzing heart rate data from wearables worn for about a year by more than 92,000 individuals. They came across resting heart rates as low as 40 bpm and as high as 109 bpm — an unexpectedly wide range. Factors such as age, sex, body mass index (BMI) and average daily sleep duration accounted for less than 10% of this variation in heart rate between individuals.
But even among those with rather extreme resting heart rates, the authors found that the values for each individual seldom fluctuated by more than 10 bpm over the course of the year. Quer concluded that, even if there is no such thing as a "normal" heart rate, there is most certainly a normal resting heart rate for each individual.
"It was surprising to see how vastly different the average resting heart was for different people … but how stable an individual’s resting heart rate can be over time," Quer told Live Science.
As access to wearable sensor technology increases — more than one-fifth of U.S. consumers now own a smartwatch or wearable device capable of capturing heart rate — Quer suspects that even healthy individuals may ultimately benefit from continuous monitoring over the conventional, "snapshot" approach to taking vitals. "This may become a way to monitor both healthy and higher-risk people in a more precise, individualized manner," Quer said. "The technology to do this already exists," he said. However, much more research is needed, including studies that follow people for many years, before scientists can "truly understand" the value of resting heart rate, he added.
Originally published on Live Science . | null | minipile | NaturalLanguage | mit | null |
A Moran Voter in Montclair
For now, Fred Lambe is for Brian Moran.
Lambe, who lives in Montclair in Prince Williams County, said he voted for Moran today but might change his mind come November. He said he wants a governor who will best address transportation and the state budget deficit.
"I look foward to the debates," he said. "Depending how each addresses the deficit and how it will impact me tax-wise, that's when I could leave my party line."
Lambe, who commutes to work in Arlington, said wants a governor who supports mass transit and multiple transportation options.
The 50-year-old said he chose Moran because of the Democrat's experience. McAuliffe, he said, had plenty of money but few refreshing ideas. | null | minipile | NaturalLanguage | mit | null |
Introduction
============
Autosomal dominant hypercholesterolemia (ADH) is a relatively common autosomal dominant condition with a prevalence of around 1 in 500 in the United Kingdom population. ADH is associated with a greatly increased risk of early onset cardiovascular disease; this risk is reduced by treatment with statin drugs (Neil et al. [@b14]). Clinical diagnosis in the United Kingdom is guided by the Simon Broome criteria based on cholesterol levels, presence of tendon xanthomata, family history of premature cardiovascular disease and hypercholesterolemia, and molecular testing to assign a diagnosis of definite or possible familial hypercholesterolemia (FH) (Scientific Steering Committee on behalf of the Simon Broome Register Group [@b18]). Most cases of ADH are caused by mutations in the *LDLR* gene, which encodes the low-density lipoprotein receptor (LDLR) protein, which binds LDL particles at the cell membrane and internalizes them for hepatic processing and excretion. Rare autosomal dominant gain-of-function mutations in *PCSK9* (proprotein convertase subtilin-kexin-type 9) can cause a severe form of ADH. A pathogenic mutation at residue 3527 in *APOB* (apolipoprotein B), the specific ligand for binding of LDL to the LDLR, has been known for over two decades to cause the autosomal dominant condition familial defective apolipoprotein-B100 (FDB), a form of ADH (Soria et al. [@b19]), and a second variant in this region, Arg3558Cys, has also been associated with hypercholesterolemia (Pullinger et al. [@b16]). In a recent study, exome sequencing identified two further variants in this region of *APOB*, each in one unrelated ADH family (Motazacker et al. [@b13]). In individuals with these mutations, LDL with the defective APOB has reduced affinity for the LDLR, impairing LDL clearance and causing hypercholesterolemia with a phenotype similar to that caused by *LDLR* mutations. *APOB* is a large and highly polymorphic gene, complicating identification of pathogenic variants. Screening of this gene in ADH families has therefore mainly focussed on the region of exon 26 around residue 3527.
The detection rate for pathogenic mutations in ADH varies depending on the diagnostic criteria and molecular techniques used, from 50% to 60% with stringent clinical criteria and full gene screening, to around 20--30% in standard lipid clinic populations (Taylor et al. [@b20]). A comprehensive study sequencing known genes in a cohort of children with suspected ADH in the Netherlands detected mutations in 95% of cases, suggesting that a minimum of 1 in 20 FH families has a causative mutation which is yet to be identified (van der Graaf et al. [@b9]).
Exome sequencing has become established as an effective tool for gene identification in Mendelian disease, particularly in combination with linkage analysis, as it provides a comprehensive list of candidate variants in linked genetic loci of any size, without any prior assumption of disease mechanism (Gilissen et al. [@b7]). We present here results of linkage and exome sequencing in a family with ADH, providing further evidence of the efficacy of this approach in this common treatable disease.
Methods
=======
Family members were recruited under ethics approval REC 2002/6451. Sequencing of *LDLR*, *APOB* exon 26, and *PCSK9* in I:2 identified no causative mutations. Libraries were prepared with the Agilent (Santa Clara, CA) SureSelect All Exon 50 Mb kit followed by Illumina (San Diego, CA) 100 bp paired-end sequencing (see Supplementary methods online). Read mapping used BWA (Li and Durbin [@b11]), and variant calling used GATK (McKenna et al. [@b12]). Analysis of *APOB* used the RefSeq sequence NM_000384.2. Genome-wide genotyping was carried out using Illumina Human CytoSNP-12 v2.1 beadchips; the data were analyzed with Merlin linkage analysis software (see Supplementary methods online) (Abecasis et al. [@b1]). LDL from three affected family members (I:2, II:2, and II:5), one unaffected family member (I:1), and an unrelated control was purified from plasma by single ultracentrifugation (Chung et al. [@b4]). Wild-type and mutant peptides were quantitated by mass spectrometry (see Supplementary methods online).
Results
=======
The pedigree is shown in Figure [1](#fig01){ref-type="fig"}, with lipid profiles given in Table [1](#tbl1){ref-type="table"}. Linkage analysis was carried out in all individuals in generations I, II, and III shown in Figure [1](#fig01){ref-type="fig"}, assigning affected status to the four individuals with high cholesterol and tendon xanthomata (I:2, II:1, II:2, and II:5), and unknown clinical status for II:4 with high cholesterol but no xanthomata. Two additional family members in whom DNA but no phenotypic data were available were included in the genotyping to assist with haplotype identification. Overall, 20 linkage regions were identified with maximum log of odds (LOD) score 1.2, covering a total of 245 Mb, approximately 8% of the genome.
######
Lipid profiles of family members prior to initiation of lipid-lowering therapy
Individual Age at measurement BMI Total cholesterol (mmol/L) Triglycerides (mmol/L) HDL (mmol/L) LDL (mmol/L)
------------------------------------ -------------------- ----- ---------------------------- ------------------------ -------------- --------------
I1[1](#tf1-1){ref-type="table-fn"} 71 24 5.4
I2 69 26 11.5 2.1 0.9 9.5
II1 50 24 8.3 0.9 1.9 6
II2 46 24 8.4 0.9 1.9 6.1
II3 57 26 5.6 1 1.3 3.8
II4 43 28 7.3 1.2 1.4 5.4
II5 49 27 8.3 1 1.9 5.9
III1 22 21 3.9 2.2 1.2 1.7
Affected individuals are shaded in gray. BMI, body mass index; HDL, high-density lipoprotein; LDL, low-density lipoprotein.
A full lipid profile was not available prior to lipid-lowering therapy, which was initiated for secondary prevention of coronary vascular disease in this individual some years after his myocardial infarction.
{#fig01}
Exome sequencing generated an average of 176 million reads for each of seven family members (I:1, I:2, II:1, II:2, II:3, II:4, and II:5 in Fig. [1](#fig01){ref-type="fig"}), of which 83% mapped within targeted regions or the 200 bp flanking these regions. Average coverage within the targeted regions was 64-fold (range 55- to 87-fold), and 86% of targeted bases were covered at minimum 10-fold. A total of 54,745 variants were identified in the seven individuals. Capillary sequencing of a subset of coding variants confirmed correct calls of 146 genotypes at 21 loci with no false positives. From the exome sequence data 4932 variants were identified within loci identified by linkage analysis, of which 1275 were nonsynonymous, essential splice site, truncating or frameshift variants. Of these, 41 segregated with the disease (i.e., were heterozygous only in the affected individuals), and 12 were novel or had minor allele frequency (MAF) less than 0.01 in dbSNP (Sayers et al. [@b17]), 1000 genomes project database (The 1000 Genomes Project Consortium [@b21]), and the NHLBI exomes project (Exome Variant Server, NHLBI Exome Sequencing Project \[ESP\], Seattle, WA \[<http://evs.gs.washington.edu/EVS/>\]). The 12 rare or novel segregating variants identified within linked loci are shown in [Table S1](#SD1){ref-type="supplementary-material"} together with a summary of known functions of these genes. Eleven of the genes have known functions that are not related to lipid metabolism; the 12th was the missense variant p.Arg50Trp (c.148C\>T) in *APOB* (NM_000384.2), which is a likely candidate for disease causation. Capillary sequencing confirmed the presence of this variant in the individuals with hypercholesterolemia and tendon xanthomata (I:2, II:1, II:2, and II:5) and its absence in all other available family members (I:1, II:3, II:4, and III:1). *APOB* Arg50Trp was absent from dbSNP, NHLBI ESP, and 1000 genomes project data. *In silico* tools were used to predict its effect on protein structure and function: Polyphen-2 predicted Arg50Trp to be probably damaging (score 1.0) (Adzhubei et al. [@b2]), the SIFT prediction was deleterious (score 0) (Kumar et al. [@b10]), and the Condel prediction was also of deleterious effect (score 0.762) (González-Pérez and López-Bigas [@b8]). This arginine residue is conserved in 27 of 29 mammals and in seven of eight of the lower species with 1:1 orthologues of this region of *APOB* identified by the Ensembl database. Overall, these *in silico* predictions suggest a functional effect of this variant. Haplotypes within the *APOB* locus are shown in Figure [1](#fig01){ref-type="fig"}.
*APOB* encodes the protein component of the LDL particle, forming a shell around a core of lipid molecules. LDL is cleared from the circulation by interaction with the LDLR, and this interaction has been shown to be disrupted by the FDB-causing mutations Arg3527Gln, Arg3527Trp, and Arg3558Cys (Gaffney et al. [@b6]; Pullinger et al. [@b16]). One of the methods used to study the effects of these FDB mutations is determination of the mutant:wild-type protein ratio in the circulation. Defective interaction between LDL and the LDLR results in reduced clearance of mutant LDL, while wild-type LDL is cleared normally from the circulation. Wild-type LDL therefore represents less than 50% of circulating LDL. For the Arg3527Gln mutation, the mutant:wild-type ratio has been found to be around 70:30, while for the Arg3558Cys mutation the ratio averaged 59:41 using dynamic laser light scattering (Pullinger et al. [@b16]). We determined the abundance of mutant and wild-type LDL in individuals with Arg50Trp and control samples using mass spectrometry (Fig. [2](#fig02){ref-type="fig"}). The mutant peptide was present at concentrations 2.5- to 3.5-fold higher than wild-type peptide in all three affected individuals, giving a ratio of mutant:wild-type peptide between 72:28 and 78:22. The technique used to generate these ratios was different from previously reported techniques and therefore the ratios may not be directly comparable, but these results suggest that mutant APOB accumulates in the circulation as with other hypercholesterolemic *APOB* mutations, most likely due to defective hepatic uptake and clearance.
![Mass spectrometry of APOB peptides. Following digestion with GluC, wild-type peptide (NVSLVCPKDATRFKHL[R]{.ul}KYTYNYE) was present in all samples, and mutated peptide (NVSLVCPKDATRFKHL[W]{.ul}KYTYNYE) was present only in affected individuals II:5, I:2, and II:2 and not in unaffected family members or the unrelated control. The abundance of the two peptides was quantified from the peak intensities using synthetic peptides in three replicate experiments (A). In all patient samples, the mutant peptide was present at 2.5- to 3.5-fold greater concentration than wild-type peptide (B).](mgg30001-0155-f2){#fig02}
Discussion
==========
In recent years, exome sequencing of large numbers of individuals has revealed many thousands of coding variants in every genome, and distinguishing pathogenic variants among these has proved a significant challenge. However, combining exome sequencing with linkage data in this family reduced the number of candidate variants by 91%, and applying knowledge of the inheritance pattern of the disease allowed further reduction by focusing on segregating variants. Increasing availability of databases of rare coding variation improves detection of novel variants, although the databases may contain genuine pathogenic variants in some phenotypes, and must therefore be used with caution when excluding variants from further analysis. This is particularly likely with conditions such as hypercholesterolemia, as "control" individuals from these databases may not have had their lipid profile analyzed. Interpreting the potential functionality of variants identified by exome sequencing is frequently complex, especially where candidate variants are found within genes about which little is known. In this family, the most significant variant was within *APOB*, a gene which has been extensively studied in the context of hyperlipidemia, allowing *ex vivo* functional studies to be designed which were able to establish a difference between the wild-type and mutant proteins, lending strong support to this variant as the causative mutation in this family. A recent report of exome sequencing in ADH patients demonstrated retrospectively that individual I:2 from this family was included in another research cohort; *APOB* Arg50Trp was detected in this individual in this project, but no segregation or functional data was generated, and the mutation was presented as a variant of unknown significance (Futema et al. [@b5]).
Previous studies have used dynamic laser light scattering to establish the proportions of wild-type and variant APOB. This technique relies on the variant of interest being present on the same haplotype as a common polymorphism, which is detected by binding of the MB19 monoclonal antibody. For higher frequency mutations such as Arg3527Gln and Arg3558Cys this was an effective technique, but it is not applicable to rare variants in *APOB* because many families will be wild-type for the MB19 polymorphism, as with the family presented here. Mass spectrometry was therefore used for quantification of wild-type and mutant peptide in this family, to show allele imbalance for the circulating levels of APOB. This technique should also be adaptable to study LDL obtained from families with other rare *APOB* variants, in order to establish the range of mutations in *APOB* which cause hyperlipidemia. Previous studies have used mass spectrometry to quantify *APOB* in human samples (Agger et al. [@b3]), but this study represents the first report of the use of mass spectrometry to determine the ratios of wild-type and mutant proteins. Other studies have used trypsin to digest APOB, but trypsin cleaves at arginine residues and therefore a single peptide encompassing the Arg50Trp variant could not have been generated using the standard digestion approach. Digestion with GluC was used instead which generated two peptides from LDL of affected individuals with identical length, but differing in one amino acid (NVSLVCPKDATRFKHL[R]{.ul}KYTYNYE and NVSLVCPKDATRFKHL[W]{.ul}KYTYNYE).
In order to determine accurately the ratio of mutant to wild-type peptide, internal standards with known concentrations were used (ThermoFisher Scientific, Waltham, MA). The standard peptides had identical sequences to the peptides of interest, but contained a heavy labeled lysine causing a mass shift of 8 Da. The standard peptides were spiked into the digests and used to calculate the abundance of the endogenous peptides and determine the ratio of mutant to wild-type peptide. This allowed the ratios to be determined accurately and with high precision, with coefficients of variance (CVs) for the individual peptide abundances between 3% and 10% and CVs for the mutant:wild-type ratio between 6% and 12%. The small CVs indicate that using standard peptides provided satisfactory correction for technical variation resulting from the slight difference in the amino acid composition of the mutant and wild-type peptides, such as differential ionization or recovery.
Exon 3 of the *APOB* gene is 116 base pairs in length and contains little reported variation: one synonymous SNP (rs12720850) at residue 43, and two rare variants, Tyr56His (rs150496608) and Ala73Asp, both of which have been found in a single individual in the 6500 exome sequences in the NHLBI Exome Variant Server. The synonymous SNP rs12720850 is the only variant in exon 3 found in the 1000 genomes project database. This lack of nonsynonymous variation suggests an important functional role for this region of the protein. The APOB protein is structurally organized into five alternating β-sheet and α-helical domains. Mutations currently known to cause ADH are located in exon 26 in the β2 domain, which interacts directly with LDLR (Prassl and Laggner [@b15]). Exon 3 forms a small part of the first domain (βα1), which is a compact globular structure. This domain is predicted to direct hepatic assembly of lipoprotein molecules, as well as to affect the interaction of LDL particles with lipases and macrophage scavenger receptors. Detailed information on the specific role of exon 3 in these processes is not available, but the high level of amino acid conservation in this exon, together with the predicted damaging effect of Arg50Trp on protein function, and its absence in control datasets, suggest that this exon and in particular this nucleotide substitution are functionally important and the likely cause of hypercholesterolemia in this family. Two mechanisms could account for this. First, conformational changes in this highly conserved region of APOB could affect the interaction of LDL with LDLR and thereby increase levels of circulating LDL. Second, the mutant APOB protein could be protected from degradation prior to LDL particle assembly, stimulating the release of increased numbers of mutant very low density lipoprotein particles (VLDL) into the circulation, with the downstream effect of increasing LDL concentration. Triglyceride (and therefore VLDL) levels in the affected members of this family were within the normal range despite elevated LDL (Table [1](#tbl1){ref-type="table"}). This suggests that reduced hepatic clearance of LDL due to defective interaction with LDLR is more likely than increased production of mutant lipoprotein particles, but further investigation of the exact mechanism in this family is beyond the scope of this article.
Haplotypes around the *APOB* locus are shown in Figure [1](#fig01){ref-type="fig"}. The background haplotype on which the Arg50Trp mutation lies is identical in I:1 and I:2; it is possible that this has occurred due to the distant consanguinity in the family, which would indicate that the Arg50Trp mutation arose within the three generations above generation I in this pedigree. This would be consistent with rare variants of large effect being of recent origin in evolutionary terms. However, within 1000 genomes data, 17.4% of individuals of British origin (GBR) shared this background haplotype, and the presence of this haplotype in I:1 and I:2 may therefore be unrelated to the consanguinity in the family.
This study represents the first report of a mutation in *APOB* outside exon 26 causing ADH, suggesting that a wider range of APOB domains can influence the interaction between APOB and LDLR than was previously considered. In order to determine which regions of this large and highly polymorphic gene can be mutated to cause ADH, sequencing of all 29 coding exons of *APOB* will be required in large patient cohorts using the increased sequencing capacity of high-throughput platforms. Follow-up of rare and novel variants in families using the mass spectrometry protocol presented here will enable distinction of variants causing ADH from nonfunctional polymorphisms. This is likely to increase the number of families with a detectable molecular cause for ADH, enabling cascade screening in these families and potentially increasing the understanding of the interactions between the LDL particle and the LDLR.
We acknowledge funding from the MRC Clinical Sciences Centre (to T. J. A., A. K. S., and A. P. S.), the Imperial BHF Centre of Research Excellence (to S. S. A., and T. J. A.), the Imperial Biomedical Research Centre (to T. J. A.), and from a Wellcome Trust Fellowship (to E. R. A. T.).
Conflict of Interest
====================
None declared.
Supporting Information
======================
Additional Supporting Information may be found in the online version of this article:
**Data S1.** Online supplementary methods.
**Table S1.** Rare (MAF \<0.01) segregating missense/frameshift variants mapping to regions of linkage.
[^1]: Current address: London Research Institute, Cancer Research UK, Clare Hall Laboratories, South Mimms, Herts, EN6 3LD, United Kingdom
[^2]: **Funding Information** This study was supported by MRC Clinical Sciences Centre (to T. J. A., A. K. S., and A. P. S.), the Imperial BHF Centre of Research Excellence (to S. S. A. and T. J. A), the Imperial Biomedical Research Centre (to T. J. A.), and from a Wellcome Trust Fellowship (to E. R. A. T.).
| null | minipile | NaturalLanguage | mit | null |
Beauty Advice: How to Keep Skin and Hair Healthy This Winter
Protect Yourself from Harsh Weather
There’s no denying that winter is the toughest season on your skin and hair. Wind, rain, snow, and dry air all have a negative effect on your skin, especially on your face. Try these tips to keep yourself healthy and looking good in the coming months.
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Adjust Your Shower Routine
We all have hair washing habits. But if you’re willing to make some changes in the winter, there are relatively simple ways to ensure that your locks don’t get too damaged this season. First, consider washing your hair less often. This may seem counter intuitive, but it actually helps keep the natural oils that protect your hair in place rather than clearing them out with shampoo. Also, try showering with warm water instead of a blistering hot spray. Overheated water can do harm to already sensitive hair. (A lower shower temp helps keep your skin from getting too dry as well, so it’s a double win!)
Having excessively dry skin can cause problems all over your body. But you can stay moisturized as the weather attempts to ruin your skin. Take a bath with a few drops of olive oil mixed in. Pick up an all-over body lotion that’s specifically designed to fight winter dryness. Wear rubber gloves while you wash the dishes to protect the skin on your hands. If you normally moisturize your face at night, consider doing it in the morning too before you step out into the wind.
It’s easy to slip into eating comfort foods all winter, but remember that a nutritious, vitamin-rich diet will help your skin and hair. And don’t forget about water! Hydration from within will help you win the fight against dryness. If you can’t do cold water when it’s cold outside, try drinking tea or hot water with lemon. For foods, stock up on vegetables and fruits, and consider adding a multivitamin to your daily routine. | null | minipile | NaturalLanguage | mit | null |
Health & Medicine Events in Berlin
Heart Failure Congress 2010
Heart Failure Congress is a world renowned conference which is dedicated to all the professionals involved in the wide-ranging problems concerned with heart failure.Date : 29-05-2010 ~ 01-06-2010Venue : ICC Berlin
XXXIst International Congress of the ISBT
The XXXIst International Congress of the ISBT is a major event that provides a comprehensive overview of the recent advances in transfusion medicine.Date : 26-06-2010 ~ 01-07-2010Venue : ICC Berlin
Frontiers in CardioVascular Biology
Frontiers in CardioVascular Biology is intended for providing a ground-breaking platform for the exchange of ideas and expertise in cardiovascular science, in Europe.Date : 16-07-2010 ~ 19-07-2010Venue : Charité - Universitätsmedizin Berlin
Disclaimer : The content on Trade shows/Exhibitions/Conferences given on this site is informative in nature and has been gathered from various sources.
We do not hold any responsibility of miscommunication or misinformation regarding the venue / date etc of the Trade show / Exhibitions/Conferences
mentioned here. Kindly confirm the dates / venue etc of the Trade Fairs / Exhibitions/ Conferences from the relevant authorities for last minute changes. | null | minipile | NaturalLanguage | mit | null |
Pyrosequencing on a glass surface.
We demonstrate the use of open-surface microfluidics to sequence DNA by pyrosequencing at the plain hydrophobically coated surface of a microscope glass cover slip. This method offers significant advantages in terms of instrument size, simplicity, disposability, and functional integration, particularly when combined with the broad and flexible capabilities of open-surface microfluidics. The DNA was incubated on superparamagnetic particles and placed on a hydrophobically coated glass substrate. The particles with bound DNA were moved using magnetic force through microliter-sized droplets covered with mineral oil to prevent water evaporation from the droplets. These droplets served as reaction "stations" performing pyrosequencing as well as washing stations. The resequencing protocol with 34-mer single-stranded DNA (ssDNA) was used to determine the reaction performance. The de novo sequencing was performed with 51-mer and 81-mer ssDNA. The method can be integrated with previously shown sample preparation and PCR into a single sample-to-answer system on a plain glass surface. | null | minipile | NaturalLanguage | mit | null |
February 12, 2007 – FlaLawhttps://www.law.ufl.edu/flalaw
University of Florida Levin College of LawMon, 22 Feb 2016 20:06:23 +0000en-UShourly1https://wordpress.org/?v=4.7Leonard Riskin Brings Mindfulness to Teaching of Dispute Resolutionhttps://www.law.ufl.edu/flalaw/2007/02/leonard-riskin-brings-mindfulness-to-teaching-of-dispute-resolution/
Mon, 12 Feb 2007 18:36:28 +0000http://www.law.ufl.edu/wpflalaw/?p=1429After more than 20 years at the University of Missouri School of Law, where he worked as director of the Center for the Study of Dispute Resolution (CSDR), Leonard L. Riskin has relocated to Gainesville.
Last week, as temperatures in Columbia, Missouri hovered near freezing, Riskin sat back in a chair in his office at the University of Florida Levin College of Law and smiled. Outside, the sun was shining and the temperature was rising toward 70 degrees.
“This is a terrific law school,” Riskin replied when asked why he came to UF Law. “There are lots of great people on the faculty, great students, a great dean.” Then, Riskin added: “And I like avoiding the ice and snow.”
A noted authority in alternative dispute resolution, Riskin began teaching his first classes at UF Law in January. He teaches the course “Negotiation, Mediation, and Other Dispute Resolution Processes,” and a one-credit pass/fail lab course attached to that course on “Mindfulness.”
Under his direction, the CSDR distinguished itself as the premier law school dispute resolution center in the nation. Riskin has written several books and numerous articles on alternative dispute resolution, articles on law and medicine and torts, and essays for popular magazines. In recent years, he has written about the benefits of mindfulness meditation for lawyers and mediators. He also has been chair of the sections on Law and Medicine and Dispute Resolution of the Association of American Law Schools.
Riskin has been teaching mindfulness meditation to law students, lawyers and mediators since 1999. He describes mindfulness as “a particular way of paying attention—moment to moment without judgment—to whatever passes through the mind or through any of the senses.”
It’s of particular value to lawyers and law students, he said, to help them deal better with stress and to help them perform better. Riskin noted there’s a great deal of anxiety and depression in the legal profession, from law students to lawyers and judges.
“It also can help people perform better by increasing their ability to be calm and to focus moment-to-moment while they’re doing any of the activities that a lawyer does like listening or negotiating or advocating,” he explained.
Riskin has taught mindfulness meditation to law students, law faculties, and lawyers throughout the United States and abroad. While he acknowledges meditation is not for everybody, greater awareness of meditation across society as whole has led to a growth in its use in many more areas in recent years, including medicine and athletics, as well as in large corporations and law firms.
Riskin said, “I was interested in trying to address a lot of the unhappiness and suffering that I saw in the legal profession—in law school and in practice. And I thought that some of the suffering was attributable to the adversary process, and to the fact that the adversary process was the model for law school education bred a lot of misery. Education in alternative dispute resolution and mindfulness can help address this problem.”
The prevalence of alternative dispute resolution in Florida was a factor that attracted Riskin to UF. Alternative dispute resolution has been utilized by the Florida Court System to resolve disputes for over 30 years, starting with the creation of the first citizen dispute settlement center in Dade County in 1975. Since then, the uses of mediation and arbitration have grown as the Florida Legislature and judiciary have created one of the most comprehensive court-connected mediation programs in the country. “Florida is a terrific laboratory for studying dispute resolution,” he said.
Riskin’s principal emphasis is on teaching courses in dispute resolution and mindfulness, in addition to writing a book on mindfulness for lawyers. In the meantime, he and his wife, Catherine Damme (she goes by the name of Casey), are enjoying their first winter in Gainesville, along with their two border collies, Barney and Matilda. Their house is just a 10-minute walk from the law school.
“I like it a lot,” Riskin said. “It’s been very friendly and stimulating. And the weather’s been terrific.”
]]>Gift Establishes Endowment to Honor Former UF President Criserhttps://www.law.ufl.edu/flalaw/2007/02/gift-establishes-endowment-to-honor-former-uf-president-criser/
Mon, 12 Feb 2007 18:33:29 +0000http://www.law.ufl.edu/wpflalaw/?p=1425In a tribute to former University of Florida President Marshall Criser, fellow UF Levin College of Law alumnus Lewis Schott (BA ’43, LLB ’46) of Palm Beach, Fla., has given $600,000 to the university to create a permanent lecture series.
The gift, announced last week, will be used to establish an endowment fund for the series to be named the Marshall M. Criser Distinguished Lecture Series at UF’s Levin College of Law.
“The goal of the speaker series is to host two prestigious national and international speakers annually on topics of particular interest to law students,” said Robert Jerry, dean of the law school.
Criser served as president of UF from 1984 to 1989 and was appointed by then-Gov. Jeb Bush to be a founding member of the newly formed UF Board of Trustees in 2001. He served as chairman of that board until he stepped down in 2003 to become chairman of Scripps Florida Funding Corp., where he served until Dec. 21, 2006.
During his legal career, Criser spent 31 years as an attorney in the Palm Beach law firm of Gunster, Yoakley, Criser & Stewart before coming to UF. After his presidency at UF he practiced law in Jacksonville until he retired as a partner of the national firm McGuireWoods. Criser now resides in Gainesville.
“Marshall Criser has devoted a major part of his life to the University of Florida,” said Schott. “As president, trustee, healthcare advocate, legal counsel, state regent and student he has played many roles. It is an honor to be able to continue his influence at UF by establishing this lecture series in his name.”
Criser earned his bachelor’s degree in business administration from UF in 1949 and his law degree in 1951. He also has served as a trustee for the UF Law Center Association and as president of the Florida Bar. “The outstanding leadership Marshall Criser has shown throughout his career provides an example for the aspirations we want our students to hold,” said Dean Jerry. “In honoring Marshall with the named lecture series, Lewis Schott has also again enhanced the law school in a way that will enrich the academic experience of our students.”
Schott’s gift is eligible for matching funds from the state of Florida’s Major Gifts Trust Fund, which could increase the speaker series endowment to more than $1 million.
A longtime contributor to UF, Schott gave $100,000 to the law school in 2004 to honor his late wife, Marcia Whitney Schott. The two earned law degrees from UF in 1946. The college’s courtyard is named in her honor.
]]>Scholarship and Activities: Christopher Sloboginhttps://www.law.ufl.edu/flalaw/2007/02/scholarship-and-activities-christopher-slobogin/
Mon, 12 Feb 2007 15:43:53 +0000http://www.law.ufl.edu/wpflalaw/?p=1790Stephen C. O’Connell Chair; Associate Director, Center on Children and Families • Co-authored a chapter titled “Federal Prosecutorial Power and the Need for a Law of Counts” in Joan MacLeod Heminway, ed., Martha Stewart’s Legal Troubles.
]]>Scholarship and Activities: Michael Seigelhttps://www.law.ufl.edu/flalaw/2007/02/scholarship-and-activities-michael-seigel/
Mon, 12 Feb 2007 15:42:41 +0000http://www.law.ufl.edu/wpflalaw/?p=1788Professor • Co-authored a chapter titled, “Federal Prosecutorial Power and the Need for a Law of Counts” in, Joan MacLeod Heminway, ed., Martha Stewart’s Legal Troubles.
]]>Scholarship and Activities: Pedro Malavethttps://www.law.ufl.edu/flalaw/2007/02/scholarship-and-activities-pedro-malavet/
Mon, 12 Feb 2007 15:41:39 +0000http://www.law.ufl.edu/wpflalaw/?p=1786Professor • Appointed to a term on the Association of American Law Schools Membership Review Committee.
]]>CAREER SPOTLIGHT William S. Henry (JD 95), The Florida Bar Young Lawyers Division Liaison to UF Lawhttps://www.law.ufl.edu/flalaw/2007/02/career-spotlight-william-s-henry-jd-95-the-florida-bar-young-lawyers-division-liaison-to-uf-law/
Mon, 12 Feb 2007 15:32:51 +0000http://www.law.ufl.edu/wpflalaw/?p=1774As a law student at the University of Florida, Bill Henry kept himself busy with leadership positions in organizations throughout law school. He served as the managing editor and student works editor for the Journal of Law and Public Policy, was vice president of the Board of College Councils, and treasurer of the Law College Council. He was also treasurer of Phi Alpha Delta and a member of the John Marshall Bar Association.
Today, in addition to being the liaison to UF for The Florida Bar’s Young Lawyer Division, Henry serves as the hiring attorney for his law firm, Burke, Blue, Hutchison, Walters & Smith, a position that provides him with insight into how law students can best position themselves to land a job when they graduate.
“Employers certainly look at any leadership or community involvement type position,” he said by telephone from his Panama City office. “One of the things that we do look at, in addition to people who did well in school, we also look for folks who are outgoing and are interested in becoming involved and taking those sort of leadership roles.”
Emphasis on community involvement and leadership continues for attorneys at the firm, Henry explained. While many firms base compensation and bonuses strictly on productivity, Henry’s firm takes a broader view and rewards attorneys who take on more community involvement activities. “It enhances your profile and provides recognition in the community which benefits the firm,” he said.
In addition to presenting programs at UF Law to help students prepare for entering the profession, The Florida Bar’s Young Lawyers Division annually awards scholarships, giving out 10 $2,000 scholarships to law students throughout the state last year. Information on these scholarships and other YLD programs is available on their website at http//www.flayld.org/. | null | minipile | NaturalLanguage | mit | null |
The Frenchman was left out of Spurs' match-day squad during last week's defeat to Newcastle United after he was knocked unconscious by Belgian forward Romelu Lukaku's knee in their stalemate with Everton. He was also not part of the Europa League squad that beat Sheriff Tiraspol last Thursday.
After the incident at Goodison Park, Andre Villas-Boas tried to substitute Lloris but he adamantly refused and played the last 20 minutes of the game - a decision that was widely condemned.
However, after failing a concussion test during the week he wasn't risked at White Hart Lane for the matches on Thursday or Sunday.
The 26-year-old, signed from Lyon in August last year, has been a huge hit since his arrival, earning praise for his punching ability as well his speed and awareness off his line.
He has kept an impressive seven clean sheets in Spurs' first 11 games in the 2013/14 campaign. And, France will want him at his best tomorrow night in Ukraine as the side attempt to book their ticket to next year's World Cup in Brazil.
If he comes through both matches unscathed, Lloris is likely to make his return to the Lilywhites first team as they enter a crucial period of the season, starting with Manchester City at the Etihad Stadium on November 24th before Manchester United travel to north London a week later.
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Hemodynamic effects of intravenous amiodarone.
Amiodarone is a potent antiarrhythmic agent that is effective in controlling both atrial and ventricular arrhythmias. Recently, intravenous administration was demonstrated to be effective in the acute management of rhythm disorders and, in addition, appeared to shorten the loading period normally required for oral drug administration. This investigation examined the hemodynamic effects of amiodarone after both acute intravenous bolus and continuous intravenous administration. Patients with a left ventricular ejection fraction greater than 0.35 experienced improved cardiac performance due to both acute and chronic peripheral vasodilation. However, patients with a lower ejection fraction developed a 20% decrease in cardiac index and clinically significant elevation of right heart pressures after acute bolus administration; these changes were variably compensated for by peripheral vasodilation when the drug was administered intravenously over 3 to 5 days continuously. Therefore, intravenous amiodarone can result in significant impairment of left ventricular performance in patients with preexisting left ventricular dysfunction. | null | minipile | NaturalLanguage | mit | null |
Following the election of Donald Trump to the presidency of these United States of America—still getting used to that—there have been well-reasoned arguments that Facebook and its ability to spread fake news had a role in the result. But Mark Zuckerberg is not having that.
According to a report from TechCrunch, Zuckerberg disavowed the notion that News Feed had anything to do with the country swinging in Trump’s favor while speaking at the Techonomy16 conference. “I’ve seen some of the stories you are talking about around this election and personally I think the idea that fake news on Facebook, of which it’s a very small amount of the content, influenced the election in any way is a pretty crazy idea,” he said. “You know voters make decisions based on their lived experience. We really believe in people. You don’t generally go wrong when you trust that people understand what they care about and what’s important to them and you build systems that reflect that.” Zuckerberg ultimately concluded that the problem his company needs to tackle isn’t false information, but getting people to “engage with” a wider variety of it.
This response would only serve to prove Max Read’s point in a New York magazine piece that: “Facebook has seemed both uninterested in and incapable of even acknowledging that it has become the most efficient distributor of misinformation in human history.” All together now: MARK! | null | minipile | NaturalLanguage | mit | null |
Q:
Covariance of a mixture of Gaussians
I have seen this question asked, but in a strange way that I do not think is equivalent. If someone can show that the formulations are identical, I would be grateful.
Suppose with probability $p$, one draws points from a Gaussian distribution $N(0,\hat\Sigma_1)$, and with probability $1-p$ from a distribution $N(0,\hat\Sigma_2)$, where $\hat\Sigma_1$ and $\hat\Sigma_2$ are both $p,p$ matrices. After $n$ such draws, one can compute the covariance matrix of your points $\Sigma$.
Can we have an explicit formula for $\Sigma$?
A:
The distribution of the variable is
$$
X = 1_{U<p} X_1 + 1_{U\ge p} X_2
\sim 1_{U<p} N(0, \hat\Sigma_1) + 1_{U\ge p} N(0, \hat\Sigma_2)
$$
(with $U\sim U[0,1]$ is independent of the rest)
which as expected value $0$ and second moment
\begin{align}
E[X_iX_j]
&= E[(1_{U<p} X_{i,1} + 1_{U\ge p} X_{i,2})(1_{U<p} X_{j,1} + 1_{U\ge p} X_{j,2})]
\\&= E[1_{U<p} X_{i,1} X_{j,1}] + E[1_{U\ge p} X_{j,2} X_{j,2}]
\end{align}
now if you expand everything and use the independence of $U$ and $X_{1,2}$ you should get the matrix
$$
p\hat\Sigma_1 + (1-p)\hat\Sigma_2
$$
| null | minipile | NaturalLanguage | mit | null |
Delegates at the 19th International Aids conference in Washington, DC, in the United States this week were convinced the world was on the cusp of a major advance against HIV and that a medical device, known as the PrePex, could help 14 African countries, including South Africa, to speed up male circumcision to achieve a goal of circumcising 80% of men between the ages of 15 and 49 by 2015. | null | minipile | NaturalLanguage | mit | null |
SAVES Project: results of the first year
Main menu
The first year of the SAVES project has come to an end and with it the Student Switch Off campaigns for the academic year 2014/2015. The SAVES project encourages 25,000 students living in dormitories in five partner countries (UK, Sweden, Greece, Cyprus and Lithuania) to save energy by means of simple everyday actions. The students participate in energy saving competitions throughout the academic year and win prizes. This year 17% of all students signed up to the campaign (over 4,000 students), with hundreds submitting photos to our competitions, and thousands taking part in our climate quizzes.
So how much electricity was saved over the 2014-15 academic year at all the participating dormitories? Overall the students saved an impressive 1.5 million kWh of electricity and over 600 tCO2, which equates to an average of 4,44% savings. Congratulations to all the students that made this happen! The result was calculated by comparing the electricity usage at each dormitory in 2014-15 to the electricity usage prior to the Student Switch Off campaign starting. The dormitory at each of the 17 participating universities that saved the most energy was rewarded with a celebration.
At the national level, the following dormitories have saved the most energy and therefore have been crowned national winners:
The overall SAVES winner for 2014-15 that saved the most energy throughout the five countries is Teme student dormitory from the University of Worcester, United Kingdom. Katy Boom, Director of Sustainability at University of Worcester, commented ‘This is fantastic news for our students living in Teme Hall, we are very proud of their achievement. Through their efforts of small changes in behaviours such as not over filling the kettle each time they made a hot drink, and cooking with the lids on saucepans they have saved the most energy. This is not just in the UK, but across our partners in Europe. We are all thrilled. The Students’ Union and University do work together on a many behaviour change campaigns and this result really does help everyone see their efforts and enthusiasm have been worthwhile. A fantastic result.’
Joanna Romanowicz, Project Manager of the SAVES project said: ‘It’s so exciting to see the project successfully adapted in all our participating countries. Students across Europe have been taking lots of initiative, getting their friends involved and learning more about energy saving actions. For next year we want to build up on this, and continue to make our students feel part of a Europe-wide international Student Switch Off community. Well done to all our students, and in particular students living in Teme dormitory, for all their efforts!’.
For more SAVES news, please visit the project website or one of the many Student Switch Off Facebook pages. | null | minipile | NaturalLanguage | mit | null |
It is desirable to make boxes in a quick and efficient manner to manufacture them inexpensively. It is also desirable to make boxes with aesthetic appeal to entice customers to buy the product within the box.
It has been known in the art to make single piece boxes where the top and bottom of the box are one connected unit, see, e.g., U.S. Pat. Nos. 4,771,886 and 4,641,750. Boxes made according to these patents, however, may only be made from materials that may be molded, and the manufacturing processes require a separate step in which a label may be affixed to the boxes.
Processes are also known for forming single-piece boxes from two pieces, a board blank and a wrap, wherein the wrap primarily functions as a decoration or a label. Previously known processes of this type, however, do not provide for a sealed spine so that the wrap at the spines of the boxes formed by said prior art processes have a tendency to bunch up and separate from the board blank. Additionally, the prior art processes for making one-piece boxes have not provided for automatic stacking and counting of boxes made thereby, but rather have required manual counting of the boxes. | null | minipile | NaturalLanguage | mit | null |
Can’t We Talk About It? — The Coming Financial Crisis
At the beginning of February the financial media celebrated the rally in the markets with jovial commentators cheering as the Dow Jones closed above the 12,000 mark for the first time since 2008.
“The worst is behind us,” they parroted one another.
But this sanguinity may prove to be yet another extraordinary popular delusion as the possibility of a financial crisis still looms but is wholly ignored.
Nothing has been learned, it seems, from 2006 when those warning of a housing bubble and impending financial crisis were practically laughed off the air. Once again the signs are all around us. Yet, with corporations posting record profits, who cares to listen?
The truth is that the rally in the markets is based on fiscal stimulus as money rolls off printing presses around the world but especially in Washington. Ultra-low interest rates have further distorted the value of money as easy borrowing pushes the money supply and investors seeking higher yields are forced from bonds into equities.
The current market rally—which pulls the wool over the eyes of investors—is being subsidized by the U.S. government and pushed further by a high real rate of inflation (look at the rising prices of commodities, many goods and certain services, not the U.S. Consumer Price Index which undercounts food, a necessity to survive). The so-called recovery is not a recovery but life-support to an ailing economy. To make matters worse, the U.S. government is practically broke.
According to the Congressional Budget Office, the U.S. federal deficit for 2011 will be nearly $1.5 trillion. Social Security will have a deficit of $45 billion in 2011, which will rise to more than $600 billion over the next decade.
The overall public debt of the United States is over $14 trillion dollars, and will likely be nearly 100% of GDP for 2011. Since foreigners hold much of the debt, interest payments are leaving the country instead of being paid to U.S. citizens. Interest payments will grow dramatically as the U.S. debt increases and interest rates rise.
It is not just the U.S. government that relies on credit; U.S. citizens, pushed to spend, spend, spend, are turning to credit as well. The media recently reported with near glee that credit card spending had risen in December for the first time in 26 months. Surely another sign of an improving economy, right?
But wait, with the unemployment rate holding steady (more on that below), foreclosures mounting, home prices dropping and consumer prices rising, where are people getting all this extra money? Their credit cards! Duped by the blather on news networks that an economic recovery is in full swing, why not go back to the old ways of swiping plastic before counting change?
People could be forgiven for thinking things are improving since the unemployment rate is apparently dropping. It’s an easy misconception to have since the media fails to specify that, because of how the unemployment rate is calculated, a significant amount of the drop is due to people giving up on looking for work altogether, in which case they are no longer counted as “unemployed.” That’s right, when you’re so unemployed you have given up hope of finding a job, you’re no longer counted as unemployed. Obviously.
The media has also done a poor job of reporting on the debt ceiling that will be reached and will need to be raised by or around March of this year. If the debt ceiling is not raised, the U.S. would eventually be forced to default on its debt, which would cause “catastrophic damage to the economy, potentially much more harmful than the effects of the financial crisis of 2008 and 2009,” according to Timothy F. Geithner, the Secretary of the Treasury of the United States.
“Default would have prolonged and far-reaching negative consequences on the safe-haven status of Treasuries and the dollar’s dominant role in the international financial system,” Geithner wrote to Congress on January 6, 2011, “causing further increases in interest rates and reducing the willingness of investors here and around the world to invest in the United States.”
Though defaulting seems extremely unlikely, Republicans who now hold a majority in the House of Representatives have promised to use raising the debt limit and the new budget to force the government to make spending cuts. No one in their right mind could argue that significant budget cuts are unnecessary, but the government runs the risk of being shut down over the issue. Republicans will push hard to obtain spending cuts once March 4th rolls around and the current appropriations resolution that keeps the government running expires.
Regardless, the government will need to borrow more money just to meet its obligations. As Geithner wrote, “even if Congress were immediately to adopt the deep cuts in discretionary spending of the magnitude suggested by some Members of Congress, such as reverting to Fiscal Year 2008 spending levels, the need to increase the debt limit would be delayed by no more than two weeks.”
To add to this, especially as stimulus money begins to dry up, there is a very real possibility of a series of defaults in the municipal bond market. Already investors have been running for the exits, withdrawing billions of dollars, and returns on municipal securities plummeted in the fourth quarter of 2010.
The U.S. dollar seems set to continue its downward trend. As the Fed creates more money and the money supply increases, people will lose faith in the purchasing power of the dollar and prices will rise. Already emerging economies are battling inflation caused by excessive liquidity in the financial system.
China’s central bank has said the Fed’s monetary easing was pushing up prices, and that it may cause risks of competitive currency depreciation. It accused the Fed of creating imported inflation and short-term capital inflows, pressuring emerging markets.
Asians in particular are turning to gold and silver as a hedge against inflation. Demand in China is notably rising, and it is believed China took in around 620 tons of gold in 2010 through production and imports. The price of gold is set to soar even higher due to central banks around the world becoming net buyers, gold production peaking, and movement away from the U.S. dollar as the world’s reserve currency.
It should come as no surprise that people are turning to gold and silver, time-tested stores of wealth. Gold is the money of kings. Debt is the money of slaves. As governments print money almost without restraint the value of their currencies will fall. Nearing its end, the emperors of the Roman Empire began to take precious metals out of their coins. The debasement continued until the coins were rendered virtually worthless, and it ensured the empire’s collapse.
With the myriad problems many developed and emerging economies are currently facing (problems that will inevitably be compounded by food revolts around the world as prices soar), it is completely naïve to believe that governments would be able to rush to the U.S. economy’s rescue were a crisis to develop. Not to mention that global direct public sector debt is over $50 trillion. As John Brown, Senior Market Strategist for Euro Pacific Capital and former member of Britain’s Parliament, writes, “Against this total, even the wealth of cash-rich nations such as China ($2.85 trillion in foreign-exchange reserves) and Japan ($1.1 trillion in reserves) pale into insignificance. With so little credit to soak up the future financing needs of the US and the EU, it is no wonder that both their currencies are coming under pressure.”
“Possible because a major currency collapse is unprecedented in living memory, investors have been slow to react,” Brown continues. “While the markets are calm at present, we mustn’t forget that the nature of panic is that it is sudden. It can erupt quickly and overwhelm the unprepared. When it does, even supposedly rock-solid assets like Treasury bonds may be discounted severely. In such a climate, gold and silver are as faithful as Old Yeller.”
With the rally and recovery based on such tenuous polices as money printing and borrowing, the unrestrained optimism in the markets and in the media is simply not warranted. Those who do not share this sense of optimism and warn of tears to come are readily dismissed as doomsday sayers or alarmists.
Facing the possibility of another crisis, like facing disease, old age or death, takes courage. Those who ignore the signs or symptoms are left wholly unprepared.
Those who wish to use the Dow Jones to measure the economy’s wellbeing need to be reminded that as Zimbabwe marched towards hyperinflation and ruin, its stock exchange was among the best performing in the world.
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About the Author
Barnabe Geisweiller comes from a Political Science background and holds a Master’s in Journalism from Columbia University. He has resided and worked around the world, and currently works with gold exploration companies based out of Vancouver. | null | minipile | NaturalLanguage | mit | null |
-1. What sort of musician was Signourey Weaver in Ghostbusters?-2. Which talk-show hostess made her movie debut in Hairspray?-3. Which 1963 movie starring Ava Gardner was set in the time of the 1900 Chinese Boxer uprising?-4. Who became known as the "First Lady of the Silent Screen"?-5. Which 2001 WWII movie tells the story of two snipers stalking each other through the ruins of Stalingrad?-6. Cliff Robertson starred in the 1961 TV drama based on the short story "Flowers for Algernon". Seven years later he starred in the movie version called...? -7. Little Richard starred with Richard Dreyfus and Bette Midler in which 1986 movie?-8. Who played former secret agent 006 Alec Trevelyan in the 1995 Bond film Goldeneye-9. In which state is Nell set?-10. In Speed, the bomb will detonate if the bus drops below what speed?-11. Censorship and self-regulation in the early days of film by overseen by which group?-12. The actors have been removed but can you name the film?: | null | minipile | NaturalLanguage | mit | null |
Morgan Spurlock, Alex Gibney and others release a letter to protest U.S. government harassment of Laura Poitras
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On Sunday, Glenn Greenwald reported that Laura Poitras – the Oscar- and Emmy-nominated filmmaker behind “My Country, My Country” and ”The Oath” – has been subject to extraordinary and deeply troubling scrutiny by American officials. Poitras has been detained by the U.S. government 36 times in the last six years – almost every time she’s returned to the country from work abroad. The filmmaker has repeatedly been subject to harassment, intimidation and unwarranted, invasive searches, while her phone, laptop, reporter’s notebook and other materials have been confiscated and copied. Last week, she was prohibited from taking notes on her own interrogation because her pen “could be used as a weapon.”
As Greenwald pointed out, Poitras’ case is a glaring example of the government’s continued disregard of Fourth Amendment rights as they apply to journalists and documentary filmmakers working on subject matter related to U.S. military operations, American foreign policy and any other domain claimed by the Department of Homeland Security.
Now, nonfiction filmmakers are speaking out. Yesterday, the Cinema Eye organization released an open letter and petition in protest of DHS actions, calling on the Obama administration to investigate this “chronic abuse of power” and to put an end to violations of “America’s bedrock principle of a free press.” The letter was signed by the Cinema Eye Executive Board and their Filmmaker Advisory Board, including well-known nonfiction filmmakers Alex Gibney, Albert Maysles, Morgan Spurlock and many others. The full letter is reproduced below:
April 9, 2012 – New York, New York – Cinema Eye, the film organization that hosts the Cinema Eye Honors and advocates for artistry and craft in nonfiction filmmaking, is releasing a statement today to vigorously protest the Department of Homeland Security’s treatment of our valued colleague, Laura Poitras.
The letter is signed by the full Cinema Eye Executive Board as well as our Filmmaker Advisory Board, of which Poitras serves as Chair. The letter is also signed by 25 Cinema Eye nominated filmmakers, including five Academy Award winners.
Statement from Cinema Eye on Laura Poitras:
As members of the nonfiction filmmaking community, we want to express our outrage over the ongoing harassment of our colleague Laura Poitras by the US government and the Department of Homeland Security. We call on the Obama administration to investigate this abuse of power and to bring an end to this persistent violation of America’s bedrock principle of a free press.
Laura Poitras is one of America’s most important nonfiction filmmakers, the recipient of the 2011 Cinema Eye Honor for Outstanding Achievement in Direction for her landmark film, The Oath, and the chair of our Filmmaker Advisory Board. She was nominated for a Best Documentary Feature Oscar and twice has been nominated for an Independent Spirit Award for her work. Her long list of credits, awards and impeccable credentials would be easy for anyone to verify.
Over the course of the last several years, as Laura has been working to chronicle the post-9/11 world and the effect of American policies here and abroad, she has been repeatedly harassed, detained, interrogated and has had her cameras and computers seized by Homeland Security officials as she attempts to re-enter her home country.
Not once in more than three dozen detentions and interrogations has Homeland Security found anything to justify this chronic abuse of power.
Within the last week, as Laura was returning from a recent trip abroad, she was once again detained. This time, however, she was also threatened with being handcuffed for attempting to take notes during her interrogation.
Nonfiction filmmakers perform a vital role in a democratic society, serving as observers and investigators of the world around us. It is unacceptable for any American nonfiction filmmaker or journalist to be treated in this manner. They must be able to return to their own country without fear of arrest or fear that their work product will be seized, solely because they are investigating or chronicling subject matter that may be sensitive or controversial.
We ask other members of the nonfiction film and journalism communities to protest this affront to a free press and we reiterate our call on the Obama administration to end these draconian and un-American policies once and for all.
Overdevelopment, Overpopulation, Overshoot
Overdevelopment, Overpopulation, Overshoot
Slide 13
Airplane Contrails: Globalized transportation networks, especially commercial aviation, are a major contributor of air pollution and greenhouse gas emissions. Photo of contrails in the west London sky over the River Thames, London, England.
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Overdevelopment, Overpopulation, Overshoot
Fire: More frequent and more intense wildfires (such as this one in Colorado, USA) are another consequence of a warming planet. | null | minipile | NaturalLanguage | mit | null |
Q:
Error to receive file on socket inside a thread
I'm having trouble to receive a byte array containg a PNG file.
When the code is executed in OnClientRead event it works fine, already when transfered for a thread, happens an error of MemoryStream that says:
Out of memory while expanding memory stream.
At this point:
if SD.State = ReadingSize then
I want to know how to solve this specific trouble and also how can I check if I'm receiving a data that contains a file or a simple String?
The code:
type
TSock_Thread = class(TThread)
private
Socket: TCustomWinSocket;
public
constructor Create(aSocket: TCustomWinSocket);
procedure Execute; override;
end;
type
TInt32Bytes = record
case Integer of
0: (Bytes: array[0..SizeOf(Int32)-1] of Byte);
1: (Value: Int32);
end;
TSocketState = (ReadingSize, ReadingStream);
TSocketData = class
public
Stream: TMemoryStream;
Png: TPngImage;
State: TSocketState;
Size: TInt32Bytes;
Offset: Integer;
constructor Create;
destructor Destroy; override;
end;
{ ... }
constructor TSock_Thread.Create(aSocket: TCustomWinSocket);
begin
inherited Create(true);
Socket := aSocket;
FreeOnTerminate := true;
end;
procedure TSock_Thread.Execute;
var
s: String;
BytesReceived: Integer;
BufferPtr: PByte;
SD: TSocketData;
Item: TListItem;
begin
inherited;
while Socket.Connected do
begin
if Socket.ReceiveLength > 0 then
begin
s := Socket.ReceiveText;
{ SD := TSocketData(Socket.Data);
if SD.State = ReadingSize then
begin
while SD.Offset < SizeOf(Int32) do
begin
BytesReceived := Socket.ReceiveBuf(SD.Size.Bytes[SD.Offset],
SizeOf(Int32) - SD.Offset);
if BytesReceived <= 0 then
Exit;
Inc(SD.Offset, BytesReceived);
end;
SD.Size.Value := ntohl(SD.Size.Value);
SD.State := ReadingStream;
SD.Offset := 0;
SD.Stream.Size := SD.Size.Value;
end;
if SD.State = ReadingStream then
begin
if SD.Offset < SD.Size.Value then
begin
BufferPtr := PByte(SD.Stream.Memory);
Inc(BufferPtr, SD.Offset);
repeat
BytesReceived := Socket.ReceiveBuf(BufferPtr^,
SD.Size.Value - SD.Offset);
if BytesReceived <= 0 then
Exit;
Inc(BufferPtr, BytesReceived);
Inc(SD.Offset, BytesReceived);
until SD.Offset = SD.Size.Value;
end;
try
SD.Stream.Position := 0;
SD.Png.LoadFromStream(SD.Stream);
SD.Stream.Clear;
except
SD.Png.Assign(nil);
end;
Item := Form1.ListView1.Selected;
if (Item <> nil) and (Item.Data = Socket) then
Form1.img1.Picture.Graphic := SD.Png;
SD.State := ReadingSize;
SD.Offset := 0;
end; }
end;
Sleep(100);
end;
end;
procedure TForm1.ServerSocket1Accept(Sender: TObject; Socket: TCustomWinSocket);
var
TST: TSock_Thread;
begin
TST := TSock_Thread.Create(Socket);
TST.Resume;
end;
UPDATE:
The code in the answer is not working for me because ServerType=stThreadBlocking blocks all clients connections with the server. And because of this, I'm searching for something like this (ServerType=stNonBlocking, TThread and OnAccept event):
type
TSock_Thread = class(TThread)
private
Png: TPngImage;
Socket: TCustomWinSocket;
public
constructor Create(aSocket: TCustomWinSocket);
procedure Execute; override;
procedure PngReceived;
end;
// ...
// ===============================================================================
constructor TSock_Thread.Create(aSocket: TCustomWinSocket);
begin
inherited Create(true);
Socket := aSocket;
FreeOnTerminate := true;
end;
// ===============================================================================
procedure TSock_Thread.PngReceived;
var
Item: TListItem;
begin
Item := Form1.ListView1.Selected;
if (Item <> nil) and (Item.Data = Socket) then
Form1.img1.Picture.Graphic := Png;
end;
procedure TSock_Thread.Execute;
var
Reciving: Boolean;
DataSize: Integer;
Data: TMemoryStream;
s, sl: String;
begin
inherited;
while Socket.Connected do
begin
if Socket.ReceiveLength > 0 then
begin
s := Socket.ReceiveText;
if not Reciving then
begin
SetLength(sl, StrLen(PChar(s)) + 1);
StrLCopy(@sl[1], PChar(s), Length(sl) - 1);
DataSize := StrToInt(sl);
Data := TMemoryStream.Create;
Png := TPngImage.Create;
Delete(s, 1, Length(sl));
Reciving := true;
end;
try
Data.Write(s[1], Length(s));
if Data.Size = DataSize then
begin
Data.Position := 0;
Png.LoadFromStream(Data);
Synchronize(PngReceived);
Data.Free;
Reciving := false;
end;
except
Png.Assign(nil);
Png.Free;
Data.Free;
end;
end;
Sleep(100);
end;
end;
procedure TForm1.ServerSocket1Accept(Sender: TObject; Socket: TCustomWinSocket);
var
TST: TSock_Thread;
begin
TST := TSock_Thread.Create(Socket);
TST.Resume;
end;
This code has an error of conversion of data at this line:
DataSize := StrToInt(sl);
How can I fix this?
A:
how solve this specific trouble
You are not using TServerSocket threading the way it is meant to be used.
If you want to use TServerSocket in stThreadBlocking mode (see my other answer for how to use TServerSocket in stNonBlocking mode), the correct way is to:
derive a thread class from TServerClientThread
override its virtual ClientExecute() method to do your I/O work (via TWinSocketStream)
use the TServerSocket.OnGetThread event to instantiate the thread.
If you don't do this, TServerSocket will create its own default threads (to fire the OnClient(Read|Write) events in the main thread), which will interfere with your manual threads.
Also, you don't need the state machine that I showed you in my answer to your other question. That was for event-driven code. Threaded I/O code can be written linearly instead.
Try something more like this:
type
TSock_Thread = class(TServerClientThread)
private
Png: TPngImage;
procedure PngReceived;
protected
procedure ClientExecute; override;
end;
type
TInt32Bytes = record
case Integer of
0: (Bytes: array[0..SizeOf(Int32)-1] of Byte);
1: (Value: Int32);
end;
procedure TSock_Thread.ClientExecute;
var
SocketStrm: TWinSocketStream;
Buffer: TMemoryStream;
Size: TInt32Bytes;
Offset: Integer;
BytesReceived: Integer;
BufferPtr: PByte;
begin
SocketStrm := TWinSocketStream.Create(ClientSocket, 5000);
try
Buffer := TMemoryStream.Create;
try
Png := TPngImage.Create;
try
while ClientSocket.Connected do
begin
if not SocketStrm.WaitForData(100) then Continue;
Offset := 0;
while Offset < SizeOf(Int32) do
begin
BytesReceived := SocketStrm.Read(Size.Bytes[Offset], SizeOf(Int32) - Offset);
if BytesReceived <= 0 then Exit;
Inc(Offset, BytesReceived);
end;
Size.Value := ntohl(Size.Value);
Buffer.Size := Size.Value;
BufferPtr := PByte(Buffer.Memory);
Offset := 0;
while Offset < Size.Value do
begin
BytesReceived := SocketStrm.Read(BufferPtr^, Size.Value - Offset);
if BytesReceived <= 0 then Exit;
Inc(BufferPtr, BytesReceived);
Inc(Offset, BytesReceived);
end;
Buffer.Position := 0;
try
Png.LoadFromStream(Buffer);
except
Png.Assign(nil);
end;
Synchronize(PngReceived);
end;
finally
Png.Free;
end;
finally
Buffer.Free;
end;
finally
SocketStrm.Free;
end;
end;
procedure TSock_Thread.PngReceived;
var
Item: TListItem;
begin
Item := Form1.ListView1.Selected;
if (Item <> nil) and (Item.Data = ClientSocket) then
Form1.img1.Picture.Graphic := Png;
end;
procedure TForm1.ServerSocket1GetThread(Sender: TObject; ClientSocket: TServerClientWinSocket; var SocketThread: TServerClientThread);
begin
SocketThread := TSock_Thread.Create(False, ClientSocket);
end;
how i can check if i'm receiving a data that contains a file or a simple String?
The client needs to send that information to your server. You are already sending a value to specify the data size before sending the actual data. You should also preceed the data with a value to specify the data's type. Then you can handle the data according to its type as needed.
| null | minipile | NaturalLanguage | mit | null |
Q:
What is causing this error on nginx server – 502 Bad gateway
I have a site built in Drupal 7 on a nginx server. A few times a week when I edit any content and press save, or when I log in to the site, or when I change some configuration, I get a white screen with the message "502 Bad gateway". The error is never showed to anonymous visitors, only when logged in and saving changes. It doesn't seem to matter what kind of changes I do. I can press the back button in the browser, which takes me back to the edit screen and press save again, and save the change successfully.
The error happened again this morning at 08:09, so I looked at the PHP log:
2016/10/20 08:09:00 [error] 20703#20703: *3297348 recv() failed (104: Connection reset by peer) while reading response header from upstream, client: 195.198.76.66, server: www.example.com, request: "POST /node/88/edit HTTP/1.1", upstream: "fastcgi://unix:/run/php/php-fpm.sock:", host: "www.example.com", referrer: "http://www.example.com/node/88/edit"
And here is the nginx log at that same time:
[20-Oct-2016 08:09:00] WARNING: [pool www0] child 10909, script '/srv/www/example/public_html/index.php' (request: "POST /index.php") execution timed out (8189.954999 sec), terminating
[20-Oct-2016 08:09:00] WARNING: [pool www0] child 10909 exited on signal 15 (SIGTERM) after 19080.476683 seconds from start
[20-Oct-2016 08:09:00] NOTICE: [pool www0] child 13002 started
Can anyone see what is happening here?
A:
I had a HTTP 502 problem on a setup with nginx & php-fpm. It seems that many timeouts & limits must be modified according to the data transfer time. What was happening in this case is that the keepalive timeout was too short.
Here are some settings that might help solve 502 problems:
In nginx.conf: keepalive_timeout
In the site's configuration file (which is in thesites-available folder):
send_timeout
fastcgi_connect_timeout
fastcgi_send_timeout
fastcgi_read_timeout
in php.ini:
max_execution_time
max_input_time
The real source of the problem can be any of these settings.
| null | minipile | NaturalLanguage | mit | null |
Tuesday, April 10, 2012
Many folks take into account finding a tattoo completed sooner or later inside their lifestyles, handful of understand the particular attention which should be obtained for your tattoo to be able to cure appropriately. Stick to these kinds of basic tattoo attention guidelines offered in this post to see the particular gorgeous tattoo come out because it repairs...
Maybe you have already been bitten from the tattoo insect? Can it possible that pin the consequence on those who find themselves partial to tattoo. The particular gorgeous models drawn in multi-colored printer are really luring. Any tattoo is manufactured simply by completing printer inside the epidermis simply by initial building a leak using a filling device. Because the injure repairs a lovely layout having the particular printer that has been inserted engrossed comes out. Finding a tattoo completed requires several soreness and also will take time and energy to cure. It really is possibly because of this purpose that numerous folks cannot determine whether or not to have a single completed. Nonetheless, tattoo attention guidelines are usually basic of course, if implemented appropriately, the particular tattoo cure without the issues.
Just How to Manage Tattoo
Abandon In which Bandage About: Usually do not eliminate the bandage your tattoo performer attached above the layout right after this individual done rendering it. Any tattoo has to be gorgeous yet understand that right up until that repairs it really is refreshing injure. Abandon in which bandage about regarding no less than a couple of hrs once you've that completed. The particular bandage help keep bacterias out from the injure and also prevent virtually any contamination in which they could be brought on. You will need to understand that specific tattoo performers protect the particular tattoo using a plastic-type place. Although buying a tattoo performer, validate just what substance this individual makes use of to pay the particular injure. Avoid tattoo performers which place refreshing tattoo inside plastic-type since this may suffocate the particular injure and also protract the particular therapeutic moment.
Rinse and also clear: When you eliminate the bandage, clear the particular tattoo together with slight detergent and also lukewarm h2o. In terms of soap are involved, making use of a single together with anti-microbial or perhaps anti-bacterial attributes is the most suitable choice. Avoid bathroom towels to eliminate salve, blood vessels or perhaps plasma that could be oozing out from the tattoo. They could be coarse around the soft epidermis. Rinse the hands together with detergent and also have used them to be able to carefully clear the location. To be able to dry up the location work with a papers bath towel or even a bath towel is good. Usually do not wash yet terry the location carefully with the entire bath towel. Whether it be any papers bath towel or even a material bath towel make certain it is CLEAR. Material bathroom towels typically possess bacteria’s which could result in contamination in your community. Thus make sure you have got disinfected the particular bath towel just before deploying it. Although cleansing that together with h2o usually do not uncover that with a primary apply. Somewhat allow the h2o merely trickle straight down the particular tattooed surface area.
Moisturize: Allow the location dried up for approximately 10 moments and use several antibiotic product or even a mild lotion for the surface area. You can get these kinds of goods coming from retailers especially designed for tattoo therapeutic. The tattoo performer is the better particular person regarding advice on tattoo care products. Utilize the goods since focused around the tag. Utilize this product for approximately weekly to be able to retain the wetness with the location. Nonetheless, usually do not above use product around the location.
Working with Scab: One of many crucial areas of tattoo attention is always to withstand the particular attraction regarding yanking over epidermis in which starts off peeling right after a short time. Because the epidermis repairs, scabs may well kind as well as the epidermis may turn to be able to peel from the lime. Usually do not scuff or perhaps display the particular deceased epidermis. Allow it happen alone. The reason why the epidermis will come away to helps wealthier shade inside the tattoo. Consequently, usually do not get worried when shade will come away from together with scabbing.
Tattoo Aftercare Guidelines
Right after eliminating the particular bandage the tattoo performer acquired attached across the tattoo, usually do not re-bandage that.Retain away from private pools, domestic hot water bathrooms tubs, and also schools regarding no less than a couple weeks right after having the tattoo completed.Make an effort to keep out from the sunshine for approximately two weeks. Usually do not uncover that to be able to sun tanning hair salon light bulbs for approximately monthly. After the tattoo provides recovered use any unblock each and every time an individual walk out inside the sunshine.
Because the tattoo repairs it's going to itch. Withstand irritation. This kind of is probably the most critical tattoo aftercare guidelines plus the most challenging to check out. You might like to work with a product to ease the particular irritation experience.
By no means feel the particular tattoo together with dried up or perhaps tired palms.Steer clear of sporting limited appropriate garments because the cloth may well caress contrary to the surface area and also result in irritability. Use garments which can be reducing understanding that enable oxygen to be able to rotate across the location.
In the event there is certainly puffiness in your community, use snow delivers.These kinds of tattoo attention guidelines reviewed are very effective inside caring for tattoo. Nonetheless, how a epidermis acts with a tattoo as well as the moment taken up cure, may differ coming from one individual to another. Many people may well produce allergies for the goods which they utilize right after having the tattoo completed. When these kinds of could be the circumstance, look at the tattoo performer or perhaps view a medical doctor.
Ezequiel Lavezzi created his international debut for the Argentine national team team against Chile on eighteen April 2007. In 2008 Lavezzi was selected to the Argentina Olympic soccer team that represented Argentina at the 2008 Olympics, throughout the Olympic games he scored 2 goals, one against Australia on ten August 2008, and a penalty against Serbia on thirteen August 2008. Lavezzi conjointly appeared within the final minutes of additional time against Nigeria. Lavezzi's club type wasn't enough to examine him included in Diego Maradona's 2010 FIFA World Cup squad. On the seventeenth of November 2010, Argentina faced Brazil during a friendly match in Qatar, during which Argentina won by a goal from Lionel Messi within the injury time once an outstanding one-two play with Lavezzi. He has become an everyday member below Sergio Batista. He scored the goal within the friendly match against Albania played on twenty one June 2011. The match ended 4-0 in favor of Argentina. Lavezzi was replaced by Sergio Agüero within the sixty fifth minute of the match. He was named in Argentina's Copa America Squad by Sergio Batista.
Dennis Rodman has a rare quantity of tattoos, covering his six ft eight in body. His tattoos embrace, 2 giant bulls on both sides of his chest, and an intensive quantity of huge tribal tattoos on his abdomen and conjointly round the shoulders and neck space. He includes a cross with a couple of stars around his belly button, and his last name "Rodman" on the rear of his neck. The tattoos on his right arm embrace an outsized sun with a shark within the middle, a red dice, a tribal style of types, a motorbike among alternative items of design down his arm. The tattoos on his left arm and shoulder embrace alittle cross, a devil woman with pitchfork, a large squid, and varied alternative styles that are troublesome to visualize clearly. Checkout these footage of Dennis Rodman and his several tattoos.
Rodman experienced an sad childhood and was back and introverted in his early years. once aborting a suicide try in 1993, he reinvented himself because the prototypical "bad boy" and have become notorious for varied controversial antics. He dyed his hair in artificial colours, presented himself with several piercings and tattoos and often disrupted games by clashing with opposing players and officers. He famously wore a marriage dress to push his autobiography. Rodman pursued a high-profile affair with singer Madonna and was briefly married to actress Carmen Electra.
In fourteen NBA seasons, Rodman played in 911 games, scored 6,683 points and grabbed eleven,954 rebounds, translating to seven.3 points and thirteen.1 rebounds per game in mere thirty one.7 minutes played per game NBA.com lauds Rodman as "arguably the most effective rebounding forward in NBA history and one in all the foremost recognized athletes within the world" however adds "enigmatic and individualistic, Rodman has caught the general public eye for his ever-changing hair color, tattoos and unorthodox lifestyle". On the hardwood, he was recognized jointly of the foremost successful defensive players ever, winning the NBA championship 5 times in six NBA Finals appearances (1989, 1990, 1996–1998; solely loss 1988), being topped NBA Defensive Player of the Year twice (1990–1991) and creating seven NBA All-Defensive initial groups (1989–1993, 1995–1996) and NBA All-Defensive Second groups (1994). He additionally created 2 All-NBA Third groups (1992, 1995), 2 NBA All-Star groups (1990, 1992) and won seven straight rebounding crowns (1992–1998) and eventually led the league once in field goal share (1989). However, he was recognized because the prototype bizarre player, beautiful basketball fans together with his artificial hair colours, varied tattoos and body piercings, multiple verbal and physical assaults on officers, frequent ejections, and his tumultuous non-public life. He was ranked #48 on the 2009 revision of Slam Magazine's high fifty Players of All-Time.
Boateng incorporates a Ghanaian father and a German mother. His father, Prince Boateng, Sr., left Ghana in 1981 hoping for an opportunity in Germany, where he wished to check administration, but was unsuccessful and he ended up disc jockeying and dealing as a waiter. Boateng was one-and-a-half-years-old when his father left the family home. His mother, Catherine Boateng, ended up operating long hours to require care of Boateng and his brother George. His uncle, Robert Boateng could be a former member of the Ghana national team and his maternal grandfather could be a cousin of legendary German soccer star Helmut Rahn, scorer of the winning goal within the 1954 FIFA World Cup Final. further as Boateng's brothers, George and Jérôme, he has one sister, Avelina. each brothers are soccer players, with the youngest of the 2 brothers, Jérôme, additionally having previously been at Hertha BSC and currently wiggling with Bayern Munich and also the German national team.
Boateng calls himself "The Ghetto Kid" as a result of he was said within the poor Wedding district of Berlin. In official documents, his name is given as Kevin Boateng, however he himself prefers the name Prince and Kevin-Prince in honour of his father, Prince Boateng, Sr. He married his future girlfriend Jennifer 2 days once signing with Tottenham Hotspur. Boateng has twenty six tattoos. Here you see Africa and Ghana from my father. "I have the name of my wife and also the town of my birth, Berlin on my biceps. "I have 2 jokers; one is smiling and also the different crying. It means that laugh currently, cry later." Kevin-Prince Boateng – Speaking concerning a number of his twenty six tattoos.
In September 2011, Boateng divorced his German wife Jennifer, ending their four-year wedding, and since the beginning of October 2011, he has been dating Italian-American model Melissa Satta. Following Boateng's divorce, his ex-wife came back to Germany with their son, Jermaine-Prince.
Earlier on in his career, Boateng developed a significant looking addiction as a results of personal issues. Boateng claims that he still owns "around a hundred 59Fifty caps and a hundred Billionaire Boys Club caps, around twenty Martin Margiela leather jackets, and a hundred and sixty pairs of Berluti shoes" following the ordeal. different things the footballer is understood to possess bought embrace a Lamborghini Aventador and a Lamborghini Murciélago, a Hummer H3, and a Cadillac CTS-V. Boateng has since overcome this drawback and sold all four of his cars, citing how he, "was broken in another world" owing to the consequences of it.
Cahill includes a tattoo that nearly coated the complete left arm. Men born December vi, 1979 This tattoo was created when the grandmother who died of Samoan descent. Tattooing was a tribute to the mother, additionally to the Samoan culture. Constrained owing to respect for his ancestral culture, tribal-style tattoo pattern Samoa. On the sidelines of a tribal tattoo’s, Everton star was slipped the names of relations. Unmitigated, Cahill enter the name of grandparents, father-mother, brother and sister, wife, youngsters up to the name of brother and sister-in-law at his tattoo. Hmm, this is often a tattoo or a family card, huh?
Timothy Filiga "Tim" Cahill (born vi December 1979) may be a soccer (soccer) player of Australian nationality who plays for Everton and also the Australian national soccer team. Cahill plays as an attacking midfielder, however has additionally played as a striker on many occasions and captains Everton in Phil Neville's absence. Cahill has become one among the very best profile footballers within the Asian soccer Confederation. Cahill scored the primary goal by an Australian at a FIFA World Cup, and has additionally scored the foremost goals by any Australian within the World Cup. In 2007, he additionally became the primary Australian player to get at an Asian Cup. Cahill is understood for his adept heading ability, outstanding leap despite being average height and scoring the bulk of his goals together with his head.
Liverpool's Daniel Agger makes a new tattoo when his team meets Denmark England in friendly games. Agger scored the opening goal in a match that was eventually won by the Three Lions 1-2. At trial he showed a tattoo of a Viking standing in the middle of his back dipemakaman. He also wrote the Latin 'Mors chert, Hora Incerta' over the tattoo which roughly translates to "Death is coming for sure and can not be predicted '. At the ankle while it says "Suffering is only temporary, victory for good 'or' Pain is temporary, Victory is forever '. The Reds star is indeed very crazy about tattoos, proved he already has about 25 tattoos. In addition to playing his own ball Agger is known as a tattoo artist.
Let's start the discussion. Many people must be familiar with Center Back Liverpool nationals Denmark, Daniel Agger. He's one of the world's soccer player who loved the art of Tattoo. So do not be surprised by tattooing her body almost filled her own homemade creations. even his teammate tela Agger Agger tattoo became a regular customer because he was already an expert in the tattoo to the body. This painting he elaborated before he joined Liverpool.
Let's start with the meaning of tattoo Daniel Agger found him back section which is where he is the creation of art strategically tattoo
Tattoo found on the back of her Latin inscribed '"Mors chert Incerta Hora" which means "Death is certain, but uncertain times"
His left elbow is surrounded by tribal images and there are some pictures of china caisar. There is a tattoo on his arm it is decorated paper Balaton "Momento mori" (remember, you will die) or the means to remember, you will surely die. For further explanation of the meaning of an ane tattoo daniel agger been discussed, ane got the full picture. In the upper back near his left arm shows the image of the Viking Kings, Sven Forkbeard who took power in 1013 who had never mastered the English brutally
In the back amid Agger, there is a pictorial tattoo Gorm of the gold which the King of Denmark is the first in the nation's oldest monarchy in the world
Agger back in the middle, there is a picture of the bone Holger is one symbol of Denmark, which means that the country is threatened, they are ready to fight
At the back of the right part shows the image of Harold Bluetooth, which is the name of the king who unites three Scandinavian region as well as Sweden, Denmark and Norway
5. other at the bottom there is a picture of King Canute the viking king who controlled England in 1016 until 1036
And in other body parts that ane can not sempet picture, the left side of his chest he inscribed the name of brother and sister sister. He was crowned as "footballer with fully qualifed tattoo artist" | null | minipile | NaturalLanguage | mit | null |
1. Technical Field
The present invention pertains to safety valves useful to control flow in well conduits. This invention pertains to a safety valve, particularly useful in gas storage systems, which automatically closes when production mass flow reaches a predetermined rate at a particular ambient pressure.
2. Background Information
A considerable number of pressure-differential type safety valves are known for wells, which are direct-controlled, i.e., actuated, to close because fluid flow through generates differential pressure and sufficient closing force in these valves. An example of a direct-controlled (or flow actuated) safety valve is shown on page 142 of "Otis Products and Services" (OEC 5516), a September, 1989 publication of Otis Engineering Corporation, Belt Line at Webbs Chapel Roads, P.O. Box 819052, Dallas, Tex. 75381-9052. Another example of a direct-controlled safety valve is shown in application Ser. No. 07/699,368, filed in the United States Patent and Trademark Office May 13, 1991, for applicants William W. Dollison and John C. Gano.
Other examples of flow actuated safety valves are shown in the following U.S. Patents. U.S. Pat. No. 4,708,163 to Deaton discloses a valve which compares pressure of fluid flowing through the valve to pressure exterior of the valve. If the differential pressure exceeds a predetermined value, a pressure sensitive bellows is actuated to close the valve.
U.S. Pat. No. 4,664,195 to Deaton covers another direct acting (controlled) safety valve. If the rate of change of fluid pressure flowing through this valve exceeds a preselected value, a pressure sensitive piston will close the valve.
U.S. Pat. No. 4,339,001 to Paschal, Jr., is for a differential operated safety valve which is held open until the difference in pressure between fluid in a chamber inside the valve and fluid flowing through the valve exceeds a preselected value causing the valve to close.
U.S. Pat. No. 3,881,511 to Dollison discloses a well safety valve utilizing a poppet type valve which is actuated to close when the flow rate through the valve induces sufficient pressure differential in the valve to actuate the valve to close.
Inventor Phillip S. Sizer utilizes a ball type valve in the safety valve structure of U.S. Pat. No. 3,236,255. The ball valve is rotated to close in one form of the safety valve when the pressure above the ball valve drops below a predetermined value and in another form when the flowing pressure differential across the ball valve exceeds a predetermined value.
U.S. Pat. No. 3,070,119 to G. M. Raulins shows another direct controlled safety valve structure which is actuated to close when a predetermined value of differential flowing pressure below and above an orifice is reached.
All previously noted patents are incorporated herein for reference. | null | minipile | NaturalLanguage | mit | null |
Janet Burks retired after 31 years as a child support case manager at Wyandot County Department of Job and Family Services.
Burks celebrated with family, friends and co-workers during her final day in the office Wednesday.
MOUNT BLANCHARD — Riverdale’s Carrol Pauley and Kyle Evans are no strangers to the competition of the Division III state track and field meet.
The Riverdale seniors both will be making their third appearances in Columbus this week when Pauley competes for the Falcons in the discus and shot put, and Evans puts on his running shoes in the 400 dash and as a member of the team’s 3200 relay.
SYCAMORE — After being on the cusp of the state meet in the girls 3200 relay for the past two years, Mohawk finally broke through this year.
Juniors Destini Oler and Anna Stillberger, freshman Alexa Konkle and sophomore Madison Fredritz earned a spot in Friday’s state race by holding on for fourth place last Wednesday in the Fairfield Union regional meet.
CAREY — Carey’s historic softball season could have been derailed early by tragedy.
There was a full week between its first game of the season, a 10-0 win in five innings over Riverdale, and its second game, an 8-4 loss at Upper Sandusky.
TIFFIN — On April 28, 2017, Dr. Robert J. Dornauer, Oral and Maxillofacial Surgeon, attended the first American Association of Oral and Maxillofacial Surgeons Anesthesia Patient Safety Conference at the American Society of Anesthesiologists headquarters in Schaumburg, Illinois, a northern suburb of Chicago.
Elks Exalted Ruler Zak Amert (third from left) announced the group’s Middle School Students of the Year honorees during a recent Awards Night at Union Middle School.
Kaylan Shock (left) and Emery Pahl (right) received certificates and gift cards for their achievements this school year.
Recent Headlines
FREDERICK, Md. — Two Wyandot County youth captured regional titles earlier this month through the Elks Soccer Shoot competition.
Sophie Lucas of Nevada and Gabe Randall of Upper Sandusky represented Ohio in the Mid-Atlantic Elks Soccer Shoot over the first weekend of March in Frederick, Maryland, and both took home first-place honors.
CAREY — The Dorcas Carey Library received a substantial donation Thursday evening from Upper’s Winter Fantasy of Lights.
Representatives from the Fantasy of Lights presented a check for $35,000 to library staff and board members in a brief ceremony.
The Fantasy of Lights donates to a different local non-profit each year.
An Upper Sandusky man was arrested Wednesday after the Wyandot County Major Crimes Unit recovered over 100 marijuana plants from an Upper Sandusky residence.
William S. Rimmer, 37, of Upper Sandusky, was arrested in Marion County and transported to Wyandot County where he faces felony charges. | null | minipile | NaturalLanguage | mit | null |
Report: Jays interested in OF Cain
TSN.ca Staff
Lorenzo Cain
, John Williamson/Getty Images
The Toronto Blue Jays are in the market for outfielders and speed, according to Jon Heyman of FanRag Sports they have interest in Former Kansas City Royals centrefielder Lorenzo Cain, a player that could potentially provide both.
Jays have interest in Lorenzo Cain. They’re believed to prefer a four-year deal. However he’s thought to have strong market.
The report indicates that the team would like to ink the free agent to a four-year deal, but that other teams are also in the mix.
The 31-year-old appeared in 155 games last season for the Royals, hitting 15 homers while providing 49 RBIs. He also hit .300 with a .363 on base percentage and stole 26 bases while getting caught only twice.
Cain is an eight-year Major Leaguer, with all but one season spent with the Royals, he made his MLB debut in 2010 with the Milwaukee Brewers.
The Blue Jays struggled with team speed last season finishing the season with only five triples, a record low. Cain had five triples last season among his career high 175 hits. | null | minipile | NaturalLanguage | mit | null |
include/master-slave.inc
Warnings:
Note #### Sending passwords in plain text without SSL/TLS is extremely insecure.
Note #### Storing MySQL user name or password information in the master info repository is not secure and is therefore not recommended. Please consider using the USER and PASSWORD connection options for START SLAVE; see the 'START SLAVE Syntax' in the MySQL Manual for more information.
[connection master]
include/stop_slave.inc
set @save.slave_parallel_workers= @@global.slave_parallel_workers;
set @@global.slave_parallel_workers= 4;
include/start_slave.inc
include/diff_tables.inc [master:d32.t8, slave:d32.t8]
include/diff_tables.inc [master:d32.t7, slave:d32.t7]
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include/diff_tables.inc [master:d16.t2, slave:d16.t2]
include/diff_tables.inc [master:d16.t1, slave:d16.t1]
include/diff_tables.inc [master:d15.t8, slave:d15.t8]
include/diff_tables.inc [master:d15.t7, slave:d15.t7]
include/diff_tables.inc [master:d15.t6, slave:d15.t6]
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include/diff_tables.inc [master:d14.t8, slave:d14.t8]
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set @@global.slave_parallel_workers= @save.slave_parallel_workers;
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| null | minipile | NaturalLanguage | mit | null |
This research proposes a mental health study to accomplish a prospective longitudinal assessment of the differential impact which institutionalization of a parent has on the adult child. The goal of the study is to identify those factors which may influence the intensity, duration, and frequency of negative consequences of coping with the stressor. The specific aims of the study are to examine the role of stressors, resources, and subjective perceptions of stressors as they affect: (1) the roles which the adult child plays vis-a-vis his/her institutionalized parent, and (2) the level of crisis/adaption experienced by the adult child. The study proposes to sample approximately 400 adult children whose parents are currently permanent residents of long-term care facilities. At intake to the study, parents will have experienced institutional stays of different lengths. Three interviews each at six month intervals will be done with each adult child during the course of one year. This procedure, which combines cross-sectional and longitudinal designs would yield information regarding the stresses experienced by adult children during the full course of institutionalization. The study would examine crisis and adaptation responses on the part of the adult child over time and extends previous life event research by considering the impact of a chronic, long-term stressor. The design provides for a stream of variation in stressors, allowing a regorous empirical test of the theoretical medel described by Hill (1949) and extended by McCubbin and Patterson (1982). Results are expected to provide the basis for testing and modifying an integrative model of crisis and adaption. The study is expected to provide significant new information relevant to identifying appropriate interventions and policies which could significantly reduce social and emotional problems experienced by adult children of institutionalized elderly and enable more positive parent-child and child-institution interactions to occur, thereby increasing the well-being of both adult children and their elderly institutionalized parents. | null | minipile | NaturalLanguage | mit | null |
Q:
Probability of sumprocess
Consider $(X_n)_{n\ge 1}$ iid with $P(X_1=1)=P(X_1=-1)=\frac{1}{2}$. Then there is the sumprocess $S_n:=\sum_{i=1}^n X_i$ and the stopping times $$T_{a,b}:=\min\{n\ge 1:S_n\in\{a,b\}\},$$ $$T_{a}:=\min\{n\ge 1:S_n=a\},$$
of first moment when $S_n\in\{a,b\}$, in the second case, when $S_n=a$.
I already was able to show, that
$$P(T_{a,b}>n(b-a))\le(1-\frac{1}{2^{b-a}})^n$$ by induction,
$$E[T_{a,b}]<\infty$$
by using estimations with the probability above,
$$P(S_{T_{a,b}}=a)=\frac{b}{b-a}$$
by using Wald's equation.
Now, by using this last result, I want to show that
$$P(T_a<\infty)=1$$
and
$$E[T_a]=\infty.$$
It may be again useful to use Wald's equation (maybe by contradiction?), but I do not really see how $T_{a,b}$ and $T_a$ are connected.
A:
First of all, note that for any $k \in \mathbb{N}$
$$\left\{S_{T_{a,k}}=a \right\} \subseteq \{T_a < \infty\}. \tag{1}$$
Indeed: If $\omega \in \{S_{T_{a,k}}=a\}$, then $S_{T_{a,k}}(\omega)=a$, and in particular there exists $n \in \mathbb{N}$ such that $S_n(\omega)=a$ (namely, $n=T_{a,k}(\omega)$).
It follows from $(1)$ that
$$\mathbb{P}(T_a<\infty) \geq \mathbb{P} \left( S_{T_{a,k}}=a \right) = \frac{k}{k-a}. \tag{2}$$
As $k \in \mathbb{N}$ is arbitrary, this implies
$$\mathbb{P}(T_a<\infty) \geq \sup_{k \in \mathbb{N}} \frac{k}{k-a}=1.$$
This proves the first assertion. To prove that $\mathbb{E}(T_a)=\infty$ we can indeed use a proof by contradiction. If $\mathbb{E}(T_a)$ was finite, then Wald's equation would imply $\mathbb{E}(S_{T_a})=\mathbb{E}(S_0)=0$; this is clearly wrong as $S_{T_a}=a$ a.s. implies $\mathbb{E}(S_{T_a})=a$.
| null | minipile | NaturalLanguage | mit | null |
The idea of the Spime proposed by Bruce Sterling is outrageous and extraordinary. I love the concept of being able to track an object's existence from cradle to grave. Here a small retailer is trying to use QR codes, or meta tags to help track the life of their art pieces.
Itizen is a very neat site and offers an interesting experience. I think the challenge is that it is going to require a lot more participation to get to the critical mass it needs. Bruce would say embed an RFID chip and forget about it, but I like the requisite interaction - makes you feel more part of the story of the object.
Yes, it is the day after social media day and the internet is still standing. The wireless access got a bit buggy thanks to all of the tweets, and Foursquare chek-ins, and live streams but we survived. We also learned something - that social media is really about being social. People did not celebrate social media day by sitting at home chatting online. They got together in bars, and at events in person to celebrate the uniting power of the technology.
Just remember that when considering a marketing campaign or strategy. Social media brings people together for a reason. The key is giving them a reason to get together! | null | minipile | NaturalLanguage | mit | null |
Controlling basal expression in an inducible T7 expression system by blocking the target T7 promoter with lac repressor.
Effects of placing a lac operator at different positions relative to a promoter for bacteriophage T7 RNA polymerase were tested. Transcription can be strongly repressed by lac repressor bound to an operator centered 15 base-pairs downstream from the RNA start, but T7 RNA polymerase initiates transcription very actively from this T7lac promoter-operator combination in the absence of repressor, or in the presence of repressor plus inducer. Sequence changes in the transcribed region were found to make transcription from some T7 promoters, including the T7lac promoter, more sensitive to inhibition by T7 lysozyme. The pET-10 and pET-11 series of plasmid vectors have been constructed to allow target genes to be placed under control of the T7lac promoter and to be expressed in BL21(DE3) or HMS174(DE3), which carry an inducible gene for T7 RNA polymerase. These vectors carry a lacI gene that provides enough lac repressor to repress both the T7lac promoter in the multicopy vectors and the chromosomal gene for T7 RNA polymerase, which is controlled by the lacUV5 promoter. Very low basal expression of target genes is achieved, but the usual high levels of expression are obtained upon induction. Addition of T7 lysozyme can reduce basal expression even further and still allow high levels of expression upon induction. Genes that are very toxic to Escherichia coli can be maintained and expressed in this system. | null | minipile | NaturalLanguage | mit | null |
Introduction {#Sec1}
============
Iron deficiency is a major global public health problem, common in adolescence, in menstruating women and in elderly, and particularly evident in developing countries. In addition, several diseases cause iron deficiency, including intestinal parasite infections, malaria, gastric and duodenal ulcers, gastrointestinal cancer and rare mutations in genes encoding ion transporters^[@CR1],\ [@CR2]^. Iron deficiency can be efficaciously controlled by iron supplementation or food fortification. Unfortunately, the water-soluble and bioavailable ferrous sulphate, fumarate or gluconate, that are currently used therapeutically, affect the gastrointestinal tract with significant side effects such as constipation, diarrhoea and nausea^[@CR3]^; moreover, iron salts cause unacceptable changes in the colour and taste of foods^[@CR4]^. In contrast, poorly water-soluble compounds cause fewer sensory changes, but present limited bioavailability. Recently, the use of NPs in iron supplementation and fortification has been suggested since their use may combine high bioavailability, good product stability, limited side effects and absence of changes of taste and colour of the fortified foods^[@CR5]--[@CR8]^. Moreover, *in vitro* and *in vivo* experiments have shown that iron NPs can be considered safe^[@CR9],\ [@CR10]^. Nanoformulations have also found their way into the fortification of animal feeds^[@CR11]--[@CR13]^. Ferritin, which is well absorbed^[@CR14]^, is itself composed of an iron oxide nanocore surrounded by a protein shell and, recently, a nanoparticulate mimetic of the ferritin core was proposed as a potentially side effect-free form of cheap supplemental iron^[@CR15]^.
In the gut lumen, dietary iron is present as heme and non-heme (inorganic) iron; inorganic iron can be found in two oxidation states: ferrous (Fe^2+^) iron and, predominantly, as ferric (Fe^3+^) iron. Ferric iron is reduced to ferrous iron by duodenal cytochrome b, an enzyme present on the plasma membrane of the enterocyte brush border; Fe^2+^ is eventually transported into the cytoplasm by means of the divalent metal transporter DMT1^[@CR1],\ [@CR16]^ Nanoparticulate iron might follow a different route to access enterocyte cytoplasm. Powell and colleagues^[@CR15],\ [@CR17]--[@CR19]^ have suggested that nanoparticulate iron, like ferritin^[@CR20]^, enters cells by endocytosis reaching the cytoplasm by lysosomal escape. Endocytosis is, indeed, the canonical mechanism by which NPs are known to be up-taken^[@CR21]^, but it might not be the only one. The work on ferritin core mimetics focused on highly disperse NPs with an outer layer of charged short-chain carboxylates^[@CR15]^, however, poorly charged or 'naked' (i.e. lacking an outer coating) NPs may behave differently. In effect, it has been recently postulated that some metal NPs might also cross the plasma membrane by a non-endocytotic pathway^[@CR22]--[@CR28]^ gaining a direct access to the cytoplasm. Indeed, we have recently confirmed this pathway for cobalt oxide NPs. This pathway, which involves perforation of the lipid bilayer, is usually poorly considered and challenges the idea of non-permeability of membranes to hydrophilic molecules or supramolecular structures.
To verify this possibility, we have studied commercially available iron based NPs that do not comprise a dispersing outer layer. We have characterized their size and surface charge and, through a recently developed protocol, we have followed the cytoplasmic concentration dynamics of iron, demonstrating that iron oxide NPs, but not zerovalent iron NPs, were up-taken. We have also shown that the NP crossing of the plasma membrane is accompanied by a transient increase of membrane conductance, but this crossing did not occur when the iron oxide NPs were aggregated or surrounded by a protein corona.
Results and Discussion {#Sec2}
======================
Calcein and *Xenopus laevis* oocytes for monitoring intracellular iron increase {#Sec3}
-------------------------------------------------------------------------------
As a preliminary step, we have tested the ability of Calcein to detect intracellular iron concentration increases in fully-grown *Xenopus laevis* oocytes. Fully-grown oocytes are large cells arrested at prophase of meiosis I, which provide a simple system for the study of membrane transport. Calcein is a divalent metal ion chelating fluorochrome whose fluorescence, at physiological pH, is strongly quenched by cobalt, nickel, copper, iron and manganese divalent cations.
To this aim, we have prepared transfected *Xenopus* oocytes expressing the Divalent Metal ion Transporter 1 from rat (rDMT1). This membrane protein is a proton dependent transporter of divalent metal ions such as Fe^2+^, Mn^2+^, Co^2+^, Ni^2+^ and Cd^2+^ ^[@CR29]--[@CR32]^. We have performed voltage-clamp experiments in transfected (i.e., injected with DMT1 cRNA) and in non-transfected (control) oocytes exposed to FeCl~2~, both at pH 5.5 and 7.6. We have calculated transport currents as the difference between the currents recorded in the presence and in the absence of 100 µM FeCl~2~ in the external solution. As shown by the current-voltage (I-V) relationship (Fig. [1A](#Fig1){ref-type="fig"}), no transport currents were recorded in non-transfected (control) oocytes when exposed to iron ions confirming the absence of endogenous electrogenic Fe^2+^ transporters in the oocyte plasma membrane. Conversely, in rDMT1 transfected oocytes, at pH 5.5, but not at pH 7.6, the presence of FeCl~2~ in the extracellular solution elicited large inward currents at negative potentials. This indicates that, at pH 5.5, a transmembrane transport of iron ions occurs in rDMT1 transfected oocytes.Figure 1Calcein as iron detector. (**A**) Current-voltage (I-V) relationships of Non-Transfected (NT) oocytes and DMT1-expressing oocytes at pH 5.5 and 7.6; note that only DMT1-transfected oocytes at pH 5.5 are able to transport iron ions causing large inward currents. (**B**) Calcein quenching is plotted versus time as the ratio of the fluorescence (F~I~) and the fluorescence recorded at time 0 (F~0~); again only DMT1-transfected oocytes at pH 5.5 are able to transport iron ions causing the increase of their intracellular concentration. (**C**) Representative images of oocytes injected with Calcein and increasing amount of iron ions to obtain the standard curve of panel D. (**D**) The mean values of fluorescence, normalized to the mean values of fluorescence measured in oocytes injected with Calcein alone are plotted versus intracellular iron concentration; (from 60 to 80 from 3 batches for each concentration) of oocytes for each iron concentrations; data were fitted with a logistic curve (K~0.5~ = 3.97 ± 2.09 µM).
We repeated the same experimental plan in oocytes previously injected with Calcein (25 µM) to demonstrate that Calcein was able to detect an intracellular increase of Fe^2+^ concentration. As shown in Fig. [1B](#Fig1){ref-type="fig"}, we monitored the reduction of Calcein fluorescence for 30 min in transfected and in non-transfected oocytes exposed to 100 µM FeCl~2~ at pH 5.5 and 7.6. The results clearly show that a significant quenching of the fluorescence occurred only in DMT1 expressing oocytes at pH 5.5. It has to be noted that in DMT1 expressing oocytes at pH 7.6 no current (Fig. [1A](#Fig1){ref-type="fig"}) and no Calcein quenching (Fig. [1B](#Fig1){ref-type="fig"}) was recorded, according to the transporter pH dependence. These experiments, taken together, demonstrate that Calcein can detect an increase in the concentration of intracellular iron ions, and that oocytes are devoid of endogenous iron transporters.
To define the sensitivity of the method, we have injected oocytes with a fixed amount of Calcein together with increasing amounts of FeCl~2~. We have then measured the residual fluorescence for each iron concentration and we have recorded a dose dependent reduction of the emission values (Fig. [1C](#Fig1){ref-type="fig"}) that we have fitted with a logistic equation (Fig. [1D](#Fig1){ref-type="fig"}). Given an oocyte volume of about 1 µl, the K~0,5~ resulted 3.97 ± 2.09 (SE) µM. By means of this curve, we can estimate the concentrations of iron ions in the cytoplasm of *Xenopus* oocytes. Indeed, Fig. [1B](#Fig1){ref-type="fig"} shows that DMT1 transfected oocytes reach, 30 min after exposure to FeCl~2~, quenching values corresponding to concentrations of about the 5 µM.
After 30 min of exposure of *Xenopus* oocytes to radioactive iron, Marciani and colleagues^[@CR33]^ reported concentrations slightly higher. Their experimental approach based on radioactive ^55^Fe^2+^, however, considered the total amount of iron that entered the cytoplasm through DMT1. Since a large amount of iron might become protein-bound, they estimated the total concentration of the iron ions.
Iron oxide NPs cross the plasma membrane of *Xenopus laevis* oocytes {#Sec4}
--------------------------------------------------------------------
After having verified that we were able to detect an increase of iron ions in the cytoplasm of *Xenopus* oocytes that were filled with Calcein, we have used them to reveal the possible permeation of iron NPs inside the cell. To this aim, we have chosen iron NPs in two different forms, zerovalent (Fe) and oxide (Fe~3~O~4~). Similarly to other metal NPs^[@CR10],\ [@CR21],\ [@CR34]^, iron^[@CR35]^ and iron oxide^[@CR36],\ [@CR37]^ NPs undergo dissolution releasing iron ions that, as we have here demonstrated, can be detected by Calcein quenching. As such, we exposed Calcein-filled oocytes to iron NPs. In oocytes obtained from different batches, iron oxide NPs constantly induced a quenching of Calcein fluorescence (Fig. [2](#Fig2){ref-type="fig"}, blue column). This fluorescence decrease, although lower than that occurring in rDMT1 expressing oocytes exposed to 100 µM FeCl~2~ (Fig. [2](#Fig2){ref-type="fig"}, dark blue column), was significantly greater than that occurring in non-transfected oocytes either exposed (Fig. [1B](#Fig1){ref-type="fig"}, black squares) or not exposed (Fig. [1B](#Fig1){ref-type="fig"}, white diamond and Fig. [2](#Fig2){ref-type="fig"}, white bar) to FeCl~2~. These results suggest that Fe~3~O~4~ NPs interact with the plasma membrane of the oocyte, cross it and, once in the cytoplasm, dissolve causing the observed Calcein quenching. Zerovalent iron NPs, instead, did not cause a reduction of fluorescence (Fig. [2](#Fig2){ref-type="fig"}, dark cyan column) suggesting that, in this case, NPs do not cross the plasma membrane of the oocyte.Figure 2Iron oxide NPs induce intracellular iron increase. Histogram of the means of the F~30~/F~0~ values calculated as the fluorescence values at time 30 min normalized for the fluorescence values at time 0. Fe~3~O~4~ NPs (blue column) caused a statistically significant quenching of Calcein compared to the controls, i.e., Calcein injected oocytes exposed to external control solution at pH 7.6 (white column). Conversely, Fe NPs (green column), aggregated Fe~3~O~4~ NPs (blue barred column) and BSA modified Fe~3~O~4~ NPs (cyan column) did not induce quenching; rDMT1 transfected oocytes exposed to iron chloride were used as positive controls (dark blue column). Bars represent ± SEM; from 10 to 40 oocytes for each column deriving from 2 to 8 batches were used. Statistical analysis was performed with One-way ANOVA and orthogonal comparisons with Holm-Bonferroni post hoc test (\*\*\*p \< 0.005).
In a previous paper, we attributed the different biological behaviour (capacity to cross cell membranes) between metal oxide and zerovalent metal NPs to the chemical and physical characteristics of their surfaces. To better understand the causes of these differences, in this paper, we have measured z-potentials and described the aggregation dynamics of both NPs. The z-potentials, as determined by Laser Doppler Micro-electrophoresis (Fig. [3](#Fig3){ref-type="fig"}, top), were −5.0 ± 0.2 mV and −2.2 ± 0.1 mV for zerovalent iron and iron oxide NPs, respectively. Thus, both types of NPs are poorly charged when suspended in external control solution and this does not explain the difference in capacity to cross cell membranes, but explains why both NPs rapidly aggregate into micronized assemblies when added to media (Fig. [3](#Fig3){ref-type="fig"}, bottom) despite prior ultrasonication. Indeed, z-potentials above 30 mV or below −30 mV are generally required to maintain NPs disperse in solution through electrostatic repulsion. However, the rate of aggregation, as determined by Static Light Scattering (Fig. [3](#Fig3){ref-type="fig"}, bottom), differed between zerovalent NPs, which aggregated very rapidly, and iron oxide NPs, which retained a sub-micron population for at least 5 min (Fig. [3](#Fig3){ref-type="fig"}, insets of bottom graphs). We think that the NPs that constitute this sub-micron population are those that can cross the plasma membrane possibly because these remained below a not yet determined upper particle size limit for plasma permeation. Physical penetration of lipid bilayer membranes by NPs has been demonstrated to possibly occur by dissipative particle dynamics simulations for single NPs and for very small clusters. Aggregated NPs, instead, are likely too large to penetrate the lipid bilayer^[@CR28]^. Indeed, when the oocytes were exposed to aggregated NPs, we did not record Calcein quenching (Fig. [2](#Fig2){ref-type="fig"}, blue barred column).Figure 3Charge and hydrodynamic size of zerovalent iron (Fe^0^) (A and C) and iron oxide (Fe~3~O~4~) (B and D) NPs in external control solution (0.1 mg/mL). Zeta potential (top graphs) was determined by Laser Doppler Micro-electrophoresis as −5.0 ± 0.2 mV and −2.2 ± 0.1 mV for zerovalent iron and iron oxide NPs, respectively (N = 3). Hydrodynamic size was determined over time by Static Light Scattering (bottom graphs).
NPs do not impair oocyte plasma membrane integrity, but open a transient conductance {#Sec5}
------------------------------------------------------------------------------------
To learn more about the interactions of NPs with the plasma membrane of the oocytes, we have followed possible changes of its integrity due to exposure to Fe~3~O~4~ NPs by Two Electrodes Voltage Clamp (TEVC). With a similar approach, Bernareggi and colleagues^[@CR38]^ have recently evaluated the effects of asbestos fibres on *Xenopus* oocyte membrane.
We have measured membrane capacitance, resting potential and resistance during a 30 min period of exposure to Fe~3~O~4~ NPs. Since we have noticed that the alterations of membrane parameters occur within the first 5 min, we have decided to perform the electrophysiological measurements after 5 and 20 min of exposure; we have also exposed oocytes to NPs that, after sonication, were left undisturbed for 30 min. A statistically significant decrease of membrane resistance, as shown in Fig. [4](#Fig4){ref-type="fig"}, occurs only in oocytes exposed for 5 min and disappears completely in oocytes exposed for 20 min. A slight decrease of resting potential, statistically significant, accompanied the decrease of membrane resistance. Membrane capacitance, instead, remained unaffected by Fe~3~O~4~ NPs treatment.Figure 4Effects of Fe~3~O~4~ NPs on oocyte membrane electrical properties. Mean values of membrane electrical parameters registered from oocytes exposed to control conditions (white columns), to a Fe~3~O~4~ NP suspension for 5 min (blue columns) or for more than 20 min (green columns), and to NPs that after sonication, were left undisturbed for 30 min (blue barred columns). Membrane capacitance of control and treated oocytes showed no significant differences at any incubation times. Resting potential and Membrane resistance significantly diminishes in oocytes treated 5 min with Fe~3~O~4~ NPs compared to their controls; the difference disappears in oocytes treated for 20 min and in oocyte treated with aggregated NPS. Bars represent mean ± SEM; 14 to 30 oocytes from 2 oocyte batches were used. Statistical analysis was performed with one-way ANOVA and orthogonal comparisons with Holm-Bonferroni post hoc test (\*p \< 0.05--\*\*p \< 0.01).
The decrease of membrane resistance can be attributed to the opening of a small transient conductance. On the other hand, the constancy of membrane capacitance is an indication that no large endocytosis phenomena occur after exposure to iron oxide NPs^[@CR39]^, while the small reduction of the resting potential proves that the membrane has maintained its integrity^[@CR40]^, notwithstanding a small increase of ion permeability.
To investigate further this transient conductance, we have performed a protocol to obtain I-V curves. Figure [5A](#Fig5){ref-type="fig"} shows representative current traces recorded after imposing voltage steps in a control oocyte and in an oocyte exposed to Fe~3~O~4~ NPs for 5 min. We have calculated the average currents at each potential and reported these data in the I-V curves of Fig. [5D](#Fig5){ref-type="fig"}. At potentials more negative than −40 mV and more positive than +30 mV, a slight increase of the currents obtained in exposed oocytes, compared to those in the control condition, is evident. This current increase is statistically significant only in oocytes tested within 5 min of the NPs treatment and it tends to disappear in oocytes exposed for more than 20 min and is not present in oocytes exposed to NPs that, after sonication, were left undisturbed for 30 min. The I-V curves confirm the onset of a conductance caused by the exposure to Fe~3~O~4~ NPs for 5 min and its transient nature.Figure 5Membrane currents recorded in oocyte exposed or not to Fe~3~O~4~ NPs. (**A**) Voltage Protocol: from holding potential of −40 mV, 10 mV steps of 1 s were applied from −80 mV to +50 mV. Representative traces recorded from oocytes not exposed (**B**) or (**C**) exposed for 5 min to Fe~3~O~4~ NPs. In D, the averages of steady state membrane currents are reported as I-V relationships. After 5 min of NP exposure (blue circles), a slight, but statistically significant current increase is recorded at the curve extremes; after 20 min (blue triangles), no more statistically significant differences can be appreciated. Aggregated NP treatment generated in oocytes currents (red diamonds) almost overlapping with controls (black squares) and 20 min treatment currents, and that is an indication of the inefficacy of this treatment (\*p \< 0.05, \*\*\*p \< 0.005; one-way ANOVA, Holm-Bonferroni post hoc orthogonal comparison; 14 to 30 oocytes from 2 batches).
Protein corona impedes plasma membrane crossing and the opening of the transient conductance {#Sec6}
--------------------------------------------------------------------------------------------
To verify our hypothesis concerning the role of the interactions between NPs and plasma membrane, we tested uptake of Fe~3~O~4~ NPs in bovine serum albumin (BSA) containing media. These molecules create a coating around the NPs, referred to as protein corona. This corona is highly dynamic and its formation and stability depends on NP characteristics and environmental variables^[@CR41]^. BSA is negatively charged in water, but not in this media (Supp Figure [S1](#MOESM1){ref-type="media"}) presumably due to the presence of positively charged calcium and magnesium ions. Consequently, the addition of BSA did not alter the surface charge of the iron oxide NPs (zeta potential was −1.3 ± 0.2 mV; Fig. [6](#Fig6){ref-type="fig"} top). However, the addition of BSA did increase dispersibility as determined by the presence of the sub-micron fraction for the duration of the assay (Fig. [6](#Fig6){ref-type="fig"}). As shown above, plasma membrane crossing occurs in the presence of disperse colloids; however, exposure to BSA-coated Fe~3~O~4~ NPs did not cause fluorescence quenching (Fig. [2](#Fig2){ref-type="fig"}, cyan column). Therefore, protein corona prevents or significantly reduces the interactions between NPs and the oocyte plasma membrane blocking or limiting the passage of NPs into the cytoplasm. These findings are also in agreement with experiments where the interaction of cationic polystyrene NPs with artificial lipid bilayers were eliminated with serum proteins^[@CR42]^.Figure 6Zeta potential distribution (top) and particle size distribution over time (bottom) of a suspension of Fe~3~O~4~ NPs (0.1 mg/mL) in external control solution with 1 mg/mL BSA. Zeta potential was determined by Laser Doppler Micro-electrophoresis as −1.3 ± 0.2 mV (N = 4).
To confirm this hypothesis, we have performed TEVC experiments to obtain I-V curves (Fig. [7](#Fig7){ref-type="fig"}). After having verified that BSA *per se* does not affect membrane conductance, we have compared oocytes exposed to BSA-modified Fe~3~O~4~ NPs with unexposed oocytes, and to oocytes exposed to Fe~3~O~4~ NPs. These experiments suggest that, when NPs are surrounded by a protein corona, they become unable to modify membrane resistance.Figure 7Protein corona affects NP capacity to elicit membrane currents. I-V relationships of control oocytes and oocytes treated for 5 min with BSA are compared in the left panel and no statistically significant differences are present, indicating that BSA does not affect per se membrane resistance. In the central panel, it is shown that Fe~3~O~4~ NPs that were coated with a BSA corona do not cause a decrease of the membrane resistance suspension. In the right panel, the I-V relationships of oocytes treated for 5 min with Fe~3~O~4~ NPs and BSA coated Fe~3~O~4~ NPs are compared. Their difference is statistically significant, indicating that the presence of a protein corona around Fe~3~O~4~ NPs diminishes their capacity to elicit membrane currents. Statistical analysis was performed with one-way ANOVA and orthogonal comparisons with Holm-Bonferroni post hoc test (\*p \< 0.05); 27 to 61 oocytes for each condition from 3 to 4 batches were used.
Conclusions {#Sec7}
===========
In conclusion, we have added further evidence to the possibility of cytomembranes being permeable to uncoated NPs. Endocytosis is the typical mechanism cells use to uptake NPs that, in this way, gain access to the endosomal compartment. Conversely, by directly crossing lipid bilayers, NPs enter cytoplasm and other cellular compartments. Moreover, we have shown that the penetration by NPs of the lipid bilayer opens a transient conductance that does not impair plasma membrane integrity.
Whether we should favour NP presence in the cytoplasm or avoid it, we have to understand the mechanisms that regulate their uptake and consider how physicochemical properties of NPs impact on their fate. In this work, we have also learned that, unlike iron oxide NPs, zerovalent iron NPs do not cross plasma membranes. We have explained this different behaviour with the very fast aggregation rate of zerovalent iron NPs. In addition, we have shown that the crossing of metal oxide NPs can be impeded by a protein corona. Indeed, proteins are abundant in the tissue fluids, but NPs could be functionalized to become corona-free^[@CR43]^, thus potentially enabling the non-endocytic pathway. For example, superparamagnetic iron oxide NPs can be induced to rotate around their axes by a remote magnetic field^[@CR44]^ and have been used to kill cancer cells through mechanical rupture^[@CR45]^. Understanding the mechanisms that regulate NP uptake or their interactions with the cellular membrane could help in potentiating the anticancer properties of such NPs.
We also understand that the conditions iron NPs find in the gastrointestinal tract greatly differ from those of the simple model system we have used. In particular, the intestinal millieu comprises a diverse group of soluble species, ranging from small carboxylates throught bile acids to high molecular weight mucins^[@CR46]--[@CR48]^, many of which may interact with the surface of uncoated NPs and, in doing so, may alter their behaviour. This now merits assessment in future studies using conditions that are representative of the complex gastrointestinal environment.
Materials and Methods {#Sec8}
=====================
Solutions {#Sec9}
---------
ND96 solution had the following composition (in mM): NaCl 96, KCl 2, CaCl~2~ 1.8, MgCl~2~ 1, HEPES 5, pH 7.6; NDE solution was composed of ND96 plus 2.5 mM pyruvate and 50 µg/mL Gentamycin sulphate; external control solution contained (in mM): NaCl 98, MgCl~2~ 1, CaCl~2~ 1.8, HEPES or MES 5, pH 7.6 or 5.5; intracellular solution contained (in mM): KCl 130, NaCl 4, MgCl~2~ 1.6, EGTA 5, HEPES 10, glucose 5, pH 7.6. The final pH values of 5.5 or 7.6 were adjusted with HCl and NaOH.
Oocytes collection and preparation {#Sec10}
----------------------------------
Oocytes were obtained from adult *Xenopus laevis* females. Animals were anaesthetised in 0.1% (w/v) MS222 (tricaine methansulfonate) solution in tap water; after carefully cleaning the frog abdomen with an antiseptic agent (Povidone-iodine 10%)^[@CR49]^, laparotomy was performed and portions of the ovary were collected. The oocytes were treated with 0.5 mg/mL collagenase (Sigma Type IA) in ND96 calcium free for at least 30 min at 18 °C. Healthy and fully grown oocytes were selected and stored at 18 °C in NDE solution^[@CR50]^. The oocytes to be transfected with the cRNA coding for rDMT1 were injected with 25 ng of cRNA in 50 nL of water, the day after the removal, using a manual microinjection system (Drummond Scientific Company, Broomall, PA) and incubated at 18 °C for 3--4 days before electrophysiological or fluorescence experiments. The experimental protocol was approved locally by the Committee of the "Organismo Preposto al Benessere degli Animali" of the University of Insubria (OPBA-permit \#02_15) and nationally by Ministero della Salute (permit nr. 1011/2015).
NP preparation and incubation conditions {#Sec11}
----------------------------------------
Zerovalent (Fe, 25 nm, IOLITEC, Salzstrasse 184, D-74076 Heilbronn) and oxide (Fe~3~O~4~, \<50 nm TEM determined, Sigma-Aldrich) iron NPs were prepared as 10 mg/mL stock suspensions in deionised water and sonicated before addition of 10 μL to the test chamber (4 wells plate) containing 990 μL of external control solution (pH 7.6). Oocytes were then added to the chamber.
For electrophysiological experiments, the oocytes were transferred to the TEVC recording chamber within 5 min or after 20 min from the beginning of the exposure. For the fluorescence assay, recordings start immediately after oocytes addition to the test chamber. Treatments with the aggregated NPs were performed adding oocytes to the suspension of NPs that were let to aggregate in the test chamber for 30 min after sonication.
All experiments were carried out at room temperature.
Fluorescence Assay {#Sec12}
------------------
Oocytes were injected with a 50 nL drop of intracellular solution containing 25 µM Calcein. In dose-response evaluation experiments (Fig. [1C and D](#Fig1){ref-type="fig"}), solutions containing Calcein and increasing amounts of FeCl~2~ were co-injected in oocytes. Effective intracellular metal concentrations were calculated using the nominal oocyte volume of 1 µL^[@CR51]^. Images were acquired for every oocyte at fixed acquisition parameters, calculated on control oocytes.
In experiments with NPs, images of single oocytes were acquired every 2 min for 30 min with a fluorescence microscope (AxioVert 200, Carl Zeiss with a 4x objective, COLIBRI fluorescence filters, 470 nm excitation - 515 to 565 nm emission) equipped with CCD camera (Axiocam ICM1, Carl Zeiss).
Electrophysiology {#Sec13}
-----------------
The two-electrode voltage clamp was performed with an Oocyte Clamp OC-725B (Warner Instruments, Hamden, CT, USA) that was controlled by Clampex 10.2 (Molecular Devices, Sunnyvale, CA, USA, [www.moleculardevices.com](http://www.moleculardevices.com)). Intracellular glass microelectrodes, filled with 3 M KCl, had tip resistances in the 0.5--4 MΩ range. Agar bridges (3% agar in 3 M KCl) connected the bath electrodes to the experimental chamber. The holding potential applied (V~h~) was −40 mV for all the experiments performed. The I-V curves of Fig. [1A](#Fig1){ref-type="fig"} were obtained applying 20 mV steps of 200 ms from −140 to +40 mV.
Oocytes were transferred in the recording chamber (Warner- RC-1Z) (warneronline.com) and impaled with microelectrodes; to recover from possible damage they were left for 2 min in a continuous solution flux. Only oocytes with resting potential equal or lower than −20 mV were used for the experiments. The number of discarded oocytes was not significantly different between treated and controls.
The capacitance and resistance values that were reported in Fig. [4](#Fig4){ref-type="fig"} were obtained applying 10 mV steps of 20 ms every 200 ms in voltage clamp conditions. The protocol for the I-V curves of Fig. [1](#Fig1){ref-type="fig"} was previously described^[@CR52]^ and for Figs [5](#Fig5){ref-type="fig"} and [7](#Fig7){ref-type="fig"} is shown in Fig. [5A](#Fig5){ref-type="fig"} (10 mV steps of 750 ms from −80 to +40 mV).
Data analysis {#Sec14}
-------------
Data were analysed using Clampfit 10.2 software (Molecular Devices, Sunnyvale, CA, USA, [www.moleculardevices.com](http://www.moleculardevices.com)) while OriginPro 8.0 (OriginLab Corp., Northampton, MA, USA, [www.originlab.com](http://www.originlab.com)) was used for statistics and figure preparation. For the Voltage Step protocol, current values were measured for every voltage step at the steady state condition; mean values at every voltage were calculated and plotted.
Fluorescence decay images were analysed with ImageJ (Rasband, W.S., ImageJ, U. S. National Institutes of Health, Bethesda, Maryland, USA, <http://imagej.nih.gov/ij/>, 1997--2015). For F~30~/F~0~ quantification, the fluorescence intensity at time 0 (F~0~) and at time 30 min (F~t~) was calculated in the entire area of the oocyte. In dose-response experiments, images were analysed calculating fluorescence intensity on the entire area of oocytes and normalized to the control oocytes. Mean values were calculated for every condition and used to determine through a non-linear fitting (Logistic Fitting, OriginPro8) the K~0.5~, relating residual fluorescence to metal concentration.
Static light scattering (SLS) {#Sec15}
-----------------------------
SLS was performed on a Mastersizer 2000 with a Hydro 2000µP Micro Precision sample dispersion unit (Malvern Instruments Limited). Baseline correction was carried out with fresh external control solution (prepared as described above). Next, 200 µL of 10 mg/mL stock suspension was added to the 20 mL dispersion cell to achieve a final concentration of 0.1 mg/mL (as per Oocyte assays). The dispersion unit was run at 1000 rpm and care was taken to prevent bubble formation. The stock suspension was carefully sonicated prior to introduction to the dispersion cell, after which data acquisition was immediately initiated. Size measurements then were carried out over a period of 60 min (refractive index: 2.42; absorption 1.0; dispersant refractive index: 1.33).
Zeta potential {#Sec16}
--------------
The zeta potential of suspensions of iron NPs was determined by Laser Doppler Micro-electrophoresis (Zetasizer NanoZS, Malvern Instruments Ltd) using disposable folded capillary cells (DTS1070). Measurements (N = 3) were carried out using the diffusion barrier as per instrument manufacturer instructions. Briefly, the zeta cell was filled with 100 mM NaCl solution and then 100 µL sample (0.1 mg/mL suspension of NPs in external control solution) was gently injected to the bottom of the cell with a gel-loading tip. Electrophoretic mobility of particles was converted into zeta potentials by Dispersion Technology Software 7.11 using the Smoluchowski approximation, and a viscosity of 0.8872 cP and dielectric constant of 78.5 for the dispersant.
Electronic supplementary material
=================================
{#Sec17}
supplementary info S1
**Electronic supplementary material**
**Supplementary information** accompanies this paper at doi:10.1038/s41598-017-11535-z
**Publisher\'s note:** Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This work was supported by a grant of Fondazione Cariplo (2013-1052) to R.G. We thank Dr. Raffella Cinquetti for her help in performing experiments. This work was supported by the Medical Research Council (programme grant number: MC_U105960399).
All authors designed the experiments and reviewed the manuscript. D.Z., E.B. and C.B. performed the experiments and prepared the figures, E.B., N.F., R.G. and G.B. wrote the manuscript.
Competing Interests {#FPar1}
===================
The authors declare that they have no competing interests.
| null | minipile | NaturalLanguage | mit | null |
Re: st: replace and strpos
I have a list of around 300 postcodes that are string variables. I need
to change the postcode strings into their corresponding borough. I
succeeded in doing this to some extent by writing commands for each
string value using replace and strops. E.g.:
replace borough = "Camden" if strpos(postcode, "NW1")
A problem arises when I run all the commands and it comes to a postcode
that contains some characters that are also in another postcode, i.e. it
overwrites the original.
E.g. the above "Camden" is overwritten by "Westminster" when this
command is run:
replace borough = "Westminster" if strpos(postcode, "W1")
Because it shares the "W1".
Is there any way I can tell Stata to look for the EXACT postcode? I've
looked all around and can't figure it out. | null | minipile | NaturalLanguage | mit | null |
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Classic Night Cream Complex: Reverse harsh sun damage and refresh skin with a moisturizing cream that will alleviate all signs of aging. The hypo-allergenic Night Cream Complex revitalizes skin overnight so you can wake up feeling and look reenergized and new. | null | minipile | NaturalLanguage | mit | null |
Faint yellow dots can barely be seen in this image taken by the Electronic Frontier Foundation
“We didn’t advertise it much to the people that had [the printers],” While technology has clearly advanced since the early age of laser printers, microdots are still very much present — something discovered in a top secret NSA document published by The Intercept earlier this month.
“We didn’t not tell them if they asked. The salespeople were told, ‘Don’t lead with it in any sales, but if they ask you about it, you can tell them we have the security feature in there’.”
While technology has clearly advanced since the early age of laser printers, microdots are still very much present — something discovered in a top secret NSA document published by The Intercept earlier this month.
Unbeknown to the publication at the time, the published document contained a hidden code that identified NSA contractor Reality Winner as the source of the leak.
Security expert Rob Graham explained by downloading the document and inverting the colours in a photo editing program, he was able to reveal a pattern.
When plotted against a grid, these yellow dots denoted specific hours, minutes, dates and numbers.
Thus by reverse-engineering the grid pattern, researchers were able to discover the document had come from a printer with the serial number 535218 or 29535218 — more than enough information to reveal the source.
Funnily enough investigators didn’t need to get so crafty, with an affidavit released by the Department of Justice explaining Winner had actually sent the document to the media outlet from her work email and this is how she was captured.
“The US Government Agency determined that six individuals printed this reporting. Winner was one of these six individuals,” the affidavit read.
“A further audit of the six individuals’ desk computers revealed that Winner had email contact with the News Outlet. The audit did not reveal that any of the other individuals had email contact with the News Outlet.”
While helpful in instances such as this, the yellow dots are also instrumental in helping to expose fraudsters trying to pass a forged document printed in the past six months as something from 2005.
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UNSOCIAL MEDIA
Facebook Messenger DOWN across parts of Europe and North America
GAME SHAME
YouTube flooded with hardcore sex videos from Roblox, a video game for KIDS
RUN RABBIT RUN!
Astonishing pictures show a murder of crows swooping on bunny and pecking it to death before one flies off with it in its beak
“The encoding scheme used by snow relies on the fact that spaces and tabs (known as whitespace), when appearing at the end of lines, are invisible when displayed in pretty well all text viewing programs,” he wrote.
“This allows messages to be hidden in ASCII text without affecting the text’s visual representation. And since trailing spaces and tabs occasionally occur naturally, their existence should not be sufficient to immediately alert an observer who stumbles across them.”
We pay for your stories! Do you have a story for The Sun Online news team? Email us at [email protected] or call 0207 782 4368 | null | minipile | NaturalLanguage | mit | null |
The protein synthesis inhibitors, oxazolidinones and chloramphenicol, cause extensive translational inaccuracy in vivo.
The oxazolidinone family is a new class of synthetic antibiotics that bind to the bacterial 50S ribosomal subunit. Two members of the family, linezolid and XA043, were examined for their effects on translational fidelity using a lacZ reporter gene in vivo. Both promoted highly significant frameshifting and nonsense suppression. Chloramphenicol, a peptidyl transferase inhibitor, affected translational fidelity in a similar fashion. Neither the oxazolidinones nor chloramphenicol stimulated misincorporation of amino acid residues at position 461 in the lacZ gene. In contrast, the aminoglycosides gentamicin and paromomycin, which interact with the decoding region of the 30S subunit, caused significant misincorporation but only modest increases in frameshifting or stop codon readthrough of the lacZ gene. We conclude that effects on translational fidelity may play a significant role in the mechanism of action of the oxazolidinones. | null | minipile | NaturalLanguage | mit | null |
Q:
Cache it or not Cache it(generate it), that is the questiion
I have a collection of say 100 double values that has to be divided by a fix int variable MANY times:
unsigned int current_interval = double_value / int_value;
I need to know if the following simple cache would be a cheaper calculation or not(and why?):
std::map<double_value,current_interval> cache;
//...
unsigned int get_interval(double_value / int_value){
if((it = cache.find(double_value)) != cache.end()
{
return it->second;
}
unsigned int current_interval = double_value / int_value;
cache[double_value] = current_interval;
return current_interval;
}
thank you
A:
Summary: Doing the repeated division is probably faster than looking up the value in a map
Details:
I thought this was an interesting question. At least from the perspective of execution time for a map lookup compared to floating point division. Before addressing this though I want to reiterate two of the comments:
1) If you really only have 100 doubles that you are dividing by a fixed value and then using many times, I expect that you should be able to transform your algorithm to use this result directly. I expect that would be more efficient than the proposed caching algorithm.
2) Don't use a double as a key in a map.
Now on to the main question. To answer it I wrote two small programs. The first simply looks up values in a map of size 100. The second performs floating point division. I've included the full source code in case anyone wants to replicate my results. Also for the second program I've included some extra code simply to keep the same structure, but what matters in the second loop.
map.cpp
#include <map>
#include <stdlib.h>
std::map<int,int> testmap;
int main(int argc, char **argv) {
int count = atoi(argv[1]);
int val = atoi(argv[2]);
int total = 0;
for(int i = 0; i < 100; i++) {
testmap[i] = val + i;
}
for(int i = 0; i < count; i++) {
for(int j = 0; j < 100; j++) {
total += testmap[j];
}
}
return total;
}
double.cpp
#include <map>
#include <stdlib.h>
std::map<int,int> testmap;
int main(int argc, char **argv) {
int count = atoi(argv[1]);
double val = atof(argv[2]);
double total = 0;
for(int i = 0; i < 100; i++) {
testmap[i] = val + i;
}
for(int i = 0; i < count; i++) {
for(int j = 0; j < 100; j++) {
total += val / j;
}
}
return total;
}
I compiled with both O1 and O3 to make sure the compiler wasn't optimizing away the loop. And I also tested with a few different iteration sizes to make sure the execution time scaled with the iteration count.
I ran my tests on a Intel(R) Xeon(R) CPU E3-1275 v3 @ 3.50GHz system compiling with g++ (GCC) 4.9.2
For O1 my results running with 10000000 iterations are:
map: 7.1 seconds
double: 3.6 seconds
For O3 my results are:
map: 5.3 seconds
double: 3.5 seconds
So the difference is not that large, but clearly the division implementation is faster in the small micro-benchmark I wrote here. And also it is what is simpler to implement. So I think it is highly unlikely that trying to memoize the results of division, and then look them up in a map, will be faster than simply calculating the values when you need them. For the memoization to be useful the basic operation would need to be more expensive than floating point division which is heavily optimized in modern CPUs.
| null | minipile | NaturalLanguage | mit | null |
[Synovial cysts of unusual localization. 2 cases and review of the literature].
Two patients with true synovial cysts in atypical sites (internal compartment of knee and inguinal hollow) were investigated by radioarthrography, ultrasound and computed tomography imaging. The cyst in the hip region originated from a dilated serous bursa of the iliopsoas muscle that did not communicate or was no longer in communication with the joint. In contrast, the cyst of the knee appeared to be a lateral synovial capsule hernia. Positive diagnosis in both cases was dependent on combined ultrasound-CT scan imaging, this eliminating a tumor (sarcoma) of soft tissues. However, affirmation of the synovial origin (mesothelial covering of the wall) of the lesion was obtained by histology only, this allowing differentiation from a "capsular" (fibrous wall) cyst, which probably provokes similar ultrasound and CT scan images. | null | minipile | NaturalLanguage | mit | null |
Kansas has refused to contract with math teacher Esther Koontz over her support of the Israel boycott. (ACLU)
A Kansas law requiring state-contracted individuals or companies to file written certification that they are “not currently engaged in a boycott of Israel” is being challenged in a federal lawsuit.
The complaint was filed on Wednesday by the American Civil Liberties Union on behalf of a public high school math teacher, Esther Koontz, who participates in the consumer boycott of Israeli goods.
It marks the first time that a federal lawsuit seeks to challenge a state law against the Palestinian-led boycott, divestment and sanctions (BDS) campaign. Boycotts are a constitutionally protected free speech right.
Though the ACLU told The Electronic Intifada it cannot specify whether or not this is also the first time an individual boycott supporter has faced professional consequences under such a law, the group is “aware that this law, and similar laws in other states, are being enforced.”
The ACLU states that the Kansas law violates the First Amendment for several reasons: “It compels speech regarding protected political beliefs, associations and expression; restricts the political expression and association of government contractors; and discriminates against protected expression based on its content and viewpoint.”
Koontz is a member of the Mennonite Church USA, which passed a resolution in July in support of divestment from companies that profit from violations of Palestinian rights.
The ACLU said that in accordance with the church’s call for boycott and her own protest of Israel’s treatment of Palestinians, Koontz decided to not buy products made by Israeli companies as well as international companies that operate inside Israeli settlement colonies.
All of Israel’s settlements in the occupied West Bank are illegal under international law.
“Not in good conscience”
In addition to teaching math, Koontz trains other teachers as a contractor with the Kansas Department of Education’s Math and Science Partnerships program.
When she was asked to sign a formal declaration certifying that she does not participate in a boycott of Israel, as dictated by the new state law, Koontz said that “she could not sign the form in good conscience,” the ACLU states.
By not signing the form, Kansas refused to award Koontz a contract and she is now unable to participate in the state’s educational training program.
“You don’t need to share my beliefs or agree with my decisions to understand that this law violates my free speech rights,” Koontz stated. “The state should not be telling people what causes they can or can’t support.”
“I’m disappointed that I can’t be a math trainer for the state of Kansas because of my political views about human rights across the globe,” she added.
Legal experts say that as support for Palestinian rights continues to grow, Israel lobby groups have accelerated their promotion of legislation aimed at chilling free speech and blacklisting advocates for Palestinian rights.
“This lawsuit, the first to challenge an anti-BDS law, will send a clear message to those Israel advocacy groups and legislators who have shown a willingness to trample on constitutional rights in order to shield Israel from criticism and accountability,” said Dima Khalidi, director of Palestine Legal.
Precedence
If the ACLU’s lawsuit successfully upends the Kansas anti-BDS law, it could set a precedent for activists and civil rights groups to challenge similar legislation passed in 20 other states and the US Congress.
Thomas Dresslar, an ACLU spokesperson, told The Electronic Intifada that the group hopes the lawsuit “will serve as a reminder to state legislators that the First Amendment protects the right to boycott, forbids ideological litmus tests and prohibits the government from using its economic leverage to silence one side of a public debate.”
Over the summer, the Israel lobby group AIPAC pushed a bill in Congress that could impose large fines and long prison sentences on companies and their personnel if they are deemed to be complying with a boycott on Israel or its settlements called for by an international organization.
The Israel Anti-Boycott Act currently has 261 sponsors in the House and 49 in the Senate.
The ACLU condemned the act for violating constitutional free speech rights.
Due to sustained pressure from legal groups and activists, a handful of US lawmakers have pulled their support of the bill.
In August, 100 civil and human rights organizations endorsed a statement urging lawmakers to reject the bill outright.
But the bill remains a threat, especially given the current administration’s antipathy toward anti-racist protesters and protest movements more generally.
“In the Trump era especially, we must vigilantly safeguard our right to dissent, including the First Amendment right to support boycotts for Palestinian rights,” Palestine Legal’s Khalidi said.
“Elected officials should be in the business of safeguarding our constitutional rights, not legislating them away.” | null | minipile | NaturalLanguage | mit | null |
Field Goals
Field Goal %
Rebounds
Assists
Turnovers
Pts off Turnovers
2nd Chance Pts
Pts in the Paint
Fastbreak Pts
Bench Pts
On Sunday afternoon, the Oglethorpe women's basketball team hosted Birmingham-Southern at Dorough Field House. The Stormy Petrels dominated early in the contest, shooting over 50 percent from the field in the first quarter, and 43 percent in the second. This allowed the Petrels to double the Panthers in points by halftime, 44-22. The Petrels held on to their impressive lead in the final two quarters, securing a 62-44 victory over their SAA rival. The victory increased the Oglethorpe winning streak out to seven games. The Petrels improved to 15-5 on the season and remain in sole possession of first place in the SAA with a 7-1 record.
The Petrels had three players reach double figures in points: sophomore guard Sydney Long with 10 points and an impressive six steals, sophomore guard Taylor Dodson with 18 points to lead her team, and finally freshman forward Savannah LeGate with 14 points and 10 rebounds, recording another double-double, her 14th of the season. Junior guard Bailey Charles served as a spark plug for the Petrels on offense and defense, grabbing six rebounds, scoring seven points, dishing out four assists, and totaling three steals.
The Petrels recorded an impressive 14 steals, which led to them scoring 16 points off of turnovers. The Petrels also nearly doubled the Panthers in assists, recording 11 compared to Birmingham-Southern's six.
The Petrels jumped ahead 5-2 early in the contest. The Panthers were able to recapture the lead at 9-8 with 5:21 remaining in the first quarter, however, that would be the last time the Petrels would ever trail in the game. They would create an 8-0 run and never look back from there. The Petrels finished the first period leading 20-15 and shooting 53 percent from the field.
Dodson could barely miss in the second period, connecting on 3-of-4 from beyond the arc and 4-of-6 from the field overall, earning 13 points in just that quarter. Additionally, three different Petrels recorded two steals, including Sydney Long, Taylor Dodson and Bailey Charles. This helped the Petrels force eight turnovers and outscore the Panthers 24-7 in the second.
The Petrels pushed out to their largest margin of 27 points three different times in the third quarter. The Petrel defense also pressured the Panthers, creating five steals and outrebounding the Panthers 15-8 in the third period. The Petrels entered the fourth quarter winning 59-32.
The Petrels only shot 1-for-13 from the field in the final period, but the first half lead proved to be too much for the Panthers to overcome.
The Petrels will have their final two regular season home games next weekend on Friday and Sunday. On Friday, the Petrels will challenge the second-place Hendrix Warriors at 6 p.m. in a battle for first place in the league. On Sunday, the Petrels will take on third-place Rhodes at 1 p.m. | null | minipile | NaturalLanguage | mit | null |
“Was it that I was really in a state of clairvoyance, and that I knew that death does not exist- that
those two little cold images of wax were not my children, but merely their cast-off garments?
That the souls of my children lived in radiance, but lived for ever?”
Isadora Duncan recalls finding her children, Deirdre, 7, and Patrick, 2, after drowning with their
nanny in the Seine following an automobile accident. For Duncan, regarding them as “cold
images of wax," the grotesque is a matter of texture. Thirteen years earlier she is in Paris, being
caressed by a devout Rodin following a performance, in whose hands
“marble seemed to flow like molten lead...he ran his hands all over my neck, breasts, stroked my
arms and ran his hands over my hips, my bare legs and feet. He began to knead my whole body
as if it were clay, while from him emanated heat that scorched and melted me.”
There is an inherent animism in the works of both artists: Rodin in his ability to reveal
carnal postures and lifelike energy from clay; Duncan in her regard for nature and the divine.
Entering a Duncan class after studying classical ballet, one feels enlivened by the imagery with
which her gestures are described; that one may be reaching to pick a flower, swaying with a tree,
one may be rising with the sun or bowing reverentially to the earth pulling her down. Her style of
dancing was one of the first to regard the force of gravity, and posed a stark contrast to the stiff
lifelessness which so dismayed her in the Parisian classical ballet academies:
“The ballet school taught the pupils that [the] spring was found in the centre of the back at the
base of the spine. From this axis, says the ballet master, arms, legs, and trunk must move freely,
giving the result of an articulated puppet. This method produces artificial mechanical movement
not worthy of the soul.”
Duncan regards this “spring” as not the lower back but the solar plexus - the heart centre,
and the “centrifugal force” which allows light and energy to come up through the chest.
Although in dance it is necessary that the energy travel upward through the body, the ribs and
chest are more flexible than in classical ballet, and with regard for gravity Duncan dancers take
on far more naturalistic human postures than in traditional ballet. This type of movement, not at
war with gravity, allows for what one may already associate Isadora Duncan with, and that is
skipping: skipping down a stage as freely as one would do at the beach or in a field if one was
met with a sudden surge of elation or was inclined to skip. However, even with this sense of
freedom Duncan’s choreography cannot be taken as an opportunity to flail. In skipping, the legs
and feet must retain their fluidity, as there are no stark positions to take as there are in ballet.
Duncan technique arms always correspond with the movement of the chest in a naturalistic way,
and all “lines” of the body are direct rather than counterintuitive: if the eyes are up, the head
chest and arms are also up, sending a tremendous amount of energy upward.
Isadora’s aesthetic also has a certain hellenistic sensibility. Aside from her performance
and rehearsal garb of the tunic, Duncan’s resting pose mirrors contrapposto in sculpture. Duncan
would scour the Louvre with her brother, Raymond, sketching and studying the Greek vases for
inspiration. It is fitting, then, that she would eventually find Rodin, Pygmalion-esque in his
artistic capabilities, whom she refers to as “the Great God Pan himself.”
How, then, does such an artist, who strives to release the light in one’s soul and conjure
all that is alive in nature, contend with death? The shared death of both her children and their
carer plays like a Greek tragedy in suddenness and spectacle. However, the motions and poses of
Terpsichore have no place in mourning. Friends and relations were abhorred to find that she’d
had her children’s bodies cremated, “to remain hereafter but a pathetic handful of ashes.” She
was disgusted by the performative mourning rituals of the day, seeing in it the artificial gestures
which she despised most in dancing: the reluctant and unconscious funeral procession, the
expected dropping of one’s head, even the repetitive gesture of bringing a hand to one’s eye to
wipe away a tear, calling it “useless ugly mummery which makes Death a macabre horror instead
of an exaltation.”
In the throes of her grief Duncan conjectures that perhaps the souls of dead children
return discreetly to the home of their mothers in death:
“What is this flesh but a house, large enough, perhaps to contain many unsuspected guests. They
lodge in the subconsciousness, when the body is rich enough to nourish them, and each day they
clamber for predominance. My children whom I have grieved for, lamented and longed for, are
perhaps safely lodged within me, saying, ‘Why do you not give us voice?’”
The body is the house and encasement of the soul. However, when the body is trained to
express the whims of the soul, how can one readily accept the space between the two? This
jarring division brought Isadora to a state of stillness, one bereft of the aliveness of her radiant
postures:
“When real sorrow is encountered there is, for the stricken, no gesture, no expression. Like
Niobe turned to stone, I sat and longed for annihilation in death.”
Stripped of artifice, Isadora’s stillness is a reflection of her unwavering devotion to
naturalism. All attempts at touching the divine in her dance were undermined by the great wave
of weight, darkness, and grief that overtook Isadora following Deirdre and Patrick’s deaths.
However, almost fatefully, her wish to join her children was granted in a similarly strange
automobile accident. In Nice, France, on September 14th in 1927, Isadora zoomed away in her
lover’s car, only to have the decadently flowing scarf she was wearing become trapped in a
wheel, effectively snapping her neck. Duncan was a Soviet citizen at the time of her death,
having fulfilled a life that proclaimed her an outsider from a young age and saw her scour Europe
in ardent aesthetic appreciation.
Deirdre and Patrick’s deaths posed one of the most salient questions of Isadora’s art: the
limitation of the human body, and whether there is true unity and alignment with the soul.
However, Duncan's genius still lies in the ability to dance between the threshold of the ethereal
and the physical. For her movements are not a test of “stiff and commonplace gymnastics”, that
do not extend past the arch of one’s foot, but an extension of intention and energy, using the body
as a channel for the soul that transcends the earthly limits of the mortal dance. The tragedy was a
stretch in the direction of the divine, to ascertain a celestial connection, and into the earth, to the
realm of time and human suffering:
“Behind the mask, with any clairvoyance, one can divine the same uneasiness and suffering.
Perhaps in this world so-called happiness does not exist. There are only moments." | null | minipile | NaturalLanguage | mit | null |
Produce Encyclopedia
Produce
Produce Express carries a variety of organic and conventionally grown produce from small family farmers and growers to supply our customers with the freshest local, seasonal produce throughout the year.
We send our experienced buyer to the San Francisco market six nights a week to personally select our specialty produce items. We take great pride in being able to procure almost any specialty item overnight.
The Hass avocado is known for its quintessentially tumbled leathery fairly thick skin that turns near black when fully mature. The Hass avocado is an ideal avocado; it ripens evenly, it peels easily, its pit is easy to remove and it has a rich, nutty flavor with a creamy texture.
Broccoli is the dense, unopened budding sprouts of a member of the cabbage family. Broccoli belongs to the same family as kohlrabi, cauliflower, Brussels sprouts, kale, collard greens, and all the cabbages.
What food is more synonymous with summer than freshly picked corn on the cob? Corn grows in "ears," each of which is covered in almost uniform rows of tightly packed kernels (a single ear of corn can contain up to 400 kernels). | null | minipile | NaturalLanguage | mit | null |
Cytokines and macrophages: implications for normal and abnormal renal development.
Work with transgenic animals and in vitro manipulation of organs in culture has highlighted an increasing number of genes that are important in the normal development of the kidney and whose disruption inhibits nephrogenesis. The phenotype seen with some agents resembles that of the congenital renal anomaly renal dysplasia, in which there appears to be an arrest of normal development. Such molecules include inflammatory cytokines, factors that have traditionally been described as intercellular messengers in the immune system. Although the mechanisms of action of cytokines in organogenesis have not yet been fully delineated, these may include alterations in normal expression patterns of adhesion molecules, modulation of extracellular matrix, influencing the levels of other cytokines and interactions with transcription factors. Furthermore, macrophages are among the first haematopoietic cells to be found in the kidney and other embryonic tissues. Their numbers and activation status are closely regulated by cytokines and evidence is accumulating that as well as scavenging cellular debris, macrophages themselves may induce cell death during organogenesis. Disruption of any of these carefully regulated and interdependent processes may cause disease. | null | minipile | NaturalLanguage | mit | null |
Vista Eng'g Corp. v Everest Indem. Ins. Co. (2019 NY Slip Op 01813)
Vista Eng'g Corp. v Everest Indem. Ins. Co.
2019 NY Slip Op 01813
Decided on March 13, 2019
Appellate Division, Second Department
Published by New York State Law Reporting Bureau pursuant to Judiciary Law § 431.
This opinion is uncorrected and subject to revision before publication in the Official Reports.
Decided on March 13, 2019
SUPREME COURT OF THE STATE OF NEW YORK
Appellate Division, Second Judicial Department
ALAN D. SCHEINKMAN, P.J.
MARK C. DILLON
HECTOR D. LASALLE
VALERIE BRATHWAITE NELSON, JJ.
2017-03825
(Index No. 6960/15)
[*1]Vista Engineering Corporation, et al., appellants,
vEverest Indemnity Insurance Company, respondent, et al., defendants.
Baxter Smith & Shapiro, P.C., Hicksville, NY (Sim R. Shapiro and Bryan R. Forbes of counsel), for appellants.
Kennedys CMK, LLP, New York, NY (Ann M. Odelson of counsel), for respondent.
DECISION & ORDER
In an action for declaratory relief, the plaintiffs appeal from an order of the Supreme Court, Queens County (Darrell L. Gavrin, J.), dated January 30, 2017. The order denied the plaintiffs' motion for summary judgment declaring that the defendant Everest Indemnity Insurance Company did not issue a timely disclaimer of coverage in connection with an underlying action entitled Fernandes v Vista Engineering Corporation, commenced in the Supreme Court, Queens County, under Index No. 6116/12, and is obligated to defend and indemnify the plaintiffs in the underlying action, and granted that defendant's cross motion for summary judgment declaring that it is not obligated to defend or indemnify the plaintiffs in the underlying action.
ORDERED that the order is modified, on the law, (1) by adding the words "without prejudice to renewal upon the completion of discovery" after the words "the plaintiff[s'] motion is denied" in the penultimate paragraph thereof, and (2) by deleting the provision thereof granting that defendant's cross motion for summary judgment declaring that it is not obligated to defend or indemnify the plaintiffs in the underlying action, and substituting therefor a provision denying that cross motion without prejudice to renewal upon the completion of discovery; as so modified, the order is affirmed, without costs or disbursements, and the matter is remitted to the Supreme Court, Queens County, for further proceedings consistent herewith.
The plaintiff Vista Engineering Corporation (hereinafter Vista) was hired as a general contractor for a project at an elevated structure known as the Queensboro Plaza Station. Vista then subcontracted work to the defendant East Coast Painting & Maintenance (hereinafter East Coast). The subcontract identified the project owner as the plaintiff Metropolitan Transportation Authority (hereinafter MTA) and the "Architect/Engineer" as the plaintiff New York City Transit Authority (hereinafter NYCTA). The subcontract contained an indemnity/hold harmless clause and required East Coast to procure an insurance policy that named Vista and MTA as additional insureds.
The defendant Everest Indemnity Insurance Company (hereinafter Everest), a New Jersey insurance company, issued a commercial general liability policy to East Coast, a New Jersey limited liability company, covering the period of July 6, 2010, to July 6, 2011. Thereafter, an additional insured endorsement was issued naming NYCTA and MTA as additional insureds.
On April 19, 2011, East Coast employee Jose Fernandes was injured at the job. In March 2012, Fernandes commenced a personal injury action entitled Fernandes v Vista Engineering Corporation (hereinafter the underlying action), naming Vista, NYCTA, and MTA as defendants. [*2]On September 28, 2011, Vista's insurer, Argonaut Insurance Company, through its claim administrator Colony Specialty, tendered the underlying action to Everest, seeking for Vista a defense and indemnification for the action commenced by Fernandes. By letter dated December 5, 2011, FARA Insurance Services, a third-party claims administrator for Everest, disclaimed defense and indemnity to Vista, based upon a "Third Party Action Over Exclusion Endorsement" in the policy, which excluded coverage for bodily injury to employees of East Coast. Vista, MTA, and NYCTA (hereinafter collectively the plaintiffs) then commenced this action for declaratory relief. The plaintiffs moved for summary judgment declaring that Everest did not issue a timely disclaimer of coverage in connection with the underlying action as required by Insurance Law § 3420(d)(2) and is obligated to defend and indemnify the plaintiffs in the underlying action. Everest cross-moved for summary judgment declaring that it is not obligated to defend or indemnify the plaintiffs in the underlying action. The Supreme Court denied the plaintiffs' motion and granted Everest's cross motion. The plaintiffs appeal.
Subsequent to the Supreme Court issuing the order appealed from, the Court of Appeals, on November 20, 2017, issued its decision in Carlson v American Intl. Group, Inc. (30 NY3d 288, 306). In relevant part, the Court of Appeals held that "section 3420 applies to policies that cover insureds and risks located in the state" of New York, and further determined that a company was "located in" New York if it had a "substantial business presence" there (id. at 305, 306). Upon the record before us, we cannot determine whether East Coast had a substantial business presence in New York (see Vista Eng'g Corp. v Everest Indem. Ins. Co., 161 AD3d 596). Since the record is insufficiently developed concerning East Coast's business presence in New York, we remit the matter to the Supreme Court, Queens County, to allow the parties to conduct further discovery, develop the record, and give the Supreme Court an opportunity to meaningfully review the case.
SCHEINKMAN, P.J., DILLON, LASALLE and BRATHWAITE NELSON, JJ., concur.
ENTER:
Aprilanne Agostino
Clerk of the Court
| null | minipile | NaturalLanguage | mit | null |
What is an optimal location to place the TPLinkwifi.net Router?
Select a spot where the router will not expose to the moisture or excessive heat.
Prefer a location to position your router where you can connect it to the wireless devices as well as to the power source easily.
Try to place your router on a shelf or desktop.
Keep your router away from any electronic devices such as microwaves, Bluetooth, cordless phones, etc.
HOW TO TPLINKWIFI.NET SETUP ROUTER –
The TP-Link router setup is quite simple and takes a very short period of time to get the installation done because of its responsive web-based interface. TP-Link router appears with a responsive web interface that enables its users to set up their TP-Link wireless router without any nuisance, and the best part is that you don’t need the access to the Internet connection on your computer. You can set up your wireless router even without having access to the Internet connection, but a hardware connection is necessary for your physical devices. Here are the simple steps for the TP-Link router setup shown in a much easier way because this question “how to setup TP-Link router” arises among most of the people. Here are the steps to set up the TP-Link router for the first time:
Connect the desktop computer to any of the LAN ports of the router using the Ethernet cable. Make sure the connections made are proper.
Connect the modem to the WLAN port of the router using another Ethernet cable. Make sure the connections are proper.
Switch off the modem, router, and the desktop computer and then switch them on. Wait for all the devices to complete booting up.
Launch any internet browser and visit www.tplinkwifi.net address. A login page will display.
You will prompt to enter the default login credentials. The default username and password are “admin”.
After logged in, the Quick Setup will display. Click Next to start personalizing your network.
How to reset TP-Link router to factory defaults
There are two ways in which you can reset your router to factory defaults:
Method 1 ：Hard reset/By pressing the RESET button –
A hard reset method will restore your device to factory default settings. You should reconfigure the device from the grind, or you can load the configuration file you have backed up before the reset.
With the Router powered on, press and hold the WPS/RESET button on the Rear panel/the Front Panel for at least 10 seconds until the SYS LED evolves quick-flash from slow-flash. Then release the button and wait for the Router to reboot to its factory default settings.
Method 2 ：By Router’s Web Interface –
Initially, log in to the web-based interface of the Wi-Fi Router, then go to Advanced > System Tools > Backup & Restore > Factory Default Restore page. The restore page displays.
Now, click on Factory Restore and wait till the Router reboot to its factory default settings.
Why Fail to access tplinkwifi.net
Sometimes you may fail to access tplinkwifi.net, getting the error information, or even no response at all. There are many reasons why this issue occurs of not getting access to tplinkwifi.net setup, and here are some strategies to troubleshoot this issue.
Step 1
Make sure you have connected your device to your TP-Link Router’s network. Otherwise, you cannot access the login page with the domain address tplinkwifi.net.
Step 2
If you receive an error message from TP-Link, you may have cached the default IP address of tplinkwifi.net. You should clear your browser cache and history according to the browser.
Google Chrome
Internet Explorer
Mozilla Firefox
Apple Safari
For example, if you generally use Google Chrome, then try using Mozilla Firefox to access tplinkwifi.net.
Step 3
Try using your Router’s IP address 192.168.0.1 or https://192.168.1.1 to login instead of the domain address tplinkwifi.net setup.
Note: maybe 192.168.0.1 or 192.168.1.1 is not your Router’s IP address if the network manager has changed it before.
Step 4
If you keep multiple network connections at the same time, such as wired, wireless, and VPN, then it is advised to disable or disconnect all your internet and VPN connections and only keep the wired connection to your TP-Link Router.
Step 5
Power cycle your Router and Modem, and if convenient, restart your desktops, laptops, or phones required to access www.tplinkwifi.net.
You can plug out/in the power cable, or press on the power button twice to reboot your TP-Link Router.
Step 6
Temporarily disable your firewall and antivirus software at some time, it thinks the login webpage insecure and blocks them.
You can go to the Control Panel of your Windows PC to disable the firewall.
Step 7
If the above methods, however, fail to access your Router’s login page, then you must perform a factory reset to this Router.
Note: after you perform a factory reset, all your Router settings and configurations will reset to the factory settings, including your personalized SSID and password, login username and password, and other advanced functions tplinkwifi.net setup.
Step 8
If all the above methods, however, erred, you need to contact TP-Link support to troubleshoot your issue tplinkwifi.net login. | null | minipile | NaturalLanguage | mit | null |
Remember Madballs? No, we didn’t spend the weekend binge-watching I Love the ’80s. But we are exclusively revealing that geek-friendly collectibles company Mondo is putting its own spin on the deliberately disgusting, advertised-on-TV toys with what the company is calling MondoBalls.
The first three characters depicted on MondoBalls will be Skull Face, Horn Head, and Slobus, all three of which will be familiar to Madballs aficionados. That initial trio of MondoBalls will be available to pre-order soon via Mondo’s official site. The company has also struck a licensing deal with Marvel, the initial fruit of which will be a MondoBall featuring the character, Venom.
“This line is one of the most fun projects I’ve ever had a chance to work on!” Mondo’s creative director of toys/collectibles Brock Otterbacher said in a statement. “We’re super excited to launch these gross little guys.”
Mondo also has plans to release MondoBalls featuring characters from the Gremlins and Friday the 13th franchises.
Image zoom | null | minipile | NaturalLanguage | mit | null |
Efforts to reconcile Sinn Fein with the senior partner in the Belfast government, the Democratic Unionist Party, have foundered over a number of issues, including a failure to agree on how to deal with unpunished crimes committed during the Troubles.
Image A still from a video posted on Twitter by Barry McElduff with a loaf of Kingsmill bread.
South of the border, Sinn Fein is now the third-largest political party in the Dublin Parliament. It decided in November that it was willing to be a junior partner in a future coalition government there — the latest shift from its original policy of refusing to recognize or sit in any parliament or government other than one representing a united Ireland.
However, the party’s previous links to I.R.A. violence and racketeering are still problematic for some southern voters, who might otherwise be attracted to its center-left social platform and strong constituency work.
Last November, the party’s veteran president, Gerry Adams, who has led Sinn Fein since 1983, announced that he would stand down at the next election, a move interpreted as passing the torch to a new generation of leaders with no personal involvement in what republicans term the “armed struggle.”
Mr. McElduff himself was convicted on charges stemming from his role in the I.R.A.’s false imprisonment of a suspected police informant and was given an 18-month suspended sentence in 1992.
A blurb on the Sinn Fein Bookshop website describes him as an “irrepressible republican raconteur and wit.” In the video on Twitter, since taken down, he jokes: “I’m in the Classic service station here, but I’m just wondering, where does McCullough’s keep the bread?”
The post was immediately condemned by a range of politicians and community leaders. Arlene Foster, the leader of the Democratic Unionist Party, which draws most of its support from Protestants, said in a post on Twitter: “Shame on any elected rep who posted that inhuman video. I feel sorry for IRA victims & West Tyrone who have McElduff as their MP. All murder was wrong. Glorifying any murderer is sickening. Mocking is depraved.” | null | minipile | NaturalLanguage | mit | null |
The present invention relates to a crystalline form of N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine and to methods for the production of that crystalline form.
N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine of formula (1) is a known substance having therapeutic utility in depressing blood glucose levels. ##STR1##
N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine is disclosed in Japanese Patent Application Laid Open No. 63-54321 (equivalent to EP-A-196222 and US 4,816,484) and in J. Med. Chem. 32, 1436. The Japanese application describes how the compound may be crystallized from aqueous methanol to yield crystals having a melting point of 129.degree. to 130.degree. C. These crystals are in a crystalline form referred to herein as "B-type". The X-ray powder diffraction pattern and infra-red spectrum of B type crystals are shown in FIGS. 1 and 2 respectively.
The known B-type crystals suffer from problems of instability, especially when subjected to mechanical grinding. The instability results, for example, in conversion of the B-type crystals into other forms. The instability of the B-type crystals means that they are not ideal for use in medicine. It is in general desirable that a medicinal product containing a crystalline active ingredient have a composition which is well defined and stable in terms of the crystalline form of the active ingredient. Conversion of one crystalline form into unknown amounts of different, or amorphous, forms during processing or storage is undesirable and in many cases would be regarded as analogous to the appearance of unquantified amounts of impurities in the product.
The present inventors have discovered a method for producing a crystalline form of N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine having improved stability over the known B-type. For instance, the crystals according to one aspect of the present invention have enhanced stability to grinding. Such crystals are therefore more suitable for use in medicines than those of the B-type. The crystals having enhanced stability have been designated "H-type" by the inventors. | null | minipile | NaturalLanguage | mit | null |
Disposable absorbent articles typically comprise three basic components: a liquid permeable topsheet that is located closest to the skin of the wearer when the article is in use, an absorbent core, and a liquid impermeable barrier sheet which is located on the opposite side of the absorbent core. Other components such as fastening tapes, leg and waist elastics, etc. are also commonly used.
The absorbent core receives and retains liquids that pass through the liquid permeable topsheet and typically comprises a batt of wood fluff fibers. Superabsorbent materials, typically in powder form, are often distributed within the absorbent core to enhance its liquid holding capacity and liquid retention properties.
One problem associated with absorbent articles is the inefficient utilization of the total absorptive capacity of the absorbent core material. This is due in part because absorbent articles normally have an elongated rectangular or hourglass shape and the liquid introduction or insult and spreading of liquid is often confined to the central area of the absorbent core.
Another problem associated with absorbent articles is the inability of the absorbent core to absorb liquids rapidly enough when large amounts of liquid are discharged into the absorbent core over short periods of time. This often results in undesirable side leakage.
To improve the liquid acquisition and lateral spreading properties of absorbent articles, many products have utilized a wicking layer of tissue or crepe. This wicking layer can be located between the liquid permeable topsheet and the absorbent core, in the center of the absorbent core, or in the absorbent core in a location closer to the liquid impermeable barrier sheet. However, tissue and crepe tend to promote isotropic spreading of liquids. That is, liquid tends to spread at similar rates in both the lengthwise and width directions of the absorbent article. As a result, in many instances where the core is elongate, the liquid will leak beyond the side edges of the absorbent article before it has an opportunity to spread to the ends of the absorbent core.
Numerous other approaches have been suggested for improving the liquid distribution and absorption properties of absorbent articles. Most of these approaches have involved the use of channels, reservoirs, apertures, etc. that have been introduced into the wood fluff absorbent core or tissue wicking layer by embossing or corrugation techniques. See, for example, U.S. Pat. Nos. 4,676,786 (Nishino), 4,678,464 (Holtman), 4,655,759 (Romans-Hess et al.), and 5,030,229 (Yang).
U.S. Pat. No. 4,735,624 (Mazars) discloses a disposable diaper comprising an absorbent pad constituted by an absorbent material consisting essentially of hydrophilic fibers joined to one another to form a coherent mass. The pad is narrow in the crotch area and widens out in the front and rear areas of the diaper with branches.
Other approaches have been taken such as the use of nonwoven inserts as flow control zones, as disclosed in U.S. Pat. Nos. 4,795,453 (Wolfe) and 4,908,026 (Sukiennik et al.), or the use of a plastic netting material to promote the unidirectional spreading of liquids in absorbent pads, as disclosed in European patent 0 174 152 B1. The use of certain complex shaped fibers, in tow or staple form, that are capable of spontaneously transporting liquid in absorbent articles is disclosed in European patent application 0 391 814 A2 (Phillips et al.).
U.S. Pat. No. 4,798,604 (Carter) discloses a contoured polymeric film which is apertured and contains a pattern of raised areas that may be employed to form the body contacting surface, i.e, topsheet, in absorbent devices.
Despite these previously known technologies, additional improvements to obtain more efficient and speedier absorption by absorbent cores without leaking are desired. | null | minipile | NaturalLanguage | mit | null |
Product Information
Description:
This is a pre-1923 historical reproduction that was curated for quality. Quality assurance was conducted on each of these books in an attempt to remove books with imperfections introduced by the digitization process. Though we have made best efforts - the books may have occasional errors that do not impede the reading experience. We believe this work is culturally important and have elected to bring the book back into print as part of our continuing commitment to the preservation of printed works worldwide.
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Publisher : BiblioLife
Number of Pages : 0492
Book Format : Paperback
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Bibliolife
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Bibliolife
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9781115757416
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UBM9781115757416
ISBN
1115757415
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What is a refurbished product? A refurbished product refers to an item that was returned to the seller or manufacturer. These items are tested for quality and verified to perform like a new product. Refurbished products also contain the original or equivalent accessories of a new product. Other retailers may refer to refurbished products as factory-reconditioned, recertified or repackaged.
Where can I find refurbished products on Rakuten.com? Refurbished products are marked as Refurbished in the product title and the Condition field. You can also filter your search results to only include refurbished products by selecting Condition: Refurbished on the Search sidebar. | null | minipile | NaturalLanguage | mit | null |
Prospective randomized controlled trial comparing laser lithotripsy with pneumatic lithotripsy in miniperc for renal calculi.
The energy source used for stone fragmentation is important in miniperc. In this study, we compared the stone fragmentation characteristics and outcomes of laser lithotripsy and pneumatic lithotripsy in miniperc for renal calculi. After Institutional Review Board approval, 60 patients undergoing miniperc for renal calculi of 15 to 30 mm were equally randomized to laser and pneumatic lithotripsy groups. Miniperc was performed using 16.5F Karl Storz miniperc sheath and a 12F nephroscope. Laser lithotripsy was performed using a 550-μm laser fiber and 30 W laser with variable settings according to the need. Pneumatic lithotripsy was performed using the EMS Swiss lithoclast. Patient demographics, stone characteristics, intraoperative parameters, and postoperative outcomes were analyzed. The baseline patient demographics and stone characteristics were similar in both groups. The total operative time (P = 0.433) and fragmentation time (P=0.101) were similar between the groups. The surgeon assessed that the Likert score (1 to 5) for fragmentation was similar in both groups (2.1 ± 0.8 vs 1.9 ± 0.9, P=0.313). Stone migration was lower with the laser (1.3 ± 0.5 vs 1.7 ± 0.8, P=0.043), and fragment removal was easier with the laser (1.1 ± 0.3 vs 1.7 ± 1.1, P=0.011). The need for fragment retrieval using a basket was significantly more in the pneumatic lithotripsy group (10% vs 37%, P=0.002). The hemoglobin drop, complication rates, auxiliary procedures, postoperative pain, and stone clearance rates were similar between the groups (P>0.2). Both laser lithotripsy and pneumatic lithotripsy are equally safe and efficient stone fragmentation modalities in miniperc. Laser lithotripsy is associated with lower stone migration and easier retrieval of the smaller fragments it produces. | null | minipile | NaturalLanguage | mit | null |
Q:
Ruby equivalent of python nonlocal
I am trying to write a closure in Ruby. This is the code written in Python:
def counter():
x = 0
def increment(y):
nonlocal x
x += y
print(x)
return increment
Is there a "nonlocal" equivalent in Ruby so I can access and make changes to the variable x from inside increment?
A:
The nonlocal keyword tells Python which variables to capture. In Ruby, you don't need such a keyword: all variables are captured unless explicitly mentioned otherwise.
So, the Ruby equivalent to your Python code translates almost directly:
counter = -> {
x = 0
->y {
x += y
puts x
}
}
i = counter.()
i.(2)
# 2
i.(3)
# 5
It would probably be more idiomatic to use a method for counter, though:
def counter
x = 0
->y {
x += y
puts x
}
end
i = counter
i.(2)
# 2
i.(3)
# 5
| null | minipile | NaturalLanguage | mit | null |
OverCriminalized: Alternatives to Incarceration?
America's prisons and jails are filled with people arrested for crimes connected to homelessness, mental health issues, and drug addiction. “Overcriminalized,” a series of videos from Brave New Films launching today spotlights attempts to offer alternatives to incarceration in three cities: Salt Lake City, Utah, Seattle, Washington, and San Antonio, Texas.
Nowhere to go but Jail
In 2014 100 cities criminalized sitting or lying in public places. “The homeless end up in criminal justice systems, because there hasn't been a better alternative” says Lloyd Pendleton, Director of Utah Homeless Task Force. Salt Lake City adopted a “Housing First” approach to homelessness. As Gordon Walker, Director of Housing and Community Development in the city explains that means “instead of asking people to change their lives before we gave them housing, we chose to give them housing, along with the supportive services and then allow them to change their lives if they wanted.”
The War on People
“I really can't remember what the first thing I got arrested for (was)” says Misti Barrickman as she recalls a long list of drug related arrests. Law Enforcement Assisted Diversion, or LEAD, is a pre-booking diversion program for minor drug offenses that provides people in the Seattle, Washington area with treatment programs. According to the Drug Policy Alliance, “drug arrests in Seattle fell more than 30 percent from 2010 to 2011 – and local jail populations appear to be declining too” at least in part due to LEAD. The Drug Policy Alliance also praised the program for marking a shift away from an “enforcement-first” approach to one focused on health.
Arrested for Needing Help
Prisons and jails contain a disproportionate number of people with serious mental health issues. “Mental illness is the only disease that when you're in a crisis, the cops are called” says Michelle Mata in this video “you're having a heart attack, you don't call the police.” A 2012 investigation by the Portland Press Herald/Maine Sunday Telegram found “at least half of the estimated 375 to 500 people shot and killed by police each year in this country have mental health problems.” In San Antonio, Texas, police officers are given a 40 hour crisis intervention training. | null | minipile | NaturalLanguage | mit | null |
Efficacy and safety of rupatadine in Japanese patients with seasonal allergic rhinitis: A double-blind, randomized, multicenter, placebo-controlled clinical trial.
Rupatadine is a novel non-sedating second-generation H1-antihistamine with antiplatelet-activating factor activity, first marketed in Spain in 2003. It is used for treating allergic rhinitis in more than 80 countries. This study investigated its efficacy and safety in Japanese patients with seasonal allergic rhinitis (SAR). This was a randomized, placebo-controlled, double-blind study conducted at 4 medical institutions in Japan (JapicCTI-152785). Adolescent and adult SAR outpatients aged 12-64 years entered a 1-week placebo run-in period. After eligibility was confirmed, patients orally received placebo, rupatadine 10 mg, or 20 mg once daily for 2 weeks. The primary endpoint was a change from baseline to second week of treatment in total 4 nasal symptom score (T4NSS). Nine hundred patients were randomly assigned to placebo, rupatadine 10 mg, or rupatadine 20 mg (302, 298, and 300 patients, respectively). The least squares mean difference in the primary endpoint between rupatadine and placebo was -1.085 for 10 mg, and -1.415 for 20 mg (analysis of covariance, both P < 0.001). The rates of adverse events were 6.6%, 14.1%, and 15.0% for placebo, rupatadine 10 mg, and rupatadine 20 mg, respectively. Somnolence was most frequently reported: 7.0% for rupatadine 10 mg and 7.3% for rupatadine 20 mg. No serious adverse drug reactions were observed, and no adverse events resulted in premature discontinuation. Rupatadine 10 and 20 mg were significantly superior to placebo in improving nasal and ocular symptoms of SAR, and were well tolerated. | null | minipile | NaturalLanguage | mit | null |
Lawmakers Gone Wild Four-star dining! Luxury cars! European getaways! An exclusive investigation reveals how Illinois politicians are living large on their campaigns’ dime.
Above: *These are actors, not real politicians Photo: Taylor Castle
Push open the heavy door to Mart Anthony’s Italian Restaurant and Steakhouse, on the corner of Hubbard and Racine in the West Loop, and you feel you’ve stepped back in time. This is the kind of cozy place where the tablecloths are white linen, the walls are wood paneled, and, according to the restaurant’s website, the customers “are well-fed and have their cocktail of choice at hand.”
On any given week, chances are good that one of those customers—perhaps washing down the $32 steak Vesuvio with a $75 Napa cabernet—will be Joe Berrios. In the first nine months of 2012, Berrios ate lunch or dinner at Mart Anthony’s 58 times, ringing up a tab of $8,747. How do we know this? Because Berrios—who is not only the Cook County assessor (salary: $125,000) but also the county’s Democratic Party chairman and the committeeman for the 31st Ward on the Northwest Side—used political campaign funds to pay the bills.
Those Mart Anthony’s meals were actually “meetings,” according to his quarterly mandatory disclosure filings with the State of Illinois. Turns out Berrios, 60, has held “meetings” at lots of restaurants since the beginning of 2007: 989 of them, totaling $186,080. That’s right: On average, the veteran pol dined out on the campaign dime at least every other workday at $188 a pop.
Given that Berrios’s full-time campaign office is just two blocks from the County Building, where he works, it’s puzzling that he must hold so many meetings at gourmet restaurants. Equally puzzling is that not a single meal he charged to his ward committeeman fund—the account that’s supposed to be used for ward-related politics—was eaten inside his ward.
(Through a spokesperson, Berrios—who recently told reporters that the county’s ethics rules barring nepotism in hiring don’t apply to him—declined to be interviewed for this article. In response to a Freedom of Information Act request seeking details of who attended the meetings and what they were about, Berrios’s office first claimed that he doesn’t keep a calendar. It later sent one xeroxed page of one month in a datebook with four appointments penciled in.)
Using campaign funds to live high on the hog is a time-honored tradition among certain Illinois politicians. How else are they supposed to afford frequent fine dining and other luxuries on a public servant’s salary?
It’s also supposed to be verboten. Under both state and federal law, elected officeholders and political candidates can spend campaign money only on things with a campaign- or government-related purpose. They’re not allowed to use the funds to enrich their lives. But by stretching the definition of “campaign-related” like taffy, politicians “can still parlay [campaign contributions] into a pretty good life,” says Ronald Michaelson, a campaign finance expert who was the executive director of the Illinois State Board of Elections from 1976 to 2003.
To learn how widespread such shenanigans are in Illinois, Chicago and the nonprofit Better Government Association recently analyzed campaign disclosure records from January 1, 2007, through September 30, 2012 (the most recent available as of presstime) for thousands of political campaign committees. The politicians those committees fund include all state senators and representatives, most suburban mayors, all Cook County commissioners and township committeemen, all Chicago aldermen and ward committeemen, and other major county and state elected officials.
While no serious red flags popped up for most of these politicians, a significant minority appear to treat their campaign coffers as giant slush funds for big spending on luxuries—Lexus sedans, spa services, overseas jaunts—that mere mortals at a similar salary level couldn’t dream of affording and that arguably have little to do with getting elected. Some, including Country Club Hills mayor Dwight Welch, state senator Terry Link, and Berrios himself, appear to live virtually all-expenses-paid lifestyles. (In interviews, both Link and Welch defended their spending as directly related to and necessary for their political activities.)
Most galling of all, such spending goes on largely unnoticed and mostly unquestioned. “We have a culture here [in Illinois] of you take what you can get,” says David Morrison, the deputy director of the Illinois Campaign for Political Reform. “I don’t know of any other states where this would be an issue.”
In the spring of 1993, Robert LeFlore Jr., 62, a Democratic state representative from the West Side, died in office after a long illness. The costs of his funeral ($4,400) and his burial plot ($3,200) were paid not by his family but by his still-active campaign fund. Recalls Kent Redfield, a political scientist at the University of Illinois at Springfield and a campaign finance specialist: “The joke at the time was that if people were told that the money they were giving politicians was being used to bury them, they’d be much more willing to contribute to their campaigns.”
The bigger joke was the fact that using campaign funds to pay for your own funeral—could there be a more patently nonelection-related expense?—wasn’t illegal. Before 1998, Illinois imposed no restrictions on how political candidates and officeholders could spend campaign money they raised. None. “It was the Wild West,” says Michaelson. “Fur coats for the wife, country club dues, new cars, college tuition”—using political war chests to cover such expenses was all perfectly legit.
Thus, when he was governor from 1977 to 1991, James Thompson, a Republican, was able to use thousands of dollars in campaign funds to pay his family’s babysitters. Jane Byrne, the Democratic mayor of Chicago from 1979 to 1983, used her campaign fund to buy her daughter a new $14,000 Mustang.
Democratic state senator John D’Arco Jr. took $45,000 to pay legal bills during his 1991 federal trial on bribe-taking and influence-peddling charges. A year later, Democratic alderman Fred Roti withdrew triple that amount for his own legal defense.
Back then, reformers were focused not so much on how candidates spent their contributions but on who donated the money in the first place. “It’s the cash coming in, the income on the front end, that offers the greatest risk of corruption,” says Morrison.
When it came to spending reform, the federal government was way ahead of Illinois. In 1979, Congress passed a law banning federal candidates and legislators from using campaign money for personal expenses. (That statute applies to federal lawmakers such as Jesse Jackson Jr., the ex-congressman who at presstime was being investigated for allegedly using campaign funds to decorate a lavish home and buy a $40,000 Rolex.)
Many states passed similar laws. But in Illinois, the tipping point wasn’t until around 1995, when a series of scandals, including a massive Medicaid fraud, erupted. The FBI and state police busted staffers from Governor Jim Edgar’s office and officials from the state’s public aid office for accepting gifts and bribes from Management Services of Illinois, a major campaign contributor that overbilled the state by about $12 million.
The MSI scandal underscored the rampant corruption in Illinois’s government and stoked voter wrath. Even Michael Madigan, the old-school Speaker of the House, had to acknowledge that the tide had turned. “Conditions have reached the point where action should be taken to eliminate the gravy train in Springfield,” he told reporters in 1997.
The next year, the state’s four legislative leaders finally formed a special bipartisan task force—which included a young freshman senator from Chicago named Barack Obama—to draw up a campaign finance reform bill. Asking legislators to pass a law cutting their own goodies was a mighty tall order. “Once you get the perks, you want to keep the perks,” says Bob Stern, the former president of the Center for Governmental Studies at UCLA, who helped write California’s landmark campaign reform act in 1974.
In the end, the task force was able to get rank-and-file lawmakers to pass the bill only by inserting a grandfather clause allowing Illinois politicians to keep all the campaign money they collected before June 30, 1998, and spend it however they like, as long as they pay income taxes on any personal expenses.
On the plus side, the law did spell out nearly a dozen specific expenditures that are forbidden. Buying a house, for example. Paying off a mortgage. Covering school tuition, country club dues, or dry cleaning bills.
Unfortunately, the law was “a crap sandwich” with “more holes in it than St. Andrews’s golf course,” Jim Howard, the former executive director of the campaign reform group Illinois Common Cause, told reporters after it passed. For instance, the law allows the following exception to the tuition ban: “governmental or political purposes directly related to a candidate’s or public official’s duties and responsibilities.” Stretch the definition of “political purposes” far enough, apparently, and you can tap your campaign coffers to pay your tuition at Harvard University plus flights to and from Boston. Howard Kenner did just that in 2002, to the tune of $15,500, while he was a South Side state representative.
There’s also a ban on using campaign dollars to pay travel expenses “unless the travel is necessary for fulfillment of political, governmental, or public policy duties, activities, or purposes.” One can only imagine what political necessities drove Michelle Harris, the 8th Ward alderman, to travel to Turkey last year on her campaign’s dime. Or what required Richard Mell, the 33rd Ward alderman and father-in-law of former governor Rod Blagojevich, to pay $6,617 in campaign funds for a three-night stay at the opulent Bellagio in Las Vegas with four of his precinct captain buddies in 2009. (In 2008, Mell took the same group on a $4,651 jaunt to Aruba.)
And then there’s this sweeping statement toward the end of the statute: “Nothing in this section prohibits the expenditure of funds of a political committee controlled by an officeholder or candidate to defray the customary and reasonable expenses of an officeholder in connection with the performance of governmental and public service functions.” As a practical matter, says Morrison, such vague wording means that what does or doesn’t count as a campaign expense is pretty much up to each candidate: “It’s essentially the honor system.”
Even if characterizing lavish personal spending as campaign spending is deemed legal in Illinois, “it looks bad,” Redfield points out. It casts public officials as arrogant, out-of-touch profiteers who are less interested in their constituents than in feathering their own nests—an especially poor image with so many Illinoisans struggling in this still-weak economy.
The campaign headquarters of Dwight Welch, the mayor of southwest suburban Country Club Hills, can be difficult to find. On the outskirts of the town’s business district, it is practically indistinguishable from the surrounding ranch-style residences dotting a quiet neighborhood with broad lawns. That’s because the office is in his house’s three-car garage.
Welch, 63, who is white, has been mayor of this mostly African American community since 1987. He rehabbed his garage/office in 2008, expanding it and putting in a new kitchen, bathroom, and party area. To do this, he withdrew $40,000 in campaign funds, the Illinois Board of Elections calculated at the time. When the Sun-Times questioned him about the project—and about the red flags raised by the election board—Welch pleaded ignorance and dismissed the whole thing as “no harm, no foul.” (Welch says that he repaid his campaign.)
With his spanking-new office built, Welch again dipped into his campaign kitty for tens of thousands of dollars to add furniture, office supplies, a furnace, a security alarm, and a sound system. He withdrew thousands more to cover property insurance and his home’s monthly utility bills, including cable TV, records show. Last but not least, he used his campaign account to pay himself rent for use of the garage/office: $28,750 from February 2009 to May 2012.
Lest you assume that Welch was driven to such extremes by pitifully low compensation, you should know that Country Club Hills—population 16,000—pays him $145,000 a year, one of the highest mayoral salaries in the Chicago suburbs. He also enjoys a $32,000-a-year expense account funded by taxpayers. The mayor even gets his wheels for free: Country Club Hills provides a town-owned undercover police vehicle for his use. Perhaps it’s not to Welch’s taste, however, because until recently he also leased a $600-a-month Volkswagen SUV—billed, natch, to his campaign fund. (He recently traded in the Volkswagen for an Acura SUV.)
Welch is unapologetic about his campaign spending. “You raise and spend money for elections—duh,” he says. “That’s what I do. I’m not ashamed of it. I try to follow all the rules.” As for his garage/office? “We have parties there all year round. People enjoy it. . . . I’m doing the will of the people. It’s not like I’m gaining anything.”
Because it’s perfectly legal to use campaign funds to rent campaign offices, many Illinois politicians, like Welch, choose to locate the offices inside property that they (or a family member) already own. Consider Alderman Mell, 74, he of the Vegas getaway. Mell bought a single-story brick storefront on the Northwest Side for $210,000 in 1996, according to public records; he has owned it free and clear since 2004. From January 2008 to August 2012, he used campaign money to pay himself $231,000 in rent on the place and is currently collecting around $4,450 per month. Mell says that there is nothing illegal about it: “It’s convenient, and it’s in the ward.”
Vehicles are another major area of questionable campaign spending. The Chicago/BGA analysis found that more than 100 lawmakers and candidates have used nearly $1.3 million in campaign funds to lease or buy cars, often high-end models, over the past five years. For example, Patrick O’Connor, the 40th Ward alderman and the mayor’s floor leader, paid $7,500 in campaign cash to McGrath Lexus in 2011 for a four-door sedan; he has since billed the campaign $1,100 every month in lease payments.
But that pales in comparison with Jesse White, Illinois’s secretary of state. Records show that White has spent more than $77,000 in campaign money on cars since the start of 2007, including two 2007 GMC Yukons, one of which he keeps in Chicago and one in Springfield. This despite the fact that White, like Welch, has a car provided for his use. (How does he get from Chicago to Springfield, you might ask? According to his spokesperson, sometimes he takes the state plane.)
Mind you, all this is legal as long as the cars in question are used for campaign or official purposes. So is using campaign funds to cover car insurance, repairs, fuel, and parking costs. We found many examples of politicians dipping into campaign coffers still deeper to add satellite radio, buy vehicle stickers, and pay parking tickets.
There are literally hundreds of other examples of dubious campaign spending, many almost amusingly penny ante. Angelo “Skip” Saviano, a ten-term Republican state representative from Elmwood Park who lost his reelection bid in November, dropped $210 at Sosa Cigars, an upscale lounge in Disney World. O’Connor spent $500 at Cinzia, a fancy spa in Myrtle Beach, South Carolina. Holiday cards, flowers, wedding gifts—they’re all commonly found in candidates’ spending reports. “They’ll tell you it’s all ‘constituent services,’ ” Morrison says.
The numbers climb from there. Did state representative David Harris, a Republican from Arlington Heights, really need a $6,152 Segway electric scooter for campaign work? (Yes, he says: “I wanted to draw attention to myself and, second, meet all the voters I could.”) Is every dollar of the $912,782 that Michael Madigan has spent on Cubs ($456,027), White Sox ($305,116), Bulls ($143,155), and Notre Dame football ($8,484) tickets since the start of 2007 really part of his election effort? (Says Madigan’s spokesperson, “He sees [the tickets] as a way to encourage people to be active in political campaigns,” adding that when Madigan uses the tickets himself, he always reimburses his campaign.)
Pretty soon you reach the Spinal Tap level: a campaign spending knob that goes beyond 10 to 11, just like Nigel Tufnel’s amplifier. Terry Link, the veteran state senator from Waukegan and chairman of the Lake County Democrats, is a master of the form. Campaign-paid car? Check. A dazzling variety of things charged to his campaign, down to a $221 People magazine subscription? Check. Link even reported that he used campaign coffers to pay for dry cleaning, in violation of one of the law’s few clear prohibitions. (When asked to explain that one, Link called back and said that the bills were to clean not his own clothes but items collected for a coat drive. “I didn’t want to give people dirty coats,” he said.)
As you’ll recall, using campaign funds to purchase a home is forbidden. Link, 65, says he used his own money to buy a $32,000 two-bedroom “manufactured house” years ago. He keeps it at the mobile home park Woodland Acres in Springfield and stays there when the state legislature is in session, he says. During those times, he bills his campaign fund the $280 lot lease fee that Woodland Acres charges.
This might not be an issue if it weren’t for the fact that Link also collects a taxpayer-provided $111 per diem, according to the Illinois comptroller’s records (each member of the General Assembly gets that amount to cover meals and hotel rooms while the legislature is in session). “He’s just so blatant,” says one legislator who requested that his name not be used. “He’s getting a windfall and not claiming it as a personal benefit.”
Responds Link: “I’m doing nothing that’s illegal. If I had anything to hide, I wouldn’t report it.”
Campaign finance observers say that few politicians start out trying to game the system. In their first runs for office, they tend to spend their hard-earned cash on staples such as consultants, pollsters, bumper stickers, and advertising.
Fast-forward several terms. Now sitting pretty in safe districts with token opposition or none at all, they no longer need to use their campaign war chests, flush with cash from big-money special interests, to appeal to voters. Still, they campaign full-time, year-round, despite the actual election being years away. This campaigning begets more spending: office overhead, fundraising, staff meetings, social events, and so on. That’s on top of the traditional get-out-the-vote expenses that hit right before each election.
Here’s where some can fall into a trap. Regularly wined and dined and fawned over by donors and lobbyists, they start to indulge in luxuries not necessarily related to their elections. “You convince yourself it’s all part of the job, and it’s not a lot of money, and that sort of thing,” says Redfield. “It’s very corrosive.”
Pretty soon some start charging practically everything to their campaigns, including everyday necessities, like groceries, that average folks have to pay for themselves. Michaelson says the everyday expenses can be more insidious than the big-ticket ones. “Buying a second house in Florida—that just stands out like a sore thumb,” he says. “It’s the daily stuff, the more routine stuff, that can all add up to a lot of money.”
Most of the money that flows into politicians’ campaign coffers comes not from ordinary citizens but from special interest groups. Three out of every four contributions, in fact. And that’s what particularly troubles Redfield. “If a candidate uses campaign funds to supplement his lifestyle, you’re creating a conflict of interest,” he says. “You depend on your contributors to keep contributing to you if you want to maintain your lifestyle. Does that give your contributors leverage? Does it bleed over to how you deal with public policy?”
“People should be outraged,” says Melanie Sloan, the executive director of the D.C.-based political watchdog group Citizens for Responsibility and Ethics in Washington. “If you don’t want to live on a lawmaker’s salary,” she adds, “don’t be a lawmaker.”
Campaign donors aren’t raising a stink. According to Stern, they couldn’t care less if the money they give a politician goes toward personal expenses. “They just care,” he says, “that the money has influence.”
It’s the commissioners of the Illinois State Board of Elections—four Democrats and four Republicans appointed by the governor—who have the power to investigate possible campaign spending violations and impose fines.
But by statute, the board lacks the power to audit campaign disclosure forms to stop violations in progress. (By contrast, the boards in Wisconsin and Minnesota, among others, do have such power.) The board can ask candidates to clarify expenses that seem fishy, but it cannot, for the most part, challenge their legitimacy. In other words, it can’t question whether a politician’s $395 tab at Gibsons on a Valentine’s Day three years before his next election is really a “political meeting” or a campaign-paid date night. It can investigate on its own but usually only does so if a “verified complaint” is received.
And the fines it can impose are basically wrist slaps: They top out at $500, plus the value of each improper expenditure over $500. “I think there’s a lot of areas where the board would like more statutory authority,” says former board director Michaelson. “But where does that come from? The state legislature. The men and women who are going to be directly affected by it. The status quo. They’re not eager to pass reforms.”
By many accounts, the board commissioners are too accommodating, emphasizing negotiation over prosecution and reluctant to side against a politician in their own party. “The last thing they want to be doing is policing the expenditures of the people who pass their budgets,” says Redfield—especially given that the board’s budget has shrunk from $118 million in 2007 to $39 million last year even as its workload has grown.
And when the board does issue fines, it rarely bothers to collect. A 2011 Daily Herald investigation found that of the $21.5 million in fines issued by the board to candidates and political organizations since 1999, only $1.2 million had been paid. “What [the commissioners] really need is more backbone,” says Morrison.
Rupert Borgsmiller, the executive director of the Illinois State Board of Elections, responds that the agency does its best with the resources it has. The board prefers to work with politicians to make sure they comply with the law, not to play gotcha. Borgsmiller also points to the language of the statute: “That’s what we have to work with. It is what it is.”
In fairness, politicians’ expenses can be difficult to track, given the dizzyingly large number of small expenditures, often spread out over months or years, listed in separate reporting periods and sometimes filed by multiple political committees. Think about it: In Illinois there are some 40,000 elected officials in about 6,000 units of government, according to the elections board (though many down-ballot elected officers don’t have campaign accounts). Plus, there are hundreds more political action committees that aren’t affiliated with elected candidates but have to be monitored.
To further complicate matters, politicians aren’t required to provide any corroborating receipts or paperwork for their campaign spending. They can and do list vague descriptions, such as “meetings,” that may obscure the real purchases. In March 2011, for example, Ray Suarez, the Democratic alderman of the 31st Ward, reported that his campaign spent $3,760 in “miscellaneous expenditures” for the purpose of—wait for it—“miscellaneous expenses.”
“You can fudge these things all the time,” says one prominent Chicago election lawyer who requested anonymity. “We don’t have robust enough disclosure requirements to really expose all of the skeletons in the closet.”
Because state legislators have lacked the will to criminalize campaign spending abuses, it has mostly fallen to federal authorities to prosecute possible violators. But such indictments are extremely rare, and only a handful of Illinois politicians have actually been convicted. (The most recent: George Ryan, the former Republican governor, in 2003, for making personal use of $80,000 in campaign funds and failing to pay income taxes on the money.)
As for prosecutions, the latest significant one came against William Beavers, the longtime South Side alderman turned Cook County commissioner. Last February he was indicted on federal charges that he didn’t pay taxes on more than $225,000 he took from his campaign funds and county expense account to gamble and sweeten his city pension. (Beavers has called the charges “horseshit.”)
In practice, the IRS and federal prosecutors tend to look into questionable campaign spending only during the course of a separate public corruption investigation. “Unless it’s very flagrant or repeated, it wouldn’t be worth basing a case on,” says Byram Tichenor, a former IRS special agent who headed Chicago’s criminal investigative division from 2005 to 2007. “The government has to show clear evidence of fraud.”
That’s not so easy, says Joel Levin, a former assistant U.S. attorney who helped prosecute Ryan, in part because most politicians have campaign treasurers, accountants, and lawyers—often trusted friends or family members—who can insulate them from questions about possible misconduct. Recall how, during her unsuccessful mayoral bid in 2011, Carol Moseley Braun blamed her former campaign treasurer and longtime friend after her campaign failed to report how it spent $315,000 in campaign funds?
The way to fix systemic campaign spending abuse, of course, is better laws. One good start might be for Illinois to offer public financing to political candidates who agree to limit their spending during each race, as 24 other states already do. In one of them—Minnesota—the maximum cost of a statehouse race is $34,300. By contrast, in the 2010 elections (the latest year for which data are available), the average candidate for the Illinois House spent $90,000; some spent in the hundreds of thousands.
At the very least, say campaign finance experts we interviewed, Illinois legislators should impose more and clearer restrictions on use of campaign cash. Take restaurant meals: Stern suggests that candidates be allowed to spend only what the state allots for its governmental per diems. He further proposes that candidates be allowed to expense campaign meals only during a defined election cycle, not anytime they please.
What’s more, the Illinois Board of Elections should have the power to audit campaign committees and to impose mandatory fines with real bite. Redfield even suggests stripping the board of enforcement powers altogether and giving them to the state inspector general, a more credible and independent arbiter. Or creating a body such as the Government Accountability Board in Wisconsin, which consists of six former judges who are nominated by a panel of state appellate court judges and so are almost completely removed from politics.
Barring such reforms, Sloan doesn’t see anything curbing politicians’ bad behavior except “a couple prosecutions . . . [that create] a scandal.”
But do convictions actually deter politicians? I asked Levin.
“That’s the $64,000 question,” he answered.
Or to put it another way: That’s the question whose value—using Joe Berrios math—would equal the cost of 340 restaurant meals charged to his campaign funds. | null | minipile | NaturalLanguage | mit | null |
Q:
How do you repair a plastic kayak?
So roughly a month ago my other half and I brought ourselves each a SOT plastic kayak, we've been out on the water for maybe 2 hours total paddling time, but mine filled up with water.
We found a hole, approx. 1cm by 0.4cm, in the seam of the plastic in one of the two rear drainage holes, too small to get your hand down easily. I am currently talking to the manufacturer about a replacement.
However this has lead me to wonder (outside of warranty) how would I go about repairing a hole in a plastic kayak? Varied sized holes, and temporary and permanent fixes, I understand will vary.
A:
The main issue with repairing plastic hulls is that is that most adhesives don't bond very well to the plastic. For temporary repairs duct tape is the way to go. Its quite adhesive and waterproof. If the hole is too big use the duct tape to secure something else waterproof (e.g plyboard or plastic) in place. If possible try and do both inside and out.
If you want to do a permanent repair there seem to be two options:
Repair in a similar way to fiberglass. I.e. Sand the surrounding area and apply a fiberglass patch and epoxy. The one significant difference is that the area around the hole should be flame treated before applying the patch by lightly heating with a propane torch or similar. This helps the epoxy bond to the surface. Be careful not to burn your boat though.
The alternative, more conventional, way is to melt/weld more plastic into the hole. I suspect this is what a professional would do if you asked them to do the repair. Here's another good article on it. For smallish holes you want to get some polyethylene welding rod (presuming the boat is polyethylene) for large holes you need to get a patch. The basic idea is to melt the rod into the hole using a hot air gun or hot metal. As you've melted two of the same material together this repair should be very strong.
Disclaimer: I'm mainly a dinghy sailor so haven't actually repaired any plastic hulls. This is just based on my general understanding of boat repair and reading the internet.
A:
I've seen people use a soldering iron and a piece kf abs plastic to repair tears in the hull but the best answer is short and simple to use for small holes: epoxy putty.
just follow instructions on the packaging, fill the hole with a small (few mm) overlap inside and out and if you want sand down when hard and paint.
A:
It's quite common to melt in some plastic - but be sure to get the same as the boat is made of. Most are PE so try to get some of that -- avoid ABS. Kits are available (random web example). The general recommendation among people I know who've done this is to use a hot air gun rather than a naked flame. You can also overfill a touch and smooth down later. The repair will be pretty good for flat-water use, but will always be a weak spot to be wary of in significant white water and to a lesser extent surf. As you've got SOTs I'm guessing/hoping you're not doing much if any river-running so you should be fine. Be sure to get all the water out first though, you don't want to trap it in there, and make sure the surface is clean before repairing it (e.g. of salt if you've been in the sea).
| null | minipile | NaturalLanguage | mit | null |
Introduction
============
We have applied two-photon (2P) excitation fluorescence (TPEF) and deep tissue optical sectioning to the human trabecular meshwork (TM) \[[@r1]--[@r5]\] to understand molecular mechanisms relevant to glaucoma. Simultaneously detecting multiple fluorophores in tissues provides important capacity for analyzing epitopes in situ, but the optimal parameters for achieving this in the human TM have not been determined.
With 2P imaging, two low-energy photons simultaneously interact to nonlinearly excite emission. 2P infrared-shifted imaging permits deeper tissue penetration, excitation of a broad range of fluorophores at a single wavelength, and use of lower energy levels with no or much less light damage to the tissue compared with one-photon (1P) imaging.
Parameters for simultaneously detecting endogenous and exogenous fluorophores in tissue are not easily predicted from standard 2P emission profiles. Tissues have significant autofluorescence (AF) with a broad emission spectrum that is expected to vary according to the tissue content and distribution of endogenous fluorophores. Even within a tissue, endogenous fluorescence itself may be heterogenous \[[@r2],[@r5]\].
For each 2P tissue application, it must be determined whether the particular tissue's endogenous signal is desirable or to be avoided. Tissue AF may interfere with the simultaneous identification of other fluorescent labels and is often considered a nuisance. In the TM, however, the structural extracellular matrix's (ECM) AF signature is useful as it provides tissue localization clues and information on cell--ECM associations \[[@r2],[@r3],[@r5]\]. Thus, there are cases where AF is to be exploited and others in which it is to be mitigated during imaging. If AF is to be used, strategies are needed to ensure the endogenous signal does not interfere with the simultaneous identification of other fluorophores.
The aim of the present study was to determine appropriate parameters for simultaneously identifying three independent fluorophores during 2P imaging of the human TM. A typical TM application would be to localize a labeled epitope of interest with reference to cells and structural ECM in situ. This is possible with double labeling: For example, Alexa-568-conjugated antibody for the epitope of interest \[[@r1]\] and Hoechst 33342 for nuclear localization \[[@r2]--[@r4]\] combined with a third signal from tissue AF. We do not quench the AF but exploit it as a reference to localize labeled epitopes or cellular structures within the tissue \[[@r2],[@r5]\].
The following basic considerations were used to optimize simultaneous detection of triple fluorescence from Hoechst 33342, Alexa-568, and AF in the human TM. The known range of optimal 2P excitation wavelengths for Hoechst 33342 is 700--820 nm and for Alexa-568 is 780--840 nm. The 2P emission spectrum maxima for Hoechst 33342 is at 440 nm but is at 25% of the maxima at 400 nm and 550 nm \[[@r6]\]. Thus, Hoechst 33342 is detectable through a green filter (500--550 nm) although bleed-through to the red spectrum (565--680 nm) may still occur. The 2P range of emission maxima for Alexa-568 is 596--603 nm, which is detectable through near-red (565--605 nm) and far-red (590--680 nm) filters. The TM AF emission spectrum is broad, detectable through blue and green filters, and may bleed through as far as the near-red range (565--605 nm). For this reason, we chose a far-red filter (590--680 nm) to segregate detection of Alexa-568 fluorescence from AF. A green filter (500--550 nm) allowed detection of AF and Hoechst 33342 fluorescence. Despite being spectrally similar when detected through the same filter, Hoechst 33342--labeled TM nuclei and the autofluorescent structural ECM are easily distinguished by their respective morphologies. Depending on 2P excitation wavelength, they may also have different fluorescence emission intensities. We empirically determined an optimal 2P excitation wavelength that would yield balanced emission intensities for the three fluorophores as detected through green and red emission filters.
Methods
=======
Human donor corneoscleral rim tissue was generously provided by physicians of the Doheny Corneal Service with institutional review board approval, in compliance with the Declaration of Helsinki, and adherence to the ARVO statement on human subjects. Tissue was received immediately after cornea harvesting for transplantation, within 6 days postmortem as previously described \[[@r2]\] and maintained in Optisol GS transport media (Bausch & Lomb, Rochester, NY) at 4 °C. This tissue is typically discarded after transplant surgery but was salvaged and repurposed for research because it contains the intact TM. The work presented here is based on observations in tissues from 44 donors.
Tissue viability screening
--------------------------
Tissue was sectioned into wedges, and a sampling of wedges from each donor was colabeled with calcein AM (Life Technologies, Waltham, MA) and propidium iodide (PI; Life Technologies) to assess live cellularity and viability as previously described \[[@r4],[@r7]\]. Wedges were incubated with 0.3 μl calcein AM and 1 μg/ml PI in Dulbecco's PBS (1X; 137 mM NaCl, 2.7 mM KCl, 8.1 mM Na~2~HPO~4~, 1.5 mM KH~2~PO~4~, pH 7.4; Cat. No. 21--031, Corning Life Sciences, Tewksbury, MA) for 30 min at 37 °C and 8% CO~2~. TPEF optical sectioning through the TM was performed, and calcein-positive cells and PI-positive cells in z-stacks were counted. The percentage of calcein-positive cells relative to total cells (i.e., total cells=calcein-positive cells + PI-positive cells) was used to quantify live cellularity. Minimum live cellularity of 50% was needed to verify that a tissue was viable.
We previously found that two thirds of human corneoscleral donor tissues retrieved right after transplant surgery had a TM live cellularity rate of 70% or greater based on calcein AM positive labeling. By comparison, tissues not deemed viable, under 50% typically, had live cellularity rates of around 10% \[[@r7]\], confirmed with positive propidium iodide nuclear labeling in the non-viable cells. These "dead" cells remain in the trabecular meshwork; they do not float away. The same method we used previously was employed here \[[@r7]\].
Tissue fixation and staining
----------------------------
For labeling, tissue wedges were placed in 24-well plate wells, washed twice with 1 ml PBS, fixed for 30 min in 1 ml 4% paraformaldehyde, permeabilized for 2 h in 1 ml of 5% Triton X-100 in PBS rocking at 4 °C, and blocked in 1% BSA (BSA) for 30 min at room temperature. Wedges were placed in 96-well plate wells and incubated with 150 μl of Alexa Fluor©-568-conjugated phalloidin (Life Technologies) and Hoechst 33342 (Life Technologies) in 0.1% BSA/PBS overnight (16 h) at 4 °C on a rocking platform. They were transferred to fresh 24-well plates and washed five times with 1 ml PBS for 5 h at room temperature.
Imaging setup
-------------
Tissue wedges were imaged with a Leica TCS SP5 AOBS MP confocal microscope system (Leica Microsystems, Heidelberg, Germany) coupled to a Chameleon Ultra-II multiphoton laser (Coherent, Santa Clara, CA). The wedges were placed TM-side down on a glass-bottom microwell dish. Incident light was focused, and the emitted signals collected, with an inverted HCX PL APO CS 63X/1.3NA glycerol objective (Leica). The laser was centered at 750, 800, 850, or 900 nm to excite AF, indirect epifluorescence, and Hoechst 33342 fluorescence. TPEF signals were collected in epifluorescence configuration, split with a dichroic mirror, passed through multiphoton bandpass filters (green=525/50 nm (500--550 nm); near-red=585/40 nm (565--605 nm; Leica); or far-red=635/90 or 590--680 nm (Chroma, Bellows Falls, VT)) and guided onto a non-descanned photomultiplier tube detector (Hamamatsu, Bridgewater, NJ). 1P images were generated using 488 nm argon laser and a 543 nm helium neon laser excitation and tunable prism-based spectrophotometric detectors (SP mirrors) adjusted to emission windows of 500--535 nm for green fluorescence and 555--700 nm for red fluorescence. All images were captured at a resolution of 1024 × 1024 pixels and color depth of 16 bits. Images were captured at relative depths of 7--8 μm (from the surface of the uveal meshwork) unless otherwise specified.
The imaging was performed within a standard 2P setup that includes a dual-channel non-descanned photomultiplier tube (PMT) detector and two emission filters, a commonly used 2P setup. "Non-descanned" geometry refers to PMT positioning in the light path immediately after the objective. This improves detection sensitivity for deep tissue scanning. In contrast, less sensitive descanned detectors used with 1P imaging are separated from the objective with a series of dichroics, mirrors, filters, and a pinhole to collect a specific wavelength of in-focus photons.
Image analysis
--------------
Five regions of interest (ROIs) of equal size were placed in fixed positions across each analyzed image. The mean gray values in the ROIs were calculated in image analysis software (Leica LAS AF Lite). Average fluorescence intensities (0--65535) for pixels in the ROIs of the images captured through the red and green filters were recorded, representing red and green values, respectively. Yellow values were calculated as red-to-green ratios.
In a separate analysis, 12 small ROIs were used to isolate regions of ECM AF alone and Hoechst 33342 nuclei labeling alone (six ROI each). Mean gray values were calculated for each ROI (Leica LAS AF Lite). Average fluorescence intensity (0--65535) per pixel was reported for the nuclear ROI and the AF ROI. These mean gray values were used as a control to check that changes in the mean gray values in the red channels were not attributable to fluctuations in AF and/or Hoechst 33342 fluorescence intensities or their bleed-through into the red channels. The Hoechst 33342-to-ECM AF ratios for average fluorescence intensity per pixel values were calculated from these results.
Results
=======
Comparison of 1P and 2P excitation
----------------------------------
Differences between TM AF, Hoechst 33342, and Alexa-568 fluorescence due to 1P excitation as detected through red (555--700 nm) and green filters (500--535 nm), and 2P excitation through red (565--605 nm) and green (500--550 nm) filters were evident, as shown in [Figure 1](#f1){ref-type="fig"}. One-photon excitation at 543 nm and 488 nm revealed Alexa 568 phalloidin fluorescence in the red channel ([Figure 1A](#f1){ref-type="fig"}; 555--700 nm) and autofluorescent trabecular beams in the green channel ([Figure 1B](#f1){ref-type="fig"}; 500--535 nm), respectively. Hoechst 33342--labeled nuclear fluorescence was not observed in the 1P green (500--535 nm) or red (555--700 nm) channels ([Figure 1A](#f1){ref-type="fig"}-) as it requires a shorter wavelength emission filter to be seen. Hoechst 33342 nuclear labeling was detected in the 2P channels (*arrows* point to Hoechst 33342--labeled nuclei captured with 2P ([Figure 1D,E,H](#f1){ref-type="fig"}), primarily in the green channel (500--550 nm), with some bleed-through into the near-red channel (565--605 nm), especially with 750 nm excitation.
{#f1}
Autofluorescence intensity varies between tissues and with 2P excitation wavelength
-----------------------------------------------------------------------------------
AF intensity varied between tissues from different individuals, as shown in [Figure 2A-D](#f2){ref-type="fig"} (four donors). Pixel fluorescence intensity in autofluorescent beams decreased with 2P excitation wavelength; at 750 nm excitation, mean intensity was 2495±1331 (mean ± standard deviation (SD); maximum range: 1--65355); at 800 nm, mean intensity was 2448±1200; at 850 nm, 986±456; and at 900 nm, 337±232.
{#f2}
2P-excited Hoechst 33342 nuclear fluorescence
---------------------------------------------
Hoechst fluorescence intensity in the green channel (500--550 nm) was highest with 2P excitation at 750 nm, but emission intensity diminished with longer excitation wavelengths (compare [Figure 1E,H](#f1){ref-type="fig"}; shown for 850 nm excitation). Relative intensity of Hoechst 33342 fluorescence diminished with increasing excitation wavelength (compare [Figure 3A,C,B,D](#f3){ref-type="fig"}, blue ROIs; [Figure 4](#f4){ref-type="fig"}, white bars), becoming virtually imperceptible with 900 nm excitation (see [Figure 3E,F](#f3){ref-type="fig"}, blue ROIs).
{#f3}
{ref-type="fig"}. AF-to-Hoechst 33342 ratios increased sharply with increasing excitation wavelength (800 nm to 900 nm). The y-axis (mean gray value of fluorescence intensity) is set to a logarithmic (base 10) scale. Error bars=standard deviation.](mv-v22-203-f4){#f4}
Bleed-through of Hoechst 33342 fluorescence into the near red channel (565--605 nm) was analyzed at excitation wavelengths of 750, 800, 850, and 900 nm in the fixed tissues, as shown in [Figure 5](#f5){ref-type="fig"}. ECM AF bleed-through intensity sharply decreased with longer wavelengths. Hoechst 33342 colabeling did not significantly alter the ECM AF bleed-through. Hoechst 33342--labeled nuclear bleed-through was an order of magnitude higher than ECM AF bleed-through across all excitation wavelengths. The Hoechst 33342 bleed-through intensity decreased with 2P excitation wavelength; 2354±1577 (mean ± SD) at 750 nm; 594±520 at 800 nm; 26±37 at 850 nm; and 9±13 at 900 nm excitation.
{#f5}
2P-excited autofluorescence
---------------------------
ECM AF intensity modestly decreased with longer 2P excitation wavelengths ([Figure 4](#f4){ref-type="fig"}, black bars), the corresponding Hoechst 33342 intensity decrease was more dramatic (white bars). Thus, Hoechst 33342 and AF viewed together, ECM AF was less apparent with shorter 2P excitation wavelengths (especially 800 nm; [Figure 3A,C,E](#f3){ref-type="fig"}) as overall image brightness had to be reduced to accommodate the overwhelmingly intense Hoechst 33342 signal (see [Figure 4](#f4){ref-type="fig"} for 800 nm excitation).
Balancing 2P excited autofluorescence and Hoechst 33342 fluorescence
--------------------------------------------------------------------
Two-photon-excited Hoechst 33342 and AF emission overlapped over a broad spectrum ([Figure 1E,H](#f1){ref-type="fig"}). Both were seen not only in the green channel (500--550 nm) but also as bleed-through into the red channel ([Figure 1D](#f1){ref-type="fig"}), especially with 750 nm excitation. Higher Hoechst 33342 fluorescence intensity with 750 nm or 800 nm excitation was associated with virtually imperceptible AF ([Figure 1E](#f1){ref-type="fig"}, asterisk; [Figure 3A](#f3){ref-type="fig"}), corresponding to a Hoechst:AF intensity ratio of at least 10:1. With 850 nm excitation, however, autofluorescence and Hoechst 33342 fluorescence were easily seen together ([Figure 1H](#f1){ref-type="fig"}, asterisk; green channel), with the fluorophores emitting at more balanced intensities (Hoechst:AF ratio about 2:1; [Figure 4](#f4){ref-type="fig"}). At 900 nm excitation, although the Hoechst:AF ratio was nearly 1:1, labeled nuclei were barely perceptible.
Alexa 568 phalloidin fluorescence following 2P excitation
---------------------------------------------------------
Fluorescence intensity of Alexa-568-phalloidin (for F-actin) diminished with increasing 2P excitation wavelength from 800 nm to 850 nm to 900 nm. Alexa-568 pixel intensity was 18,348 for 800 nm ([Figure 6C](#f6){ref-type="fig"}), 4,064 for 850 nm ([Figure 6G](#f6){ref-type="fig"}), and 871 for 900 nm excitation ([Figure 6K](#f6){ref-type="fig"}). Pixel intensity of Alexa-568 emission through near-red (565--605 nm) and far-red filters (590--680 nm) decreased with increasing 2P excitation wavelength, as did AF intensity, as shown in [Figure 7](#f7){ref-type="fig"}. At 850 nm excitation, Alexa-568 emission intensity through the far-red filter was more than 200% that of Alexa-568 emission detected through the near-red filter or AF detected through the near-red or far-red filter.
{#f6}
{ref-type="fig"}). In the absence of Alexa-568 (-Red Dye), red channel fluorescence was attributed to broad spectrum Hoechst 33342 and autofluorescence (AF) bleed-through. Alexa-568-to-AF bleed-through mean gray value ratios decreased with increasing excitation wavelength (800 to 900 nm) and were highest through a far-red filter (590--680 nm). For the ratio values, see [Table 1](#t1){ref-type="table"}.](mv-v22-203-f7){#f7}
Effect of 2P excitation and filter wavelength on fluorophore bleed-through
--------------------------------------------------------------------------
Hoechst 33342 and AF bleed-through contributed to some of the fluorescence detected in the red channel (565--680 nm), as shown in [Figure 1D](#f1){ref-type="fig"} (arrows). [Figure 6A,B,E,F,I,J](#f6){ref-type="fig"} depict Hoechst 33342 and AF bleed-through into the red channels (near-red: 565--605 nm; far-red: 590--680 nm). Hoechst 33342 bleed-through was highest for shorter excitation wavelengths (800 nm; [Figure 6A](#f6){ref-type="fig"}, arrows) and virtually absent for longer wavelengths (900 nm; [Figure 6I](#f6){ref-type="fig"}, arrows). AF bleed-through into the near-red channel (565--605 nm) was more at higher excitation wavelengths (compare 800 nm with 850 nm and 900 nm; [Figure 6A,E,I](#f6){ref-type="fig"}; asterisks). Total Hoechst 33342 fluorescence and AF bleed-through into the red channel was less with a far-red filter (590--680 nm) than with a near-red filter (565--605 nm): by 41% for 800 nm excitation, 28% for 850 nm excitation, and 17% for 900 nm excitation (compare [Figure 6A,E,I](#f6){ref-type="fig"} to [Figure 6B,F,J](#f6){ref-type="fig"}; also [Figure 7](#f7){ref-type="fig"}, green bars).
The extent to which Hoechst 33342 and AF bleed-through affected interpretation of the Alexa-568 signal depended on 2P excitation wavelength and choice of near-red (565--605 nm) or far-red filter (590--680 nm), as shown in [Table 1](#t1){ref-type="table"} and [Figure 6](#f6){ref-type="fig"}. Alexa-568-phalloidin signal-to-noise ratios (i.e., representing Alexa-568 signal above AF bleed-through in the red channel) were higher in the far-red channel (590--680 nm) than in the near-red channel (565--605 nm) by 144% for 800 nm excitation, 180% for 850 nm excitation, and 284% for 900 nm excitation ([Figure 6C,D,G,H,K,L](#f6){ref-type="fig"}; [Figure 7](#f7){ref-type="fig"}; and [Table 1](#t1){ref-type="table"}).
###### Effect of red filter bandpass on signal-to-noise ratio.
**Emission Filter Wavelength Range (nm)** **Near Red: 565--605** **Far Red: 590--680**
------------------------------------------- ----------------------------------------- ----------------------- ---------- ---------- ---------- ---------- ----------
**-Red Dye** AF Bleed-Through 6774 4290 2904 3972 3096 2398
**+Red Dye** Alexa-568 in Red Channel 18,348 4064 871 27,776 8736 3626
Ratio of Alexa-568-to-
AF Bleed-Through **2.71** **0.95** **0.30** **6.99** **2.82** **1.51**
Pixel intensity was calculated in five regions of interest (ROI) positioned in each image frame (see [Figure 6](#f6){ref-type="fig"}). In the absence of Alexa-568 (-Red Dye), fluorescence in the near-red (565--605 nm) and far-red (590--680 nm) channels was attributed to Hoechst and autofluorescence (AF) bleed-through (AF Bleed-Through) and considered background signal or "noise." In the presence of Alexa-568 dye (+Red Dye); intensity measurements in the same ROIs represented a mix of Alexa-568 signal and background noise. The signal-to-noise ratio (Ratio of Alexa-568-to-AF Bleed Through) decreased with increasing excitation wavelength (from 800 to 900 nm) and use of a far-red filter (590--680 nm).
Optimizing 2P-excited multiple fluorophore detection and minimizing bleed-through
---------------------------------------------------------------------------------
Overall, human TM 2P excitation at 850 nm provided well balanced and reasonably bright Hoechst 33342--labeled nuclear fluorescence and AF ([Figure 4](#f4){ref-type="fig"}) in the same green channel (500--550 nm) with no measureable Alexa-568 bleed-through. With 2P 850 nm excitation, Alexa-568-phalloidin fluorescence had a favorable balance of brightness and signal-to-noise ratio through a far-red filter (590--680 nm). Hoechst 33342 and AF bleed-through from the green channel (500--550 nm) into the far-red channel (590--680 nm) was minimal ([Table 1](#t1){ref-type="table"}).
Discussion
==========
We have sought to optimize 2P excitation of endogenous and exogenous fluorophores in the human TM to simultaneously visualize multiple fluorophores through two emission filters. Hoechst 33342 and Alexa-568-phalloidin were exogenous fluorophores while AF originated from ECM endogenous fluorophores with broad-spectrum emissions. Ideally, we wanted: (a) minimal Hoechst 33342 and AF bleed-through into the red channel, in which Alexa-568-phalloidin--associated fluorescence was viewed; (b) a high Alexa-568-phalloidin signal-to-noise ratio (bleed-through/background fluorescence) in the red channel; (c) reasonably matched Hoechst 33342 and AF intensities in the green channel (500--550 nm), allowing both signals to be seen and clearly distinguished in the same pass simultaneously; and (d) minimal or no Alexa-568 bleed-through into the green channel.
2P excitation at 850 nm, short-wavelength emission detection in a green channel (500--550 nm) and long-wavelength emission detection in a far-red channel (590--680 nm) met our criteria. We used these parameters to visualize three fluorophores---Hoechst 33342 (nuclei), AF (structural ECM), and Alexa-568-phalloidin (F-actin) ---allowing simultaneous visualization of a specific mix of endogenous and exogenous fluorophores in the human TM with reasonably balanced intensities and minimal bleed-through based on the following observations:
1\) 850 nm 2P-excited Alexa-568-phalloidin fluorescence intensity was relatively high, but with scant bleed-through into the green channel (500-550 nm; [Figure 1](#f1){ref-type="fig"}). Although shorter 2P excitation wavelengths (e.g., 750 nm and 800 nm) yielded even higher Alexa-568-phalloidin fluorescence intensities, Alexa-568 bleed-through into the green channel (500--550 nm) was pronounced.
2\) Bleed-through from Hoechst 33342 and AF into the red channel diminished with longer excitation wavelengths, with bleed-through least for 900 nm and most for 800 nm excitation. Alexa-568-phalloidin fluorescence was barely seen with 900 nm 2P excitation in the red channel, but it was relatively strong at 850 nm. Thus 850 nm 2P excitation yielded an optimal Alexa-568-phalloidin fluorescence signal-to-noise ratio, with minimal Hoechst 33342 and AF bleed-through into the red channel.
3\) With 850 nm excitation, the Hoechst 33342 nuclear fluorescence and AF intensities were closely matched, with balanced intensities, and structures easily distinguished in the green channel (500--550 nm) in the same pass. At lower wavelength excitation (e.g., 800 nm), Hoechst 33342 nuclear fluorescence intensity was high, requiring overall image intensity reduction to a level that rendered the dimmer AF signal imperceptible.
4\) Total Hoechst 33342 and AF bleed-through into the red channel was reduced with a far-red filter (590--680 nm) compared with a near-red filter (565--605 nm). Because of the possibility that paraformaldehyde fixation may itself induce some AF, all of the AF intensity analysis comparisons were performed under similar conditions, and never between fixed and unfixed tissue.
The basic considerations outlined here are worth keeping in mind when simultaneously imaging multiple fluorophore combinations in the human TM during tissue-based TPEF imaging. Depending on the imaging application, these considerations provide options to either use or negate the tissue AF signal. We have adapted these principles for simultaneously visualizing multiple intravital dyes of Hoechst 33342 (2P emission peak of 478 nm), calcein AM (1P emission peak of 517 nm; green) and propidium iodide (1P emission peak of 617 nm; far-red) in the TM \[[@r2]--[@r4],[@r7]\]. If a 2P setup with three or more emission filters is available, our described filter arrangement and 850 nm can still be used. But we would suggest adding a narrow-band filter designed to collect photons at a full-width half maximum wavelength of 425 nm \[[@r5]\], exactly half that of the 850 nm excitation wavelength proposed here. This permits detection of second harmonic generation (SHG) from structural collagen (between 365 and 440 nm) \[[@r8]\]. Detection of collagen SHG (at 425 nm) is not subject to AF bleed-through \[[@r5]\]. A similar setup was recently reported for 2P imaging of corneoscleral limbal structures using SHG, 4\',6-diamidino-2-phenylindole (DAPI) labeling, and 850 nm excitation \[[@r9]\].
National Institutes of Health, Bethesda, MD K08EY020863 (JCHT); P30EY03040 (Doheny Vision Research Institute Imaging Core); 1S10RR024754 (USC Multiphoton Core); Kirchgessner Foundation Research Grant (JCHT); American Glaucoma Society Mentoring for Physician Scientists Award and Young Clinician Scientist Award; Career Development Award from Research to Prevent Blindness (JCHT); and an unrestricted grant (UCLA Department of Ophthalmology) from the Research to Prevent Blindness, Inc.
| null | minipile | NaturalLanguage | mit | null |
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