Split (2)

validation · 215k rows

text stringlengths 1 3.78M	meta dict
Geometric Sequin Dress Style # 227303 {"widgetClass":"VariantMatrixWidget","backorderMessage":"Backordered","backorderMessageSingleVariant":"This item is backordered.","orderedSelection":true,"productVariantId":0,"variantIdField":"product62788_VariantId","backorderToMessageSingleVariant":"This item is backordered and is expected by {0}.","lowPrice":9999.0,"attributeIndexes":[],"productId":62788,"priceVariance":true,"backorderToMessage":"Backordered to {0}","updateLastSelector":true,"highPrice":-9999.0,"fireStatusEvents":true} Rated 5 out of 5áby Melissa777 Stunning This dress does run a bit small, so I just got a Large instead of a Medium. Otherwise this dress is stunning! June 27, 2014 Rated 1 out of 5áby FloridaCrissy NOT AS EXPECTED This dress looked amazing on the catalogue but when I got it the front looked nice but I did not like the material or the look of it. I am a true medium in bebe so I ordered a medium but felt like a stuffed sausage! It was so tight with no wiggle room or give to the fabric. Returned immediately! December 20, 2013	{ "pile_set_name": "Pile-CC" }
"There is something so cute about baby accessories that look like an adult could wear the same style. I love the mini me look and Nene Shoes has perfected it."	{ "pile_set_name": "OpenWebText2" }
SOUTH CAROLINA GAMECOCKS FOOTBALL The Gamecocks got good news Sunday with Rico Dowdle, it looks like. Will Muschamp said the training staff isn't overly worried about Rico Dowdle and the ankle he injured late in Saturday's win over Kentucky, saying they feel he should be fine moving forward. Also see: Updates from Sunday's baseball scrimmage Muschamp said Dowdle may not practice Tuesday when the Gamecocks reconviene for bye week practice but could resume practicing as early as Wednesday. Dowdle said after the game he felt fine and it was just a case where he got rolled up on. Muschamp also said Caleb Kinlaw is dealing with a shoulder injury and he'll know more about the severity of it later this week. Also see: Latest recruiting scoop Dylan Wonnum is out for the next three or four weeks with an ankle injury. Hank Manos had surgery on his ankle this week and will miss the next four weeks recovering from that. Dakereon Joyner will stay on crutches the next two days and likely won't practice this week but the coaches are expecting him to be back for the Georgia game two weeks from now.	{ "pile_set_name": "OpenWebText2" }
The company Rolling Gates NYC is providing rolling gate repair NYC, rolling gate maintenance and all repairs throughout Manhattan, Brooklyn, Queens, Harlem, Bronx and Long Island. Thursday, 27 November 2014 Exclusive and Complex Gate Repair Service We offer rolling gate repair service in New York City that operates 24 Hours a day. Whenever a situation with your rolling door, coiling door, rolling grille door, gate remote control, spring, motor, key switch, gate lock or cylinder, or any other part of your security roll up gate if it becomes damaged or disabled. We supply introduce and repair Commercial move up entryways, move up entryways, winding entryways and moving entryways. Our moving doors arrive in a verity of outlines, transparent, grille entryways or strong. We offer sturdiness, security, and utility of item. Manufactured from interlocking steel, stainless steel or aluminum drapes in a collection of support profiles. All moving entryways parts and work accompany our organization guarantee notwithstanding the maker's guarantees. Our highly trained technicians are just a phone call away. Call now to get a free quote over the phone and a free estimate at your rolling gate location. Rollinggate repair NYCservice is a very exclusive and complex area with a multitude of manufacturers of electrical powered providers and actuators. Your best bet is to seek the services of a business that is not only has certified electrical engineers to guarantee your system sets up in conformity with your regional town rule, but moreover, discovering a company that has the devices to develop or fix metal or metal gateways with the right encounter is also incredibly necessary. We can fabricate and set up any type of professional gate. We bring all the dimensions of conventional gateways, so be confident that we can manage your particular gate problem with convenience, whether the gate at side is a moving gate, a moving gate, a rolling gate, a cantilever gate or even a simple arm gate, our specialists work to the best of their highest capability to please our clients to fullest extent. Our professional technicians provide the best high quality items and solutions at a cost-effective cost. We fix the moving and shutter gateways with good raw components. There is a broader selection of top high quality items, which will help you to select the best among them. Most of the shutter gates are made of metal, like moving gates, end supports and many more. Experienced techniques are habituated with all type of items and they are also able of fixing them in the best possible way. There is a need of improving the device, particularly the techniques and components. Rolling Gates NYC are very much able to provide you at the most appealing way. Qualified to function on a 24×7 day service and is used to deal with any type of urgent scenario that comes to their direction. They hardly good care, who is a big or who is a small entrepreneurs. They deal with each and every need through an knowledgeable strategy. These gateways are perfect for subterranean car ports and the shop. Their move out checkpoint solutions is almost second to none.Generally gateways help to enhance the protection of every person. For more information visit the site http://rollinggaterepairnyc.com/ .	{ "pile_set_name": "Pile-CC" }
Q: What is the value set for NaN, POSITIVE_INFINITY and some other constants in Double class? What is the value set for NaN, POSITIVE_INFINITY and some other constants in Double class? From the source code, I see that they are set to themselves, but how does that work? public final class Double extends Number implements Comparable<Double> { public static final double POSITIVE_INFINITY = POSITIVE_INFINITY; public static final double NEGATIVE_INFINITY = NEGATIVE_INFINITY; public static final double NaN = NaN; public static final double MAX_VALUE = MAX_VALUE; public static final double MIN_VALUE = MIN_VALUE; ... } Thanks. A: At least in OpenJDK 8, OpenJDK 9 and OpenJDK 10, they are in the source code: public static final double POSITIVE_INFINITY = 1.0 / 0.0; public static final double NEGATIVE_INFINITY = -1.0 / 0.0; public static final double NaN = 0.0d / 0.0; // () public static final double MAX_VALUE = 0x1.fffffffffffffP+1023; public static final double MIN_VALUE = 0x0.0000000000001P-1022; () In case you're wondering about the "d"...	{ "pile_set_name": "StackExchange" }
8 reasons why website metrics are important Here are the eight reasons why website metrics are important…. Website metrics can be seen as the process of analysing a particular website in order to gather data for decision making purpose. In my previous articles, I have talked about some of the tools that can be used in web analytics to analyse web data. In this article therefore, I want to quickly look at eight good reasons why you need web analytics in order to perform better and take necessary actions. Follow me as we look at this together in this article. Classify KPI as part of website metrics The very first reason why you need website metrics is to classify your Key Performance Indicator. You must have come up with a baseline that will determine whether you are succeeding or not. Coming up with a metric give you something that you can look into and decide whether you are succeeding or not. Having this in place will allow you to take the necessary action in order to adjust your parameters. This will help you to come up with steps that will allow you to perform better. Overall productivity as part of website metrics One other reasons why you need website metrics for web analytics is that it will help you to determine the overall productivity of your website. You will be able to look at it at once glance and determine where you stand. You can now brainstorm with key stakeholders in order to boost the performance of your website generally. Making improvement as part of website metrics One of the other reason why you need website metrics on your website is that it will help you to make the necessary improvement on your website. The metric will picture the number of visitor and visit on your website as well as the page that is discouraging people from your website. It will also show the performance of your landing page. This will help you to make the necessary adjustments in order for you to perform better. Correcting design and graphic error as part of website metrics Another reason why you need website metrics is to allow you to correct design and graphic errors that are capable of reducing customer experience. You will be able to take a cursory look at your website and see how it contribute or militate against users experience. This will allow you to come up with practical measures in order to correct any anomalies that you have noticed along the line. Improving user interface as part of website metrics One thing about design is that, it is not something that you do at once and go to sleep. You need to make adjustment once at a time and see how users respond to changes that you have made. This will help you to make adjustment that will allow you to improve your users’ experience. Without metrics that will show you where you stand now, you may not know where adjustments need to be made. Glorify pay per click campaign as part of website metrics If you are paying for a particular pay per click. You will want to decide at every point in time whether you should continue to pay for that campaign or not. When you are paying for pay per click and it is not bring the desired impression that you want, you might decide to stop it. That is why you need metrics to know how many people are actually clicking on that particular link. Better landing campaigns as part of website metrics Another reason why you need metrics is that it will help you to design better landing pages that will deliver the right information to your target audience. You will be able to assess your landing page based on the result that you are getting. This will help you to adjust you landing pages in order to increase conversion rate on your website. Better decisions as part of website metrics Having and studying your website metrics will allow you make better decisions that will improve the web analytics of your website. You will be able to make better decision regarding campaigns, search engine optimization as well as lead generation and turning new entrants to customers on the long run. Action PointIf you enjoy our article, sign up to get our next article in your inbox. You need to confirm your subscription by clicking on the link sent to you. You can check the spam folder for it.	{ "pile_set_name": "Pile-CC" }
Browse: Happy New Year! Other traditions of the season include the making of New Year’s resolutions. That tradition also dates back to the early Babylonians. Popular modern resolutions might include the promise to lose weight or quit smoking. The early Babylonian’s most popular resolution was to return borrowed farm equipment. The Tournament of Roses Parade dates back to 1886. In that year, members of the Valley Hunt Club decorated their carriages with flowers. It celebrated the ripening of the orange crop in California. Although the Rose Bowl football game was first played as a part of the Tournament of Roses in 1902, it was replaced by Roman chariot races the following year. In 1916, the football game returned as the sports centerpiece of the festival. The tradition of using a baby to signify the new year was begun in Greece around 600 BC. It was their tradition at that time to celebrate their god of wine, Dionysus, by parading a baby in a basket, representing the annual rebirth of that god as the spirit of fertility. Early Egyptians also used a baby as a symbol of rebirth. Although the early Christians denounced the practice as pagan, the popularity of the baby as a symbol of rebirth forced the Church to reevaluate its position. The Church finally allowed its members to celebrate the new year with a baby, which was to symbolize the birth of the baby Jesus. The use of an image of a baby with a New Years banner as a symbolic representation of the new year was brought to early America by the Germans. They had used the effigy since the fourteenth century. FOR LUCK IN THE NEW YEARTraditionally, it was thought that one could affect the luck they would have throughout the coming year by what they did or ate on the first day of the year. For that reason, it has become common for folks to celebrate the first few minutes of a brand new year in the company of family and friends. Parties often last into the middle of the night after the ringing in of a new year. It was once believed that the first visitor on New Year’s Day would bring either good luck or bad luck the rest of the year. It was particularly lucky if that visitor happened to be a tall dark-haired man. Traditional New Year foods are also thought to bring luck. Many cultures believe that anything in the shape of a ring is good luck, because it symbolizes “coming full circle,” completing a year’s cycle. For that reason, the Dutch believe that eating donuts on New Year’s Day will bring good fortune. Many parts of the U.S. celebrate the new year by consuming black-eyed peas. These legumes are typically accompanied by either hog jowls or ham. Black-eyed peas and other legumes have been considered good luck in many cultures. The hog, and thus its meat, is considered lucky because it symbolizes prosperity. Cabbage is another “good luck” vegetable that is consumed on New Year’s Day by many. Cabbage leaves are also considered a sign of prosperity, being representative of paper currency. In some regions, rice is a lucky food that is eaten on New Year’s Day. AULD LANG SYNE The song, “Auld Lang Syne,” playing in the background, is sung at the stroke of midnight in almost every English-speaking country in the world to bring in the new year. At least partially written by Robert Burns in the 1700’s, it was first published in 1796 after Burns’ death. Early variations of the song were sung prior to 1700 and inspired Burns to produce the modern rendition. An old Scotch tune, “Auld Lang Syne” literally means “old long ago,” or simply, “the good old days.” The lyrics are: Should auld acquaintance be forgot and never brought to mind? Should auld acquaintance be forgot and days of auld lang syne?For auld lang syne, my dear, for auld lang syne, we’ll take a cup of kindness yet, for auld lang syne. Should auld acquaintance be forgot and never brought to mind? Should auld acquaintance be forgot and days of auld lang syne? And here’s a hand, my trusty friend And gie’s a hand o’ thine We’ll tak’ a cup o’ kindness yet For auld lang syne I always end up breaking my New Year’s Resolution’s very early in the year. I gave up going on a diet, quitting smoking and resolving to become more organized with the New Year. I am not sure if it is just that in my mind New Year’s Resolutions are meant to be broken or what. I did quit smoking for two years but then started again last Thanksgiving so that will be another springtime thing to quit again. I guess instead of resolutions for me, I would have to set goals for myself and start in April.Does the New Year start everything fresh for you? Is it New beginnings or just a continuation of the previous year? Do you believe in luck of the New Year and bring it in following some of the traditions above?Do you make New Year’s Resolutions? How long do you stay with them? What kinds of Resolutions will you make this year? We will pick a winner amongst all the posters and six winners will receive a copy of one of the following:Four copies of Last Call by Laura Pedersen, BallantineAnd two copies of Beginner’s Luck by Laura Pendersen, Ballantine I want to wish you all a Happy New Year and send good wishes to all of you 🙂 31 Responses to Happy New Year! I don’t normally make New Years resolutions. I know the odds of keeping them are practically nil. I do, however, want to make one this year. I was recently diagnosed with Type II Diabetes. I want to make the resolution to keep it in check with diet and comes to terms with the changes to my life this disease has created. To this end, I will watch my diet and continue to exercise and try to live a healthier life in 2008. I have never made New Years resolutions. But I do promise myself that I will continue to maintain good health habits that will lead to a long and productive life. SInce health does seem to be the biggest influence upon our quality of life. I’ve pretty much given up on official resolutions – I never could stay with them lol. I seem to do better if I do it on my own without announcing it to the world. I hope everyone has a very Happy New Year. Mine is to knock down my TBR this year. It is shameful how big it has become. I get so busy reviewing that I don’t stop and take the time to read my own books. I really have to read more of my own so I don’t get burned out. I don’t always do official resolutions–too easy to not achieve them and be disappointed. Some less official goals: like Scarlet, get through more of the TBR! Also, to prioritize so that the things that matter most are what I actually end up spending time on during the day 😉 We’ll see how that goes! I, for one, can’t wait for the new year! 2007 was lousy on many levels for me- I hope 2008 will be much better. I don’t do new year’s resolutions because I don’t think I’d stick to them. All the best everyone! I usually don’t make resolutions because I break them. But I do try not to. LOL! But for the new year, here are my resolutions: eat healthier, exercise, read more, keep organized, and sleep earlier (or get at least 7-8 hours of sleep). Happy New Years one and all! And I have to say I did a lot of the old traditions listed above for the holiday. As for resolutions, I always make a few and try my best to complete them. Normally I make good on my promises. This year I’m pledging to myself that I will make more of an effort to orginize things and help with shelters around here. That I will excercise more and eat healthier (everyone starts out with this wishful thought I am sure, so here’s hoping we make it happen this year), and last but not least, I plan to be more more involved with family. Lately some of my relatives have held onto grudges and kept themselves apart from my family and I, but this year I’m not letting old grudges stay. In with the new, out with the old. It’s a new year, fresh with no mistakes in it and I plan to try and keep it that way as long as possible. Good luck to all of us in 2008! I don’t make New Year’s Resolutions because I believe when you make them you are just setting yourself up to fail as statistics show. However, I do believe in setting goals and working towards them throughout the year. I also believe that you should set short-term goals, mid-term goals and long-term goals. Short-term to mid-term goals are usually easy to obtain and long-term goals can be modified if you find that you’ve over-reached yourself. LOL Then you can continue to work step-by-step toward that long-term goal just in smaller increments. Grin That being said, I just saw my doctor on the 24th of December and I’ve been told I really need to work towards improving my health and dropping a few pounds so I’ll have to start working towards that over the coming year. I don’t make resolutions. I do set myself goals – but I do that as necessary throughout the year. The new year doesn’t really feel much different to me that the last year – except for putting the holidays behind me. My mental schedule is much more academically oriented – I always feel like I’m starting a “new” year in Sept!! First, Happy New Year to everyone. May you have good health and happiness in the coming year. I don’t make New Year’s resolutions anymore. Like most of the other posters, they are easily broken and then depressing when they are. I just try to take each day as it comes, enjoy it and be a better person in whatever area I need to work on at the time. I have set a goal to spend more time with my grandchildren. They grow up so fast and time easily slips away. As far as traditions, our family does usually follow the tradition of eating certain things on New Years Day. Happy New Year. Hopefully this year will be better than the last few have been. We watch the ball drop on TV to marshall in the New Year and then we go to bed. That’s all we do for celebrating. I don’t make resolutions but I do have a few personal goals I’d like to reach this year. I want to get organized again, get my life back on solid ground, and get my books caught up. My whole life is in a state of chaos and I don’t like it one bit and my goal is to get it back to a semi-happy peaceful place. Like many of you, I don’t make resolutions anymore either. Goals (same difference if you ask me LOL!) seem to be a lot easier and nicer. If you think about it Resolution has a negative connotation (means you need to resolve something) but goals…now those are positive…things you CAN attain! I want to lose weight and work out 2-3 days a week. I actually used to be pretty good about keeping my New Year’s Resolutions for more than half the year but now that I have two kids under the age of 5 it has become very difficult for me. I haven’t ever been able to keep a New Year’s resolution, but I read in Positive Thinking magazine that by imagining yourself completing your goal successfully, you will be more likely to reach your goal. So, this year, I’m not writing a list of resolutions. Instead I am making a vision board to help me imagine myself completing some goals I have in mind (just as soon as I can find all the magazine pictures I need to clip and paste!) Nice, beneficial piece of writing We appreciate you this high-quality subject matter, I’m guessing you’ll on a regular basis get more web log, due to the fact Document i’m fascinated by this unique niche May possibly right now search for this short article describes Thank you catalog !	{ "pile_set_name": "Pile-CC" }
Correlation between dissociation and catalysis of SARS-CoV main protease. The dimeric interface of severe acute respiratory syndrome coronavirus main protease is a potential target for the anti-SARS drug development. We have generated C-terminal truncated mutants by serial truncations. The quaternary structure of the enzyme was analyzed using both sedimentation velocity and sedimentation equilibrium analytical ultracentrifugation. Global analysis of the combined results showed that truncation of C-terminus from 306 to 300 had no appreciable effect on the quaternary structure, and the enzyme remained catalytically active. However, further deletion of Gln-299 or Arg-298 drastically decreased the enzyme activity to 1-2% of wild type (WT), and the major form was a monomeric one. Detailed analysis of the point mutants of these two amino acid residues and their nearby hydrogen bond partner Ser-123 and Ser-139 revealed a strong correlation between the enzyme activity loss and dimer dissociation.	{ "pile_set_name": "PubMed Abstracts" }
265 B.R. 681 (2001) In re Marjorie Margolies MEZVINSKY, Debtor. David G. Sonders, Plaintiff, v. Marjorie Margolies Mezvinsky, Defendant. First Union National Bank, Plaintiff, v. Marjorie Margolies Mezvinsky, Defendant. Bankruptcy No. 00-11767DWS. Adversary Nos. 00-0462, 00-0463. United States Bankruptcy Court, E.D. Pennsylvania. August 1, 2001. 682 683 684 685 Zachary L. Grayson, Esquire, Jennifer L. Myers, Esquire, Philadelphia, PA, for Defendant/Debtor. Steven J. Adams, Esquire, Reading, PA, for Plaintiff First Union National Bank. Leonard P. Goldberger, Esquire, White & Williams, LLP, Philadelphia, PA, for Plaintiff David G. Sonders. Marvin Krasny, Esquire, Philadelphia, PA, Chapter 7 Trustee. Dave P. Adams, Esquire, Philadelphia, PA, United States Trustee. OPINION DIANE WEISS SIGMUND, Bankruptcy Judge. Before the Court are the Motions of (1) David G. Sonders ("Sonders") for Partial Summary Judgment ("Sonders Motion") and (2) First Union National Bank ("First Union") for Summary Judgment (the "First Union Motion") on their respective Complaints objecting to discharge of the Debtor pursuant to 11 U.S.C. § 727(a)(5).[1] In support of his Motion, Sonders presents his affidavit to support documents obtained from the official records filed with the United States Bankruptcy Court and the Office of Public Records of the United States Senate.[2] In response to the Sonders Motion, Debtor presented her affidavit[3] and certain 686 documents.[4] First Union's record consisted of its Complaint and the Debtor's Answer, the transcripts of Debtor's testimony at (i) her first meeting of creditors conducted on April 24, 2000 ("341 Transcript"); (ii) her Rule 2004 examination conducted on March 22, 2000 and June 6, 2000 ("Rule 2004 Testimony") and (iii) her deposition testimony given on February 6, 2001 and April 10, 2001 and exhibits MMM-1 through MMM-28 attached thereto ("Debtor's Dep."). First Union also incorporated by reference portions of the Sonders Motion. Memorandum in Support of First Union Motion ("First Union Mem.") at 15. Debtor provided no additional evidence in opposition to the First Union Motion but rather also incorporates portions of her response to the Sonders Motion, including her Affidavit therein.[5] For the reasons that follow below, the Court finds that Sonders and First Union (collectively the "Movants") have met their burden for entry of judgment. I will therefore sustain their objection to, and deny entry of, the Debtor's Chapter 7 discharge pursuant to § 727(a)(5). BACKGROUND The Debtor is a former member of the United States House of Representatives (One Hundred Third Congress January 3, 1993-January 3, 1995). A graduate of the University of Pennsylvania and former CBS New Foundation fellow (Columbia University), she worked as a television journalist for twenty-five years, has written three books, and has offered testimony before United States House of Representative and Senate Subcommittees on family issues. After her Congressional term concluded, she was named the head of the American delegation to the United Nation Fourth World Congress on Women in Beijing and later became the President of the Women's Campaign Fund. Debtor's Dep. at 73-75 and Exhibit MMM-5. She filed this voluntary petition for bankruptcy (the "Petition") on February 10, 2000 (the "Petition Date").[6] Sonders and First Union are creditors of the Debtor and filed their adversary proceedings on April 4 and June 23, 2001, respectively, alleging that the Debtor has failed to explain satisfactorily the disposition of significant assets in violation of § 727(a)(5) of the Bankruptcy Code. The following facts are undisputed: I. In May 1996,[7] the Debtor and her husband purchased a homeowners's insurance 687 policy from Nationwide Insurance Company ("Nationwide") obtaining coverage for personal property in which they claimed an interest valued at $810,535. First Union Complaint and Answer ("FU Compl. and Ans.") ¶ 14; Rule 2004 Exam at 287. In January 1995, Debtor's husband represented to the Pennsylvania Housing Finance Agency that he and the Debtor owned furniture and other personal property having a value of $725,000. FU Compl. and Ans. ¶ 11. At the first meeting of creditors held on April 24, 2000, Debtor did not recall any significant dispositions of personal property by herself or her husband since 1989. Id. ¶ 15. Yet in her Amended Schedule B, the Debtor claims her one-half interest in the personal property in which she and her husband claim an interest as of the Petition Date plus her interest in wearing apparel and clothing to be valued at approximately $19,217.[8] Ex. MMM-3 to Debtor's Dep.; FU Compl. and Ans. ¶ 9. II. The Debtor sold 15,595 shares of Charming Shoppes stock in February 1999 and another 1847 shares in January 2000, for which she received a total of $63,771 (the "Charming Shoppes Proceeds"). Amended Statement of Financial Affairs ¶ 10. III. On January 7, 2000, the Debtor sold ten shares of General Electric stock and seventy-one shares of PNC Bank Stock for $1,382.61 and $2,772.98, respectively (collectively the "Misc. Stock Proceeds"). Ex. MMM-24 to First Union Mot. The Misc. Stock Proceeds are not listed in the Debtor's Amended Bankruptcy Schedules nor is the sale of or disposition of the Misc. Stock Proceeds disclosed in her Amended Statement of Financial Affairs. IV. Between 1997 and 1999, the Debtor and her husband borrowed money from various friends and acquaintances in various amounts, totaling $1,477,500 (the "Personal Loan Assets").[9] The Debtor concedes that these loans were made to her and her husband jointly.[10] The Personal Loan Assets are not listed in the Debtor's Amended Bankruptcy Schedules nor are any transfers of the Personal Loan Assets 688 disclosed in her Amended Statement of Financial Affairs. V. On August 15, 1999 and February 25, 2000, the Debtor signed and filed personal financial statements, prepared by her husband, with the United States Senate in connection with her candidacy for the Senate (the "Senate Financial Disclosure"). The Senate Financial Disclosure indicates an ownership interest in various securities and note receivables valued at a minimum of $1.3 million. Rule 2004 Exam at 175; Ex. E to Sonders Motion.[11] VI. On or about September 24, and October 24, 1999, the Debtor wrote two checks in the amounts of $7,500 and $5,000, respectively, from a Prime Bank account in the name of the Debtor and her husband, to her housekeeper Roberta McClean ("the McClean Payments"). Ex. "J" to Sonders Mot. The McClean Payments are not disclosed in the Debtor's Amended Statement of Financial Affairs. VII. In January 2000, the Debtor sold several personal items to Nancy Chasen (the "Chasen Transaction") for $5,000 (the "Chasen Proceeds"). Amended Statement of Financial Affairs. ¶ 10. The Chasen Proceeds are not listed in the Debtor's Amended Schedules, but her discovery responses indicate that Ms. Chasen paid the proceeds directly to Northfield Mount Herman School, the school attended by the Debtor's son, Andrew. Debtor's Obj. and Resp. to Sonders' First Set of Interrogs. ¶ 27, Ex. "G" to Sonders Mot. DISCUSSION Summary judgment is warranted only where "the pleadings, depositions, answers to interrogatories and admissions on file, and affidavits, if any, show that there is no genuine issue of material fact and that the moving party is entitled to judgment as a matter of law." Fed.R.Civ.P. 56(c).[12] Thus, when deciding a summary judgment motion, the court's task is not to resolve questions of fact, but to determine whether there is in fact any genuine issue of fact to be resolved at trial. Anderson v. Liberty Lobby, Inc., 477 U.S. 242, 249, 106 S.Ct. 2505, 91 L.Ed.2d 202 (1986). In doing so, the court should view all facts in the light most favorable to the opposing party, Continental Insurance Co. v. Bodie, 682 F.2d 436, 438 (3d Cir.1982), including any factual inferences, and refrain from resolving a genuine issue of credibility, Pryzbowski v. U.S. Healthcare, Inc., 245 F.3d 266, 268 (3d Cir.2001) (citation omitted); Boyle v. Allegheny County, Pa., 139 F.3d 386, 393 (3d Cir.1998). It is the moving party's burden to demonstrate the absence of genuine issues of material fact. Drexel v. Union Prescription Centers, Inc., 582 F.2d 781, 790 (3d Cir.1978). Once the moving party has shouldered this burden, however, "the adverse party may not rest upon the mere allegations or denials of the adverse party's pleading, but the adverse party's response, by affidavits or as otherwise provided in this rule, must set forth specific facts showing that there is a genuine issue for trial." Fed.R.Civ.P. 56(e) (emphasis added). A party opposing summary judgment cannot hold back his evidence until trial, McIntyre v. Delaware Division of Youth Rehabilitation Services, 795 F.Supp. 668, 673, (D.Del.1992) (citations 689 omitted), nor may he demand trial on the speculative possibility that a material issue of fact may emerge at that time, Frito-Lay of Puerto Rico, Inc. v. Canas, 92 F.R.D. 384, 391 (D.Puerto Rico 1981) (rejecting assertion that discoverable evidence might arise from cross-examination at trial of the moving party's affiant). Statements in legal memoranda and oral argument are not evidence and cannot create an issue of fact. Id. Section 727(a)(5) of the Bankruptcy Code states that a court will grant the debtor a discharge unless "the debtor has failed to explain satisfactorily, before determination of denial of discharge under this paragraph, any loss of assets or deficiency of assets to meet the debtor's liabilities." 11 U.S.C. § 727(a)(5). Movants, as plaintiffs, bear the burden of proof. Fed. R. Bankr.P. 4005 ("At a trial on a complaint objecting to a discharge, the plaintiff has the burden of proving the objection"). Further, under § 727(a)(5), the plaintiff also bears the initial burden of production: i.e., to establish, by a preponderance of the evidence, that the debtor had a cognizable interest in a specific identifiable property at a time not too far removed from the bankruptcy which she now no longer possesses.[13]Pyramid Technology Corp. v. Cook (In re Cook), 146 B.R. 934, 940-41 (Bankr.E.D.Pa.1992); McGowan v. Beausoleil (In re Beausoleil), 142 B.R. 31, 37 (Bankr.D.R.I.1992); M.R. Toupin, Inc. v. Turpin (In re Turpin), 142 B.R. 491, 496 (Bankr.M.D.Fla.1992). It is insufficient to merely allege that the debtor has failed to explain losses, the plaintiff must produce some evidence of an identifiable asset loss. Carter Engineering Co. v. Carter (In re Carter), 236 B.R. 173, 180 (Bankr.E.D.Pa. 1999); La Brioche, Inc. v. Ishkhanian (In re Ishkhanian), 210 B.R. 944, 953 (Bankr. E.D.Pa.1997). Once the plaintiff has met this burden and thus made out a prima facie case, the burden of production (i.e., coming forward with evidence) shifts to the debtor to explain satisfactorily the losses or deficiencies. Cook, 146 B.R. at 941. The plaintiff's ultimate burden of proof does not obviate the debtor's obligation to come forward with a satisfactory explanation. Chalik v. Moorefield (In re Chalik), 748 F.2d 616, 619 (11th Cir.1984). What constitutes a "satisfactory" explanation is a matter of discretion for the court, Buzzelli, 246 B.R. at 117, but one of the better enunciations of this amorphous concept can be found in Slocum v. Wheeler (In re Wheeler), 38 B.R. 842 (Bankr.E.D.Tenn.1984). There, the court said: The word "satisfactorily," . . . may mean reasonable, or it may mean that the court, after having heard the excuse, the 690 explanation, has that mental attitude which finds contentment in saying that he believes the explanation he believes what the [debtors] say with reference to the disappearance or the shortage. . . . He no longer wonders. He is contented. Id. at 846 (quoting In re Shapiro & Ornish, 37 F.2d 403 (N.D.Tex.1929)). Similarly, in this circuit, it has been held that the explanation must "convince the judge" that the explanation is worthy of belief. Chusid v. First Union National Bank (In re Chusid), 1998 WL 42292, at 4 (E.D.Pa. Jan.21, 1998); Buzzelli, 246 B.R. at 117; Carter, 236 B.R. at 180 (both quoting Chalik, 748 F.2d at 619). It is important to note that, for the purposes of a § 727(a)(5) inquiry, the court is not concerned with whether the disposition of the assets was proper under the Bankruptcy Code, but rather only whether the explanation satisfactorily describes what happened to the assets. Buzzelli, 246 B.R. at 117. It is not surprising, therefore, that explanations of a generalized, vague, indefinite nature such as assets being spent on "living expenses," unsupported by documentation, are unsatisfactory. Id.; Carter 236 B.R. at 180-81. Equally unavailing is mere identification of a person with knowledge, such as an accountant or other individual who handled the financial affairs of the debtor. Chusid, 1998 WL 42292 at 5; Cook, 146 B.R. at 942. While the objections to discharge found in § 727 are to be strictly construed against the creditor and liberally in favor of the debtor, Rosen v. Bezner, 996 F.2d 1527, 1533 (3d Cir.1993), a discharge in bankruptcy is a privilege not a right which must be earned. Upon filing for bankruptcy, it is the debtor's obligation to be forthright in providing financial information. "No one is obligated to recreate the Debtor's financial affairs; that task is his alone." Goldberg ex rel. Lawrence v. Lawrence (In re Lawrence), 227 B.R. 907, 915 (Bankr.S.D.Fla.1998) (citing legislative history of 11 U.S.C. § 521 (debtor's duties)). The Bankruptcy Code makes complete financial disclosure a "condition precedent" to discharge. Id. (citing Broad Nat'l Bank v. Kadison, 26 B.R. 1015, 1018 (D.N.J.1983)). See also Meridian Bank v. Alten, 958 F.2d 1226, 1230 (3d Cir.1992) (discussing § 727(a)(3)). To that end, § 727(a)(5) works in conjunction with the other subsections of § 727 to reflect this legislative policy decision. Buzzelli, 246 B.R. at 116. For example, § 727(a)(3) ensures that the debtor maintain and supply records which are adequate to provide the creditors with sufficient information to ascertain the debtor's financial condition and track his past and present dealings. Lawrence, 227 B.R. at 916. Other subsections ensure that a debtor does not provide false oath or withhold information. Id. (citing 11 U.S.C. §§ 727(a)(4)(A) and (a)(4)(D)). In short, the global purpose of § 727 is to relieve creditors from the burden of "discovering" assets and to place it where it rightfully belongs, upon the debtor. Id. So important is this concept of disclosure, that § 727(a)(5) includes no subjective element of proving wrongful scienter such as an intent to defraud or hinder creditors. See Cook, 146 B.R. at 943 (comparing §§ 727(a)(3) and (a)(5) to §§ 727(a)(2) and (a)(4)). Further, unlike § 727(a)(3), pertaining to a debtor's duty to maintain records, which can be satisfied by a justification for the debtor's failure to do so, "the plain language of § 727(a)(5) makes clear that a debtor cannot prevail thereunder by similarly offering a justification for his or her failure to satisfactorily explain the loss or disappearance of assets." Buzzelli, 246 B.R. at 118. Thus, a debtor facing an objection to discharge under § 727(a)(5) may very well have to 691 gather or produce documents and records which she might otherwise not ordinarily keep and in fact may be justified for failing to keep under § 727(a)(3). Id. She may well have to hire professionals to locate her assets if she is unable to do so herself. See Cook, 146 B.R. at 934 (debtor had obligation to hire an accountant to explain the disappearance of assets not readily apparent from records). Applying these standards, I now examine the alleged loss and/or deficiency of assets upon which the Movants base their motions. I. Diminution of Personal Property The Movants rely upon the fact that the Debtor represented to her insurance company having an interest in personal property worth $810,535 in May 1996 and not recalling any significant dispositions of her property since 1989, while attributing approximately $19,217 of value to the personal property in which she claims an interest in her Amended Schedule B. First Union Mem. at 8-9. There is no genuine issue of fact that the Debtor made these representations as they are admitted in her Answer to the Complaint. A plaintiff makes out a prima facie case where it shows that the debtor has listed assets in her bankruptcy schedules less than she has previously presented herself to be worth. Buzzelli, 246 B.R. at 116.[14] The burden now shifts to the Debtor to explain why property valued at over $810,000 four years before the Petition Date is now worth less than five percent of that amount. Id. Before turning to the Debtor's explanation, it is clear that the comparisons urged by Movants are not completely accurate nor for that matter is the Debtor's explanation of the support for her latest estimate of value. The $810,535 valuation purports to be the value in 1996 of all tangible personal property owned by Debtor and her husband. The $19,217 value is derived from the Slosberg Appraisals which provide the orderly liquidation value of the Debtor's property as of February and April of 2000. Ex. MMM-3 to Debtor's Dep. (Amend.Sched.B).[15] To arrive at the Debtor's interest in the household goods and artwork and collectibles which represent the items appraised by Slosberg, the Schedule B attachment reflects a calculation which deducts from the total appraised value of such property approximately $15,585 of assets Debtor asserts to be holding for third parties[16] and divides 692 the remainder by two to conclude that Debtor's interest in the joint property is $16,217. By adding the $3,000 scheduled clothing and jewelry, Debtor's interest in tangible personal property is fixed at $19,217. However, a fair comparison with the $810,535 would be approximately a value of $35,434 ($16,217 × 2 + $3,000). The Debtor attributes the disparity between the property value provided to Nationwide and the value recorded in her schedules to her reliance on two different appraisals secured at different times and for different purposes.[17] Rule 2004 Exam at 287-88; Debtor's Dep. at 176. She claims that the representation to Nationwide in 1996 is based upon the Young Inventory done subsequent to a 1992 fire in her residence and supplemented by the opinion of her husband. The Young Inventory is a 93-page, hand-written document reflecting a meticulously detailed room by room listing of household items on a form dated February 2 through 6, 1992.[18] Ex. "C" to Mem. Opp. Sonders Mot.[19] While it 693 evidences under the preprinted column labeled "value" a dollar amount represented as "ACV" or "FMV or ACV" or "EST ACV" for each item listed, the document is totally devoid of explanation as to the significance of these entries nor does it in any way cumulate or present the data so any conclusions can be drawn therefrom. Instead it merely proffers 93 pages of raw data without commentary. Indeed without going through the list, item by item with a calculator, I cannot even ascertain whether this appraisal supports the representation to Nationwide that the property was valued at $810,535. The Debtor when examined about the Young Inventory had little recollection or understanding of its significance. Other than stating that it was created after a fire in the marital home, she never elucidates what its purpose was. She testifies that after the fire numerous items of furniture, rugs, clothing, and other possessions were replaced or repaired, some at great expense. Debtor's Dep. at 122, 126-27, 132, 139. However, the significance of that statement as relates to the Young Inventory was never clarified. The Slosberg Appraisal makes no mention of, much less any attempt to reconcile, itself with the Young Inventory, and the Debtor's testimony is simply too vague to bridge the gap. If the Debtor is claiming that the Young Inventory and Slosberg Appraisals explain the loss in value in her personal property, "the burden [is] on the Debtor to prove what [s]he alone claim[s] was obvious from [her] records." Cook, 146 B.R. at 942-43. See also Hughes v. Lieberman (In re Hughes), 873 F.2d 262, 264 (11th Cir.1989) (rejecting attempt to satisfy §§ 727(a)(3) and (5) by placing mass of disorganized records before the court). I recognize that a difference in valuation methodology can be a satisfactory explanation for a diminution of assets when supported by evidence. Kramer v. Poland (In re Poland), 222 B.R. 374, 382 (finding testimony and exhibits adequately explaining loss in value as the difference between "liquidation value" on bankruptcy schedules as opposed to "full value" on financial statement). However, I find the difference between $810,000 and $35,000 of asset value to be too great to be satisfied by this explanation by the Debtor without further corroboration. The Debtor argues that she has identified individuals from Slosberg and Young as well as her husband who have knowledge and whom she will subpoena for trial to provide testimony on this issue. Memorandum in Opposition to First Union Motion ("Mem. Opp. First Union Mot.") at 3-4; Mem. Opp. Sonders Mot. at 5. In relying on this response, the Debtor has misconstrued her burden of production both under the Bankruptcy Code and Rules. Under § 727(a)(5), merely identifying persons with knowledge will not suffice. Once the plaintiff has made out a prima facie case, as the Movants have here, the Debtor must come forward with a satisfactory 694 explanation as to why her personal property is now worth only a fraction of its value four years before the Petition Date. Rule 56(e), and Bankruptcy Rule 7056 by incorporation, demand that the Debtor "must, by affidavit or as otherwise provided in this rule" set forth facts showing an issue for trial. Holding back evidence until trial is not an option where the moving party has met its burden under Rule 56. McIntyre, 795 F.Supp. at 673. The Debtor has not provided any affidavit or deposition testimony from either the appraisers or her husband which might raise an issue of fact that different valuation methodologies will provide a satisfactory explanation. She cannot demand trial on mere speculation that a material issue of fact may emerge at that time. Frito-Lay, 92 F.R.D. at 391. For these reasons, I find that the Debtor has failed to satisfactorily explain the loss of approximately $775,000 worth of assets (the difference between the $810,000 represented in May 1996 and the $35,000 now claimed in her Amended Schedule B).[20] II. Loss of the Stock Proceeds 1. The Charming Shoppes Proceeds The Movants have correctly noted that the Debtor made two separate sales of Charming Shoppes stock, aggregating receipts of $63,771 (the "Charming Shoppes Proceeds"), within a year of the Petition Date. Despite disclosing the sale of the stock, the Debtor failed to account for the Charming Shoppes Proceeds in her Schedules. Amend. Statement of Fin. Affairs, ¶ 10; Amend. Sched. B. These facts are not contested by the Debtor. The Movants have thus made out a prima facie case under § 727(a)(5) by identifying a specific asset in which the Debtor had a cognizable interest (i.e., the Charming Shoppes Proceeds) at a time not too far removed from the bankruptcy and which is now no longer available. I find, however, that with respect to this asset the Debtor's testimony is sufficient to meet her burden of production. She testified, in relevant part, as follows: Q: And why did you sell [15,595 shares of] that stock in February 1999? A: It was at the request of my husband. Q: Do you know why he requested you do that? A: He needed the money. Q: And did you give that $50,140 [representing the proceeds from the 15,595 shares] to him? A: Yes Debtor's Dep. at 71-72. At this point, the Court is not concerned with whether such a transfer to her husband was proper. My inquiry under § 727(a)(5) is only whether the explanation satisfactorily describes what happened to this asset. With regard to the February 1999 proceeds, her testimony satisfactorily explains the disposition 695 of the $50,140, namely that she transferred the proceeds to Mr. Mezvinsky. The Debtor's deposition testimony as to the January 2000 sale is ambiguous when read in conjunction with her earlier testimony: Q: [You sold] 1,847 shares of Charming Shoppes and received $13,631; is that accurate? A: To the best of my knowledge. Q: Why did you sell that stock? A: For the same reason. Q: And what did you do with the $13,631? A: My husband handled it. Id. (emphasis added). The Debtor authorized the January 2000 sale of stock for the same reason as the first, because her husband needed the money. Although she fails to state as much, one could therefore infer that she also gave these proceeds to Mr. Mezvinksy. Given that I must make all inferences in favor of the Debtor and refrain from any determination as to credibility, Boyle v. Allegheny County, Pa., 139 F.3d at 393, there is at least a question of fact as to whether the Debtor can provide a satisfactory explanation, that she did in fact transfer the proceeds from the second sale of the Charming Shoppes to her husband.[21] 2. The Misc. Stock Proceeds First Union also presented brokerage account statements showing that, on January 7, 2000, the Debtor sold ten shares of General Electric stock and seventy-one shares of PNC Bank Stock for $1,382.61 and $2,772.98, respectively (collectively the "Misc. Stock Proceeds"). Ex. MMM-24 to First Union Mot. The sale of this stock is not disclosed in the Debtor's Amended Statement of Financial Affairs, nor are the Misc. Stock Proceeds accounted for in her amended schedules. First Union has thus made out a prima facie case by showing the Debtor's cognizable interest in the Misc. Stock Proceeds of $4,155.59 as of January 7, 2000, which the Debtor no longer possesses. The burden now shifts to the Debtor to satisfactorily explain the loss of the Misc. Stock Proceeds. The Debtor, however, fails to address the Misc. Stock Proceeds in her opposition to the First Union Motion. Indeed, her deposition testimony is that she has no recollection of ever having owned or sold the General Electric or PNC Bank stock. Debtor's Dep. at 16365. In light of the account statements evidencing otherwise, I find that the Debtor has failed to satisfactorily explain the loss of the Misc. Stock Proceeds, totaling $4,155.59. III. Loss of Inheritance First Union alleges that, although the Debtor disclosed a beneficial interest in the estate of her deceased mother, Mildred Margolies, estimated at $7,500 in her Amended Schedule B, her interest in the estate should have been much greater. First Union Mem. at 12. First Union relies upon account statements from brokerage accounts held by Mildred Margolies and showing that (1) Mrs. Margolies had investments worth $257,156.31 as of December 31, 1998, (2) that the accounts 696 were liquidated at some point thereafter for $312,864.28, and (3) that only $1,732.47 remained as of December 31, 1999. Exs. MMM-19, MMM-20. to Debtor's Dep. These documents fail to prove First Union's point. Under Pennsylvania law, "an interest in property established by a will takes effect at the time of the testator's death unless the testator expresses a contrary intent." Doyle v. U.S., 358 F.Supp. 300, 305 (E.D.Pa.1973) (construing Pennsylvania law). See also In re Kenin's Trust Estate, 343 Pa. 549, 555, 23 A.2d 837, 840 (1942) (all wills are ambulatory and become effective only when the will's maker dies). The relevant inquiry then is what property interest did the Debtor have at the time of her mother's death? Here, First Union has neglected to mention, much less provide evidentiary support, as to (1) when Mrs. Margolies died in order to establish when the Debtor had a cognizable interest in her estate; or (2) what the value of that estate was at the time of her death. The Debtor's testimony, however, indicates her mother passed away sometime in the year 2000. Debtor's Dep at 68. Her death then occurred after the time that the account was liquidated and before the time the Debtor's interest attached to it. It is irrelevant that Mrs. Margolies' accounts may have been liquidated at a time when the Debtor had no property interest in those accounts. With regard to the inheritance, First Union has failed to meet its initial burden of production under § 727(a)(5), namely showing that the Debtor had a cognizable property interest in an identifiable asset not too far removed from the Petition Date which she no longer possesses. IV. Loss of the Personal Loan Assets First Union correctly notes that the uncontested facts show that the Debtor and her husband borrowed the Personal Loan Assets aggregating $1,477,500 between 1997 and 1999.[22] It is likewise undisputed that the Personal Loan Assets are not accounted for anywhere in her bankruptcy schedules. Thus, First Union has made out a prima facie case by showing the Debtor had a cognizable interest in the Personal Loan Assets at a time not too far removed from the Petition Date which she no longer possesses. The burden of production now shifts to the Debtor to provide a satisfactory explanation as to the loss of or deficiency in the Personal Loan Assets. The Debtor's testimony is that, "to the best of [her] recollection," $27,500 was used for general living expenses. Rule 2004 Exam at 147. General and vague assertions that money was spent on living expenses, however, are insufficient under § 727(a)(5) absent documentary corroboration. Carter, 236 B.R. at 181. See also First Texas Savings Ass'n v. Reed (In re Reed), 700 F.2d 986, 993 (5th Cir.1983) (debtor's explanation that $19,586 was consumed by business and household expenses and gambling debts was unsatisfactory). Here, the Debtor has failed to present any corroboration to support her assertion that $27,500 was used for living expenses. Moreover, even given my discretion to assume a portion of the Personal Loan Assets was applied to living expenses, I will not do so here given that the disposition of the overwhelming bulk of $1.4 million remains shrouded in mystery. Compare Prentiss v. Gagnon (In re Gagnon), 40 B.R. 951, 952-53 (Bankr.D.Maine 1984) (allowing $3,000 to $3,500 to be attributed to 697 living expenses without corroboration where debtor accounted with specificity for almost $15,000 of the $18,000 in question). Other than the foregoing, the Debtor's testimony regarding the Personal Loan Assets is either that (a) she lacks knowledge as to how the assets were used or (b) her husband handled her financial affairs. Rule 2004 Exam at 148-49, 152-55, 209. "[T]he law, [however,] forbids the debtor from absolving himself of the responsibility of explaining the loss . . . by merely pointing the finger at another." Chusid, 1998 WL 42292 at 5 (rejecting as insufficient under § 727(a)(5) the debtor's assertion that his son handled all his finances); Cook, 146 B.R. at 942 (rejecting debtor's attempt to blame bookkeeper for inadequate records and thus his inability to explain loss of assets).[23] Finally, the Debtor asserts in her opposition brief that her husband will be subpoenaed to testify at trial and will be able to provide explanations as to what happened to the Personal Loan Proceeds. Mem. Opp. First Union Mot. at 6. This assertion, as noted above, disregards her burden of production at this stage. Once a plaintiff establishes a prima facie case of lost assets under § 727(a)(5), as First Union has here, the Debtor is obligated to provide a satisfactory explanation. Moreover, since First Union has met its burden in the context of a summary judgment motion, the Debtor cannot simply defer her response until trial. She must provide that explanation, with evidence, here and now. McIntyre, supra, 795 F.Supp. at 673; Frito-Lay, 92 F.R.D. at 391. Here, the Debtor has failed to do so and accordingly there is no basis for trial on this issue. V. Loss of Interest Under Deed of Trust First Union alleges, that on August 22, 1997, the Debtor executed an Irrevocable Deed of Trust, under which the Debtor's husband, as settlor, was to transfer certain undisclosed assets to the trust created by this document (the "Trust") and under which the Debtor was a beneficiary and co-trustee. First Union Mem. at 14-15. The Debtor authenticated her signature on the Deed of Trust, but lacked any recollection and denied understanding what the document was. Debtor's Dep. at 173-75. Although the Deed of Trust states that the settlor will transfer assets listed in "Schedule A," to the Trustees, there is no such schedule attached to the Deed of Trust. Ex. MMM-28 to Debtor's Dep. Nor has First Union provided any evidence that any assets were, in fact, ever deposited into the Trust. If there is no trust res, the trust never comes into existence. In re Cavalier, 399 Pa.Super. 637, 582 A.2d 1125, 1127 (1990). Absent evidence of a specifically identifiable asset, First Union has failed to make out a prima facie case under § 727(a)(5) with regard to the Trust. VI. The Senate Financial Statement Assets The Movants have shown that in latter 698 part of 1999[24] and on February 25, 2000, the Debtor filed the Senate Financial Disclosure with the United States Senate in connection with her candidacy for Senate,[25] disclosing the ownership interest by her, her husband or dependent child in various securities and notes receivable valued at least at $1.3 million (the "Senate Financial Disclosure Assets"). Ex. "E" to Sonders Mot. The Debtor admits to signing these statements, although she asserts, and the Court takes this assertion as true for these purposes, that her husband prepared the statements and that she did not verify the accuracy of the statements before signing them. Rule 2004 Exam at 171-75. It is undisputed that the Senate Financial Disclosure Assets are not listed or accounted for in the Debtor's Schedules or Statement of Financial Affairs. Thus, The Movants have made a prima facie case under § 727(a)(5), namely that the Debtor has at a time proximate to the filing of the Petition presented herself to be worth more than she has represented in her bankruptcy papers. The burden now shifts to the Debtor to provide a satisfactory explanation for the disposition of the Senate Financial Disclosure Assets. Turning to her deposition testimony, her sole explanation is that her husband handled her finances and prepared the Senate Financial Disclosure.[26] Rule 2004 Exam at 173. As discussed above, mere identification of an individual with knowledge is wholly insufficient to meet the burden under both § 727(a)(5) and Bankruptcy Rule 7056. I therefore find that the Debtor has failed to satisfactorily explain the disposition of the Senate Financial Statement Assets, valued at over $1.3 million. VII. The Ivory Coast Assets The Movants allege that, five months before the Petition Date, the Debtor and her husband made representations in a "Settlement Agreement" with First Union that the Mezvinskys had substantial assets in the Ivory Coast of Africa worth at least $460,000 (the "Ivory Coast Assets"). Ex. "F" to Sonders Mot. The Settlement Agreement, however, is simply too vague and unclear to make out a prima facie case for the Movants. The referenced portion of the Settlement Agreement simply states that: "The Mezvinskys have a right, title and interest in the Ivory Coast Funds and that the amount of such funds is sufficient to satisfy their payment obligations as set forth in paragraph 4 of this Agreement." Ex. "F" to Sonders Mot. at ¶ 11(c); Sonders Mem. at 13 (emphasis added). Paragraph 4, in turn, gives the Mezvinskys the option of paying either: (1) $100,000 on or before September 30, 1999; or (2) $120,000 at any time between October 1-31, 1999, plus interest at a daily per diem rate of $25.97, beginning October 1, 1999; or (3) $120,000 at any time between November 1-30, 1999, plus interest at a daily per diem of $28.33, beginning October 1, 1999; or (4) $130,000 at any time between December 1-31, 1999, plus interest at a daily per diem of $30.69, beginning October 1, 1999. Ex. "F" to Sonders Mot. at ¶ 4(b). It would thus 699 appear that, at most, the Settlement Agreement shows that the Mezvinskys represented that the Ivory Coast Assets were sufficient to cover an obligation of approximately $132,760 ($130,000 principal plus $30.69 times 90 days). This is a far cry from the $460,000 representation asserted by the Movants. Nor does the Settlement Agreement's definition of "Ivory Coast Funds" as "all funds from investments in the Ivory Coast" in which the Mezvinskys have any legal or equitable interest help meet Movants' burden under § 727(a)(5) of showing a "specifically identifiable" asset. Moreover, the definition includes a space for insertion of a bank name and account number which was never filled in, raising questions as to whether the exhibit is in fact the final agreement between the parties. Ex. "F" ¶ 10(e). The Movants have failed to make out a prima facie case with respect to the Ivory Coast Assets. VIII. Transfers to Roberta McClean The Movants also allege that the Debtor has failed to satisfactorily explain the loss of the McClean Payments totaling $12,500. First Union Mem. at 15; Sonders Mem. at 13-14. This argument is without merit. The Court's concern under § 727(a)(5) is solely a matter of identifying where assets went, not whether the transfer of assets was proper. There is perhaps no better an explanation as to where specific funds went than a check which clearly identifies a payee. In short, Movants' own allegation provides a satisfactory explanation as to where the funds went; if they existed, they went to Roberta McClean. IX. The Chasen Proceeds Finally, as it is unclear from his motion whether Sonders is raising the Chasen Transaction in the context of his § 727(a)(5) argument or simply characterizing it as a fraudulent conveyance, I address it briefly herein. As noted above, the Debtor disclosed the Chasen Transaction in her Amended Statement of Financial Affairs and explained in discovery that the Chasen Proceeds were paid by Ms. Chasen directly to Northfield Mount Herman School, the school attended by the Debtor's son, Andrew. Sonders Mem. at 14-15 (citing Debtor's response to Interrogatories). Sonders does not present any evidence, or even allege, that the Chasen Proceeds did not in fact go to Northfield Mount Herman School. As my inquiry at this point is solely whether the Debtor's explanation satisfies the Court as to where the proceeds went, not whether the payment to the school was a fraudulent transfer under the Code, I find that Sonders' own averments and supporting evidence are a satisfactory explanation under § 727(a)(5) as to the disposition of the Chasen Proceeds. CONCLUSION Sonders and/or First Union[27] have established that: (1) the Debtor represented she and her husband to have furnishings, art and other tangible personal property worth $810,535 as of May 1996; (2) the Debtor represented the value of this category of personal property to be only $35,434 in her bankruptcy schedules; (3) the Debtor borrowed $1,477,500 within two to three years of the Petition Date; (4) these loan proceeds are not accounted for in her bankruptcy schedules; (5) the Debtor made representations in August 1999 700 and February 2000, pursuant to federal disclosure laws, regarding the ownership by her, her husband and dependent children of securities and note receivables valued at over $1.3 million; (6) the Debtor's bankruptcy schedules failed to identify any interest in these assets; (7) the Debtor owned and sold stock for $4,155.59 on January 7, 2000; and (8) the Debtor's bankruptcy statements and schedules failed to identify the sale or disposition of these assets. The above facts are not disputed, and they established a prima facie case under § 727(a)(5), placing the burden upon the Debtor to provide a satisfactory explanation for the loss of or deficiency in these assets. The Debtor's responses have failed to set forth specific facts showing there is a genuine issue for trial, namely her ability to provide a satisfactory explanation. Moreover, her reliance on a proffer that the witnesses she intends to call at trial will provide satisfactory explanations, is insufficient to defeat the entry of summary judgment under Rule 56. For these reasons, I find that the Movants have met their burden of proof that there are no genuine issues of material fact regarding the Debtor's failure to explain satisfactorily the loss or deficiency of assets under 11 U.S.C. § 727(a)(5) and that they are entitled to a judgment as a matter of law. While it is well accepted that § 727 is to be construed liberally in favor of a debtor, the benefit of the discharge nevertheless comes with the condition of complete candor with the court and creditors. The Debtor is an intelligent, highly educated and sophisticated professional person. Her background is in communications. As a journalist and author, she explained the affairs of the day to the public. As a Congresswoman, she analyzed and made determinations regarding the expenditure of public funds and this nation's budget. Yet her consistent response to questions asked by her creditors about the disposition of her assets is lack of knowledge or "my husband handled it," a mantra that is completely at odds with her public persona, background, and accomplishments. In her memoranda filed in both adversary cases, she disputes the "sophisticated" label advanced by Movants contending that "she like many women of her generation, relied upon her husband, Edward Mezvinsky, to handle the financial affairs of their family." Mem. Opp. First Union Mot. at 3; Mem Opp. Sonders Mot. at 3. To the extent that this explanation could ever be found sufficient to discharge a debtor's duty to satisfactorily explain the loss or depreciation of her assets, it certainly would not be found to do so here.[28] Debtor is not at all like the women of her generation that she seeks to identify with. She was a Congresswoman, and thereafter headed the United Nation Fourth World Congress on Women in Beijing and later 701 became the President of the Women's Campaign Fund. Her deference to her husband on financial matters, especially with knowledge that he was not managing them well, Debtor's Dep. at 173, is at best puzzling, and her attempts to justify her continued ignorance of her finances as gender related are inconsistent with her clear competency to discover the surrounding facts. It is not for this Court to pass judgment on how the Debtor chose to manage her financial affairs prior to this bankruptcy case. However, when she filed for bankruptcy relief and invoked the protection of this Court, she forfeited the right to remain ignorant of the disposition of her assets. Without regard to her credibility, I must assume as true in the context of a summary judgment motion her testimony that her husband, not she, handled her financial matters without consultation with or disclosure to her of any details. However, her failure as a debtor seeking discharge to make any attempt to discover and disclose the facts surrounding the transactions put at issue by the Movants is fatal to her cause. I can only conclude that her continued ignorance and/or lack of understanding of the facts that surround the loss and deterioration of millions of dollars of assets and funds owned by her with her husband is a matter of choice. While this approach may serve her well in connection with matters in litigation elsewhere, her failure to provide a satisfactory explanation regarding the transactions at issue will preclude her from earning a discharge in this bankruptcy case. Finding that the Debtor here has not fulfilled her duty of disclosure as a debtor under the bankruptcy law, the objections of Sonders and First Union to the Debtor's discharge are granted. NOTES [1] The Sonders Motion seeks to deny the Debtor a discharge on the grounds of 11 U.S.C. §§ 727(a)(2),(a)(3), (a)(4) as well as (a)(5). At argument on the First Union Motion, Debtor's counsel acknowledged that an adverse decision on the identical (a)(5) grounds pressed by First Union and Sonders would render a decision on the other issues raised by the Sonders Motion unnecessary. I concur. Accordingly, I do not reach those other grounds. [2] Those documents are as follows: Exhibit A Schedule B, Personal Property; Exhibit B Schedule C, Property Claimed as Exempt; Exhibit D Statement of Financial Affairs; and Exhibit E United States Senate Public Financial Disclosure Report for New Employee and Candidate Reports. In re Leonard, 151 B.R. 639 (Bankr.N.D.N.Y.1992) (same), some of the Debtor's bankruptcy schedules were amended after Sonders filed his motion. As noted herein, to the extent I rely upon documents filed with this Court, I rely upon the amended versions. "Factual assertions in pleadings are judicial admissions against the party that made them", Larson v. Groos Bank, 204 B.R. 500, 502 (W.D.Tex.1996) (statements in schedules). See also In re Musgrove, 187 B.R. 808 (Bankr.N.D.Ga.1995) (same); [3] Rather than submit an affidavit of specific sworn facts, Debtor presents a general affidavit in which she swears to the truth of the facts set forth in the Memorandum in Opposition to the Sonders' Motion ("Mem. Opp. Sonders Mem."). Since much of the Memorandum is argument and many of the facts not within her first hand knowledge, it is hard to know what she is swearing to. However, for the purposes of this Motion, I will accept her attestation of facts that are capable of being known to her. [4] The documents submitted are the following: Exhibit A Indictment in United States of America v. Edward M. Mezvinsky; Exhibit B Appraisal Reports prepared by Barry S. Slosberg Inc. ("Slosberg Appraisals") and Exhibit C Young Adjustment Co. inventory ("Young Inventory"). [5] Since no similar attestation or any other evidence was submitted in opposition to the First Union Motion, Debtor relies entirely on the Sonders Motion record to support her response. Since both First Union and Debtor have utilized this "incorporation" approach, I shall deem them to have waived any objection to this evidentiary shortcut. [6] I shall take judicial notice of the docket entries in this case. Fed.R.Evid. 201, incorporated in these proceedings by Fed.R.Bankr.P. 9017. See Maritime Elec. Co., Inc. v. United Jersey Bank, 959 F.2d 1194, 1200 n. 3 (3d Cir.1991); Levine v. Egidi, 1993 WL 69146, at 2 (N.D.Ill.1993); In re Paolino, 1991 WL 284107, at 12 n. 19 (Bankr.E.D.Pa.1991); see generally In re Indian Palms Associates, Ltd., 61 F.3d 197 (3d Cir.1995). [7] The Complaint and Answer pinpoint the date of this representation to the insurance company as occurring in May 1996 while the deposition testimony refers to May 1999. Rule 2004 Exam at 287. Giving the Debtor the benefit of the doubt, I am assuming for the purpose of this adjudication that the former is correct as it would be harder to justify a major deterioration in the value of assets over the period of one year or the use by the Debtor of a 1992 appraisal some seven years later. [8] For purposes of comparison with the $810,535 insurance estimate, the Debtor's scheduled values must be doubled as to property owned jointly by her and her husband. See discussion infra § II.A. [9] The individual loans consist of the following: (1) $27,500 from Connie Williams (the "Williams Loan") within two years of filing the Petition. Rule 2004 Exam at 145-47; (2) $100,000 from Janet Boyle (the "Boyle Loan") sometime in 1998 or 1999. Rule 2004 Exam at 148-49; (3) $1,100,000 from Richard Snyder (the "Snyder Loan") in 1998 or 1999. Rule 2004 Exam at 208-09; (4) $150,000 from Gerald Segal (the "Segal Loan") over several months in 1999. Rule 2004 Exam at 153-54, 198-99; and (5) $100,000 from Donald Spero (the "Spero Loan") in 1997. Rule 2004 Exam at 152-53. [10] The Debtor expressly testified that both she and her husband signed for the Williams, Segal and Boyle Loans. Rule 2004 Exam at 196-99, 203-04. Her testimony regarding the Spero Loan does not make it entirely clear whether it was made either to her directly or to both her and her husband. Id. at 152-53. The Debtor testified as to her status as co-debtor on the Segal and Snyder Loans. Id. at 206-08. Finally, all five lenders are listed as unsecured creditors on the Debtor's Schedule F in the same amounts as the loans discussed above, and the Debtor has not contested her status as co-debtor on these loans. [11] Exhibit E to the Sonders Motion is the completed form "United States Senate Public Financial Disclosure Report for New Employee and Candidate Reports." The form requires assets to be disclosed within a range of values. The $1.3 million aggregate value represents the minimum value for each asset disclosed therein by the Debtor. [12] Federal Rule of Civil Procedure 56 is incorporated by Federal Rule of Bankruptcy Procedure 7056. [13] With respect to the time period for which a debtor is required to account for her financial condition under § 727(a)(5), one court, after reviewing Code and Act cases, that found long-term inquiry to be relevant stated: Thus, it is clear that the temporal depth of the inquiry permissible under §§ 727(a)(3) and 727(a)(5) cannot be set according to a rigid rule; it must be determined only on a case-by-case basis, bearing in mind that, under the statute, ". . . the interests protected are those of creditors and . . . the [debtor] is required to take such steps as ordinary fair dealing and common caution dictate to enable the creditors to learn what he did with his estate." Koufman v. Sheinwald, 83 F.2d 977, 980 (1st Cir.1936); In re Kinney, 33 B.R. 594, 596 (Bankr.N.D.Ohio 1983). In re Losinski, 80 B.R. 464, 473 (Bankr. D.Minn.1987) (inquiring six years before petition date). See also PNC Bank v. Buzzelli (In re Buzzelli), 246 B.R. 75, 117 (Bankr.W.D.Pa. 2000) (quoting Losinski supra) (while in the ordinary consumer case, it is probably reasonable to limit the inquiry to two years before the commencement of the filing, there is no "hard and fast rule" that dictates the time period prior to a bankruptcy filing which is relevant to an inquiry under § 727(a)(5)). [14] Notably Debtor does not contend that this alleged unexplained loss is too far removed from the filing of the bankruptcy case to be probative. If, however, the representation occurred in 1996 (see n. 2 supra), the statement to the insurance company may have occurred almost four years before the petition was filed, unlike the other representations considered here which were made within one or two years of the commencement of this case. However, the age of the representation is mitigated by the extent of the loss and the existence of other unexplained losses, and thus will be considered even if made four years ago. [15] There are actually two appraisals as exhibits to Amended Schedule B. The first lists property appraised at a total liquidation value of $34,260 as of February 5, 2000. The second appraisal is much shorter and lists personal property appraised at a total liquidation value of approximately $5,050 as of April 12, 2000. The second appraisal consisting of art and antiques is labeled an "addendum." In an attachment to Amended Schedule B, Debtor refers to the later addendum as adding value of $5,359 (versus $5,050) and includes two additional addenda to the Slosberg Appraisals which add another $8,500 to the property valued. The additional addenda are not attached. No explanation is provided for the multiple addenda. [16] Again for the purpose of § 727(a)(5), it is the existence of an explanation, not the propriety of the transfer, that is at issue. Whether these assets were transferred after 1996 so as to have been part of the $810,535 was not stated and indeed Debtor does not attribute the third party items as relevant to this inquiry. [17] The only other explanation provided by the Debtor is that some items of furniture were not as valuable as she originally thought. Debtor's Dep. at 117-21, 176. However these statements alone are too vague and generalized to provide evidence to rebut the demonstrated erosion of value of her personal property. Since the Debtor provided no specific details as to the basis of her misperception nor quantified the impact on the valuation of the furniture, the testimony is insufficient to create a factual issue for trial. [18] This is consistent with the Debtor's testimony that the fire occurred in January 1992. Debtor's Dep. at 104, 115. [19] I note that exhibits and other papers supporting and opposing summary judgment "must be of such a quality as to be admissible at trial." Kohr v. Johns-Manville Corp., 534 F.Supp. 256, 257-58 (E.D.Pa.1982). Documents attached to a summary judgment brief, absent affidavit support attesting to their validity, are not evidence. Berk v. Ascott Inv. Corp., 759 F.Supp. 245, 249, (E.D.Pa.1991) (affidavits attesting to authenticity of documents is necessary in order to present the documentation on a motion for summary judgment). While the Slosberg Appraisals are sworn and notarized and thus self-authenticating, Fed.R.Evid. 902(8), the Young Inventory is not authenticated by affidavit or deposition testimony. Thus, the Young Appraisal is inadmissable. However, it is a well accepted principle that "[a]s is true with other material introduced on a summary judgment motion, uncertified or otherwise inadmissible documents may be considered by the court if not challenged." 10A Charles A. Wright, Arthur R. Miller & Mary K. Kane, Federal Practice and Procedure § 2722, at 384 (1998). Accord Johnson v. United States Postal Service, 64 F.3d 233, 237 (6th Cir.1995) (ruling that the "failure to object to evidentiary material submitted in support of a summary judgment motion constitutes a waiver of those objections."); H. Sand & Co., Inc. v. Airtemp Corporation, 934 F.2d 450, 454-55 (2d Cir.1991) (Rule 56 does not require parties to authenticate documents "where appellee did not challenge the authenticity of the documents in the district court."); Dautremont v. Broadlawns Hospital, 827 F.2d 291, 294-95 (8th Cir.1987) (affirming summary judgment where appellant failed to object in district court to its consideration of documents not in compliance with Rule 56 and failed to demonstrate that district court's consideration of documents constituted reversible error); Giovacchini v. Perrine, 1995 WL 80102, at 3 n. 1 (E.D.Pa. Feb.27, 1995) (citing Federal Practice and Procedure § 2722) (holding that unauthenticated medical reports would be considered in ruling on motion for summary judgment since no objection was raised thereto). Another treatise offers the following insight: Rule 56(e) does not require parties to authenticate documents where the appellant failed to challenge the authenticity of the documents in district court. An evidentiary objection, not raised in district court, is waived on appeal. This rule is equally applicable to a summary judgment motion as it is for a trial. Consequently, Rule 56(e) defects such as unsworn or uncertified affidavits, deposition testimony or unauthenticated documents, are waived and those pieces of evidence will be admissible in a summary judgment proceeding if no motion to strike has been made at the district court level. 11 James Wm. Moore et al., Moore's Federal Practice § 56.14[2][c], at 56-184.1-56-185 (3d ed.2001). Neither Sonders nor First Union challenged the authenticity of the Young Inventory and thus while it has other deficiencies as evidentiary support, I will consider its lack of authenticity waived. This evidentiary flaw was apparent in a number of the documents placed of record not only by the Debtor but by Sonders and First Union as well. In no case was an objection lodged and thus the authenticity deficiencies of these documents are likewise considered waived by Debtor. [20] First Union also alleges that, while the Debtor's Amended Schedules show only $523 in cash holdings, prior to the Petition Date, she and her husband represented to various financial institutions that they had cash holdings between $50,000 and $70,000. First Union Mem. at 8. In support of this allegation, First Union simply points to a mass of financial statements and handwritten notes which appear to span the time period 1987 to 1999, Ex. MMM-6 to Debtor's Dep., making no attempt to explain how it reaches the amount of $50,000 to $75,000 or to identify when the Debtor allegedly represented herself as having these cash holdings. As noted above, it is not for this Court to make sense out of a mass of disorganized records to evaluate a party's position. Thus with respect to the alleged loss of cash, I find on this record that First Union has failed to identify an asset with sufficient specificity so as to trigger the Debtor's duty to explain. [21] I acknowledge First Union's argument that the Debtor's testimony appears somewhat inconsistent, namely that it appears that the Charming Stock Proceeds from the January 2000 sale may have been wired directly to the account of her mother, Mildred Margolies. Debtor's Dep. at 160-61. There was no questioning or testimony, however, as to whether Mr. Mezvinsky had access or control over this account. This simply raises an additional issue of material fact as to whether she can provide a credible and satisfactory explanation. [22] The Debtor concedes that these loans were made to her and her husband. See supra n. 10. [23] Debtor supports her response by reference to the U.S. Attorney's indictment against her husband: "It is clear from the allegations of that indictment that the funds at issue were handled by Edward Mezvinsky." Mem. Opp. First Union Mot. at 5-6 and Ex. A to Sonders Motion. While there is no evidentiary challenge to use of this hearsay document, see Ruffalo's Truck Serv. v. National Ben-Franklin Ins. Co., 243 F.2d 949, 953 (2d Cir.1957), it nonetheless does nothing to advance her cause. The purpose for which the indictment is offered, to prove that the Debtor's husband handled the loan proceeds in which she had a joint interest, is still an insufficient explanation of what happened to them. [24] The first page of the statement is dated by the Debtor on August 15, 1999, but the date and time stamp from the Senate indicates receipt on October 29, 1999. Ex. "E" to Sonders Mot. [25] Such disclosure, made under penalty of civil and criminal penalty for knowingly and willfully filing false testimony, is required pursuant to the Ethics in Government Act of 1978, as codified, 5 U.S.C. app. 4, § 101 et. seq. [26] The Debtor fails to address these assets whatsoever in her memoranda opposing the First Union and Sonders Motions. [27] Sonders and First Union have proven that the Debtor has failed to satisfactorily explain the loss of tangible and intangible personal property of approximately $2.0 million. First Union has also proven that the Debtor has failed to satisfactorily explain the loss of loan proceeds and miscellaneous stock of another $1.5 million. [28] Compare Wilmington Trust Co. v. Jarrell (In re Jarrell), 129 B.R. 29 (Bankr.D.Del.1991) (Debtor wife who was mere employee of business with no bookkeeping expertise would not be denied Chapter 7 discharge for failure to satisfactorily explain loss of assets, where debtor husband had acted as sole proprietor of business and had failed to satisfactorily explain loss of thousands of dollars of assets); Equibank, N.A. v. Ward (In re Ward), 92 B.R. 644, 647 (Bankr.W.D.Pa.1988) (Denial of discharge to debtor wife on grounds that she could not explain loss of equipment used by the debtors' business was not warranted given that her sole relationship to the business was employment as a sales clerk and her testimony as to her lack of knowledge that she owned any of the equipment might lack credibility if she were a "woman of the 80's"); First City Bank-Central Park v. Powell (In re Powell), 88 B.R. 114 (Bankr.W.D.Tex.1988) (Chapter 7 debtor, a housewife who took no part in conduct of husband resulting in unexplained diminution in assets of jewelry business and lack of adequate records, would be granted discharge where husband was 90% owner of company and company's officer, operator, and prime employee).	{ "pile_set_name": "FreeLaw" }
Audiograms of three subterranean rodent species (genus Fukomys) determined by auditory brainstem responses reveal extremely poor high-frequency hearing. Life underground has shaped the auditory sense of subterranean mammals, shifting their hearing range to low frequencies. Mole-rats of the genus Fukomys have, however, been suggested to hear at frequencies up to 18.5 kHz, unusually high for a subterranean rodent. We present audiograms of three mole-rat species, Fukomys anselli, Fukomys micklemi and the giant mole-rat Fukomys mechowii, based on evoked auditory brainstem potentials. All species showed low sensitivity and restricted hearing ranges at 60 dB SPL extending from 125 Hz to 4 kHz (5 octaves) with most-sensitive hearing between 0.8 kHz and 1.4 kHz. The high-frequency cut-offs are the lowest found in mammals to date. In contrast to predictions from middle ear morphology, F. mechowii did not show higher sensitivity than F. anselli in the low-frequency range. These data suggest that the hearing range of Fukomys mole-rats is highly restricted to low frequencies and similar to that of other subterranean mammals.	{ "pile_set_name": "PubMed Abstracts" }
Philadelphia Eagles quarterback Michael Vick will likely start in the regular-season finale at the New York Giants. / Howard Smith, US Presswire by USA TODAY by USA TODAY PHILADELPHIA (AP) -- Eagles rookie quarterback Nick Foles has a broken right hand, and coach Andy Reid said Michael Vick will likely start against the New York Giants in Sunday's season finale. Reid said Monday that Foles broke his throwing hand in the second quarter of a 27-20 loss to Washington, but returned to the game after X-rays at the stadium were negative. Vick hasn't played since suffering a concussion during a loss to the Cowboys on Nov. 11. He was recently cleared to return. "There's a pretty good chance Michael will be the starter," Reid said. "That's what we're looking at right now. That's the direction I'm going as we speak right now." The Eagles (4-11) went 1-5 with the 23-year-old Foles as the starter. "I banged it up a little in the first half," he said. "It didn't affect my throwing at all." An MRI taken on Monday revealed a hairline fracture, Reid said. Reid added because it's a non-displaced fracture, Foles should be 100 percent in about three weeks. "He was in quite a little bit of pain," Reid said of Foles, who threw for 345 yards. "I know at one point he was having a tough time squeezing the ball when we went into halftime. He's a tough kid and never said a word about it. . He pushed himself through and did a good job." Foles, a third-round pick out of Arizona, completed 60.8 percent of his passes for an Eagles rookie record 1,699 yards, with six touchdowns and five interceptions in seven games following Vick's injury. "It's frustrating because I'm hard on myself and I want to win, but I'm going to keep working hard, and I know my teammates are, too," Foles said after Sunday's loss. "We're going to keep sticking together. It's been a tough year." With Reid's status as head coach uncertain, it's impossible to determine whether Foles will get an opportunity with the Eagles next year. But Reid said he was impressed with what he saw over the past two months from Foles. "I think he's a winning quarterback or he's a quarterback that gives your team an opportunity to win," Reid said. "I think you're seeing him in a unique situation where he comes in later in the season. You look at the young quarterbacks who've had an opportunity to come up through and they've had time here to grow. "It wasn't really pretty when they first began and it continued to pick up as they got games under their belts. Nick got thrown in when other teams were working to their peaks. He was thrown in in that situation. "He has enough skill and ability to play." The Eagles were 3-6 in Vick's nine starts this year. Vick, in his fourth season with Philadelphia, completed 58.5 percent of his passes for 2,165 yards with 11 TDs and nine interceptions before his injury. Vick was not in uniform Sunday. Veteran Trent Edwards served as Foles' backup, and he'll be Vick's backup against the Giants. Edwards has not thrown a pass this year. "You're talking about a pretty good quarterback here that has a lot of experience," Reid said of Vick. "I think he'll be excited to be out there and I think he'll do a good job." The Giants go into the game with faint playoff hopes. They need a win over the Eagles and losses by Minnesota, Chicago and Dallas to reach the postseason.	{ "pile_set_name": "Pile-CC" }
Trending Schools FCS Football Adam Hermann \| NCAA.com \| October 12, 2017 ESPN College GameDay at JMU: What you need to know James Madison is the second FCS school to host GameDay multiple times. Share Fifteen years ago next month, ESPN's College GameDay was hosted by an FCS team (at the time, still classified as DI-AA) for the first time. The GameDay crew traveled to Philadelphia’s University City to visit Franklin Field, the oldest football stadium in the country, as Penn hosted Harvard. Lee Corso dressed up as Ben Franklin. It was quite a production. The game itself wasn’t much to watch. Penn was en route to its fifth Ivy League title under legendary head coach Al Bagnoli, and the Quakers toppled Harvard 44-9. That day, 14 years after on-campus GameDay shows began, marked a watershed moment for non-FBS schools. Since that November morning in 2002, six other GameDay shows have been hosted by FCS schools, including four — with a fifth coming up — since 2013. This weekend, James Madison will become the third FCS team to appear on the show multiple times, joining North Dakota State and Harvard. JMU will host Villanova. It began on Sunday, Oct. 8, six days and four hours before kickoff. GameDay’s announcement would come at 1:09 p.m. ET; a little after 12:45 p.m., ESPN contacted James Madison to let them know they would be Saturday’s host. The process really began back in August, when the athletic department reached out to ESPN and told them they’d be interested in hosting GameDay this season. They pointed to Oct. 14, home against Villanova, as a matchup that might pique viewers’ interest. “We said this week might be an attractive game to keep in their back pocket,” Warner said, “but ESPN doesn’t tell you very much about your chances. We knew we were being considered, but we also knew we weren’t the ‘favorites.’” Thanks to their 2015 appearance, once the call came down confirming ESPN’s decision, Warner and the athletic department leapt into action. So did ESPN. Here’s how the week works, according to Warner: Sunday, post-announcement: “Within an hour we had a packet of info from GameDay about how they set up their footprint, power needs, utility needs. Some of the basics of what the layout will look like.” Monday: “The next day they bring advance staff for a walkthrough, look at the layout, make sure they feel good. And once everybody feels good about everything, that sets the thing in motion.” Tuesday: “We had to cut down a couple tree limbs and move a few benches so trucks could get in. We had to work around the class schedule, because our spot is in the middle of campus. Right smack in the middle.” Wednesday: “They moved in at 6 a.m. this morning. It was raining, so they had to put down a bamboo lattice, or plywood, so the trucks wouldn’t dig up the grass space too much. This evening they start a little unloading. Thursday: “Tomorrow it’s the full setup of the stage and compound area.” Friday: “The talent gets here Friday, and they do talent prep.” Saturday: “Showtime.” Warner said the sheer number of people needed to coordinate this at a school, especially one like James Madison not used to gigantic ESPN productions, is sort of astounding. “The people at JMU are tremendous,” Warner said. “We have a very customer service-oriented approach across the University. Everyone bent over backwards to make this a great experience. This is a great experience to show the world the school we love. From housekeepers and electricians, to folks who help the trucks move — probably hundreds of people make this work. Then ESPN rolls the truck out Saturday, and within two hours you won’t know they were here.” It’s an undertaking, one few FCS teams have experienced. When GameDay arrives, you want to make the most of it. North Dakota State was the face of the FCS on ESPN just a few years ago, the only school to host in back-to-back years. The Bison are also the leading scorers (109) and leading defenders (0 points allowed) among FCS teams in GameDay history. The second time GameDay rolled into to Fargo, Carson Wentz, now throwing for the Philadelphia Eagles, led the Bison to 508 yards of offense and a 58-0 win over Incarnate Word. The Bison are the kings of FCS GameDay history, but this weekend presents James Madison, 0-1 in GameDay appearances after a 59-49 shootout loss to Richmond in 2015, with a chance to climb the “points scored” leaderboard. If the Dukes manage an FCS GameDay record of 60 points on Saturday vs. No. 11 Villanova, they would pass the Bison for first place. Even without 60 points, JMU is excited about the opportunity to host two GameDay shows in three years. The appearance follows last year’s national championship, the program’s first in 12 years, and signals the official return of the Dukes as an FCS power. “We’re riding a huge wave of momentum, from the first GameDay, to the championship, to this GameDay,” Warner said. “Who knows where this year goes? But this is an exciting time. I don’t know if equity in JMU football, and even JMU athletics, has ever been higher than it is right now. That’s an excitement level we want to capture, and just have everyone along for the ride.” A history of FCS teams on College GameDay Date Teams Score Nov. 16, 2002 Harvard at Penn 44-9, Penn Nov. 26, 2005 Grambling State vs. Southern 50-35, Grambling State Nov. 15, 2008 Hampton at Florida A&M 45-24, Florida A&M Sep. 21, 2013 Delaware State at North Dakota State 51-0, NDSU Sep. 13, 2014 Incarnate Word at North Dakota State 58-0, NDSU Nov. 22, 2014 Yale at Harvard 31-24, Harvard Oct. 24, 2015 Richmond at James Madison 59-49, Richmond Oct. 14, 2017 Villanova at James Madison TBD Adam Hermann has written for the Philadelphia Inquirer, the Philadelphia Daily News, Philadelphia magazine, SB Nation, and NBC Sports Philadelphia. The views on this page do not necessarily reflect the views of the NCAA or its member institutions.	{ "pile_set_name": "Pile-CC" }
[Evaluation of the degree of tryptophan residue immersion into the lipid phase of low density serum lipoproteins]. Based on the theory of inductive resonance energy transfer, it was demonstrated that in a two-phase waterlipid system the efficiency of the transfer from the donor to the acceptor, which is evenly distributed in the lipid phase, depends on the donor localization with respect to the interface. The inductive resonance energy transfer from the tryptophane residues of protein of low density serum lipoproteins (LDL) to the pyrene fluorescent probe distributed in the lipid phase of LDL was studied. The degree of immersion of the tryptophane residues with respect to the LDL surface is 11,6 +/- 2,6 A. Among the existing models of LDL where the proteins are localized at 20--80 A above the particle surface or are arranged in a monolayer on the particle surface, the first one does not coincide with the experimental data, whereas the second one agrees well with them.	{ "pile_set_name": "PubMed Abstracts" }
James Giles (painter) James William Giles ARSA (4 January 1801 – 6 October 1870) was a Scottish landscape painter. Several of his landscapes were commissioned and purchased by Queen Victoria and members of the Scottish aristocracy. He was a member of the Royal Scottish Academy. Life Giles was born in Glasgow on 4 January 1801, the son of a designer at the local calico. The family moved to Aberdeen around 1805 where his father worked in a printing factory at Woodside, Aberdeen, an artist of some repute. His father's early death threw his son at an early age upon his own resources. His mother was named Jean Hector. At 13 he maintained himself, his mother and sister by painting, and before he was 20 was teaching taught private classes in Aberdeen. Shortly afterwards he made a tour through Scotland and visited the continent, and on his return home he was introduced to the Earl of Aberdeen, with whom he became very intimate. His earliest successes were in portrait-painting, however his visit to Italy gave him a taste for classic landscape, which he never entirely lost, for the mist seldom hangs about his mountains, even when the scene is laid near "dark Lochnagar". He was a keen angler, and fond of painting the result of a successful day's fishing. These pictures were his best works. He first exhibited at the "Royal Institution for the Encouragement of the Fine Arts in Scotland", and in 1829 became an academician of the Royal Scottish Academy, and contributed numerous works to its exhibitions from that time until near the close of his career. He also exhibited frequently at the British Institution in London, and occasionally at the Royal Academy and the Society of British Artists. His last work was a painting of himself, his wife, and youngest son, which he left unfinished. He died at his residence at 62 Bon Accord Street, Aberdeen, after a lingering illness, on 6 October 1870. He is buried i the churchyard of St Machar's Cathedral in Old Aberdeen. The large monument marking his grave lies east of the church. Family He was twice married. By his first wife, Clementina Farquharson or Ruxton (a widow), he had two sons, James and John, one of whom gave great promise as an artist, but died of consumption at the early age of 21. His first wife died in 1866. His second wife was Margaret Walker (1846-1883) forty-five years his junior. Overview During his lifetime, Giles was among the first to be mentioned as one of the most vital of the Aberdeen artists - his patrons included the landed aristocracy of Aberdeenshire and Queen Victoria - but he has been little remembered in subsequent surveys in Scottish art. This is due in part to the fact that he spent most of his working life in Aberdeen – unlike his contemporaries who left the north-east to find fame in London. Work Giles was a versatile artist. He specialised in portrait and landscape painting, but in addition was a successful landscape architect, designing a number of public gardens and monuments in Aberdeen, in addition to landscaping estates in Aberdeenshire. Giles’ spiritual home was Italy, where he spent three years from 1823 to 1826. There he followed the well-trodden pathways of the 18th century Grand Tour to the many points of historic interest. The bright Italian light fascinated Giles, and all his sketches are enlivened with an impression of this Mediterranean atmosphere. The sights that he saw and recorded in Italy were to remain with him for the rest of his life. His watercolour sketches often provided materials for the oils he painted and exhibited on his return to Scotland. Museums and galleries National Portrait Gallery (6 portraits) National Gallery of Scotland (The Weird Wife) References Further reading Ferguson, O. (2001). Aspects of Landscape - A Bicentenary Celebration of James Giles RSA, Aberdeen Art Gallery. External links Paintings by Giles (Royal Collection) Study of a 'Panther' (James Harvey British Art) Windsor Forest (Bourne Fine Art Gallery) Aqua Claudia near Tivoli (Oil on Panel - Christie's) Category:1801 births Category:1870 deaths Category:19th-century Scottish painters Category:Artists from Aberdeen Category:Scottish male painters Category:Scottish watercolourists Category:Scottish landscape painters Category:Scottish portrait painters Category:Royal Scottish Academicians Category:Landscape or garden designers	{ "pile_set_name": "Wikipedia (en)" }
1. Introduction {#S1} =============== Water is essential for sustaining all life forms and access to clean and safe drinking water is a basic human need. Latest estimates of the Joint Monitoring Programme for Water Supply and Sanitation state that the world is on track to meet the Millennium Development Goals target for drinking water of "halving by 2015 the proportion of people without sustainable access to safe water and basic sanitation" \[[@R1]\] \[[@R2]\]. But this progress has been uneven. An estimated 768 million people did not use an improved source for drinking-water in 2011 and 185 million still depended on surface water (from lakes, rivers, dams, or unprotected dug wells or springs) for their daily drinking-water needs \[[@R3]\] \[[@R4]\]. India has only 3% of the world's fresh water with 20% of its population. Although, 92% - 96% of the urban population could access improved sources of water by 2010, 4% - 8% continues to use unimproved sources \[[@R4]\]-\[[@R6]\]. The World Bank estimates that, in spite of the improvement in provision for drinking water, 21% of all communicable diseases in India are related to unsafe water \[[@R7]\], with diarrhoea alone causing more than one hundred thousand deaths annually \[[@R8]\]. Groundwater constitutes 85% of the source of drinking water in India \[[@R9]\] \[[@R10]\] and none of the major Indian cities have a continuous water supply \[[@R11]\]. The Ministry of Urban Development, Government of India commissioned a study in 1999 to assess the status of water supply, sanitation and solid waste management in 305 selected Metropolitan, Class I and Class II cities and towns (of population more than 100,000). This study found that the coverage by the formal water supply was 94%. Paradoxically, coverage did not ensure quantity, quality, duration of supply or the mode of provision. In spite of 100 percent coverage in twenty-two sampled urban centres, regular daily supply was not ensured due to acute water shortage. Six sampled urban centres did not have individual house service connections. In most of the sampled cities, the duration of water supply ranged between 1 and 6 hours daily. The study also found that 43% of the sampled urban centres depended entirely on surface water, 34% depended entirely on groundwater while 22% used both surface and groundwater sources \[[@R12]\] \[[@R13]\]. The city of Ahmedabad located on the banks of a seasonal river---Sabarmati, has begun to receive water from the Narmada canal of the Sardar Sarovar project since the year 2000. This now supplements the underground water from French wells and Bore wells. This development has slowed the groundwater table depletion, but groundwater extraction is still widespread, especially in areas not provided by municipal water supply \[[@R14]\]. We investigated the drinking water surveillance parameters in one vulnerable ward of Ahmedabad. The WHO defines drinking water surveillance as the "the continuous and vigilant public health assessment and review of the safety and acceptability of drinking-water supplies". It must include an assessment of quality, quantity, accessibility, affordability and continuity of the drinking-water supply \[[@R15]\]. 2. Methods {#S2} ========== Our selection of this study ward was based on the municipal health officials' categorisation of this particular ward as the most vulnerable in the city. It is situated within the old city limits with more than 85% of its population residing in slums. The data collection for the study took place in the summer of 2012. A questionnaire was developed based on the interviews we conducted with the municipal water supply officials. This was pilot tested in the neighbouring areas before being administered at the study site. The researchers made several visits to the study ward to understand the distribution of the household clusters and water supply across the ward. We used a mixed methodology of: 2.1. Interviews with Key Informants {#S3} ----------------------------------- We interviewed field level sanitary and health workers and supervisors posted at the ward office and health centre. We also interviewed water supply personnel (engineers and operators) at the main water storage and distribution facility located in our study ward and personnel at the Water Testing Laboratory. 2.2. Secondary Analysis and Mapping of Field Test Reports {#S4} --------------------------------------------------------- Field testing for water samples by the sanitary inspector is recorded on a standard format in a register including the date, source of water supply, site of sample collection and the result. We obtained this list of locations and results of water sample field tests in the study ward for a six month period from October 2011 to March 2012. These were analysed and mapped using ArcGIS software. 2.3. A Short Survey {#S5} ------------------- We obtained lists of population settlements from field health supervisor and used this to survey households in different types of tenements across the ward. The list divided the ward population of 65,403 into two groups; 86% of them living in 11,072 households (HHs) grouped into 47 slum clusters and 14% living in 4344 households (HHs) grouped into 42 housing society clusters. We sorted these cluster types separately in ascending order of population sizes. We sampled every alternate slum cluster from 47 slum clusters and every fifth housing society from 42 housing society clusters. (Slum clusters were oversampled because we were more interested in the poorer population of the ward.) We surveyed two HHs from every sampled cluster, one close to and one away from the municipal water line on the main road which supplies each cluster. This approach enabled us to assess the reach of the municipal water to the entire slum or society cluster and check for any disparities in supply between the proximal and distal households. The survey questionnaire was administered to a member of the household, the female head being the first preference. We finally surveyed 42 HHs out of 11,072 HHs in 21 slum clusters and 14 HHs from 4344 HHs in 8 housing society clusters. In two societies we sampled only one HH each because all the apartments were grouped around the water connection. Therefore the total tally was 56 households from 29 locations ([Figure 1](#F1){ref-type="fig"}). The data was analysed in MS-Excel and EpiInfo7. The data was stored securely on a hard disk and no personally identifiable information was collected. All participants were assured of confidentiality of their responses and a formal verbal consent was taken before starting the interview. Ethical clearance for the study was sought from the Institutional Ethics Committee of the Public Health Foundation of India. Support letters were also arranged from the Ahmedabad Municipal Corporation. 3. Results and Discussion {#S6} ========================= Our interviews revealed that Ahmedabad city receives approximately 1 billion litres of water per day, which averages out to nearly 180 litres per head. Supply is maintained for 2 hours every morning throughout the year (6 to 8 am) and during summers, for an additional one hour in the evenings. Water supply is not metered anywhere in Ahmedabad and therefore the actual quantity of water consumed by residents is not recorded. The Central Water Testing laboratory tests at least 200 to 250 routine water samples (3 to 4 from each of 64 wards) each day. Additional samples are processed based on public complaints and during focal outbreaks of waterborne diseases. These samples are subjected to the following tests---turbidity, alkalinity, hardness, ${Ca}^{2 +},{Mg}^{2 +},{Cl}^{-},{SO}_{4}^{2 -}$, total dissolved solids, before being tested for faecal indicators (total coliform and fecal E. coli). The Sanitary Inspector of every ward sends two water samples to the Central Water Testing laboratory and carries out 10 Orthotoludene field tests for residual chlorine from across the ward each day. The water samples for the field tests as well as the laboratory tests are collected during morning supply hours. There was no map of the existing water supply network and water sampling was not related to the physical organisation of the distribution system. Sampling is based on an arbitrary pattern of collecting samples from select slum clusters, municipal schools, public offices, etc. which has been set in practice over the years and on complaints from residents. Analysis and mapping of the records of 217 field tested water samples in the study ward over a six month period from October 2011 to March 2012 showed that 1) all samples had been reported fit; 2) most slum clusters were sampled repeatedly; 3) but none of the housing society clusters were covered by the sampling process ([Figure 2](#F2){ref-type="fig"}). The water supply department personnel of the ward examined the list of population settlements we had obtained from field health supervisor and marked out the most probable source of water (municipal supply, bore well or both) and the probable purification method used in each of the settlements. They estimated that of the 42 housing society clusters, only two supplement their municipal supply with bore-well water and one completely depends on bore well water for all of their water needs, and 12 of the 42 housing society clusters could afford small home-based Reverse Osmosis systems. Our survey showed this to be an underestimate. 3.1. Accessibility and Continuity {#S7} --------------------------------- Our site visit revealed that, except for a tiny cluster of 250 HHs, 3.2% of the ward population which drew water from common stand posts, municipal water supply reached into the smallest and poorest of homes. Our survey of half of all the slum clusters found that all slum households depended on municipal water supply. Of the 8 housing society clusters, two tapped into groundwater while the rest depended on municipal supply. 3.2. Quantity {#S8} ------------- A visual estimation of the volume of stored water showed all HHs stored an average of 35 to 50 litres of drinking water and 600 to 1300 litres for other purposes ([Table 1](#T1){ref-type="table"}). Of the 42 slum HHs, 16% (7 HHs) used either mechanical or motorised pumps during water supply hours to get additional water. Two of the 8 housing society clusters used motorised pumps to draw ground water into their storage tanks. The proportion of HHs that were dissatisfied with the quantity and/or pressure of water during summer was 45% in the slums (19 out of 42 HHs), and 50% (7 out of 14 HHs) in the society clusters. This dissatisfaction reduced to 26% in the slums HHs (11 out of 42 HHs) and 21% (3 out of 14 HHs) society HHs during the rest of the year ([Table 1](#T1){ref-type="table"}). 3.3. Quality {#S9} ------------ All slum and 80% of housing society households directly collected municipal water for drinking after simple sieving. The rest used Reverse Osmosis systems to purify water stored in overhead tanks for drinking. This city's supply of 1 billion litres of water per day averages to 180 litres per head. This falls within the range of 100 to 200 litres per capita, estimated by WHO as the amount likely to be collected when there is optimal access to water. At this level of water usage, public health risk due to poor hygiene is expected to be very low \[[@R15]\]. Our survey data bears out that the WHO water standards were met in the study ward. The water supply in Ahmedabad is unmetered and water tax is included in annual property tax bills. Thus, water is affordable in the city, the bottleneck being the restricted supply hours and poor pressure of water. Citizens, depending on their affluence level, circumvent these shortcomings using one or more methods; by storing large quantities of water, by applying hand or motorized pumps directly on the municipal water line or by tapping into groundwater sources. In our study ward, we found that poorer ward residents depended completely on the municipal water for both quality and quantity on a day to day basis. Each day, they separately collect and store water for drinking and for other purposes. Having larger families, and unable to afford storage facilities, they spent considerable time collecting and storing water. The richer households are able to ensure quality and quantity of water they require by investing in permanent storage solutions like cement or plastic tanks. They have the option of either collecting the direct municipal supply water or use various types of water purifiers for drinking. Interestingly, in these richer housing societies, filtered and chlorinated municipal water is collected in underground storage tanks. Here, it is mixed with groundwater and thus rendered non-potable. This mixture is pumped to overhead tanks, and some of this now non-potable water is processed through Reverse Osmosis systems or other commercial water purifiers in individual households, for drinking. The engineers responsible for water supply of the ward were unaware and unable to estimate how much piped water is consumed in the study ward and the extent of groundwater usage. They surmised that since this ward was upstream, there wouldn't be any water shortage in this area. The groundwater of Ahmedabad is known to have high levels of iron, fluoride, chloride and nitrates (\[[@R16]\] \[[@R17]\]). The Municipal Corporation as well as richer housing societies routinely resort to supplementing their water supply with ground water. The present drinking water surveillance system of the municipal corporation is designed for a twenty-four hour piped distribution of treated surface water. In reality, the water supply is neither 24 hours nor exclusively treated surface water. Therefore, as suggested by WHO \[[@R15]\], the water sampling process in the city needs to include periodic surveys of water actually consumed by the citizens. The Central Water Testing Laboratory needs to expand its laboratory capacity to include more refined tests for microbial and chemical contamination. The WHO drinking water quality guidelines recommend that for every 50,000 population in a city with more than five million populations, faecal indicator testing in distribution systems should be carried out on a minimum of 12 samples with an additional 600 samples every year. By these standards, if the entire city had had an interconnected water supply network with positive pressure in the system 24 hours of the day, the city would require to test 2040 samples every year \[[@R15]\]. However, the Central Water Testing Laboratory tests a minimum of 224 water samples for faecal indicators every day and 67,200 samples every year. The water samples are subjected to only basic physical and chemical analysis. Capacity to test heavy metals (lead, cadmium, mercury, arsenic, and nitrates), trihalothanes and fluorides and advanced microbial tests for bacteriophages and spores are presently not available. 3.4. Strengths and Weakness of Our Study {#S10} ---------------------------------------- We studied only a single ward of the city, therefore, the generalizability of these findings for the city are limited. Also the ward is located close to the water supply source for the city so the researchers suspect a better water availability in the study ward than the rest of the city. The investigators did not look for the existence of water vendors and thus cannot comment on purchase of water (and its financial implications) in times of non-supply of municipal water. 4. Conclusion {#S11} ============= In conclusion, the water sampling strategy for the city of Ahmedabad needs to include periodic surveys of water actually consumed by the community and the testing strategy needs to incorporate tests for viruses, heavy metals, fluorides, trihalothanes and surface contaminants at appropriate intervals of time and distance in piped water, using maps of the water distribution systems. There is a need for consultations with experts to adjust the numbers and sophistication of tests to appropriately reflect available scientific knowledge about Drinking Water Quality Surveillance. Also, a practice of Sanitation Risk Scoring by Sanitary Inspectors of the city needs to be developed and implemented. Although there are official references to reducing groundwater exploitation \[[@R17]\], guidelines need to be developed for tapping into underground aquifers in the country. The authors gratefully acknowledge Mr. Ashish Upadhya and, Mr. Ajit Rajiva for their contributions in developing the map. We thank the officials from the Municipal Corporation for extending us all the cooperation. We thank Dr. V. S. Saravanan from the University of Bonn for his valuable suggestions. Funding This work is supported by a Wellcome Trust Capacity Strengthening Strategic Award to the Public Health Foundation of India and a consortium of UK universities. ![Description of survey methodology.](emss-60323-f0001){#F1} ![Map showing water sampling areas in the study ward.](emss-60323-f0002){#F2} ###### Salient findings from the households' survey of the ward. --------------------------------------------------------------------------------------------------------------------------------------------------- Slum clusters Society clusters ---------------------------------------------------------------------------------------- ------------------- -------------------------------------- No. of slums/societies 21 8 (+1 refused) No. of HHs 42 14 Persons per HH 6 5 Source of drinking water Municipal supply 6 municipal supply and\ 2 supplemented with private borewell Quantity Water stored (lt/HH) Drinking 41 28 Cleaning 822 1320 Per capita presence of drinking water (litres) 7 6 Per capita presence of other water (litres) 143 286 HHs complaining of low pressure and/or less quantity supply in summer rest of the year 19 (45%) 11 (26%) 7 (50%) 3 (15%) HHs using pumps 7 (16.67%) 2 (14.3%) Drinking water practices Municipal water used directly for drinking 42 (100%) 11 (75% ) Earthenware pots used for storing drinking water 42 (100%) 13 (92.9%) ---------------------------------------------------------------------------------------------------------------------------------------------------	{ "pile_set_name": "PubMed Central" }
Abedi E, Pourmohammadi K, Abbasi S. Dual‐frequency ultrasound for ultrasonic‐assisted esterification. Food Sci Nutr. 2019;7:2613--2624. 10.1002/fsn3.1115 1. INTRODUCTION {#fsn31115-sec-0001} =============== Starch is an accessible, thickening, and texturizing stabilizer, and of paramount importance when it comes to augmenting the overall quality of the products, reducing costs, and facilitating the processing procedure (Berski et al., [2011](#fsn31115-bib-0009){ref-type="ref"}; Choi & Kerr, [2003](#fsn31115-bib-0013){ref-type="ref"}); however, due to the high affinity toward retrogradation, its application is restricted in certain food products (Kaur, Ariffin, Bhat, & Karim, [2012](#fsn31115-bib-0027){ref-type="ref"}; Kaur, Sandhu, & Lim, [2010](#fsn31115-bib-0029){ref-type="ref"}). In frozen foods and desserts containing starch, resistance to syneresis of water, resistance to freeze and thaw, and reduction in retrogradation are important issues. In this regard, native starch was modified to overcome this limitation. By introducing the functional groups into the starch molecules, chemically modified starches, such as oxidized, hydroxypropylated, and acetylated starches, were employed. When starch is modified, its gelatinization, pasting, and retrogradation characteristics undergo different changes (Kaur et al., [2012](#fsn31115-bib-0027){ref-type="ref"}, [2010](#fsn31115-bib-0029){ref-type="ref"}; Singh, Kaur, & McCarthy, [2007](#fsn31115-bib-0044){ref-type="ref"}). Acetylated starch (AC) was introduced with CH~3~CO group which caused a cleavage in the hydrogen bonds inside the starch chain and resulted in amphiphilic properties (Hong, Chen, Zeng, & Han, [2016](#fsn31115-bib-0025){ref-type="ref"}). AC with a low degree of substitution (DS) is used as an emulsifier, coating, and thickening agent, which is stable and resistant to retrogradation (Chi et al., [2008](#fsn31115-bib-0012){ref-type="ref"}; Singh, Chawla, & Singh, [2004](#fsn31115-bib-0045){ref-type="ref"}). Moreover, in such kinds of modified starch, solubility, swelling power, viscosity, hardness, adhesiveness, cohesiveness, and translucency of the gels are increased, while the initial gelatinization temperature is reduced (González & Perez, [2002](#fsn31115-bib-0018){ref-type="ref"}). The replacement of the modifier groups may boost the free movement of the starch chains within the amorphous regions in the granule, owing to the disruptions taking place among the inter‐ and intramolecular hydrogen bonds. The weakened internal bond structure in the starch granules, due to the derivatized modifier groups, enhances the freeze--thaw stability, reduces the gelatinization temperature, generates high levels of peak viscosity, and leads to starch paste clarity (Han, [2010](#fsn31115-bib-0021){ref-type="ref"}; Han, Lee, Lim, & Lim, [2005](#fsn31115-bib-0022){ref-type="ref"}). Ultrasonic treatments can accelerate chemical reaction and increase yields. Under sonication, the surface area of starch granules increases due to the formation of channels and/or holes on the surface and inside the granules (Huang, Li, & Fu, [2007](#fsn31115-bib-0026){ref-type="ref"}). Several modifications have been performed upon ultrasonication, including acetylation of dioscorea starch following ultrasound treatment (Zhang, Zuo, Wu, Wang, & Gao, [2012](#fsn31115-bib-0055){ref-type="ref"}), octenyl succinate starch (Chen, Huang, Fu, & Luo, [2014](#fsn31115-bib-0011){ref-type="ref"}), carboxymethyl starch (Gao et al., [2011](#fsn31115-bib-0017){ref-type="ref"}; Shi & Hu, [2013](#fsn31115-bib-0042){ref-type="ref"}), and octenylsuccinates of carboxymethyl starch (Čížová, Sroková, Sasinková, Malovíková, & Ebringerová, [2008](#fsn31115-bib-0014){ref-type="ref"}). However, there is no information about the acetylation of starch under various frequencies of ultrasonication. The aim of this study was to optimize the AC wheat starch in various parameters such as acetic anhydride concentration, pH, and temperature under frequencies (25, 40, and 25 + 40 kHz) of bath ultrasound; the optimization was further investigated on the amount of modification (molar substitution) in the modified starch. Based on the minimal reagent consumption, the optimized samples were selected and their physicochemical properties (solubility, water absorption), X‐ray diffraction, scanning electron microscopy (SEM), Rapid Visco Analyzer (RVA), differential scanning calorimetry (DSC), and Texture Profile Analyzer (TPA) were investigated at three frequencies (25, 40, and 25 + 40 kHz). The freeze and thaw stability of AC wheat starch was further compared with that made with native wheat starch. 2. MATERIALS AND METHODS {#fsn31115-sec-0002} ======================== 2.1. Materials {#fsn31115-sec-0003} -------------- Native wheat starch was obtained from Fars Glucosin Company, Shiraz, Iran. The moisture, fat, ash, and protein of native (N) and AC wheat starch prepared under ultrasonication were specified along with the standard methods of AACC, [2000](#fsn31115-bib-0001){ref-type="ref"}. Amylose content (%) was calculated by iodine method (Pourmohammadi, Abedi, Hashemi, & Torri, [2018](#fsn31115-bib-0038){ref-type="ref"}). 2.2. Acetylation of wheat starch {#fsn31115-sec-0004} -------------------------------- We added 100 g of starch to 224 ml of distilled water and stirred for 1 hr at 24°C. The pH was set to 6.5, 8, and 9.5 with NaOH solution (1 M), and acetic anhydride (4, 6 and 8%) was slowly added to the suspension at various pHs. Whole acetylation reaction was performed at 10 min. The suspensions were sonicated at an amplitude of 24% (with an input power of up to 400 W and working frequencies of 25, 40, and 25 + 40 kHz) at 45, 60, and 75°C. The time duration of sonication in each frequency was 5 min (25 kHz: 5 min, 40 kHz: 5 min, and 25 + 40 kHz: 5 min). pH was then maintained at 4.5 with HCl solution (1 M) for 5 min. All the experiments were performed in bakers placed at known positions in ultrasonic bath (Pacisa SA) equipped with a temperature controlling system. The ultrasonic bath with internal dimensions of 300 × 150 × 150 mm^3^consisted of a rectangular tank containing four transducers at the bottom. The suspensions were completely washed, lyophilized, and milled using a laboratory mill (AlexanderWerk, Model WEL82), and manually sieved to obtain particle sizes \< 40 μm (Wojeicchowski, Siqueira, Lacerda, Schnitzler, & Demiate, [2018](#fsn31115-bib-0054){ref-type="ref"}). 2.3. Acetyl percentage {#fsn31115-sec-0005} ---------------------- The titrimetric method of Mbougueng, Tenin, Scher, and Tchiégang ([2012](#fsn31115-bib-0035){ref-type="ref"}) was employed in order to specify the acetyl group percentage (AC%) and (DS). AC (5.0 g), 50 ml of distilled water, and 24 ml of 0.45 M NaOH were added in a 240‐mL flask and mixed for 30 min at room temperature. The surplus alkali was back‐titrated using 0.2 M HCl and phenolphthalein as an indicator. The reaction mixture was put to stand for 2 hr, where the alkali was removed from the titrated sample. The native starch was also used as a blank sample. Initially, the acetyl (%) and DS were calculated according to Equations ([1](#fsn31115-disp-0001){ref-type="disp-formula"}) and ([2](#fsn31115-disp-0002){ref-type="disp-formula"}), respectively:$$\%{\mspace{6mu}\text{Acetylation}} = \lbrack\left( {V_{\text{B}} - V_{\text{S}}} \right) \times N_{\text{HCl}} \times 0.043 \times 100\rbrack/W$$ V ~B~ and V ~S~ are the volumes of the control and modified samples (0.2 M HCl basis), respectively. N ~HCl~is the normality of the consumed acid. W is the weight of the sample.$$\text{DS} = (162 \times {\text{Acetyl}\mspace{6mu}}\%)/\lbrack 4300 - (42 \times {\text{Acetyl}\mspace{6mu}}\%)\rbrack$$ 2.4. X‐ray diffraction {#fsn31115-sec-0006} ---------------------- To obtain a relative humidity of 75%, all starch samples were primarily placed, for 5 days, in a relative humidity box containing supersaturated NaCl at room temperature. X‐ray diffraction pattern of the samples was determined by use of an X‐ray diffractometer (Model D8 Advance, Germany) (Li et al., [2014](#fsn31115-bib-0032){ref-type="ref"}). Utilizing the instrument software (EVA, Version 9.0), the degree of starch crystallinity was specified through dividing the area under the peaks by the total curve area. 2.5. Solubility and water absorption {#fsn31115-sec-0007} ------------------------------------ The method of Li et al. ([2014](#fsn31115-bib-0032){ref-type="ref"}) was used to determine water swelling and solubility of the samples with a slight modification. Native and modified wheat starches (1 g) and distilled water (30 ml) were added into a centrifuge tube, and, using a vortex mixer set at high speed, they were shaken at room temperature for 5 min. Each tube was incubated in water bath for 30 min at 95°C followed by centrifugation for 15 min at 3000 g. The weights of the pellet and dried supernatants (at 120°C for about 2 hr) were further obtained. The water solubility and swelling values of the native and modified samples were calculated using Equations ([3](#fsn31115-disp-0003){ref-type="disp-formula"}) and ([4](#fsn31115-disp-0004){ref-type="disp-formula"}), respectively.$$\text{Water\ solubility}\left( \% \right) = \text{weight\ of\ dissolved\ solids\ in\ supernatant/weight\ of\ dry\ sample\ solids\ in\ the\ original\ sample} \times 100$$ $${\text{Water\ swelling}\mspace{6mu}}\left( \% \right) = \left( {\text{weight\ of\ sediment} \times 100} \right)/\left( {{\mspace{6mu}\text{weight\ of\ dry\ sample\ solids}} \times \left( {100 - \text{solubility}} \right)} \right)$$ 2.6. Pasting properties {#fsn31115-sec-0008} ----------------------- Using the method described by Pourmohammadi et al. ([2018](#fsn31115-bib-0038){ref-type="ref"}), the pasting properties of the native and modified wheat starches were determined through RVA (Newport Scientific Pty. Ltd) interfaced with a personal computer. 2.7. Thermal properties {#fsn31115-sec-0009} ----------------------- The gelatinization properties of the native and modified wheat starches were analyzed using a DSC instrument (OIT‐5000; Sanaf) equipped with STAR software making using of Pourmohammadi et al. ([2018](#fsn31115-bib-0038){ref-type="ref"}) method. The device was calibrated with indium and mercury, and an empty pan was used as a reference. Native and modified wheat starches (10 g) were weighed into the standard aluminum pan. Distilled water (30 ml) was added, and the pans were sealed and equilibrated for 24 hr at room temperature. After that, the starch slurry was gelatinized in the DSC instrument, by heating at 6°C/min, from 10 to 160°C. Following heat treatment, the samples were cooled to 25°C and then removed from the DSC. The changes in enthalpy (ΔH in J/g of dry starch), onset temperature (T ~o~), peak temperature (T ~p~), and conclusion temperature (T ~c~) for gelatinization were obtained from the exotherm DSC curves. 2.8. Microstructure determination {#fsn31115-sec-0010} --------------------------------- The microstructure of the modified starch was specified using SEM (Model Leica Cambridge) by use of the method proposed by Pourmohammadi et al. ([2018](#fsn31115-bib-0038){ref-type="ref"}). 2.9. Textural analysis {#fsn31115-sec-0011} ---------------------- Textural properties of starch gels were specified using a Texture Profile Analyzer (TA Plus; Stable Micro System). To prepare the paste of gelatinized starch, 10 g of starch was added to 100 ml of distilled water, where the slurry remained in water bath (95°C for 30 min). The hot paste was collected and transferred into a cylindrical plastic container of 10 mm diameter and 10 mm height, and kept at 4°C for 24 hr. The gels were then removed from the container and tested for their textural properties. Utilizing a cylindrical aluminum plunger with a diameter of 10 mm, the gels were packed at a test speed of 2 mm/s, pretest and post‐test speed of 5 mm/s, time interval of 10 s, and strain deformation of 24%. The recorded force--time plots were analyzed for the following: hardness (N), springiness (Length 2/ Length 1), cohesiveness, the ratio of the areas of the two resistance peaks (A2/A1), and gumminess according to Abedi, Majzoobi, Farahnaky, Pourmohammadi, and Mahmoudi ([2018](#fsn31115-bib-0002){ref-type="ref"}). Data were analyzed three times, and the results were averaged. 2.10. Freeze--thaw stability {#fsn31115-sec-0012} ---------------------------- With slight modifications in the methods described by Lawal ([2010](#fsn31115-bib-0030){ref-type="ref"}), we determined the syneresis of the starch gels belonging to the native and modified starches during cold and frozen storage. A starch suspension (5% dry basis, w/w) was heated at 95°C under constant agitation for 1 hr. 20 g of noodle strands belonging to N and AC starch was centrifuged at 2000 g for 10 min to remove free water. The free water (supernatant) was decanted, and the tubes containing starch paste were exposed to freeze and thaw cycles, followed by centrifugation at 3,500 g for 30 min. The freezing process was done at −18°C for 24 hr, and the melting process was carried out at 30°C for 4 hr. The two processes were repeated for 8 cycles, in each of which the isolated water was determined. The weight of water was taken, and the amount of syneresis was calculated as the percentage of water separated as Equation ([5](#fsn31115-disp-0005){ref-type="disp-formula"}):$$\text{Syneresis}\left( \% \right) = \text{Water\ separated}\left( g \right){\times 100)/\text{Total\ weight\ of\ sample}}\left( g \right)$$ 2.11. Statistical analysis {#fsn31115-sec-0013} -------------------------- So as to specify the regression coefficients, the Design‐Expert (version 6.0.5) methodology (Abedi, Sahari, Barzegar, & Azizi, [2015](#fsn31115-bib-0003){ref-type="ref"}) and statistical software packages SAS 9.1 (SAS Institute) were made. A Box--Behnken design from the response surface was used to study the effect of three different factors on the acetylation degrees of wheat starch. Factors associated with acetylation were acetic anhydride (4, 6, and 8%), pH (6.5, 8, and 9.5), and temperature (45, 60, and 75°C). The experimental data were fitted in accordance with Equation ([6](#fsn31115-disp-0006){ref-type="disp-formula"}) as a second‐order polynomial equation, including the linear and interaction effects of each factor:$$Y = \beta_{0} + \sum\limits_{i = 1}^{k}{\beta_{i}X_{i}} + \sum\limits_{i = 1}^{k}{\beta_{\mathit{ii}}X_{i}^{2}} + \sum\limits_{\begin{array}{l} {i = 1} \\ {i < j} \\ \end{array}}^{k - 1}{\sum\limits_{j = 2}^{k}{\beta_{\mathit{ij}}X_{i}}X_{j}}$$ where Y is the predicted response, X~i~ and X~j~ are independent factors, b0 is the offset term, bi is the ith linear coefficient, bii is the ith quadratic coefficient, and bij is the ijth interaction coefficient. All analyses were obtained in triplicates and reported as mean values. 3. RESULTS AND DISCUSSION {#fsn31115-sec-0014} ========================= 3.1. Molar substitution of AC wheat starch {#fsn31115-sec-0015} ------------------------------------------ Concerning the AC wheat starch at sonication frequencies of 25, 40, and 25 + 40 kHz, optimization was done in order to investigate the effect of acetic anhydride content, pH, temperature, and ultrasonic frequency on the amount of modification or molar substitution of the modified starch (Figure [1](#fsn31115-fig-0001){ref-type="fig"}).$$\text{Degree\ of\ acetylation}\left( \% \right)\text{at\ frequency\ 25\ kHz} = + 1.48 + 0.37 \times A + 0.18 \times B + 0.017 \times C + 0.17 \times A \times B + 0.16 \times A \times C + 0.043 \times B \times C - 0.26 \times A^{2} - 0.37 \times B2 - 0.50 \times C^{2}$$ $$\text{Degree\ of\ acetylation}\left( \% \right)\text{at\ frequency\ 40\ kHz} = + 1.02 + 0.32 \times A + 0.13 \times B + 0.13 \times C + 0.15 \times A \times B + 0.15 \times A \times C + 0.12 \times B \times C - 0.12 \times A^{2} - 0.29 \times B^{2} - 0.36 \times C^{2}$$ $$\text{Degree\ of\ acetylation}\left( \% \right){\text{at\ frequency}\mspace{6mu}}25 + 40\,\text{kHz} = + 1.52 + 0.35 \times A + 0.12 \times B - 0.14 \times C + 0.093 \times A \times B + 0.080 \times A \times C + 0.001 \times B \times C - 0.21 \times A^{2} - 0.33 \times B^{2} - 0.63 \times C^{2}$$ ![The effect of acetic anhydride (4, 6, and 8%), pH (6.5, 8, and 9.5), and temperature (45, 60, and 75°C) on the degree of wheat acetylation (A) at frequencies 25 kHz, 40 kHz, and 25 + 40 kHz. Lack of fit: not significant](FSN3-7-2613-g001){#fsn31115-fig-0001} Optimized samples were selected based on minimum reagent consumption (acetic anhydride with achieving to maximum modification). According to response surface methodology (RSM) analysis, the optimized AC wheat starch was acetic anhydride (5%), pH 8.5, and temperature 60°C with 1.22%, 1.37%, and 1.02% acetylation for 25 kHz, 25 + 40 kHz, and 40 kHz, respectively. As a result of Equations ([(6)](#fsn31115-disp-0006){ref-type="disp-formula"}, [(7)](#fsn31115-disp-0007){ref-type="disp-formula"}, [(8)](#fsn31115-disp-0008){ref-type="disp-formula"}), the effect of A (acetic anhydride content) \> B (pH) \> C (reaction temperature) is on route to the maximum acetylation. The negative effect of temperature at dual frequency (25 + 40 kHz) was more than 25 and 40 kHz; however, the effect of temperature at 25 kHz frequency was the same as 40 kHz. The addition--elimination is the main mechanism for acetylation reaction, in which hydroxyl groups are converted to acetyl. The hydroxyl groups presented different levels of reactivity. The most reactive group was the hydroxyl of Carbon 6, followed by those of Carbons 2 and 3 (Wojeicchowski et al., [2018](#fsn31115-bib-0054){ref-type="ref"}). The C* = O bond of the acetyl group was substituted in all amorphous areas and at the outer lamellae of crystalline sections due to the poor ability of acetic anhydride to penetrate granule structures (Singh et al., [2007](#fsn31115-bib-0044){ref-type="ref"}). The differences in the DS of modified starch are related to several parameters, such as starch source, amylose‐to‐amylopectin ratio, degree of crystallinity, molecular weight (MW) of amylose and amylopectin, granular size, presence of lipids, and reaction medium factors, such as pH, temperature, reaction time, mixing uniformity, and reagent content during the modification of the starches (Ayucitra, [2012](#fsn31115-bib-0006){ref-type="ref"}; González & Perez, [2002](#fsn31115-bib-0018){ref-type="ref"}; Halal et al., [2015](#fsn31115-bib-0019){ref-type="ref"}; Salcedo Mendoza, Hernández RuyDíaz, & Fernández Quintero, [2016](#fsn31115-bib-0040){ref-type="ref"}; Singh et al., [2007](#fsn31115-bib-0044){ref-type="ref"}; Sodhi & Singh, [2005](#fsn31115-bib-0047){ref-type="ref"}; Wang & Wang, [2002](#fsn31115-bib-0052){ref-type="ref"}). 3.2. Effect of ultrasonication {#fsn31115-sec-0016} ------------------------------ Under sonification, DS was increased since the solubility and swelling of granules were improved as a result of sufficient contact with reagents, which enhanced the homogeneity of the reactants. Collapse of cavitation bubbles upon ultrasonic treatment is capable of mechanically damaging and rupturing the starch granules and breaking the chains of polymers due to high‐pressure gradients, high local velocities of liquid layers, shearing force, and microstreaming. According to Amini, Razavi, and Mortazavi ([2015](#fsn31115-bib-0005){ref-type="ref"}) and Zhu ([2015](#fsn31115-bib-0057){ref-type="ref"}), ultrasound creating fracture, pore, and crack on glanular surfaces may enhance the surface area of starch, facilitate the penetration of esterifying agents (acetyl) into the granular structure, and accelerate the chemical reactions. The frequency of ultrasound is a key factor for enhancing cavitational bubble due to certain reasons (Abedi, Sahari, & Hashemi, [2017](#fsn31115-bib-0004){ref-type="ref"}): (a) Cavitation yield decreases with the increase in frequency, which is attributed to the scattering, attenuation, and shortening of the acoustic cycle at high frequencies (Abedi et al., [2017](#fsn31115-bib-0004){ref-type="ref"}). (b) Instable cavitation at low frequencies causes the bubble to collapse very quickly and violently, resulting in more rapid agitation and mass transfer (Abedi et al., [2017](#fsn31115-bib-0004){ref-type="ref"}). 3.3. Effect of temperature {#fsn31115-sec-0017} -------------------------- Temperature had a progressive effect on the DS of the modified starch, which is attributed to the swelling of starch granules, diffusion of the esterifying agents, mobility of reactant molecules for reaction with amorphous regions, destruction of the crystalline regions of the starch granules, and conversion to amorphous regions (Han et al., [2012](#fsn31115-bib-0020){ref-type="ref"}). This phenomenon can simplify the acceptability of granules in acetic anhydride and propylene glycol percolation. Temperature is an important factor, yet a very high temperature is not conducive to the absorption of the esterifying agent (acetyl) by the starch. This is because of the exothermic esterification reaction of starch (Han et al., [2012](#fsn31115-bib-0020){ref-type="ref"}; Singh et al., [2007](#fsn31115-bib-0044){ref-type="ref"}) and the facilitation of the gelatinization layer, which inhibits the contact of reagents with starch molecules (Han et al., [2012](#fsn31115-bib-0020){ref-type="ref"}; Singh et al., [2007](#fsn31115-bib-0044){ref-type="ref"}). 3.4. Effect of pH {#fsn31115-sec-0018} ----------------- DS increased following the addition of NaOH to the reaction medium, when the pH was set to 6.5, 8, and 9.5. Alkaline pH was able to enhance the DS owing to the disruption in the hydrogen bonds between molecules in amorphous and crystalline regions, and the facilitation of the percolation and penetration of the esterifying groups into the starch granular structure (Halal et al., [2015](#fsn31115-bib-0019){ref-type="ref"}; Han et al., [2012](#fsn31115-bib-0020){ref-type="ref"}). Although pH plays a major factor in the DS improvement of acetylation, very high pHs can diminish DS due to the hydrolyzation of acetic anhydride and the inhibition effect of gelatinized layer on the efficient contact between starch and acetic anhydride (Halal et al., [2015](#fsn31115-bib-0019){ref-type="ref"}; Han et al., [2012](#fsn31115-bib-0020){ref-type="ref"}). Various botanical starches have been acetylated with different degrees of acetylation, such as 0.104%--0.184% for maize starch (Singh et al., [2004](#fsn31115-bib-0045){ref-type="ref"}), 0.081 for waxy maize starch (Wang & Wang, [2002](#fsn31115-bib-0052){ref-type="ref"}), 0.087%--0.118% (Sodhi & Singh, [2005](#fsn31115-bib-0047){ref-type="ref"}) for rice starch, 0.041%, 0.059, and 0.076 for tapioca starch (Babic et al., [2007](#fsn31115-bib-0007){ref-type="ref"}), 1.85, 0.85, and 2.79% for corn starch (Chi et al., [2008](#fsn31115-bib-0012){ref-type="ref"}), 0.11 and 0.05 with 6 and 8% acetic acid consumption for oat starch (Mirmoghtadaie, Kadivar, & Shahedi, [2009](#fsn31115-bib-0036){ref-type="ref"}), and 0.9 and 2.7% for barely starch (Bello‐Pérez, Agama‐Acevedo, Zamudio‐Flores, Mendez‐Montealvo, & Rodriguez‐Ambriz, [2010](#fsn31115-bib-0008){ref-type="ref"}), 0.08%--0.21% for corn starch (Ayucitra, [2012](#fsn31115-bib-0006){ref-type="ref"}). Potato, oat, wheat, maize, and rice starches presented significant differences in their DS when acetylated under similar reaction conditions (Mirmoghtadaie et al., [2009](#fsn31115-bib-0036){ref-type="ref"}; Singh et al., [2007](#fsn31115-bib-0044){ref-type="ref"}). The high molar substitution acetylation in this study was interpreted by reaction medium under ultrasonic process, which affects the amylose regions. The extent of modification by ultrasonication in the crystallinity of starch granules depends on experimental conditions and the type of starch (Zhu, [2015](#fsn31115-bib-0057){ref-type="ref"}), and requires the introduction of acetyl group throughout the amylose or amylopectin sections. According to Singh et al. ([2004](#fsn31115-bib-0045){ref-type="ref"}), with low amylose content (low amylose/amylopectin ratio) a very high DS of acetylation can be observed. Surface of granule is another major factor affecting DS. Furthermore, González and Perez ([2002](#fsn31115-bib-0018){ref-type="ref"}) interpreted that the low degree of substitution in rice starch might be due to the lack of enough large inner channels or granular surface pores which can facilitate the access of acetic anhydride to the interior of the granule. 3.5. The crystalline structure {#fsn31115-sec-0019} ------------------------------ The X‐ray diffraction pattern of native and modified acetylated wheat starches is presented in Figure [2](#fsn31115-fig-0002){ref-type="fig"}. X‐ray diffraction analysis estimates the crystalline structure and the amount of crystal existing in the starch granules. The structure is related to amylopectin double helix. The results showed that the X‐ray pattern of wheat starch was the same as other cereals (A pattern). The native starch had sharp diffraction peaks at 15°, 17°, 18°, 23° (2θ), indicating the typical A pattern of cereal starch (Zobel, Young, & Rocca, [1988](#fsn31115-bib-0058){ref-type="ref"}). Following the esterification process, the degree of crystallinity was significantly reduced (p* \< 0.05) from N (36.89 ± 0.62) to AC at 25 kHz (17.80 ± 0.38), 40 kHz (22.43 ± 0.42), and 25 + 40 kHz (13.57 ± 0.41) frequencies of wheat starches. The X‐ray diffraction showed that with acetylation, the structures of native starch were destroyed, and new structures of esterified starches were formed. Crystalline regions are the main factors preventing the loss of granular structure during reaction with reagents, and preserving the integrity of granular structure (Sha et al., [2012](#fsn31115-bib-0041){ref-type="ref"}; Singh et al., [2007](#fsn31115-bib-0044){ref-type="ref"}). Moreover, it is to be noted that starch granules in amorphous regions are more susceptible to reagents during the modification process, while crystalline regions remain intact. Acetylation under ultrasonic conditions created fractures and cracks on granular surfaces, thereby facilitating the penetration of acetic anhydride for reaction with amorphous (granule composed of amylose) and crystalline regions. The amylose content of N (26.30 ± 0.26) was reduced to 12.68 ± 0.12, 18.93 ± 0.24, and 9.23 ± 0.36 following acetylation at ultrasound frequencies 25, 40, and 25 + 40 kHz, respectively. This means that amorphous regions reacted with acetic anhydride, a finding which is in accordance with Diop, Li, Xie, and Shi ([2011](#fsn31115-bib-0016){ref-type="ref"}); Simsek, Ovando‐Martínez, Whitney, and Bello‐Pérez ([2012](#fsn31115-bib-0043){ref-type="ref"}); Mbougueng et al. ([2012](#fsn31115-bib-0035){ref-type="ref"}); Wani, Sogi, and Gill ([2012](#fsn31115-bib-0053){ref-type="ref"}). ![X‐ray diffraction of native and acetylated wheat starch at frequencies 25 kHz, 40 kHz, and 25 + 40 kHz](FSN3-7-2613-g002){#fsn31115-fig-0002} 3.6. Solubility and water absorption {#fsn31115-sec-0020} ------------------------------------ Figure [3](#fsn31115-fig-0003){ref-type="fig"} illustrates the water absorption (WA) and solubility of native and acetylated wheat starch at different temperatures. The solubility and WA of N and AC wheat starch at various frequencies differed significantly (p \< 0.05) at all measured temperatures. The solubility and water absorption of AC wheat starch at frequencies 25, 40, and 25 + 40 kHz were 7.37--36.77 and 6.30--23.98, 6.57--34.49, and 5.83--20.94, and 8--40.77 and 7.03--27.60, respectively, which is much higher than N wheat starch (2.28--9.03 and 2.28--12.72 at temperatures ranging between 30 and 90°C, respectively). Similar increasing trends in solubility and WA due to acetylation have been reported for potato and corn starches (Singh et al., [2004](#fsn31115-bib-0045){ref-type="ref"}), waxy and normal maize (Liu, Ramsden, & Corke, [1999](#fsn31115-bib-0033){ref-type="ref"}), small and large wheat starch (Van Hung & Morita, [2005a](#fsn31115-bib-0050){ref-type="ref"}), tapioca (Babic et al., [2007](#fsn31115-bib-0007){ref-type="ref"}), normal and waxy rice starch (Liu et al., [1999](#fsn31115-bib-0033){ref-type="ref"}), rice starch (González & Perez, [2002](#fsn31115-bib-0018){ref-type="ref"}; Sodhi & Singh, [2005](#fsn31115-bib-0047){ref-type="ref"}), barely (Bello‐Pérez et al., [2010](#fsn31115-bib-0008){ref-type="ref"}; Halal et al., [2015](#fsn31115-bib-0019){ref-type="ref"}), sweet potato (Lee & Yoo, [2009](#fsn31115-bib-0031){ref-type="ref"}), oat (Mirmoghtadaie et al., [2009](#fsn31115-bib-0036){ref-type="ref"}), and corn (Diop et al., [2011](#fsn31115-bib-0016){ref-type="ref"}; Han et al., [2012](#fsn31115-bib-0020){ref-type="ref"}). Further reported is the increasing pattern of swelling and solubility properties of various starch sources under ultrasonic processes (Chan, Bhat, & Karim, [2010](#fsn31115-bib-0010){ref-type="ref"}; Herceg et al., [2010](#fsn31115-bib-0023){ref-type="ref"}; Luo et al., [2008](#fsn31115-bib-0034){ref-type="ref"}; Montalbo‐Lomboy et al., [2010](#fsn31115-bib-0037){ref-type="ref"}; Režek Jambrak et al., [2010](#fsn31115-bib-0039){ref-type="ref"}; Sujka & Jamroz, [2013](#fsn31115-bib-0048){ref-type="ref"}; Zheng et al., [2013](#fsn31115-bib-0056){ref-type="ref"}). Such increase is probably due to the destruction, disorganization, and reduction in the crystallinity degree of starch granules. ![Solubility and water absorption of native and acetylated wheat starch at frequencies 25 kHz, 40 kHz, and 25 + 40 kHz](FSN3-7-2613-g003){#fsn31115-fig-0003} The acetyl group disorganized the starch components upon acetylation due to the following: (a) disruption of hydrogen bonds in the starch granules and facilitation of water access to the amorphous region (Babic et al., [2007](#fsn31115-bib-0007){ref-type="ref"}; González & Perez, [2002](#fsn31115-bib-0018){ref-type="ref"}; Liu et al., [1999](#fsn31115-bib-0033){ref-type="ref"}), (b) repulsion force between starch molecules as well as starch chain, (c) partial depolymerization principally in the amylopectin, reducing the average molecular weight (MW) (Bello‐Pérez et al., [2010](#fsn31115-bib-0008){ref-type="ref"}; González & Perez, [2002](#fsn31115-bib-0018){ref-type="ref"}), (d) loss of granule crystallinity based on the X‐ray diffraction pattern (Bello‐Pérez et al., [2010](#fsn31115-bib-0008){ref-type="ref"}; Van Hung & Morita, [2005a](#fsn31115-bib-0050){ref-type="ref"}, [2005b](#fsn31115-bib-0051){ref-type="ref"}; Liu et al., [1999](#fsn31115-bib-0033){ref-type="ref"}), and (e) reduced interactions between the starch chains due to the introduction of acetyl groups, solubilizing and releasing the amylose to the exterior of the swollen starch granule (Salcedo Mendoza et al., [2016](#fsn31115-bib-0040){ref-type="ref"}). According to Figure [3](#fsn31115-fig-0003){ref-type="fig"}, temperature had a progressing effect on solubility and swelling of N and AC starch. The increase in the temperature of the medium induces the thermodynamic activity of starch molecules; moreover, a high granular mobility can increase the water penetration in the amorphous regions of starch granules and destroy the crystalline regions as well (Mirmoghtadaie et al., [2009](#fsn31115-bib-0036){ref-type="ref"}). 3.7. The pasting properties {#fsn31115-sec-0021} --------------------------- Figure [4](#fsn31115-fig-0004){ref-type="fig"} and Table [1](#fsn31115-tbl-0001){ref-type="table"} present the RVA profile of N and AC starch suspensions (5%, w/w) at various frequencies (25, 40, and 25 + 40 kHz) during heating from 30 to 90°C. The peak viscosity is indicated by the maximum swelling of the majority of starch granules and their subsequent collapse (Van Hung & Morita, [2005a](#fsn31115-bib-0050){ref-type="ref"}, b). The peak and final viscosity of native starch (3,757 ± 48 and 7,034 ± 34) were found to be significantly (p \< 0.05) lower than AC starches at frequencies 25 (7,188 ± 32 and 8,851 ± 31), 40 (5,846 ± 65 and 7,648 ± 66), and 25 + 40 kHz (9,423 ± 112 and 11,174 ± 131). The AC at frequency 25 + 40 kHz (50.9 ± 1.2) had lower pasting temperatures compared with 25 kHz (58.3 ± 1.4), 40 kHz (64.4 ± 1.2), and N (71.6 ± 1.6). These findings are in accordance with the results of Li et al. ([2014](#fsn31115-bib-0032){ref-type="ref"}) where the starch with higher amylose content reduced the gelatinization temperatures due to less crystalline and more amorphous regions (Li et al., [2014](#fsn31115-bib-0032){ref-type="ref"}). These results are in accordance with certain other research (González & Perez, [2002](#fsn31115-bib-0018){ref-type="ref"}; Van Hung & Morita, [2005a](#fsn31115-bib-0050){ref-type="ref"}, b; Liu et al., [1999](#fsn31115-bib-0033){ref-type="ref"}; Salcedo Mendoza et al., [2016](#fsn31115-bib-0040){ref-type="ref"}). In these studies, the modification of starch by acetylation increased the peak viscosity due to (a) the decrease in the strength of associative intermolecular forces in the amorphous regions of the granules, (b) lower degrees of crystallinity in AC compared with N wheat starches, (c) increase in solubility and swelling power (Figures [3](#fsn31115-fig-0003){ref-type="fig"} and [4](#fsn31115-fig-0004){ref-type="fig"}), (d) the solubilizing amylose released outside the swollen starch granule (Han, [2010](#fsn31115-bib-0021){ref-type="ref"}; Salcedo Mendoza et al., [2016](#fsn31115-bib-0040){ref-type="ref"}), and (e) improvement in the hydrophilic capacity of the reorganized structures (Han, [2010](#fsn31115-bib-0021){ref-type="ref"}; Salcedo Mendoza et al., [2016](#fsn31115-bib-0040){ref-type="ref"}). On the other hand, compared with the native starches, the AC wheat starches presented better stability during heating. Reassociation of amylose molecules occur when leached out from swollen starch granule, thus providing a higher resistance to thermal or mechanical forces (Colussi et al., [2015](#fsn31115-bib-0015){ref-type="ref"}). ![The RVA profiles in native (1) and acetylated wheat starch at frequencies 25 kHz (3), 40 kHz (2), and 25 + 40 kHz (4)](FSN3-7-2613-g004){#fsn31115-fig-0004} ###### Pasting profile (RVA), thermal (DSC), and textural (TPA) analysis of native (N), acetylated (AC), wheat (dry basis) starches RVA parameters Thermal parameters TPA parameters ------------------------------- ---------------- -------------------- ---------------- ------------- ------------- --------------- --------------- ---------------- --------------- --------------- ---------------- -------------- ---------------- --------------- N wheat starch 71.6 ± 1.6^a^ 3,758±48^d^ 7,034±34^d^ 1,214±84^d^ 3,576±38^a^ 56.8 ± 0.8^a^ 62.0 ± 1.4^a^ 67.4 ± 1.3^a^ 11.8 ± 0.8^a^ 1,420 ± 34^a^ 0.93 ± 0.05^a^ −234 ± 13^a^ 1.18 ± 0.09^a^ 1,321 ± 85^a^ AC wheat starch (25 kHz) 58.3 ± 1.4^c^ 7,188±32^b^ 8,851±31^b^ 3,102±18^b^ 1663±53^d^ 48.2 ± 1.0^c^ 53.4 ± 1.3^c^ 59.4 ± 1.84^c^ 6.4 ± 0.8^c^ 634 ± 28^c^ 0.87 ± 0.05^a^ −312 ± 38^c^ 0.71 ± 0.04^c^ 852 ± 34^c^ AC wheat starch (40 kHz) 64.4 ± 1.2^b^ 5,846±65^c^ 7,648±66^c^ 2,492±16^c^ 1802±67^b^ 51.0 ± 0.8^b^ 57.6 ± 1.2^b^ 62.1 ± 1.4^b^ 9.5 ± 0.4^b^ 896 ± 48^b^ 0.91 ± 0.03^a^ −281 ± 24^b^ 0.95 ± 0.08^b^ 936 ± 52^b^ AC wheat starch (25 + 40 kHz) 50.9 ± 1.2^d^ 9,423±112^a^ 11,174±131^a^ 4,011±24^a^ 1753±53^c^ 44.9 ± 1.4^d^ 50.8 ± 1.1^d^ 54.6 ± 1.8^d^ 5.8 ± 0.8^d^ 574 ± 31^d^ 0.86 ± 0.09^a^ −327 ± 30^d^ 0.62 ± 0.07^d^ 616 ± 43^d^ Different letters in each column show significant statistical difference between the values (p \< 0.05). John Wiley & Sons, Ltd 3.8. Thermal behavior {#fsn31115-sec-0022} --------------------- Table [1](#fsn31115-tbl-0001){ref-type="table"} summarizes the DSC gelatinization parameters including transition temperatures (To, Tp, and Tc) and enthalpy of gelatinization (ΔH gel) related to N and AC (under sonication at frequencies 25, 40, and 25 + 40 kHz) wheat starches. It was observed that these values were lower in AC at frequency 25 + 40 kHz compared with AC at frequency 25 and 40 kHz and N starches. Modification induced a major reduction from 56.8 ± 0.8°C for N wheat starch to 48.2 ± 1.04°C, 51.0 ± 0.8°C, and 44.9 ± 1.4 for AC wheat starches at frequencies 25, 40, and 25 + 40 kHz, respectively. Among the starches, N starch presented the highest ΔH~gel~ value (11.8 ± 0.8 J/g), followed by AC wheat starches at frequency 25 kHz (6.4 ± 0.8), 40 kHz (9.5 ± 0.4), and 25 + 40 kHz (5.8 ± 0.8). Singh et al. ([2004](#fsn31115-bib-0045){ref-type="ref"}), Babic et al. ([2007](#fsn31115-bib-0007){ref-type="ref"}), and Lee and Yoo ([2009](#fsn31115-bib-0031){ref-type="ref"}) also reported a statistically significant (p \< 0.05) decrease in the gelatinization temperature of corn, potato, tapioca, and sweet potato starches following acetylation. The starch gelatinization is controlled by two factors: (a) amylopectin molecular structures such as molar mass, integrity and order of crystallites, polydispersity, and amylopectin chain length with a degree of polymerization (DP) ranging between 5 and 12, and (b) granule structures including granule size, amylose/amylopectin ratio, crystalline zone relationship, and the quality and amount of amorphous crystallites (Tester & Morrison, [1990](#fsn31115-bib-0049){ref-type="ref"}). The enthalpy value attributed to the ordered double‐helix loss was more than the crystallinity loss. The difference in enthalpy value between the N and modified wheat starch showed that the acetylation of wheat starch with a high substitution degree generated disorganization as is shown by X‐ray, SEM, and RVA experiments. The reduction in the gelatinization parameters of acetylated starches was due to the insertion of acetyl and propyl oxide groups into the starch molecules, particularly into the amorphous areas. This further reduced the integrity of the amorphous and crystalline sections of starch granules and disrupted the inter‐ and intramolecular hydrogen bonds, destabilizing the granular structure (Babic et al., [2007](#fsn31115-bib-0007){ref-type="ref"}). ΔH indicates an overall measure of crystallinity and loss in the molecular order. The esterifying agents reduce ΔH due to (a) the change in the amylopectin double helices, (b) diminished crystallinity, (c) increase in starch chain flexibility, and (d) reduction in gelatinization temperature (Halal et al., [2015](#fsn31115-bib-0019){ref-type="ref"}). These findings are consistent with Halal et al. ([2015](#fsn31115-bib-0019){ref-type="ref"}); Bello‐Pérez et al. ([2010](#fsn31115-bib-0008){ref-type="ref"}); Mirmoghtadaie et al. ([2009](#fsn31115-bib-0036){ref-type="ref"}); Kaur, Singh, and Singh ([2004](#fsn31115-bib-0028){ref-type="ref"}). 3.9. The effects of modification on starch morphology {#fsn31115-sec-0023} ----------------------------------------------------- The morphological patterns of N and modified starches are shown in Figure [5](#fsn31115-fig-0005){ref-type="fig"} where A and B granules of wheat starch can be clearly observed. In AC wheat starches at dual frequency (25 + 40 kHz), the surfaces of all large granules were more damaged after modification, compared with those of the small granules. Meanwhile, at frequency 25 and 40 kHz of wheat starch, small granules were more affected than large granules. Starch granules indicated a partial disintegration of granules with a slight gelatinization when esterification reactions were performed in the presence of catalyst (NaOH solution; Halal et al., [2015](#fsn31115-bib-0019){ref-type="ref"}). According to Hirsch and Kokini ([2002](#fsn31115-bib-0024){ref-type="ref"}), the cross‐linked bonds formed by acetic anhydride mostly occur on the surface of the starch granules. ![Scanning electron microscopy (SEM) of native (a) and acetylated wheat starch at frequencies 25 kHz (b), 40kHz (c), and 25 + 40 kHz (d)](FSN3-7-2613-g005){#fsn31115-fig-0005} Modification by ultrasonication influenced the granule morphology through forming deep grooves in the central core zone, cracks on the starch granules, and blister‐like and doughnut‐like shapes, which is in line with the SEM morphology of Kaur et al. ([2004](#fsn31115-bib-0028){ref-type="ref"}). The major impact of acetylation on the surface of the granules is due to the reaction of acetic anhydride with starch granules under ultrasonic processes. Ultrasonic‐induced cracks, pores, and fractures on granular surfaces facilitate the penetration of chemical reagents into structure granules. According to the results of Bello‐Pérez et al. ([2010](#fsn31115-bib-0008){ref-type="ref"}), esterification of starch generated higher granule fusion, which is attributed to the increase in hydrogen bonding due to the insertion of hydrophilic groups into the starch molecules. Accordingly, coalescing starch molecules induce the fusion of starch granules (Bello‐Pérez et al., [2010](#fsn31115-bib-0008){ref-type="ref"}), which is in line with the SEM morphology in the present study (Figure [5](#fsn31115-fig-0005){ref-type="fig"}). The SEM results are also consistent with Van Hung and Morita ([2005a](#fsn31115-bib-0050){ref-type="ref"}, b). 3.10. Gel texture {#fsn31115-sec-0024} ----------------- Table [1](#fsn31115-tbl-0001){ref-type="table"} demonstrates the texture profiles of N and AC wheat starches under various frequency ultrasounds. The order of the hardness of AC wheat starch was as follows: 25 + 40 kHz \< 25 kHz \< 40 kHz. Acetylation was able to reduce the hardness of the gels due to (a) the introduction of large and hydrophilic acetyl groups which aided ultrasonication via increasing the space between the starch chain molecules and reducing retrogradation, (b) slight depolymerization of the starch molecules by the acetic anhydride under sonication (although more amylose molecules are reassociated, the depolymerization can weaken the gel), and (c) acetyl group preventing the formation of amylose gel network and the reassociation of amylose and amylopectin molecules (reducing retrogradation). There were no significant differences (p \< 0.05) between N and AC wheat starches as far as cohesiveness is concerned; however, their gumminess was reduced. Adhesiveness is the attraction between the gel and an external surface. Adhesiveness of N wheat starch gel was significantly (p \< 0.05) higher than AC wheat starch gels, which is in line with Liu et al. ([1999](#fsn31115-bib-0033){ref-type="ref"}), Choi and Kerr ([2003](#fsn31115-bib-0013){ref-type="ref"}), Babic et al. ([2007](#fsn31115-bib-0007){ref-type="ref"}), and Colussi et al. ([2015](#fsn31115-bib-0015){ref-type="ref"}). 3.11. Freeze--thaw stability {#fsn31115-sec-0025} ---------------------------- The purpose of the present research was to stabilize the starch gels from syneresis during freezing and thawing. The tendency to retrogradation of gels prepared from N and AC wheat starches was calculated by determining the syneresis (percentage of water loss) during storage at 4°C (Figure [6](#fsn31115-fig-0006){ref-type="fig"}). During the freezing cycles, the crystal size was enlarged with the reduction in their number. In the thawing stage, the ice crystals were converted to water masses easily removed from the polymer network (syneresis) (Smith & Schwartzberg, [1985](#fsn31115-bib-0046){ref-type="ref"}). Furthermore, water leakage led to the formation of sponge texture in starch. N starch gels started to retrograde following 24 hr, indicated by the increase in the percentage of water from 42.64% to 63.47% during storage (8 cycles). Acetylated starch gels prevented the separation of water from starch noodle even after five freeze--thaw treatments, showing a better freeze--thaw stability due to high DS. The percentage of water separated from AC starch gels at frequencies 25 kHz, 40 kHz, and 25 + 40 kHz reached 1.10%, 3.36, and 0.39%, respectively, indicating the lower increment in syneresis compared with the N wheat starch gel, as illustrated in Figure [6](#fsn31115-fig-0006){ref-type="fig"}. The highest resistance to freeze--thaw cycle(s) was observed in AC wheat starch at frequency 25 + 40 kHz (lowest % separated water), while the lowest belonged to N wheat starch (highest % separated water). Syneresis in freeze‐thawed gels is due to the reassociation of amylose molecules together and with amylopectin chain in starch granules at reduced temperatures which accelerates the exclusion of water from the gel structure. Amylose association takes place at the initial step of storage, while amylopectin association occurs in the following stages. Retrogradation may occur when a gelatinized starch is cooled. The increase in the amount of separated water indicates the lack of freeze--thaw stability. After acetylation, water molecules were absorbed by functional groups and were not able to freeze, thereby reducing syneresis (Han et al., [2012](#fsn31115-bib-0020){ref-type="ref"}). On the other hand, the introduction of large groups of acetyl into the starch chains reduced the inner and outer bonds. Moreover, the acetyl group is smaller in size, which is effective on water absorption and stability against water exclusion. By inserting the acetyl group, the hydrophilic nature of these reagents resulted in the electrostatic repulsion between the chains, preventing the amylose--amylose and amylose--amylopectin interactions (Kaur et al., [2004](#fsn31115-bib-0028){ref-type="ref"}; Lawal, [2010](#fsn31115-bib-0030){ref-type="ref"}). When the amylose molecules carrying acetyl group are mingled with amylopectin, the acetyl group sterically prevents the aggregation of amylopectin, entailing lower retrogradation and reduction in the percentage of water separated during freeze--thaw cycles (Kaur et al., [2004](#fsn31115-bib-0028){ref-type="ref"}; Lawal, [2010](#fsn31115-bib-0030){ref-type="ref"}). ![Freeze and thaw stability profile in N and AC wheat starch](FSN3-7-2613-g006){#fsn31115-fig-0006} 4. CONCLUSIONS {#fsn31115-sec-0026} ============== In order to increase the DS and consumption of minimum reagents, a reaction mixture was carried out under ultrasonic processes. The molar substitution optimizing AC wheat starch was 1.22%, 1.37%, and 1.02% for 25 kHz, 25 + 40 kHz, and 40 kHz, consuming 5% of acetic anhydride. High DS is due to the ultrasonic conditions at dual frequency (25 + 40 kHz) which form fractures, pores, and cracks on the surface of granules, facilitating the penetration of reagents into granule starch. Acetylation ameliorates the solubility, water absorption, resistance to freeze and thaw cycle, and viscosity peak, and reduces the gelatinization temperature. CONFLICT OF INTEREST {#fsn31115-sec-0027} ==================== The authors declare that they do not have any conflict of interest. ETHICS STATEMENT {#fsn31115-sec-0028} ================ Human and animal testing is unnecessary in this study. The authors would like to thank Dr. Mohsen Ajdari, University of Fasa, for his technical assistance.	{ "pile_set_name": "PubMed Central" }
Introduction {#s1} ============ Lysosomes and the ubiquitin proteasome system (UPS) are major degradation machineries for damaged and unwanted cellular contents in eukaryotic cells. The UPS degrades damaged and unwanted proteins that are tagged with ubiquitin, whereas large protein aggregates and damaged or dispensable organelles are degraded in the lysosome. Besides housekeeping functions, regulatory roles of these two machineries in development and differentiation are emerging in a number of organisms. Malaria parasites critically rely on these two systems, as inhibitors of the UPS and of proteases of the food vacuole, the lysosome-equivalent of Plasmodium, have been shown to block parasite development. Hence, these two proteolytic machineries are attractive targets for antimalarial drug development \[[@B1]--[@B6]\]. Erythrocytic malaria parasites critically rely on hemoglobin for amino acids, which is hydrolyzed in the food vacuole by concerted action of several different types of proteases. The major food vacuole-resident hemoglobin degrading proteases are papain-like cysteine proteases falcipains, aspartic proteases plasmepsins, the metalloprotease falcilysin, dipeptidyl aminopeptidase I, and a M1-family alanyl aminopeptidase \[[@B7]--[@B13]\]. A large body of literature indicates that the papain-like cysteine proteases falcipains, particularly falcipain-2 (FP2) and falcipain-3 (FP3), are the major hemoglobin degrading enzymes in P. falciparum \[[@B5]\]. FP2, FP3 and their homologs in other malaria parasites prefer leucine at the P2 position in substrates and inhibitors \[[@B14]--[@B24]\]. Several peptidyl inhibitors of papain-like cysteine proteases, including leupeptin (acetyl-Leu--Leu--Arg-aldehyde, with P2 leucine and aldehyde warhead), block development of malaria parasites by inhibiting FP2 and FP3 \[[@B25]\]. This selectivity for a P2 leucine residue has been exploited for optimizing inhibitors of falcipain-like proteases of malaria parasites \[[@B26]--[@B28]\]. Malaria parasites appear to have a typical 26S proteasome \[[@B29]\]. A 26S proteasome is composed of two multi-subunit assemblies: a core protease complex, called the core particle (CP) or 20S proteasome; and a regulatory element, known as the 19S regulatory particle (RP) \[[@B30]\]. The CP is a barrel-shaped complex of four stacked rings, each with 7 α or 7 β subunits, which are arranged as "αββα". Three catalytically distinct β subunits (β1, β2, and β5) in each inner ring, whose active sites line the central lumen of the CP, form a proteolytic chamber where substrates are degraded. Substrates gain access to this chamber through the pores formed by α rings on either side of the CP \[[@B31],[@B32]\], which requires the RP for opening the pores and unfolding of the substrate. Active site mutagenesis of the three protease subunits together with the use of defined peptide substrates revealed that a typical 26S proteasome possesses three types of activities \[[@B33]--[@B35]\]: 1) caspase-like or peptidyl-glutamyl peptide hydrolyzing (PGPH) activity, which cleaves after acidic residues; 2) trypsin-like activity that cleaves after basic residues; and 3) chymotrypsin-like activity, which cleaves after large hydrophobic residues. The majority of available proteasome inhibitors, including MG132, epoxomicin, and lactacystin, block the chymotrypsin activity \[[@B6],[@B36]--[@B39]\]. Dual inhibition of falcipains and the UPS with optimal selectivity could offer higher potency and less risk of development of drug resistance by the parasite than individual inhibitors of these two proteolytic systems. One such compound might be MG132 (Z-Leu-Leu-Leu-CHO), as it contains P2 leucine, a falcipain preferred residue, and an aldehyde group that reacts with catalytic cysteine residue of cysteine proteases and threonine residues of protease units of the proteasome. MG132 is a first choice inhibitor for studying UPS in a variety of organisms, including malaria parasites. It is commonly used at micromolar concentrations to study the UPS in a variety of human cell lines, with reported 50% cytotoxic concentrations in the range of 2.5-21 µM depending on the cell type and treatment duration \[[@B40]--[@B43]\]. MG132 has also been shown to inhibit the papain-like cysteine proteases cathepsin L and B and the calcium dependent cysteine proteases calpains \[[@B44],[@B45]\]. However, the cysteine protease inhibitory property of MG132 remains underappreciated compared to its extensive use as an UPS inhibitor. Hence, we hypothesized that this compound is a dual-target inhibitor of malaria parasites, blocking hemoglobin degradation by inhibiting falcipains and also inhibiting UPS. To test this hypothesis, we assessed the effects of specific inhibitors of cysteine proteases (E64) and UPS (epoxomicin, lactacystin, and MG132) on parasite development, hemoglobin degradation, proteasome and cysteine protease activities in P. falciparum extracts, and activity of recombinant falcipains. We demonstrated that MG132 blocks asexual erythrocytic development of P. falciparum by inhibiting both hemoglobin degradation and the UPS. Materials and Methods {#s2} ===================== Materials {#s2.1} --------- The P. falciparum 3D7 strain was obtained from the Malaria Research and Reference Reagent Resource Centre (MR4). MG132, epoxomicin, and lactacystin were from Santa Cruz Biotechnology; all other biochemical reagents were from Sigma or Serva. Plasmid isolation kits were from Qiagen or MACHEREY-NAGEL; cell culture reagents were from Lonza and Invitrogen; restriction and DNA modifying enzymes were from New England Biolabs; and SYBR Green 1 was from Invitrogen. Human blood was collected from healthy volunteers after written consent under medical supervision at the medical dispensary of the institute, and the protocol (IEC-2/2010) for blood collection for this study has been approved by the Institutional Ethical Committee of CCMB. Parasite culture {#s2.2} ---------------- In vitro parasite culture was done according to the protocols approved by the Institutional Biosafety Committees of CCMB and UCSF. P. falciparum was cultured in human erythrocytes at 2% haematocrit in the presence of a gas mixture (5% CO~2~, 5% O~2~, and 90% N~2~) in RPMI 1640 medium supplemented with 41.1 mg/litre hypoxanthine, 300 mg/litre glutamine, 2.5% human serum, and 0.5% Albumax II \[[@B46]\]. Synchrony was maintained by serial treatment with 5% D-sorbitol \[[@B47]\]. For parasite isolation, the culture was centrifuged at 894g for 5 min, the supernatant was aspirated off, the pellet was treated with ice-cold 0.05% saponin (in PBS) for 5 min to lyse erythrocytes, and the sample was centrifuged at 12,096g for 5 min at 4°C. The supernatant was discarded, the pellet was washed twice with ice-cold PBS to remove residual hemoglobin, and parasites were recovered by centrifugation at 12,096g for 5 min at 4°C. Genomic DNA (gDNA) was isolated from late trophozoite/schizont stage parasites using the Puregene Blood Core Kit B (Qiagen). Parasite growth inhibition assays {#s2.3} --------------------------------- Inhibitors of the proteasome (epoxomicin, lactacystin, and MG132), cysteine proteases (L-trans-epoxysuccinyl-leucyl-amido(4-guanidino)butane; E64), and aspartic proteases (pepstatin) were assessed alone and in combinations for inhibition of P. falciparum erythrocytic stage development. 200 x stocks of inhibitors were made in DMSO and serially diluted 2-fold in 100 µl culture medium across rows of a 96 well tissue culture plate. Control wells contained DMSO (0.05%) or 500 nM chloroquine. 100 µl of parasite suspension (1% ring-infected erythrocytes at 4% haematocrit) was added to each well, and plates were incubated in a modular incubator chamber (Billups-Rothenberg, Inc.) with the gas mixture at 37°C for 50 hours. At the end of incubation, 100 µl culture medium was carefully removed from each well, and 100 µl lysis buffer (20 mM Tris-Cl, 5 mM EDTA, 0.008% saponin, 0.08% Triton X-100, pH 7.5) with SYBR Green 1 (at the manufacturer's recommended dilution) was added to each well. The plate was incubated at 37°C for 30 min, and fluorescence was measured (Ex: 485 nm, Em: 530 nm, gain setting: 50) using an Infinite M200 multimode microplate reader (TECAN) as described previously \[[@B48]\]. The fluorescence of chloroquine-treated culture was subtracted from inhibitor-treated and DMSO-containing cultures to account for background fluorescence. Fluorescence values of inhibitor-treated cultures were normalized as percentage of DMSO-treated cultures, plotted against inhibitor concentrations, and analyzed using nonlinear regression analysis to determine IC~50~ concentrations for the inhibitors as described earlier \[[@B12]\]. For assessing the effect of inhibitor treatment on parasite morphology, ring stage parasites were cultured with DMSO (0.1%) or inhibitors (21.7 µM E64, 0.024 µM epoxomicin, 0.820 µM lactacystin, 0.133 µM MG132, and 220.6 µM pepstatin; concentrations are nearly 3 times the IC~50~) for 48 hours. Samples were collected at various time points, and thin smears were stained with Giemsa and observed under a 100 x lens using a bright field microscope. To investigate the effect of inhibitors on different developmental stages, highly synchronized parasites (3% rings) were cultured for 60 hours in the presence of DMSO (0.25%) or inhibitors (21.7 µM E64, 0.024 µM epoxomicin, and 0.133 µM MG132; concentrations are nearly 3 times the IC~50~), which were added at different time points of the development. DMSO was added in the beginning (T0), and inhibitors were added in the beginning and at 12, 24 and 36 hour time points. Thin smears were prepared after 48 hours and 60 hours, stained with Giemsa, and observed using a bright field microscope under a 100 x objective. At least 200 parasites were observed to evaluate parasite morphologies and the number of different parasite stages. To determine if MG132 irreversibly blocks parasite development, inhibitor washout experiments were performed for three development cycles (^≈^150 hours). Ring stage parasites (3% parasitemia) were cultured in the presence of DMSO (0.25%) or chloroquine (500 nM) or inhibitors (21.7 µM E64, 0.024 µM epoxomicin, 0.133 µM MG132; concentrations are nearly 3 times the IC~50~) for 50 hours in a 96-well tissue culture plate (250 µl culture volume, four wells for each treatment). The culture media was removed at the end of the incubation period; cells were washed twice with fresh culture medium, and then resuspended in 250 µl of fresh culture medium. 100 µl of this culture was used for measurement of parasite growth by the SYBR Green 1 assay, 50 µl was transferred to a well of another 96-well plate containing 200 µl culture medium with fresh erythrocytes (at 2% haemetocrit) for assessing parasite viability and growth, and the remaining culture was used for making smears for Giemsa-staining. For measuring parasite viability and growth, the plate was incubated in a modular incubator chamber (Billups-Rothenberg, Inc.) with the gas mixture at 37°C for 50 hours, and then each culture was processed for measurement of parasite growth by the SYBR Green 1 assay, assessing parasite viability and growth in the next development cycle, and making smears for Giemsa-staining as described above. The fluorescence values of chloroquine-treated, inhibitor-treated, and DMSO-containing cultures were compared to assess parasite growth. In parallel, Giemsa-stained smears were observed to assess parasite morphology and determine parasitemia. At least 1000 cells were counted to determine parasitemia, and 200 parasites were observed to assess morphology. Effect on hydrolysis of hemoglobin and ubiquitinated proteins {#s2.4} ------------------------------------------------------------- To test if MG132 targets hemoglobin hydrolysis and the UPS, a 100 ml culture of early trophozoite stage P. falciparum parasites (at 11% parasitemia) was divided into 4 equal parts; DMSO (0.1% final) was added to one part, and inhibitors (21.7 µM E64, 0.024 µM epoxomicin, and 0.133 µM MG132; all at concentrations nearly 3 times the IC~50~) were added to the remaining 3 parts. The cultures were grown for 10 hours, and parasites were isolated as described above. The parasite pellet from each culture was suspended in 150 µl reducing SDS-PAGE sample buffer, boiled for 10 min, and centrifuged at 27,216g for 15 min at room temperature, and the supernatants were then separated. For hemoglobin analysis, supernatants (corresponding to ^≈^2.5 x 10^7^ parasites) were run in 15% SDS-PAGE, and the gel was stained with coomassie blue. For analysis of ubiquitinated proteins, supernatants (corresponding to ^≈^5 x 10^7^ parasites) were run in 10% SDS-PAGE, and resolved proteins were transferred onto an Immobilon-P membrane (Millipore). The membrane was blocked (5% nonfat dry milk and 3% BSA in TBST (100 mM Tris-Cl, 0.5 M NaCl, 0.05% Tween-20, pH 7.5), incubated with mouse anti-ubiquitin antibodies (Santa Cruz Biotechnology, Cat No. sc-8017; 1/500 dilution in the blocking buffer), and then incubated with HRP-conjugated goat anti-mouse IgG (Invitrogen; diluted 1/10,000 dilution in blocking buffer). The signal was developed with the SuperSignal West Pico Chemiluminescent kit (Pierce) on X-ray film. MG132 cytotoxicity for human peripheral blood mononuclear cells (PBMCs) {#s2.5} ----------------------------------------------------------------------- 10 ml human blood was collected aseptically in heparinized tubes, mixed with 10 ml complete medium (RPMI1640 with 10% FBS), layered over an equal volume of Histopaque-1077, and centrifuged at 400g for 20 minutes at room temperature. The interphase containing PBMCs was transferred to a fresh tube, mixed with 10 ml complete medium, and centrifuged at 350g for 10 minutes. The cells were washed twice with 10 ml complete medium. The washed cells were suspended in complete medium (5.5 x 10^5^ cells/ml) and grown for 20 hours at 37°C in a CO~2~ incubator. The cells were suspended in fresh culture medium, 100 µl cell suspension was added to the wells of a 96 well tissue culture plate (7 x 10^4^ cells/well), and the plate was incubated for 4 hours at 37°C in a CO~2~ incubator. 100 µl complete medium with 0.025% DMSO or varying concentrations of MG132 was added to the wells (three wells for DMSO and each concentration of MG132), and the plate was incubated in a 37°C CO~2~ incubator for 48 hours. MG132 cytotoxicity was determined following the quick protocol for MTT assay (Invitrogen). Briefly, 20 µl MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide; 5 mg/ml in Hanks' balanced salt solution (HBSS)) was added to each well, and the plate was incubated in a 37°C CO~2~ incubator for 3 hours to label cells. The plate was centrifuged at 894g for 5 minutes, the culture medium was removed, and the cells were washed with 150 µl of HBSS. The plate was centrifuged again at 894g for 5 minutes, and the supernatant was removed. The insoluble MTT product formazan in cells was solubilized with DMSO (150 µl/well), and absorbance was read at 540 nm for formazan and at 690 nm for plate background. The plate background was subtracted from the 540 nm reading, and the absorbance values of MG132-treated cultures were normalized as percentage of DMSO-treated cultures, plotted against MG132 concentrations, and analyzed using the Four Parameter Logistic Function dose response curve (Sigma Plot) to determine the 50% cytotoxic concentration. Effect of MG132 on falcipain-2 knockout parasites {#s2.6} ------------------------------------------------- To determine susceptibility of FP2 knockout (FP2KO) parasites to MG132, the knockout and parental wild type parasites were cultured in the absence (control) or presence of various concentrations of MG132 or chloroquine in RPMI 1640 containing 10% human serum at 37°C for 50 hours. Parasitemias in control and inhibitor-treated cultures were determined by flow cytometry and compared to determine IC~50~ values of inhibitors as described earlier \[[@B7],[@B12]\]. Effect of inhibitor combinations on parasite growth {#s2.7} --------------------------------------------------- To determine the effect of inhibitor combinations on parasite growth, 300 x stocks of combinations (E64-MG132, epoxomicin-lactacystin, E64-epoxomicin, and E64-lactacystin in the ratio of 1:5, 1:3, 1:1, 3:1, and 5:1 of their IC~50s~; E64-pepstatin, MG132-pepstatin, and epoxomicin-pepstatin in the ratio of 2:1 and 1:1 of their IC~50s~) were serially diluted 2-fold in 100 µl culture medium across rows of a 96 well tissue culture plate. 100 µl of parasite suspension (1% ring-infected erythrocytes at 4% haematocrit) was added to each well, cultures were grown for 50 hours, and the 50% inhibitory concentration of each inhibitor in the combination was determined as described above. The 50% inhibitory concentration of each inhibitor in the combination was used to determine the fractional inhibitory concentration (FIC) as described previously (FIC = concentration of a compound that caused 50% inhibition in the combination/concentration of the compound required for 50% inhibition when used alone) \[[@B49]\]. The FICs obtained at different combination ratios of compound 1 and compound 2 were plotted using linear regression analysis (GraphPad Prism) to construct an isobologram, and the two axes of the isobologram were connected at points corresponding to FIC 1.0. The sum of FICs (ΣFIC: FIC of compound 1 + FIC of compound 2 in the combination) at all combinations was used to determine mean ΣFIC, which was used to determine the nature of interactions (ΣFIC 0.5-1.0, \<0.5, and \>1.5 are indicative of additive, synergistic and antagonistic interactions, respectively). Inhibition assay with parasite extracts {#s2.8} --------------------------------------- A synchronized P. falciparum culture with trophozoite/schizont stage parasites (10% parasitemia) was processed for isolation of parasites as described above. The parasite pellet was suspended in 600 µl lysis buffer (10 mM Tris, pH 7.0, 1 mM EDTA, 1 mM PMSF, 1 mM DTT, 1 mM ATP, and 10 µM pepstatin), subjected to 2 cycle of freeze-thaw (in liquid N~2~) and sonication for 3 min (pulses of 9 seconds on/off and 20% amplitude at 4°C; Sonics). The lysate was centrifuged at 13,000g for 15 min at 4°C, the supernatant was transferred to a fresh tube, its protein content was estimated using Bio-Rad protein assay reagent (Bio-Rad), and it was used for inhibition assays. Identical aliquots of the extract (corresponding to 16 µg protein) were added to 100 µl cysteine protease assay buffer (100 mM sodium acetate, pH 5.5, 10 mM DTT, 1 mM EDTA, 1 mM PMSF, 10 µM pepstatin) or proteasome assay buffer (50 mM Tris, 1 mM ATP, 5 mM MgCl~2~, 40 mM KCl, 1 mM DTT, 1 mM PMSF, 10 µM pepstatin, pH 7.5), which contained DMSO (1.25% final) or individual inhibitors (10 µM E64, 1 µM epoxomicin, or 1 µM MG132) or combinations of inhibitors (10 µM E64 + 1 µM epoxomicin, 10 µM E64 + 1 µM MG132, or 1 µM epoxomicin + 1 µM MG132). The reactions were incubated for 10 min at 37°C, substrates (Z-LR-AMC for cysteine protease activity, Suc-LLVY-AMC for chymotrypsin-like proteasome activity, Ac-nLPnLD-AMC for caspase-like proteasome activity, and Ac-RLR-AMC for trypsin-like proteasome activity) were added to the reactions, and protease activities were determined by monitoring substrate hydrolysis for 30 min at 37°C using an Infinite M200 (TECAN) or SpectraMax M5 (Molecular Devices) microplate reader (excitation 355 nm; emission 460 nm). Enzyme activities with Z-LR-AMC and Ac-RLR-AMC were expressed as relative fluorescence units/min (RFU/min), and those with Suc-LLVY-AMC and Ac-nLPnLD-AMC were expressed as total increase in RFU over 30 min. Enzyme activities of inhibitor-containing reactions were compared with those of DMSO-containing reactions, expressed as percent inhibition, and plotted against the inhibitors. Assays with recombinant falcipains {#s2.9} ---------------------------------- For production of recombinant FP2 and FP3, portions of the FP2 and FP3 genes corresponding to the carboxy-terminus regions of the prodomains (FP2, 36 amino acid residues; FP3, 35 amino acid residues) and the entire mature protease domains were PCR amplified from 3D7 gDNA and expressed in bacteria using pRSETA (for FP2) and pQE-30 (for FP3) expression plasmids. Recombinant proteins were purified from isopropyl-1-thio-β-D-galactopyranoside (IPTG) induced bacteria by nickel-nitrilotriacetic acid (Ni-NTA) chromatography under denaturing conditions as described earlier \[[@B15],[@B50]\]. The purified FP2 and FP3 were refolded into active forms as described earlier \[[@B15],[@B50]\], with a modification that involved dialysis of denatured proteins against refolding buffers, and used for inhibition assays. Concentrations of active FP2 and FP3 were determined by active site titration using E64. Briefly, enzymes were incubated with DMSO (1% final) or varying concentrations of E64 in sodium acetate buffer (100 mM sodium acetate, 10 mM DTT, pH 5.5) for 30 min at room temperature, Z-LR-AMC was added (25 µM final) to the reactions, and enzyme activity was determined by monitoring the release of AMC upon substrate hydrolysis over 30 min at 37°C as described above. Enzyme activities as RFU/min for DMSO and inhibitor-containing reactions were plotted against inhibitor concentrations, and analyzed using the ORIGIN program (OriginLab) to determine enzyme concentrations. To determine if FP2 and FP3 are inhibited by proteasome inhibitors, FP2 (5 nM) or FP3 (10 nM) was incubated with DMSO (1% final) or with inhibitors (MG132, epoxomicin, lactacystin, E64, and pepstatin; each at 10 µM) in sodium acetate assay buffer for 30 min at room temperature. Z-LR-AMC was added to the reaction (25 µM final), and enzyme activity was measured by monitoring substrate hydrolysis for 30 min at 37°C as described above. Enzyme activities of inhibitor-containing reactions were compared with those of DMSO-containing reactions, expressed as percent inhibition, and plotted against the inhibitors. To determine association rate constants of inhibitors for FP2 and FP3, enzymes (1 nM FP2 or 2 nM FP3) were added to 200 µl reactions (100 mM sodium acetate, pH 5.5, 10 mM DTT, 25 µM Z-LR-AMC) with DMSO (1% final) or varying concentrations of E64 (at concentration \>10 times the enzyme concentration) or MG132 (2-10 nM), and enzyme activity was measured by monitoring the release of AMC upon substrate hydrolysis for 30 min at 37°C as described above. The activity progress curves (fluorescence vs time) without and with inhibitors were analyzed by non-linear regression analysis (GraphPad software) using the pseudo-first-order equation. y = A\[1 − exp(−k ~obs~ t)\] + B; where y is the fluorescence intensity at time t, A is the amplitude of the reaction, and B is the offset. k ~obs~ vs inhibitor concentration \[I\] was linear. The association rate constant k ~ass~ was determined by linear regression using k ~ass~ = (k ~obs~/\[I\])(1 + \[S\]/K ~m~); where \[S\] is the substrate concentration. Results and Discussion {#s3} ====================== MG132 inhibits P. falciparum development, hemoglobin degradation and the UPS {#s3.1} ------------------------------------------------------------------------------ To determine if MG132 exerts antimalarial activity by inhibition of hemoglobin degradation and/or by inhibiting the UPS, we assessed the effects of inhibitors of falcipain cysteine proteases (E64), the UPS (epoxomicin, lactacystin, and MG132), and plasmepsin aspartic proteases (pepstatin) on P. falciparum erythrocytic development. All these inhibitors blocked parasite development ([Table 1](#tab1){ref-type="table"}), but the inhibited parasites showed different morphologies. As has been previously described, E64 caused enlargement of food vacuoles ([Figure 1](#pone-0073530-g001){ref-type="fig"} \[[@B9]\]), which is indicative of accumulation of undegraded hemoglobin due to inhibition of falcipains. MG132, but not epoxomicin or lactacystin, also caused enlargement of the food vacuole, suggesting that MG132, like E64, inhibited hemoglobin degradation. However, MG132-treated parasites were much smaller than E64-treated parasites. Pepstatin, an inhibitor of the food vacuole-resident plasmepsins, resulted in pyknotic parasites without swollen food vacuoles. This result is consistent with previous studies demonstrating normal hemoglobin catabolism in plasmepsin knockout parasites \[[@B51],[@B52]\]. ###### Inhibition of intraerythrocytic parasite development. Inhibitors IC~50~ ^a^ (µM) ---------------- --------------------- E64 7.6 ± 1.22 Epoxomicin 0.0077 ± 0.00027 Lactacystin 0.276 ± 0.038 MG132^b^ 0.0476 ± 0.0058 Pepstatin 74.3 ± 8.8 ^a^ Mean IC~50~ with standard deviation from three independent experiments, each in duplicate. ^b^ The IC~50~ for PBMCs was 10.8±0.04 µM. ![Morphologies of inhibitor-treated parasites.\ Parasites were cultured without (control) or with indicated inhibitors (21.7 µM E64, 0.024 µM epoxomicin, 0.812 µM lactacystin, 0.133 µM MG132, and 220.6 µM pepstatin; concentrations are nearly 3 times the IC~50~) for 48 hours, and the morphologies of parasites on Giemsa-stained smears were evaluated at indicated time points. Note that both E64- and MG132-treated parasites have enlarged food vacuoles occupying almost the entire parasite, whereas parasites treated with epoxomicin, lactacystin, and pepstatin are pyknotic.](pone.0073530.g001){#pone-0073530-g001} The 50% cytotoxic concentration of MG132 for PBMCs was 10.8 µM ([Table 1](#tab1){ref-type="table"}), which is remarkably higher than its IC~50~ for inhibition of parasite growth (0.0476 µM), and indicates its selective toxicity for malaria parasites. The previously reported 50% cytotoxic concentration of MG132 for PMBCs was somewhat higher (20 µM), but was based on a shorter (24 hour) incubation with the inhibitor \[[@B43]\]. To determine if MG132-treated parasites had accumulated undegraded hemoglobin, total lysates of control and inhibitor-treated parasites were analyzed by SDS-PAGE. Both E64- and MG132-treated parasites, but not controls and those treated with epoxomicin, showed significant accumulation of undegraded hemoglobin ([Figure 2A](#pone-0073530-g002){ref-type="fig"}), confirming inhibition of hemoglobin degradation by MG132. Immunoblots with anti-ubiquitin antibodies showed a high molecular weight signal, which was markedly more intense in lanes containing MG132- and epoxomicin-treated parasites than lanes with control and E64-treated parasites ([Figure 2B](#pone-0073530-g002){ref-type="fig"}), indicating accumulation of ubiquitinated proteins upon inhibition of the UPS. Thus, unlike the other inhibitors tested, MG132 appears to inhibit both UPS and hemoglobin degradation, and both of these activities likely contribute to its action against asexual P. falciparum erythrocytic development. ![Accumulation of undegraded hemoglobin and ubiquitinated proteins in inhibitor-treated parasites.\ Cultures containing equal number of early trophozoite stage parasites were grown in the presence of 0.1% DMSO (control) or indicated inhibitors (21.7 µM E64, 0.024 µM epoxomicin, and 0.133 µM MG132; all at concentrations nearly 3 times the IC~50~) for 10 hours. Parasites were lysed and equal amounts of supernatants were used to assess accumulation of undegraded hemoglobin (A) and ubiquitinated proteins (B) as described in the Materials and Methods section. A. Coomassie-stained SDS-PAGE gel, showing significantly more amount of undegraded hemoglobin (marked with arrow) in parasites treated with E64 and MG132 than control and epoxomicin-treated parasites. B. Western blot using anti-ubiquitin antibodies showed markedly more intense high molecular weight signal in the MG132 and epoxomicin samples than in control and E64 samples, which is indicative of accumulation of ubiquitinated proteins in the MG132 and epoxomicin samples. The experiment was repeated twice, samples from each experiment were analyzed three times for A and two times for B, and the results were reproducible. M, molecular weight in kD; Hb, hemoglobin.](pone.0073530.g002){#pone-0073530-g002} MG132 is effective against all asexual erythrocytic stages and irreversibly blocks parasite development {#s3.2} ------------------------------------------------------------------------------------------------------- To determine if MG132 is effective against all erythrocytic stages, parasites at different stages of development (ring, T0 and T12; early trophozoite, T24; late trophozoite, T36) were treated with inhibitors (E64, epoxomicin, and MG132), and the number of newly formed rings was counted at the end of the development cycle (48 hours) and 12 hours after the end of the cycle (60 hour). The control parasites developed normally and formed new rings upon completion of the development cycle ([Table 2](#tab2){ref-type="table"}). Treatment with MG132 and epoxomicin at ring and early trophozoite stages completely blocked the development, and that with E64 resulted in a very small number of new rings ([Table 2](#tab2){ref-type="table"}). Treatment at the late trophozoite stage also had significant inhibitory effect, as only 3-11% of the total parasite population was of new rings ([Table 2](#tab2){ref-type="table"}). The number of rings in the control increased from 40% at 48 hour time point to 80% at 60 hour time point; the inhibitor-treated parasites had 0-11% rings at 48 hour time point, and this number almost remained the same (0-12%) at 60 hour time point regardless of the stage when inhibitors were added, which suggests that inhibitors blocked maturation of parasites. Both E64 and MG132, but not epoxomicin, caused food vacuole enlargement in the majority (88%) of parasites regardless of the treatment time point. Thus, MG132 inhibits development of all asexual erythrocytic stages. ###### Stage-specific effects of inhibitors. Post synchronization stage at which treatment started % Rings (R) at 48 hours and 60 hours post-synchronization in cultures containing DMSO (control) or inhibitors ----------------------------------------------------------- ------------------------------------------------------------------------------------------------------------------- ----------------- ----------------- ----------------- 48/60 hours 48/60 hours 48/60 hours 48/60 hours 0 Hour 41 (±15)/80 (±12) 5 (±3)/5 (±0) 0/0 0/0 12 Hour \- 6 (±6)/5 (±2) 0/0 0/0 24 Hour \- 6 (±6)/6 (±1) 0/0 0/0 36 Hour \- 11 (±3)/12 (±0) 3 (±3)/10 (±0) 6 (±6)/0 Ring stage parasites were treated with DMSO (control) or inhibitors (21.7 µM E64, 0.024 µM epoxomicin, and 0.133 µM MG132; all at concentrations nearly 3 times the IC~50~) at different stages of development (ring, T0 and T12; early trophozoite, T24; late trophozoite, T36), and the number of rings was counted at the end (48 hours) and 12 hours after the end (60 hours) of the development cycle. At least 200 parasite-infected cells were observed, and the table shows the percentage of rings for control and the inhibitor-treated cultures. The data are mean with standard deviation from three (for 48 hour) and two independent experiments (60 hour) done in duplicates. ^a^ DMSO was added at the start of the experiment (T0) only. To test if the inhibition of parasite development by MG132 is permanent we performed inhibitor washout experiments in which parasites were cultured for one cycle in the presence of DMSO (control) or chloroquine (an irreversible inhibitor) or inhibitors (MG132, E64, and epoxomicin), and then without any treatment for two cycles. In SYBR Green-based assay, which is a measure of overall parasite growth, control parasites showed almost 3.5-6 times higher fluorescence than chloroquine-treated parasites in all three cycles ([Figure 3](#pone-0073530-g003){ref-type="fig"}), which indicated robust growth in the control culture. The E64-treated parasites showed similar to 2.5 times higher fluorescence than chloroquine-treated parasites, particularly in cycle 1, which suggested partial growth during treatment and recovery of parasites after E64 was washed out. The fluorescence values of MG132- and epoxomicin-treated parasites were similar to that of chloroquine-treated parasites at the end of all three cycles, which suggested that both MG132 and epoxomicin irreversibly blocked parasite development in cycle 1. Giemsa-stained smears of the control culture showed 3.5-6 fold increase in parasitemia (10 to 18% parasitemia) over the starting parasitemia in all three cycles, which is consistent with the results of SYBR Green assay. Parasitemia did not increase in cultures containing the inhibitors and chloroquine at the end of cycle 1. Dark-stained dots (cycle 2) or no parasites (cycle 3) were observed in MG132- and epoxomicin-treated cultures after the inhibitors had been washed out, indicating that MG132 and epoxomicin, like chloroquine, irreversibly block parasite development. On the other hand, washing out E64 led to partial recovery of a fraction of parasites in subsequent cycles (^≈^1% parasitemia). Thus, both SYBR Green assay and the assessment of Giemsa-stained parasite smears indicate that MG132 irreversibly blocks parasite development. ![Effect of inhibitor washout on parasite growth.\ Ring stage parasites were cultured in the presence of DMSO (control) or chloroquine or indicated inhibitors (21.7 µM E64, 0.024 µM epoxomicin, 0.133 µM MG132; concentrations are nearly 3 times the IC~50~) for one cycle, and then without any treatment for next two cycles as described in the Materials and Methods section. Parasite growth was measured at the end of each cycle using the SYBR Green-1 dye. The results with standard deviation error bars from three independent experiments, each in triplicate, are shown as arbitrary fluorescence units of the dye. Similar fluorescence values of parasites treated with MG132, epoxomicin, and chloroquine indicate that MG132 and epoxomicin, like chloroquine, irreversible block parasite development.](pone.0073530.g003){#pone-0073530-g003} MG132 inhibits the UPS and cysteine protease activities in parasites {#s3.3} -------------------------------------------------------------------- To further test the predicted actions of MG132, we determined whether cysteine protease and proteasome activities of a total soluble parasite extract are inhibited by MG132. FP2 and FP3 contribute almost exclusively to the acidic cysteine protease activity of P. falciparum erythrocytic stages; this is routinely measured by monitoring hydrolysis of Z-LR-AMC and is blocked by the cysteine protease inhibitor E64. Malaria parasites appear to contain a typical 26S proteasome, but the proteasome-associated activities have not been characterized. A typical 26S proteasome possesses three types of activities \[[@B33]--[@B35]\]: peptidyl-glutamyl peptide hydrolyzing (PGPH) activity that cleaves after acidic residues; trypsin-like activity that cleaves after basic residues; and chymotrypsin-like activity that cleaves after large hydrophobic residues. These three activities are routinely measured using fluorogenic peptide substrates (Z-nLPnLD-AMC for PGPH, Ac-RLR-AMC for trypsin, and Suc-LLVY-AMC for chymotrypsin) \[[@B53]\]. The chymotrypsin activity is inhibited by the majority of proteasome inhibitors, including MG132 and epoxomicin \[[@B36]--[@B39]\]. Control inhibitors of other proteases (EDTA, metalloproteases; PMSF, serine proteases; and pepstatin, aspartic proteases) were included in all reactions. E64 and MG132 completely inhibited Z-LR-AMC hydrolyzing activity of the extract, suggesting that MG132, like E64, inhibits falcipains ([Figure 4A](#pone-0073530-g004){ref-type="fig"}). Epoxomicin alone did not inhibit Z-LR-AMC hydrolyzing activity of the extract, but it completely inhibited the same activity when combined with E64 or MG132, suggesting that it does not inhibit falcipains. ![Inhibition of cysteine protease and proteasome activities by MG132.\ A. Inhibition of total soluble extracts of P. falciparum. Extracts of trophozoite/schizont stage parasites were prepared by freeze-thaw lysis and ultrasonic treatment of cells. Identical aliquots were treated with 1.25% DMSO (control), 10 µM E64, 1 µM epoxomicin (Epox), 1 µM MG132, or the indicated inhibitor combinations (10 µM E64 + 1 µM epoxomicin, 10 µM E64 + 1 µM MG132, or 1 µM epoxomicin + 1 µM MG132) for 10 min at 37°C, and protease activities were determined by monitoring hydrolysis of fluorogenic peptide substrates for 30 min at 37°C as described in Materials and Methods. The substrates used were Z-LR-AMC (LR) for cysteine protease activity, Suc-LLVY-AMC (LLVY) for chymotrypsin-like proteasome activity, and Ac-RLR-AMC (RLR) for trypsin-like proteasome activity. Activities of inhibitor-containing reactions were compared with those of controls and expressed as percent inhibition. The results shown are means of two independent experiments, each performed in duplicate. B. Inhibition of recombinant falcipains. Recombinant FP2 (5 nM) or FP3 (10 nM) was incubated with 1% DMSO (control) or indicated inhibitors (all 10 µM) in sodium acetate assay buffer for 30 min at room temperature. Z-LR-AMC (25 µM) was added to the reaction, and enzyme activity was measured by monitoring substrate hydrolysis for 30 min at 37°C. Enzyme activities of inhibitor-containing reactions were compared with those of controls and expressed as the percent inhibition. The results shown are means of three independent experiments, each performed in triplicate.](pone.0073530.g004){#pone-0073530-g004} The hydrolysis of the chymotrypsin substrate Suc-LLVY-AMC was inhibited by E64, MG132, and epoxomicin to varying degrees ([Figure 4A](#pone-0073530-g004){ref-type="fig"}). As E64 and epoxomicin specifically target falcipains and UPS, respectively, it seems that both falcipains and the UPS contribute to the total Suc-LLVY-AMC hydrolysing activity. MG132 alone was as effective (83.6%) as E64-epoxomicin combination (84.3%) in inhibiting the Z-LR-AMC hydrolyzing activity of the extract, suggesting that MG132 has both cysteine protease and proteasome inhibitory activities. This dual-inhibitory property of MG132 also explains comparable inhibition of Suc-LLVY-AMC hydrolysis by MG132 alone and together with E64 (83%) or epoxomicin (88%). The parasite extract showed negligible hydrolysis of the PGPH substrate Z-nLPnLD-AMC (1.75 RFU/min), which may be due to different substrate preference of the Plasmodium proteasome. All three inhibitors marginally inhibited Z-nLPnLD-AMC hydrolyzing activity, and the inhibition levels were not clearly distinguishable, hence the data is excluded from [Figure 4A](#pone-0073530-g004){ref-type="fig"}. Hydrolysis of the trypsin substrate Ac-RLR-AMC was almost completely inhibited by E64 and MG132, and only slightly inhibited by epoxomicin, suggesting that falcipains primarily contributed to the hydrolysis of Ac-RLR-AMC. As in the case of Z-LR-AMC hydrolysis, combinations of E64, MG132, and epoxomicin were as effective as E64 or MG132 alone. Complete inhibition of Ac-RLR-AMC hydrolysing activity by MG132 alone, as by the specific cysteine protease inhibitor, further supports the falcipain-inhibitory property of MG132. The hydrolysis of Ac-RLR-AMC by falcipains was not surprising, as these and other papain-family enzymes readily hydrolyze substrates with Arg or Lys at the P1 position \[[@B18]\]; falcipains prefer Leu at the P2 position and can also degrade peptide substrates containing P3 Arg \[[@B19]\]. Taken together, the demonstration of inhibition of both cysteine protease and UPS activities by MG132 and the accumulation of undegraded hemoglobin and ubiquitinated proteins in parasites after treatment with this compound are all consistent with the conclusion that MG132 blocks parasite development by inhibiting hemoglobin degradation and the UPS. MG132 is a potent falcipain inhibitor {#s3.4} ------------------------------------- As MG132 caused accumulation of undegraded hemoglobin in parasites and inhibited cysteine protease activity of the parasite extract, we assessed it for inhibition of recombinant FP2 and FP3. MG132 and E64 inhibited hydrolysis of Z-LR-AMC by both enzymes ([Figure 4B](#pone-0073530-g004){ref-type="fig"}), confirming that MG132 is a falcipain inhibitor. Identical concentrations of epoxomicin and pepstatin did not inhibit, and of lactacystin marginally inhibited the enzymes. A kinetic analysis revealed that, compared to E64, MG132 is 18 and 100 times more potent in the inhibition of FP2 and FP3, respectively ([Table 3](#tab3){ref-type="table"}). Furthermore, MG132 was twice as effective against FP3 as FP2, which is of importance for drug development efforts, because only FP3 seems to be essential for erythrocytic development of P. falciparum \[[@B7],[@B12]\]. ###### Association rate constants (M^-1^. S^-\ 1^) for recombinant falcipains^a^. Inhibitors FP2 FP3 ---------------- ------------------ ------------------ E64 10,260 ± 714 4,090 ± 277 MG132 188,570 ± 24,840 412,460 ± 35,080 ^a^ Means ± standard deviations for at least three independent experiments, each in duplicate. Previous studies have demonstrated that loss of FP2 in FP2 knockout parasites renders them almost 2.5 times more sensitive than wild type parasites to E64 \[[@B7],[@B12]\]. We evaluated FP2 knockout parasites for sensitivity to MG132. The FP2 knockout parasite was as susceptible as the wild type parasite to the control drug chloroquine (IC~50~: FP2KO, 5.3±1.5 nM; wild type, 4.5±0.3 nM), but almost twice as susceptible to MG132 (IC~50~: FP2KO, 15.5±1.4 nM; wild type, 26.6±4.1 nM), which further supports inhibition of falcipains by MG132. Joint inhibition of falcipains and UPS has an additive antiparasitic effect {#s3.5} --------------------------------------------------------------------------- A comparison of the IC~50s~ of MG132 and E64 for parasite inhibition ([Table 1](#tab1){ref-type="table"}) indicated that MG132 is 160 times more potent than E64, which could be explained by superior potency for fa1cipains, improved cell permeability/intracellular accumulation, and simultaneous inhibition of both falcipains and UPS by MG132. Malaria parasite genomes encode 115--137 putative proteases of all five classes (aspartic, cysteine, metallo, serine, and threonine), and MG132 may target other proteases in addition to falcipains and UPS \[[@B54],[@B55]\]. To further explore effects on the two targets, we evaluated antiparasitic effects of inhibitors of the proteasome (epoxomicin, lactacystin, and MG132), falcipains (E64), and plasmepsins (pepstatin). Combinations of proteasome-specific inhibitors (epoxomicin-lactacystin) showed additive effects, which was expected as both the inhibitors target the same enzyme ([Figure 5](#pone-0073530-g005){ref-type="fig"}). Combinations of E64 with epoxomicin, lactacystin or MG132 also had additive effects ([Figure 5](#pone-0073530-g005){ref-type="fig"}). Effects were more remarkable with pepstatin, as combination with MG132 showed synergy, with E64 showed a trend towards synergy, and with epoxomicin showed antagonism ([Figure 6](#pone-0073530-g006){ref-type="fig"}). Synergistic antiparasitic effects of MG132-pepstatin and E64-pepstatin agree with proposed joint roles of falcipains and plasmepsins in hemoglobin degradation, and were consistent with a previous result showing synergism of E64 and pepstatin \[[@B56]\]. The antagonistic effect of pepstatin-epoxomicin is unexplained. One explanation could be the accumulation of plasmepsins, which are major food vacuole aspartic proteases, in the presence of epoxomicin, as plasmepsin II has been shown to be a target for ubiquitin-proteasome-mediated degradation \[[@B57]\]. The accumulation of plasmepsins would decrease susceptibility of parasites to pepstatin, potentially mediating the antagonistic effect of the pepstatin-epoxomicin combination. The additive to slightly synergistic anti-parasitic effect of the UPS and falcipain inhibitors suggests therapeutic benefits of either combined chemotherapy based on the UPS and falcipain targets or a single agent, such as MG132, that inhibits both targets. ![Antimalarial effects of combinations of proteasome and falcipain inhibitors.\ Parasites were cultured in the presence of varied combinations of the indicated inhibitor, and the 50% inhibitory concentration of each combination was determined to calculate fractional inhibitory concentrations (FIC). FICs from three independent experiments, each carried out in duplicate were used to construct isobolograms as described in Materials and Methods section. Mean FICs (ΣFIC) 0.5-1.0, \<0.5, and \>1.5 are indicative of additive, synergistic and antagonistic interactions, respectively. A. The isobolograms indicate additive interactions for the indicated combinations.](pone.0073530.g005){#pone-0073530-g005} ![See figure 5 for legend.\ The isobolograms indicate additive, synergistic, and antagonistic antiparasitic effects of E64-pepstatin, MG132-pepstatin, and epoxomycin-pepstatin combinations, respectively.](pone.0073530.g006){#pone-0073530-g006} MG132 has also been shown to inhibit calpains, with IC~50~ values of 1.2 µM for purified and \>100 µM for intracellular calpains \[[@B45]\]. However, as MG132 inhibits parasite growth at much lower concentrations (0.0476 µM), it is unlikely that inhibition of parasite and/or host calpains by MG132 contributes to its antimalarial effects. Inhibition of the UPS is being actively pursued as a strategy to treat cancer; bortezomib is a proteasome inhibitor approved for treating multiple myeloma. Bortezomib has also been shown to kill P. falciparum intraerythrocytic stages with an IC~50~ concentration 2-4 times lower than levels achieved at recommended doses in human plasma \[[@B1]\], supporting consideration of proteasome inhibitors as antimalarials. MG132 is an inexpensive and potent inhibitor of the UPS, and for these reasons it has been widely studied as a proteasome inhibitor in a number of cell types, including several protozoan parasites. The reported 50% cytotoxic concentrations of MG132 for mammalian cell lines are in the range of 2.5-21 µM depending on the cell type and treatment duration \[[@B40]--[@B43]\]. In our studies MG132 was over 200 times more potent for inhibition of development of malaria parasites (IC~50~ 0.0476 µM) than for human PBMCs (10.8 µM), indicating that it is selectively toxic to the parasite. This selective toxicity could be due to the simultaneous inhibition of the two vital proteolytic systems of the parasite, the UPS and the falcipains, establishing it as a dual-target inhibitor of malaria parasites. MG132 may thus be considered a lead compound to design potent antimalarials acting against two parasite proteolytic systems. The authors thank Dr. V. Vijayalakshmi, National Institute of Nutrition, India, for providing access to a fluorescence microplate reader. We thank Dr. Sunit Kumar Singh and Ms. Ruhi Verma for advice on isolation and culture of PBMCs. [^1]: Competing Interests:The authors have declared that no competing interests exist. [^2]: Conceived and designed the experiments: RP A PJR PSS. Performed the experiments: RP A VKK JL NS RN. Analyzed the data: RP A PJR PSS. Wrote the manuscript: RP A PJR PSS.	{ "pile_set_name": "PubMed Central" }
Pros and cons of automatic milking in Europe. During the last several decades, new milking management systems have been introduced, of which development of automatic milking (AM) systems is a significant step forward. In Europe, AM has become an established management system and has shown to be much more than milking management. Factors such as milking, milk quality, feeding, cow traffic, grazing, and animal behavior are essential elements of AM. This system offers possibilities for more frequent milking and can be adapted to lactational stage. Increased milk yield with AM has been observed, but lack of increased production has also been reported from the field, probably due to less attention paid to the total management system. The AM system provides consistent milking routines, with those for teat stimulation and feeding during milking giving an adequate oxytocin release and milk ejection. Initially, reduced milk quality, such as increased FFA, total bacteria count, and somatic cell count (SCC), was observed. Increased FFA could be due to increased milking frequency or handling of the milk, although this has not yet been determined. The elevated total bacteria count was probably due to mismanagement because later studies indicated that teat cleaning in AM is sufficient to reduce spores and dirt on the teats. Significant positive effects on udder health and teat treatment were observed in some studies, possibly as an effect of quarter milking, a procedure whereby an individual teat cup is detached when milk flow is below the preset level for detachment. Well-functioning cow traffic is a prerequisite for successful AM system performance to obtain an optimal number of visits to the feeding area and the milking parlor for all cows. Technical stoppages in the AM system (i.e., the milking unit) increased milk SCC, and the variation and length of the milking interval seem to contribute to elevated SCC. Grazing is a common management routine in many countries. Different ways to motivate the cows to visit the milking parlor, such as shorter distance between barn and pasture, supplement feeding, access to water, and use of acoustic signals, have been tested. It was concluded that use of AM and grazing systems together is possible as long as the distance from the milking parlor to pasture is short. With proper management routines, it is possible to achieve a production level and animal well-being in AM systems that are at least as good as in conventional milking systems.	{ "pile_set_name": "PubMed Abstracts" }
Main menu Post navigation Matchmaking Before you get me wrong, I have not become a shadchan overnight. The matchmaking I am referring to is the art of associating French and Swedish students for our exchange. We have had an exchange with a Swedish high school for over ten years now and it usually works fine. I tend to think that pairing the students wisely is a major key to a successful exchange but this is not an easy task. Last week I received the last Swedish files sent by our collegues in Boras and started matching the students according to the criteria I have set up with years. – Same sort of backgrounds. I reckon a ten day-trip is not the perfect time for teenagers to discover completely different lifestyles. The kids are apprehensive enough: they are going to a country they don’t know and will have to speak a foreign language; this in itself is stressful enough. – Similar tastes. When the students fill in the forms we give them, they are requested to write about their extra-curricular activities and I try to find at least one common hobby. There again I hope that a football player or a pianist will relax more easily if they attend a match or a concert during the exchange, or even just a training session. It is something they can relate to and they will find it interesting to share and compare. – Same size families. This is more difficult and does not always work but I gather that an only child may find it more difficult to adapt in a large household where he/she will not get the attention they are used to. I have found that only children tend to get homesick more than other kids. – Juggling with imperatives. Sometimes the obvious matching is impossible because one student is allergic to cats while the seemingly perfect counterpart has two cats. There are also the vegetarians, the parents who insist their child be in a smoke-free environment and this year the daughter of Jehovah Witnesses. – Flair, unless you prefer to call it luck. The less rational criterion I admit but a necessary ingredient. Feel free to comment, add your own criteria or criticize. It is always interesting to get different perspectives. Share this: Like this: Related 4 thoughts on “Matchmaking” The idea of living with someone else’s family for a lengthy period of time sounds stressful to me. I guess ten days does not sound that long, but I once lived with a family in Israel for a week, and I wasn’t that comfortable. Then I stayed with my cousins for a week, and I LOVED that experience. I think teens really don’t know themselves what are their comfort levels or boundaries. I remember hearing about someone who stayed with a family in Washington DC for a weekend. The family complained she ate nothing the whole weekend. Later they found an empty box of crackers in her room. Talk about being uncomfortable in a different setting! Leora: Even though the kids choose to take part in the exchange, I try to remember that living with stangers is not always easy. A few years ago, the host family did not want to keep a student; they never told us why. Last year two girls fell out and so we had to find a new family for the Swedish girl. Mrs.S.: We take a group of 20-25 students and three teachers go with them. It is difficult to match them up. Hopefully all the students have written a lot on the paper so you have all the information. Years ago I was working in USA and I am very happy that I wrote a lot on my paper so I got the perfect summer job! Hope it all will work out – when my children are older I will send them to you…	{ "pile_set_name": "Pile-CC" }
Q: C# Setup Issue. private void ReadText(string text) { string add = "http://translate.google.com/translate_tts?tl=ta&q="; add += HttpUtility.UrlEncode(text, Encoding.GetEncoding("utf-8")); try { using (var client = new WebClient()) { try { client.Headers[HttpRequestHeader.UserAgent] = "Mozilla/5.0 (Windows NT 6.1; WOW64; rv:7.0.1) Gecko/20100101 Firefox/7.0.1"; } catch { MessageBox.Show("Intenet error"); } try { client.DownloadFile(add, "mp3CriationTest.mp3"); } catch { MessageBox.Show("NAudio Error"); } } } catch (WebException e3) { MessageBox.Show("ReadText error: " + e3); } } I am using nAudio to do google text-to-speech(tts). This code working much better for me when I run on visual studio debug(F5). But When I created setup file I ll get the exception message "NAudio Error". So its obvious there is a problem on saving/creating "mp3CriationTest.mp3" on Application folder of my setup. But Creating "mp3CriationTest.mp3" on debug folder is works fine when I use Visual Studio debug(F5). Can anyone know what was the issue? Plaese help. A: You cannot write directly into the program files folder unless you have administrative privileges. You can save the file to the application data folder (environment specified); like string fileName = Environment.GetFolderPath(Environment.SpecialFolder.ApplicationData) + "\\" + "mp3test.mp3"; client.DownloadFile(add, fileName);	{ "pile_set_name": "StackExchange" }
Mice heterozygous for mutation in Atm, the gene involved in ataxia-telangiectasia, have heightened susceptibility to cancer. Ataxia-telangiectasia is characterized by radiosensitivity, genome instability and predisposition to cancer. Heterozygous carriers of ATM, the gene defective in ataxia-telangiectasia, have a higher than normal risk of developing breast and other cancers. We demonstrate here that Atm 'knock-in' (Atm-Delta SRI) heterozygous mice harboring an in-frame deletion corresponding to the human 7636del9 mutation show an increased susceptibility to developing tumors. In contrast, no tumors are observed in Atm knockout (Atm(+/-)) heterozygous mice. In parallel, we report the appearance of tumors in 6 humans from 12 families who are heterozygous for the 7636del9 mutation. Expression of ATM cDNA containing the 7636del9 mutation had a dominant-negative effect in control cells, inhibiting radiation-induced ATM kinase activity in vivo and in vitro. This reduces the survival of these cells after radiation exposure and enhances the level of radiation-induced chromosomal aberrations. These results show for the first time that mouse carriers of a mutated Atm that are capable of expressing Atm have a higher risk of cancer. This finding provides further support for cancer predisposition in human ataxia-telangiectasia carriers.	{ "pile_set_name": "PubMed Abstracts" }
Vision 2030 Significant Progress Of The Kingdom Of Saudi Arabia On All 17 SDGs Many of Saudi Vision 2030 initiatives are oriented towards efforts to achieve the Sustainable Development Goals (SDGs). The Kingdom, as part of its wider effort to develop in a manner that is aligned with long-term global aims, participated in the United Nation’s High-level Political Forum (HLPF) on Sustainable Development which took place in New York, from July 9 to July 18 2018. Goal 17. Strengthen the means of implementation and revitalize the Global Partnership for Sustainable Development that will be considered each year. As part of the self-assessment process, the Kingdom of Saudi Arabia participated in the VNR’s- Voluntary National Review, to control its own progress towards SDGs. The Kingdom’s delegation was led by the Ministry of Economy and Planning and was comprised of various public, as well as, private entities and NGOs, reflecting Saudi Arabia’s active collaboration with all stakeholders to achieve the SDGs by the year 2030. The Kingdom is making progressive steps towards all 17 SDGs, 6 in particular stand out: clean water and sanitation, affordable and clean energy, sustainable cities and communities, responsible consumption and production, life on land, and partnerships for the goals.	{ "pile_set_name": "Pile-CC" }
Books by Derek Maul Wednesday, December 19, 2012 God has not been expelled from school! (Note: The views expressed in this blog are entirely my own. They are fluid, subject to change over time, and quite possibly entirely wrong. I tend to disagree with myself on a regular basis. However, at this time of writing, I suspect that I am right. Feel free to build on my opinion, disregard it, or disagree; just be polite in the process – DEREK) have to be honest, I’ve started and stopped work on today’s post probably ten times already. I wanted to write something to distance myself from the offensive parade of strident religious voices that have been spewing junk-theology, judgment, confusion, and lies about God – yet again – but then I hit “delete,” unable to bring myself to give the subject the time of day. I’m in a quandary, so I guess I’ll just write my way through it and let the chips fall where they may. GOD BANNED FROM SCHOOL? This is a response to the sentiments expressed by conservative “Christian” radio host Bryan Fischer (American Family Association) and others that,“God could have protected the victims of this massacre (Newtown), but didn’t because God is not going to go where he is not wanted….” But, I want us to be clear on this, GOD HAS NEVER BEEN FORCED OUT OF THE PUBLIC SCHOOLS. The assertion God has been effectively expelled from school is a lie, a distortion that attempts to play on people’s fears and emotions in the wake of another horrifying tragedy. Don’t believe it; stop passing on those ridiculous emails; and please don’t buy the lie that God is that calloused, or that easily manipulated. TIPPING POINT: So I think I’ve reached a tipping point when it comes to holding hands and singing “Kum-bah-ya” around the Christian campfire. The bottom line, for me, is this growing realization that, sometimes, I’m not sure we’re even talking about the same God anymore. You see, I honestly don’t recognize the religion these people are pushing. I am a disciple of Jesus; I call myself a “Jesus-Follower,” and I invest the majority of my creativity and my writing life to further my commitment to be what the 1st Century believers referred to as “A Follower of The Way.” It is my joy to talk about Jesus and to invite others to follow him too, and it’s my prayer that these posts contribute something to your journey – as a challenge, as an encouragement, or as an inspiration. TIME TO DRAW THE LINE: If I were to be classified under any resource heading, I’d like it to be “Derek Maul: Contemporary Christian Thinker.” So today, after years of thinking, conversation, and writing in this area, it’s time to say I believe there’s a clear distinction between “Following The Way of Jesus” and the fundamentalist hard-line religion espoused by the folk who like to leverage tragic events (such as hurricanes, earthquakes, and the Newtown, Connecticut school shootings) by blaming them on people who disagree with their narrow interpretations of scripture. I don’t know the God they’re talking about. And I think it’s important that those who are curious about becoming followers of Jesus, or who want to understand more about this “Life-Charged Life,” are clear that I’m not even remotely on the same page. Follow Jesus TRY JESUS: Jesus’ invitation is to “Love the Lord your God with all your heart and with all your soul and with all your mind;” and to, “Love your neighbor as yourself.” Jesus said everything else that’s important “hangs on these two commandments” (Matthew 22:36-40). And Jesus makes this promise, “Surely I am with you always, to the very end of the age” (Matthew 28). That is so true; it’s true in my experience, and I know it’s true in our public schools. No comments: The Life-Charged Life (This blog's home) About Me Life is good. It's about living in partnership with my wife, Rebekah, about serving God in the context of our church home, about being the parent of two amazing children, and of both honing and using my particular gifts in order to make this world a better place.	{ "pile_set_name": "Pile-CC" }
Sign wars are omnipresent Regarding Susan Wessels’ letter to the editor, “Luther signs took Democrats’ place,” really nothing can be done about overzealous volunteers if, in fact, this really happened — which I doubt. This is an old Democrat trick and probably a falsehood. They can’t argue on issues, so they smear with lies. As the fiscal agent for N.H. state rep candidate Val Ogden (Hillsborough District 26), I can certainly tell you about missing signs. Ten Val Ogden signs went missing in Mason over a period of three weeks. I did not replace them yet, but, believe me, I will. Others are still in place. However, in two of the Mason locations, five Democrat-candidate signs replaced Val’s signs; a similar pattern? I’d say so.	{ "pile_set_name": "Pile-CC" }
On October 11, 2016, the U.S. Supreme Court is scheduled to hear oral arguments in the long-running Apple-Samsung litigation. The issue is whether Apple, by virtue of having its design patents infringed by Samsung, is entitled to all of Samsung’s profits made from the infringing phones (regardless of how much that design contributed to the value of the phone). This case—in which EFF submitted an amicus brief arguing the award of Samsung’s total profit is improper—is important for many reasons. But one reason stands out: it is trivially easy to get a design patent on trivial designs and, unless the Supreme Court changes the law, that can lead to anything-but-trivial awards in court. This month’s stupid patent, a design patent, shows just how broken the current system of design patents is. Design patents, unlike the utility patents we usually feature, consist only of a single claim followed by pictures. It is generally the pictures that inform the public as to what is claimed. Importantly, in a design patent only the features drawn in solid lines are claimed. Anything in dotted lines is generally not part of the claim. U.S. Patent D767,583, issued on September 27, 2016, is a patent on a design for a “display screen portion with graphical user interface.” Here, the claim is to “the ornamental design for a display screen portion with graphical user interface, as shown and described.” As most design patent owners do, the patent also makes clear that “the broken line showing of the display screen in the figure forms no part of the claimed design.” Below is the sole picture from the patent showing the patented design: The only thing claimed in this design patent are the three rectangles at the top and the square beneath them. This patent is both remarkably trivial and remarkably easy to be accused of infringing. Someone who arranges three rectangles in a row with a square underneath in the way shown in the image is potentially infringing this patent. (The test for whether a design patent is infringed is described in a case called Egyptian Goddess, and is based on what an “ordinary observer” thinks and often involves a comparison to the prior art.) For example, here is an excerpt from the USPTO’s home page, showing three rectangles and something that looks close to a square beneath it: To be clear, this patent would likely not be infringed if someone arranged three rectangles and a square in a different way (say, if the rectangles were arranged vertically instead of horizontally), and the USPTO itself may not infringe as the prior art would likely narrow this patent significantly. But even the possibility of a finding of infringement may be enough to cause concern for many people who may be accused of infringing a design patent. That’s because under current law, if someone is found to infringe a design patent, the patent owner can argue that it is entitled to all of the profits from that website. The Supreme Court has a chance to fix this last issue in the upcoming Apple-Samsung decision. But that won’t change the fact that the Patent Office still issues patents on trivial designs at an alarming rate. This latest patent is just another in a long line of questionable patents.	{ "pile_set_name": "OpenWebText2" }
Researchers Reveal Details Of Printer Tracking Dots, Develop Free Software To Defeat It from the whistleblowers-of-the-world,-rejoice,-but-still-be-careful dept As Techdirt has reported previously in the case of Reality Leigh Winner, most modern color laser printers place tiny yellow tracking dots on every page printed -- what Wikipedia calls "printer steganography". The Electronic Frontier Foundation (EFF) first started warning about this sneaky form of surveillance back in 2005. It published a list of printers and whether it was known that they used tracking dots. In 2017, the EFF stopped updating the list, and wrote: It appears likely that all recent commercial color laser printers print some kind of forensic tracking codes, not necessarily using yellow dots. This is true whether or not those codes are visible to the eye and whether or not the printer models are listed here. This also includes the printers that are listed here as not producing yellow dots. Despite the EFF's early work in exposing the practice, there has been limited information available about the various tracking systems. Two German researchers at the Technical University in Dresden, Timo Richter and Stephan Escher, have now greatly extended our knowledge about the yellow dot code (via Netzpolitik.org). As the published paper on the work explains, the researchers looked at 1286 printed pages from 141 printers, produced by 18 different manufacturers. They discovered four different encoding systems, including one that was hitherto unknown. The yellow dots formed grids with 48, 64, 69 or 98 points; using the grid to encode binary data, the hidden information was repeated multiple times across the printed page. In all cases the researchers were able to extract the manufacturer's name, the model's serial number, and for some printers the date and time of printing too. It's obviously good to have all this new information about tracking dots, but arguably even more important is a software tool that the researchers have written, and made freely available. It can be used to obfuscate tracking information that a printer places in one of the four grid patterns, thus ensuring that the hard copy documents cannot easily be used to trace who printed them. Printer manufacturers will doubtless come up with new ways of tracking documents, and may already be using some we don't know about, but this latest work at least makes it harder with existing models. Follow me @glynmoody on Twitter or identi.ca, and +glynmoody on Google+ Thank you for reading this Techdirt post. With so many things competing for everyone’s attention these days, we really appreciate you giving us your time. We work hard every day to put quality content out there for our community. Techdirt is one of the few remaining truly independent media outlets. We do not have a giant corporation behind us, and we rely heavily on our community to support us, in an age when advertisers are increasingly uninterested in sponsoring small, independent sites — especially a site like ours that is unwilling to pull punches in its reporting and analysis. While other websites have resorted to paywalls, registration requirements, and increasingly annoying/intrusive advertising, we have always kept Techdirt open and available to anyone. But in order to continue doing so, we need your support. We offer a variety of ways for our readers to support us, from direct donations to special subscriptions and cool merchandise — and every little bit helps. Thank you. –The Techdirt Team Filed Under: forensics, printer dots, printers, sources, tracking	{ "pile_set_name": "OpenWebText2" }
Just got home after a 2 week vacation (left on Oct. 27th, home on Nov. 9th 1am) and came home to this loyal solider guarding my candy for me. It arrived on Nov. 1st and was sat untouched when I arrived home @ 1am on Nov. 9th. His dedication to the protection of my candy for over a week should be recognized. Having sat in the boxes for the week, the candy is just a little soft and gooey and tastes even better than normal. I've been a big fan of Star Wars for a long time, this dish is so f******ing cool. Thank you so much Santa!	{ "pile_set_name": "OpenWebText2" }
Compressive force-produced CCN2 induces osteocyte apoptosis through ERK1/2 pathway. Osteocytes produce various factors that mediate the onset of bone formation and resorption and play roles in maintaining bone homeostasis and remodeling in response to mechanical stimuli. One such factor, CCN2, is thought to play a significant role in osteocyte responses to mechanical stimuli, but its function in osteocytes is not well understood. Here, we showed that CCN2 induces apoptosis in osteocytes under compressive force loading. Compressive force increased CCN2 gene expression and production, and induced apoptosis in osteocytes. Application of exogenous CCN2 protein induced apoptosis, and a neutralizing CCN2 antibody blocked loading-induced apoptosis. We further examined how CCN2 induces loaded osteocyte apoptosis. In loaded osteocytes, extracellular signal-regulated kinase 1/2 (ERK1/2) was activated, and an ERK1/2 inhibitor blocked loading-induced apoptosis. Furthermore, application of exogenous CCN2 protein caused ERK1/2 activation, and the neutralizing CCN2 antibody inhibited loading-induced ERK1/2 activation. Therefore, this study demonstrated for the first time to our knowledge that enhanced production of CCN2 in osteocytes under compressive force loading induces apoptosis through activation of ERK1/2 pathway.	{ "pile_set_name": "PubMed Abstracts" }
Tampa Bay Lightning (2nd seed, Atlantic Division) versus New York Islanders (first Eastern Conference wild card) The Lightning reached the Stanley Cup finals in 2015 but fell short of the ultimate goal after losing to the Chicago Blackhawks. Playing in the second round is unfamiliar territory for the Islanders, who won their first playoff series since 1993. This will be an interesting series. Lighting coach Jon Cooper's group once again is playing inspired hockey despite plenty of adversity. Islanders coach Jack Capuano and the boys from Brooklyn are a gritty group and a dangerous team for the Lightning. Keeping John Tavares contained will be the priority for the Lightning. Mike Stobe/NHLI/Getty Images How they win Tampa: While the Islanders' first-round series victory over the Florida Panthers ended with a double-overtime thriller in Game 6, the Lightning have been waiting, watching, resting and preparing after their first-round series win over the Detroit Red Wings concluded on April 22. The time off will serve Tampa well, as many of its top players are bruised and banged up. Because the Lightning reached the Cup finals last season, they know any extra time off this spring is welcomed. It also helps that Tampa is backstopped by goaltender Ben Bishop, who stopped 152 of 160 shots against the Red Wings. Bishop owns a 2.08 goals-against average and a .926 save percentage in 30 career playoff games. Tampa needs Bishop's best performances in order to advance to a second straight conference finals. Like in most playoff series, special teams will be key for the Lightning. Tampa's penalty kill was 24-for-25 in the first round. On the power play, the Lightning went 4-for-23. The power play will be important because Tampa scored only eight even-strength goals against the Red Wings. Without captain Steven Stamkos, who remains sidelined after surgery to remove a blood clot in his shoulder, the once-exiled Jonathan Drouin played extremely well in the first round and will need to continue his strong play. New York: The never-say-die Islanders earned three overtime victories in the first round against the Panthers. That determination and passion needs to continue against an opponent with more postseason experience. Islanders captain John Tavares was outstanding in the first round. The organization's all-time leader in regular-season overtime goals (eight) scored two against the Panthers. He'll need to continue to be the best player on the ice for the Islanders to beat the Lightning. He enters the series with five goals and four assists for nine points this postseason. In his past 12 games, dating back to March 31, he has 11 goals and nine assists for 20 points. Goaltender Thomas Greiss was solid in the first round. He combined for 88 saves in Games 5 and 6. If he can maintain that level of success, it will be an entertaining battle between Bishop and him. How they lose Tampa: Health could be a factor for the Lightning. The flu recently wreaked havoc in the locker room and a handful of players were sick during Game 5 against the Red Wings, but the time off has helped them get better. Already without Stamkos, Cooper is waiting to see if veteran defenseman Anton Stralman (broken leg) will be available at some point. The speedy Islanders could take advantage of Tampa's blue-line corps that won't have the solid defensive pairing of Stralman and Victor Hedman. It's also not known if forward J.T. Brown (upper body) will be available this series. Forward Tyler Johnson is banged-up too. Without Stamkos' production (37 goals during the regular season), the Lightning struggled offensively in the first round, scoring 12 goals against the Red Wings -- and Nikita Kucherov had five of them. Depth could become an issue for the Lightning. Solving Ben Bishop will be the key to success for the Islanders. Bruce Bennett/Getty Images New York: The Islanders' lack of postseason experience could be a factor. As unbelievable as he's been since starter Jaroslav Halak was injured, Greiss could be exposed against an offensively talented team like the Lightning (if Tampa produces). He made timely saves in the first round and was able to control his rebounds. If he allows those second chances, though, Tampa will pounce all over them. Fancy stats 27 minutes Without Stralman in the defensive mix for the Lightning, Hedman, who should be among those considered for the Norris Trophy, averaged 27 minutes per game in the first round. His ice time should remain the same, or even increase, as the postseason progresses. Series MVP Tampa: Ben Bishop. Ben Bishop. Ben Bishop. Did we mention the importance of Ben Bishop? He was a major reason the Lightning reached the finals in 2015, and if they can advance past the second round, it will be on the shoulders of 29-year-old goaltender. He owns a 17-12 record in 30 career postseason games, including four shutouts. New York: Tavares, 25, the No. 1 overall pick in the 2009 draft, is showcasing his talent at the most important time of the season. He was outstanding in the first round and has been producing for the last month. In his past 12 games, dating back to March 31, he has 11 goals and nine assists for 20 points. He'll need more of that in the second round and beyond if the Islanders can get there. Bottom line The Islanders could be the Cinderella team that pulls off this upset. Not many thought they had a chance against the Panthers, but the Islanders played inspiring hockey en route to victory. Without Stamkos and Stralman, and based on the Lightning's emotional run to the finals last spring, Tampa could run out of gas in this series. Either way, it will be entertaining and will go the distance. When the final buzzer sounds in Game 7, it will be the Islanders that will advance to the Eastern Conference finals. Islanders in 7.	{ "pile_set_name": "OpenWebText2" }
This 18-page report does a very nice job of outlining the pros and cons along with a survey of the available research. The Rennie Center says: “Our review of research revealed little evidence to support the idea that raising the compulsory age to 18 decreases dropout rates and increases graduation rates.” Later, the report says: “We urge policymakers to first consider other policies to address the Commonwealth’s dropout crisis.” One research example cited in the Rennie report compares the year states moved to Age 18 dropout minimums and the states’ performance with the Averaged Freshman Graduation Rate statistic that is now reported by the National Center for Education Statistics. The data only ran to the 2004-05 school year, so last year I took a look at the then available AFGR data to 2007. I found out that only five states of 15 jurisdictions (included: 14 states and Washington, DC) had graduation rate trends that notably exceeded the national average growth. It is now a year later, so I have been able to update the original study with the 2007-08 graduation rate data. This new graph shows what I found. As you can see, now only four of the Age 18 states with decent trend lines – Hawaii, Oregon, Wisconsin, and Connecticut – produced graduation rates notably above the national average. That is a further decay from the performance last year when five states performed notably above the national average. Seven jurisdictions on the graph actually saw a decline in their graduation rates over time while the rest of the nation was posting improvement (*Note: Nebraska changed to Age 18 in 2004, but had five years of data to determine a useful trend line and therefore is also included). To reiterate, the latest available data shows only four of the 15 Age 18 Dropout Minimum jurisdictions in the graph had graduation rate improvements notably above the overall national average improvement from 2001 to 2008. This graph and the more extensive comments in the Rennie Center study indicate that simply raising the dropout age to 18 isn’t a sure cure for low high school graduation rates. Technical Information Averaged Freshman Graduation Rates (AFGR) for each state were obtained from several years of the Digest of Education Statistics and other documents from the National Center for Education Statistics (NCES). The AFGR was extensively researched by the NCES in the early part of the decade and the findings were made available in a two-volume report, “User’s Guide to Computing High School Graduation Rates,” in 2006. Per NCES, the AFGR represents the best comparison data currently available on high school graduation rates for the 50 states. I picked 2001 as the starting year for my analysis because the US average AFGR was in decline until the turn of the century and then began to increase again. Thus, any state with a small increase or even worse, a decline, in its graduation rate would be performing below the national norm. Most of the information concerning the first year the Age 18 minimum was adopted in each state was obtained from an e-mail from the Education Commission of the States – My thanks to Jennifer Dounay Zinth of the ECS for compiling that information. I also relied on information in the Rennie Center report and in a 2008 Scripps Howard news release for a few states where ECS was unable to locate data. I did not examine states that had only two or one year of experience with the Age 18 minimum as of 2007, as these states offered insufficient data. Once those states with at least four years of Age 18 graduation rate data were determined, I ran a regression analysis to determine the slope of the best fit line for the data points for each state. Those slopes are shown by the graph. Trackbacks [...] don’t know where the president got that notion, but my very straightforward analysis of graduation rates in states that have had age 18 laws in place lo…shows the majority of those states have seen no better improvement in their graduation rates than [...] [...] only three had a dropout age of 18. Over at Kentucky’s Bluegrass Institute, Richard Innes updated the Rennie Center report with 2008-09 dropout data, and found that while some states with a dropout age of 18 have have better graduation rates than [...] Bluegrass Institute works with Kentuckians, grassroots organizations, and business owners to advance freedom and prosperity by promoting free‐market capitalism, smaller government, and the defense of personal liberties.Join Us Search BIPPS.org Newsletter Sign up Email Address : Support Bluegrass Institute Your support will allow us to give you the information you need to make a difference in the fight to secure our liberties.	{ "pile_set_name": "Pile-CC" }
For indispensable reporting on the coronavirus crisis, the election, and more, subscribe to the Mother Jones Daily newsletter. After President Trump appointed Mick Mulvaney to run the Consumer Financial Protection Bureau in November, consumer advocates expressed concern that the former South Carolina congressman had a glaring conflict of interest: while the CFPB is tasked with regulating payday lenders—companies which target low-income borrowers for high-interest loans—Mulvaney has long been an ally of the industry. Between 2011 and 2017, he received nearly $60,000 in campaign donations from payday lenders, and sponsored several bills to loosen their supervision. The company’s PAC also gave at least $4,500 to Mulvaney’s congressional campaigns. On Monday, Mulvaney’s agency quietly closed a four-year investigation into World Acceptance Corporation, a payday lender that is among Mulvaney’s past campaign donors, according to the International Business Times. The move offers the latest indication that Mulvaney is reshaping the agency’s approach to regulating such lenders; last week, the CFPB announced that it would “reconsider” an Obama-era rule that sought to curb predatory practices by the industry, and dropped an April 2017 lawsuit it had filed against four payday lenders in Kansas. (The CFPB did not reply to a request for comment.) World Acceptance Corporation announced the investigation’s close in a Monday press release that claimed it had received a letter from the CFPB saying that the investigation was complete and that the agency had decided against enforcement action. The company’s PAC also gave at least $4,500 in donations to Mulvaney’s congressional campaigns between 2013 and 2016. “It definitely seems that Mulvaney is doing what he can to make life easier for payday lenders, which is completely contrary to what almost everybody in America thinks should happen,” said Diane Standaert, executive vice president for the Center for Responsible Lending. In recent days, Mulvaney has signaled a broader overhaul of the CFPB. Last week he sent a letter to the Federal Reserve requesting no funding for the agency over the next three months, saying it would instead spend down emergency reserves amassed by Obama’s CFPB director, Richard Cordray. On Tuesday, Mulvaney also sent a memo to the CFPB staff outlining a new vision for the agency. In drawing a contrast with his predecessor, Mulvaney wrote that the agency would no longer “push the envelope” to achieve its mission, he wrote. “We don’t just work for the government, we work for the people,” he wrote. “And that means everyone: those who use credit cards, and those who provide those cards; those who take loans, and those who make them; those who buy cars, and those who sell them. All of those people are part of what makes this country great, and all of them deserve to be treated fairly by their government. There is a reason that Lady Justice wears a blindfold and carries a balance, along with her sword.”	{ "pile_set_name": "OpenWebText2" }
Natural Disasters and Public Health. 2018 brought multiple, unprecedented natural disasters, including hurricanes, floods, and in the United States, the deadliest wildfire in California's history. After the immediate emergency is over and the media attention wanes, communities must deal with the long process of recovering and rebuilding. Yet, some of the greatest challenges that disaster victims face come not only from the disaster itself but also from the long-term health problems stemming from the event. In the immediate aftermath, physical injuries and infections must be treated and controlled. Long-term needs include mental and psychological assistance and reinstatement of the infrastructure of the health services system. While immediate casualty numbers are often cited following a natural disaster, it's the insidious and long-lasting health effects that can hurt communities for years.	{ "pile_set_name": "PubMed Abstracts" }
The primary objective of this study is to test whether the administration of supplemental oxygen to infants who develop moderate retinopathy of prematurity (ROP) will result in a reduction of at least one third in the number of infants with eyes progressing to threshold ROP. Infants receive continuous pulse oximetry saturation monitoring at one of two specified oxygen levels with weekly active at the Hospital of the University of Pennsylvania as part of a consortium of four intensive care units. Eighteen have been enrolled to date since recruitment began in 1994. Participation in this protocol will continue with enrollment of eligible patients. Ophthalomologists will continue ROP screening exams in the nursuries and will alert study personnel of babies who are at risk for developing pre-threshold ROP.	{ "pile_set_name": "NIH ExPorter" }
Q: Android HttpPost javax.net.ssl.SSLProtocolException unrecognized name I am trying to post some data to an api from an Android tablet, but I keep getting an SSLProtocolException and I can't figure out the problem. This is the error I keep getting: javax.net.ssl.SSLHandshakeException: javax.net.ssl.SSLProtocolException: SSL handshake aborted: ssl=0x7bccbdc8: Failure in SSL library, usually a protocol error error:14077458:SSL routines:SSL23_GET_SERVER_HELLO:tlsv1 unrecognized name (external/openssl/ssl/s23_clnt.c:741 0x73d67718:0x00000000) W/System.err﹕ at com.android.org.conscrypt.OpenSSLSocketImpl.startHandshake(OpenSSLSocketImpl.java:468) W/System.err﹕ at com.android.org.conscrypt.OpenSSLSocketImpl$SSLInputStream.<init>(OpenSSLSocketImpl.java:717) W/System.err﹕ at com.android.org.conscrypt.OpenSSLSocketImpl.getInputStream(OpenSSLSocketImpl.java:688) W/System.err﹕ at org.apache.http.impl.io.SocketInputBuffer.<init>(SocketInputBuffer.java:70) W/System.err﹕ at org.apache.http.impl.SocketHttpClientConnection.createSessionInputBuffer(SocketHttpClientConnection.java:83) W/System.err﹕ at org.apache.http.impl.conn.DefaultClientConnection.createSessionInputBuffer(DefaultClientConnection.java:170) W/System.err﹕ at org.apache.http.impl.SocketHttpClientConnection.bind(SocketHttpClientConnection.java:106) W/System.err﹕ at org.apache.http.impl.conn.DefaultClientConnection.openCompleted(DefaultClientConnection.java:129) W/System.err﹕ at org.apache.http.impl.conn.DefaultClientConnectionOperator.openConnection(DefaultClientConnectionOperator.java:221) W/System.err﹕ at org.apache.http.impl.conn.AbstractPoolEntry.open(AbstractPoolEntry.java:167) W/System.err﹕ at org.apache.http.impl.conn.AbstractPooledConnAdapter.open(AbstractPooledConnAdapter.java:125) W/System.err﹕ at org.apache.http.impl.client.DefaultRequestDirector.executeOriginal(DefaultRequestDirector.java:1227) W/System.err﹕ at org.apache.http.impl.client.DefaultRequestDirector.execute(DefaultRequestDirector.java:677) W/System.err﹕ at org.apache.http.impl.client.AbstractHttpClient.execute(AbstractHttpClient.java:555) W/System.err﹕ at org.apache.http.impl.client.AbstractHttpClient.execute(AbstractHttpClient.java:487) W/System.err﹕ at org.apache.http.impl.client.AbstractHttpClient.execute(AbstractHttpClient.java:465) W/System.err﹕ at com.example.casper.bilfinger.sendJSONdata.doInBackground(sendJSONdata.java:130) W/System.err﹕ at com.example.casper.bilfinger.sendJSONdata.doInBackground(sendJSONdata.java:54) W/System.err﹕ at android.os.AsyncTask$2.call(AsyncTask.java:288) W/System.err﹕ at java.util.concurrent.FutureTask.run(FutureTask.java:237) W/System.err﹕ at android.os.AsyncTask$SerialExecutor$1.run(AsyncTask.java:231) W/System.err﹕ at java.util.concurrent.ThreadPoolExecutor.runWorker(ThreadPoolExecutor.java:1112) W/System.err﹕ at java.util.concurrent.ThreadPoolExecutor$Worker.run(ThreadPoolExecutor.java:587) W/System.err﹕ W/System.err﹕at java.lang.Thread.run(Thread.java:841) W/System.err﹕ Caused by: javax.net.ssl.SSLProtocolException: SSL handshake aborted: ssl=0x7bccbdc8: Failure in SSL library, usually a protocol error W/System.err﹕ error:14077458:SSL routines:SSL23_GET_SERVER_HELLO:tlsv1 unrecognized name (external/openssl/ssl/s23_clnt.c:741 0x73d67718:0x00000000) W/System.err﹕ W/System.err﹕at com.android.org.conscrypt.NativeCrypto.SSL_do_handshake(Native Method) W/System.err﹕ W/System.err﹕at com.android.org.conscrypt.OpenSSLSocketImpl.startHandshake(OpenSSLSocketImpl.java:425) W/System.err﹕ ... 23 more And this is the code I'm using. public class sendJSONdata extends AsyncTask<String, String, String>{ String httpAuthUser=username; String httpAuthPassword=password; String Bedrijf; String Naam; String Functie; String Vestiging; String Telefoonnummer; String Email; String Opmerkingen; String GesprokenMet; Context context; @Override protected void onPreExecute() { super.onPreExecute(); } public sendJSONdata(String[] values,Context context) { Bedrijf= values[0]; Naam= values[1]; Functie= values[2]; Vestiging= values[3]; Telefoonnummer= values[4]; Email= values[5]; Opmerkingen= values[6]; GesprokenMet= values[7]; this.context=context; //System.setProperty("jsse.enableSNIExtension", "false"); } protected String doInBackground(String... strings) { ///Build JSON object and fill with your data JSONObject subpostMessage = new JSONObject(); try { subpostMessage.put("emailAdres", Email); subpostMessage.put("Naam", Naam); subpostMessage.put("Bedrijfsnaam", Bedrijf); subpostMessage.put("Telnummer", Telefoonnummer); subpostMessage.put("Functie", Functie); subpostMessage.put("Vestiging", Vestiging); subpostMessage.put("Opmerkingen", Opmerkingen); subpostMessage.put("GesprokenMet", GesprokenMet); } catch (JSONException e) { e.printStackTrace(); } //Connect to HttpClient with basic Aut HttpParams httpParameters = new BasicHttpParams(); HttpClient httpclient = new MyHttpClient(httpParameters,context);//new DefaultHttpClient(httpParameters);// HttpPost httppost = new HttpPost(*Https to php file"); String base64EncodedCredentials = "Basic " + Base64.encodeToString((httpAuthUser + ":" + httpAuthPassword).getBytes(), Base64.NO_WRAP); httppost.setHeader("Authorization", base64EncodedCredentials); String responseStr = null; try { // Add your data to te connection List<NameValuePair> nameValuePairs = new ArrayList<NameValuePair>(2); nameValuePairs.add(new BasicNameValuePair("postData", subpostMessage.toString())); httppost.setEntity(new UrlEncodedFormEntity(nameValuePairs)); Log.d("httpPost: ",httppost.getMethod()); Log.d("ValuePairs- name: ",nameValuePairs.get(0).getName()+ " val: "+ nameValuePairs.get(0).getValue()); // Execute HTTP Post Request HttpResponse response = httpclient.execute(httppost); //Recover result response responseStr = EntityUtils.toString(response.getEntity()); Log.d("JSON ATTEMPT","Response: "+responseStr); } catch (ClientProtocolException e) { Log.d("JSON ATTEMPT","Response:CPerror "+e.toString()); } catch (IOException e) { Log.d("JSON ATTEMPT","Response:IOerror "+e.toString()); } return responseStr; } protected void onPostExecute(String result) { if (result == null) { //Request Failed return; } //System.out.println("RECEIVED RESPONSE: " + result); try { JSONObject jObj = new JSONObject(result); } catch (JSONException e) { e.printStackTrace(); } } @Override protected void onProgressUpdate(String... values) { } } And the place where its called. void postJSONdata() { String[] values = new String[8]; values[0]=bnaam.getText().toString(); values[1]=naam.getText().toString(); values[2]=functie.getText().toString(); values[3]=vestiging.getText().toString(); values[4]=tele.getText().toString(); values[5]=mail.getText().toString(); values[6]=opmerking.getText().toString(); values[7]=gesprokenmet.getText().toString(); sendJSONdata task = new sendJSONdata(values,getApplicationContext()); task.execute(); } This error is thrown on any jdk I try (6,7,8), Most of the post I found suggested it had to do with SNI which was introduced in 7 but with 6 I still have the same error. A: This problem is caused by the configuration of the server, combined with no or invalid support of SNI by the client. The server will return with the unrecognized_name alert if no SNI was used or if SNI was used with the wrong name. Thus you need to make sure that you use a Java version which supports SNI, enable it and also use the correct name to access the server.	{ "pile_set_name": "StackExchange" }
Toei 7700 series The is a tramcar type operated by Tokyo Metropolitan Bureau of Transportation (Toei) on the Toden Arakawa Line in Tokyo, Japan, since May 2016. The planned fleet of eight cars is to be built from former 7000 series cars, rebuilt with new bogies and electrical equipment. Design The 7700 series cars are rebuilt from former 7000 series cars, which themselves were rebuilt in 1977 from cars dating from the 1950s with new bodies on the original underframes. The 7700 series cars reuse the bodies and air-conditioning equipment of the 7000 series cars but with new bogies identical to those used on the 8900 series cars and VVVF control equipment. The interiors have also been completely refurbished with the doorways widened from to . Interior LED lighting is used. The cost of building the 7700 series from the earlier 7000 series cars is approximately 130 million yen per car, compared to the cost of approximately 180 million yen for purchasing new 8900 series cars. Liveries The individual tramcars are finished in retro-style liveries as follows. History Toei announced details of the new 7700 series fleet in March 2016. The first car, 7701 in green livery, entered service on 30 May 2016. The two green-liveried cars will be followed by three cars in blue livery and three cars in maroon livery, all entering service by the end of fiscal 2016. Build history details The individual build histories of the tramcars are as follows. References External links Toei news release Category:Electric multiple units of Japan Category:Tokyo Metropolitan Bureau of Transportation Category:Train-related introductions in 2016 ja:東京都交通局7700形電車	{ "pile_set_name": "Wikipedia (en)" }
/* * DO NOT ALTER OR REMOVE COPYRIGHT NOTICES OR THIS FILE HEADER. * * This code is free software; you can redistribute it and/or modify it * under the terms of the GNU General Public License version 2 only, as * published by the Free Software Foundation. Oracle designates this * particular file as subject to the "Classpath" exception as provided * by Oracle in the LICENSE file that accompanied this code. * * This code is distributed in the hope that it will be useful, but WITHOUT * ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or * FITNESS FOR A PARTICULAR PURPOSE. See the GNU General Public License * version 2 for more details (a copy is included in the LICENSE file that * accompanied this code). * * You should have received a copy of the GNU General Public License version * 2 along with this work; if not, write to the Free Software Foundation, * Inc., 51 Franklin St, Fifth Floor, Boston, MA 02110-1301 USA. * * Please contact Oracle, 500 Oracle Parkway, Redwood Shores, CA 94065 USA * or visit www.oracle.com if you need additional information or have any * questions. / / * This file is available under and governed by the GNU General Public * License version 2 only, as published by the Free Software Foundation. * However, the following notice accompanied the original version of this * file: * * Written by Doug Lea with assistance from members of JCP JSR-166 * Expert Group and released to the public domain, as explained at * http://creativecommons.org/publicdomain/zero/1.0/ / package java.util.concurrent; import java.security.AccessControlContext; import java.security.AccessControlException; import java.security.AccessController; import java.security.PrivilegedAction; import java.security.PrivilegedActionException; import java.security.PrivilegedExceptionAction; import java.util.Collection; import java.util.List; import java.util.concurrent.atomic.AtomicInteger; import sun.security.util.SecurityConstants; import static java.lang.ref.Reference.reachabilityFence; /* * Factory and utility methods for {@link Executor}, {@link * ExecutorService}, {@link ScheduledExecutorService}, {@link * ThreadFactory}, and {@link Callable} classes defined in this * package. This class supports the following kinds of methods: * * <ul> * <li>Methods that create and return an {@link ExecutorService} * set up with commonly useful configuration settings. * <li>Methods that create and return a {@link ScheduledExecutorService} * set up with commonly useful configuration settings. * <li>Methods that create and return a "wrapped" ExecutorService, that * disables reconfiguration by making implementation-specific methods * inaccessible. * <li>Methods that create and return a {@link ThreadFactory} * that sets newly created threads to a known state. * <li>Methods that create and return a {@link Callable} * out of other closure-like forms, so they can be used * in execution methods requiring {@code Callable}. * </ul> * * @author Doug Lea * @since 1.5 / // 【任务执行框架】的工厂，该类负责生成：【任务执行框架】对象、Callable类型的任务对象、线程工厂对象 public class Executors { /* Cannot instantiate. / private Executors() { } /▼ 【工作池】 ████████████████████████████████████████████████████████████████████████████████┓ / /* * Creates a work-stealing thread pool using the number of * {@linkplain Runtime#availableProcessors available processors} * as its target parallelism level. * * @return the newly created thread pool * * @see #newWorkStealingPool(int) * @since 1.8 / // 并行度与处理器数量相同的【工作池】 public static ExecutorService newWorkStealingPool() { return new ForkJoinPool(Runtime.getRuntime().availableProcessors(), ForkJoinPool.defaultForkJoinWorkerThreadFactory, null, true); } /* * Creates a thread pool that maintains enough threads to support * the given parallelism level, and may use multiple queues to * reduce contention. The parallelism level corresponds to the * maximum number of threads actively engaged in, or available to * engage in, task processing. The actual number of threads may * grow and shrink dynamically. A work-stealing pool makes no * guarantees about the order in which submitted tasks are * executed. * * @param parallelism the targeted parallelism level * * @return the newly created thread pool * * @throws IllegalArgumentException if {@code parallelism <= 0} * @since 1.8 / // 并行度为parallelism的【工作池】 public static ExecutorService newWorkStealingPool(int parallelism) { return new ForkJoinPool(parallelism, ForkJoinPool.defaultForkJoinWorkerThreadFactory, null, true); } /▲ 【工作池】 ████████████████████████████████████████████████████████████████████████████████┛ / /▼ 【任务执行框架代理】 ████████████████████████████████████████████████████████████████████████████████┓ / /* * Returns an object that delegates all defined {@link * ExecutorService} methods to the given executor, but not any * other methods that might otherwise be accessible using * casts. This provides a way to safely "freeze" configuration and * disallow tuning of a given concrete implementation. * * @param executor the underlying implementation * * @return an {@code ExecutorService} instance * * @throws NullPointerException if executor null / // 不可配置 public static ExecutorService unconfigurableExecutorService(ExecutorService executor) { if(executor == null) { throw new NullPointerException(); } return new DelegatedExecutorService(executor); } /▲ 【任务执行框架代理】 ████████████████████████████████████████████████████████████████████████████████┛ / /▼ 【线程池】 ████████████████████████████████████████████████████████████████████████████████┓ / /* * Creates a thread pool that creates new threads as needed, but * will reuse previously constructed threads when they are * available. These pools will typically improve the performance * of programs that execute many short-lived asynchronous tasks. * Calls to {@code execute} will reuse previously constructed * threads if available. If no existing thread is available, a new * thread will be created and added to the pool. Threads that have * not been used for sixty seconds are terminated and removed from * the cache. Thus, a pool that remains idle for long enough will * not consume any resources. Note that pools with similar * properties but different details (for example, timeout parameters) * may be created using {@link ThreadPoolExecutor} constructors. * * @return the newly created thread pool / / 【缓冲线程池】 * 提交新任务之后，会创建一个新线程执行它，该新线程在空闲期的存活时长为60秒。 * 换句话说，每个线程在空闲60秒之后就被销毁了，所以适合做缓冲(不是缓存)。 * * 配置： * - 阻塞队列 : SynchronousQueue * -【核心阙值】: 0 * -【最大阙值】: 无限 / public static ExecutorService newCachedThreadPool() { return new ThreadPoolExecutor(0, Integer.MAX_VALUE, 60L, TimeUnit.SECONDS, new SynchronousQueue<Runnable>()); } /* * Creates a thread pool that creates new threads as needed, but * will reuse previously constructed threads when they are * available, and uses the provided * ThreadFactory to create new threads when needed. * * @param threadFactory the factory to use when creating new threads * * @return the newly created thread pool * * @throws NullPointerException if threadFactory is null / / 【缓冲线程池】，允许自行指定线程工厂 * 提交新任务之后，会创建一个新线程执行它，该新线程在空闲期的存活时长为60秒。 * 换句话说，每个线程在空闲60秒之后就被销毁了，所以适合做缓冲(不是缓存)。 * * 配置： * - 阻塞队列 : SynchronousQueue * -【核心阙值】: 0 * -【最大阙值】: 无限 / public static ExecutorService newCachedThreadPool(ThreadFactory threadFactory) { return new ThreadPoolExecutor(0, Integer.MAX_VALUE, 60L, TimeUnit.SECONDS, new SynchronousQueue<Runnable>(), threadFactory); } /* * Creates a thread pool that reuses a fixed number of threads * operating off a shared unbounded queue. At any point, at most * {@code nThreads} threads will be active processing tasks. * If additional tasks are submitted when all threads are active, * they will wait in the queue until a thread is available. * If any thread terminates due to a failure during execution * prior to shutdown, a new one will take its place if needed to * execute subsequent tasks. The threads in the pool will exist * until it is explicitly {@link ExecutorService#shutdown shutdown}. * * @param nThreads the number of threads in the pool * * @return the newly created thread pool * * @throws IllegalArgumentException if {@code nThreads <= 0} / / 【固定容量线程池】 * 线程池中常驻线程数量为nThreads * * 配置： * - 阻塞队列 : LinkedBlockingQueue * -【核心阙值】: nThreads * -【最大阙值】: nThreads / public static ExecutorService newFixedThreadPool(int nThreads) { return new ThreadPoolExecutor(nThreads, nThreads, 0L, TimeUnit.MILLISECONDS, new LinkedBlockingQueue<Runnable>()); } /* * Creates a thread pool that reuses a fixed number of threads * operating off a shared unbounded queue, using the provided * ThreadFactory to create new threads when needed. At any point, * at most {@code nThreads} threads will be active processing * tasks. If additional tasks are submitted when all threads are * active, they will wait in the queue until a thread is * available. If any thread terminates due to a failure during * execution prior to shutdown, a new one will take its place if * needed to execute subsequent tasks. The threads in the pool will * exist until it is explicitly {@link ExecutorService#shutdown * shutdown}. * * @param nThreads the number of threads in the pool * @param threadFactory the factory to use when creating new threads * * @return the newly created thread pool * * @throws NullPointerException if threadFactory is null * @throws IllegalArgumentException if {@code nThreads <= 0} / / 【固定容量线程池】，允许自行指定线程工厂 * 线程池中常驻线程数量为nThreads * * 配置： * - 阻塞队列 : LinkedBlockingQueue * -【核心阙值】: nThreads * -【最大阙值】: nThreads / public static ExecutorService newFixedThreadPool(int nThreads, ThreadFactory threadFactory) { return new ThreadPoolExecutor(nThreads, nThreads, 0L, TimeUnit.MILLISECONDS, new LinkedBlockingQueue<Runnable>(), threadFactory); } /* * Creates a thread pool that can schedule commands to run after a * given delay, or to execute periodically. * * @param corePoolSize the number of threads to keep in the pool, * even if they are idle * * @return the newly created scheduled thread pool * * @throws IllegalArgumentException if {@code corePoolSize < 0} / / 【定时任务线程池】 * 用于执行一次性或周期性的定时任务 * * 配置： * - 阻塞队列 : DelayedWorkQueue * -【核心阙值】: corePoolSize * -【最大阙值】: 无限 / public static ScheduledExecutorService newScheduledThreadPool(int corePoolSize) { return new ScheduledThreadPoolExecutor(corePoolSize); } /* * Creates a thread pool that can schedule commands to run after a * given delay, or to execute periodically. * * @param corePoolSize the number of threads to keep in the pool, * even if they are idle * @param threadFactory the factory to use when the executor * creates a new thread * * @return the newly created scheduled thread pool * * @throws IllegalArgumentException if {@code corePoolSize < 0} * @throws NullPointerException if threadFactory is null / / 【定时任务线程池】，允许自行指定线程工厂 * 用于执行一次性或周期性的定时任务 * * 配置： * - 阻塞队列 : DelayedWorkQueue * -【核心阙值】: corePoolSize * -【最大阙值】: 无限 / public static ScheduledExecutorService newScheduledThreadPool(int corePoolSize, ThreadFactory threadFactory) { return new ScheduledThreadPoolExecutor(corePoolSize, threadFactory); } /* * Creates a single-threaded executor that can schedule commands * to run after a given delay, or to execute periodically. * (Note however that if this single * thread terminates due to a failure during execution prior to * shutdown, a new one will take its place if needed to execute * subsequent tasks.) Tasks are guaranteed to execute * sequentially, and no more than one task will be active at any * given time. Unlike the otherwise equivalent * {@code newScheduledThreadPool(1)} the returned executor is * guaranteed not to be reconfigurable to use additional threads. * * @return the newly created scheduled executor / / 【定时任务线程池代理】 * 用于执行一次性或周期性的定时任务，线程池中只有一个常驻线程。 * * 配置： * - 阻塞队列 : DelayedWorkQueue * -【核心阙值】: 1 * -【最大阙值】: 无限 / public static ScheduledExecutorService newSingleThreadScheduledExecutor() { return new DelegatedScheduledExecutorService(new ScheduledThreadPoolExecutor(1)); } /* * Creates a single-threaded executor that can schedule commands * to run after a given delay, or to execute periodically. (Note * however that if this single thread terminates due to a failure * during execution prior to shutdown, a new one will take its * place if needed to execute subsequent tasks.) Tasks are * guaranteed to execute sequentially, and no more than one task * will be active at any given time. Unlike the otherwise * equivalent {@code newScheduledThreadPool(1, threadFactory)} * the returned executor is guaranteed not to be reconfigurable to * use additional threads. * * @param threadFactory the factory to use when creating new threads * * @return the newly created scheduled executor * * @throws NullPointerException if threadFactory is null / / 【定时任务线程池代理】，允许自行指定线程工厂 * 用于执行一次性或周期性的定时任务，线程池中只有一个常驻线程。 * * 配置： * - 阻塞队列 : DelayedWorkQueue * -【核心阙值】: 1 * -【最大阙值】: 无限 / public static ScheduledExecutorService newSingleThreadScheduledExecutor(ThreadFactory threadFactory) { return new DelegatedScheduledExecutorService(new ScheduledThreadPoolExecutor(1, threadFactory)); } /* * Returns an object that delegates all defined {@link * ScheduledExecutorService} methods to the given executor, but * not any other methods that might otherwise be accessible using * casts. This provides a way to safely "freeze" configuration and * disallow tuning of a given concrete implementation. * * @param executor the underlying implementation * * @return a {@code ScheduledExecutorService} instance * * @throws NullPointerException if executor null / / 【定时任务线程池代理】 * 不可自定义配置，只是对指定的【定时任务执行框架】的简单代理 / public static ScheduledExecutorService unconfigurableScheduledExecutorService(ScheduledExecutorService executor) { if(executor == null) { throw new NullPointerException(); } return new DelegatedScheduledExecutorService(executor); } /* * Creates an Executor that uses a single worker thread operating * off an unbounded queue. (Note however that if this single * thread terminates due to a failure during execution prior to * shutdown, a new one will take its place if needed to execute * subsequent tasks.) Tasks are guaranteed to execute * sequentially, and no more than one task will be active at any * given time. Unlike the otherwise equivalent * {@code newFixedThreadPool(1)} the returned executor is * guaranteed not to be reconfigurable to use additional threads. * * @return the newly created single-threaded Executor / / 【Finalizable线程池】 * 顺序执行普通任务，线程池中最多只有一个线程。 * * 配置： * - 阻塞队列 : LinkedBlockingQueue * -【核心阙值】: 1 * -【最大阙值】: 1 / public static ExecutorService newSingleThreadExecutor() { return new FinalizableDelegatedExecutorService(new ThreadPoolExecutor(1, 1, 0L, TimeUnit.MILLISECONDS, new LinkedBlockingQueue<Runnable>())); } /* * Creates an Executor that uses a single worker thread operating * off an unbounded queue, and uses the provided ThreadFactory to * create a new thread when needed. Unlike the otherwise * equivalent {@code newFixedThreadPool(1, threadFactory)} the * returned executor is guaranteed not to be reconfigurable to use * additional threads. * * @param threadFactory the factory to use when creating new threads * * @return the newly created single-threaded Executor * * @throws NullPointerException if threadFactory is null / / 【Finalizable线程池】，允许自行指定线程工厂 * 顺序执行普通任务，线程池中最多只有一个线程。 * * 配置： * - 阻塞队列 : LinkedBlockingQueue * -【核心阙值】: 1 * -【最大阙值】: 1 / public static ExecutorService newSingleThreadExecutor(ThreadFactory threadFactory) { return new FinalizableDelegatedExecutorService(new ThreadPoolExecutor(1, 1, 0L, TimeUnit.MILLISECONDS, new LinkedBlockingQueue<Runnable>(), threadFactory)); } /▲ 【线程池】 ████████████████████████████████████████████████████████████████████████████████┛ / /▼ 任务对象 ████████████████████████████████████████████████████████████████████████████████┓ / /* * Returns a {@link Callable} object that, when * called, runs the given task and returns {@code null}. * * @param task the task to run * * @return a callable object * * @throws NullPointerException if task null / // 包装Runnable任务，无返回值 public static Callable<Object> callable(Runnable task) { if(task == null) { throw new NullPointerException(); } return new RunnableAdapter<Object>(task, null); } /* * Returns a {@link Callable} object that, when * called, runs the given task and returns the given result. This * can be useful when applying methods requiring a * {@code Callable} to an otherwise resultless action. * * @param task the task to run * @param result the result to return * @param <T> the type of the result * * @return a callable object * * @throws NullPointerException if task null / // 包装Runnable任务，有返回值 public static <T> Callable<T> callable(Runnable task, T result) { if(task == null) { throw new NullPointerException(); } return new RunnableAdapter<T>(task, result); } /* * Returns a {@link Callable} object that will, when called, * execute the given {@code callable} under the current access * control context. This method should normally be invoked within * an {@link AccessController#doPrivileged AccessController.doPrivileged} * action to create callables that will, if possible, execute * under the selected permission settings holding within that * action; or if not possible, throw an associated {@link * AccessControlException}. * * @param callable the underlying task * @param <T> the type of the callable's result * * @return a callable object * * @throws NullPointerException if callable null / // 包装Callable任务，使用上下文访问权限控制器 public static <T> Callable<T> privilegedCallable(Callable<T> callable) { if(callable == null) { throw new NullPointerException(); } return new PrivilegedCallable<T>(callable); } /* * Returns a {@link Callable} object that will, when called, * execute the given {@code callable} under the current access * control context, with the current context class loader as the * context class loader. This method should normally be invoked * within an * {@link AccessController#doPrivileged AccessController.doPrivileged} * action to create callables that will, if possible, execute * under the selected permission settings holding within that * action; or if not possible, throw an associated {@link * AccessControlException}. * * @param callable the underlying task * @param <T> the type of the callable's result * * @return a callable object * * @throws NullPointerException if callable null * @throws AccessControlException if the current access control * context does not have permission to both set and get context * class loader / // 包装Callable任务，使用上下文访问权限控制器和当前线程的类加载器 public static <T> Callable<T> privilegedCallableUsingCurrentClassLoader(Callable<T> callable) { if(callable == null) { throw new NullPointerException(); } return new PrivilegedCallableUsingCurrentClassLoader<T>(callable); } /* * Returns a {@link Callable} object that, when * called, runs the given privileged action and returns its result. * * @param action the privileged action to run * * @return a callable object * * @throws NullPointerException if action null / // 包装PrivilegedAction任务 public static Callable<Object> callable(final PrivilegedAction<?> action) { if(action == null) { throw new NullPointerException(); } return new Callable<Object>() { public Object call() { return action.run(); } }; } /* * Returns a {@link Callable} object that, when * called, runs the given privileged exception action and returns * its result. * * @param action the privileged exception action to run * * @return a callable object * * @throws NullPointerException if action null / // 包装PrivilegedExceptionAction任务 public static Callable<Object> callable(final PrivilegedExceptionAction<?> action) { if(action == null) { throw new NullPointerException(); } return new Callable<Object>() { public Object call() throws Exception { return action.run(); } }; } /▲ 任务对象 ████████████████████████████████████████████████████████████████████████████████┛ / /▼ 线程工厂 ████████████████████████████████████████████████████████████████████████████████┓ / /* * Returns a default thread factory used to create new threads. * This factory creates all new threads used by an Executor in the * same {@link ThreadGroup}. If there is a {@link * java.lang.SecurityManager}, it uses the group of {@link * System#getSecurityManager}, else the group of the thread * invoking this {@code defaultThreadFactory} method. Each new * thread is created as a non-daemon thread with priority set to * the smaller of {@code Thread.NORM_PRIORITY} and the maximum * priority permitted in the thread group. New threads have names * accessible via {@link Thread#getName} of * <em>pool-N-thread-M</em>, where <em>N</em> is the sequence * number of this factory, and <em>M</em> is the sequence number * of the thread created by this factory. * * @return a thread factory / // 默认线程工厂，创建默认线程优先级的非守护线程 public static ThreadFactory defaultThreadFactory() { return new DefaultThreadFactory(); } /* * Returns a thread factory used to create new threads that * have the same permissions as the current thread. * This factory creates threads with the same settings as {@link * Executors#defaultThreadFactory}, additionally setting the * AccessControlContext and contextClassLoader of new threads to * be the same as the thread invoking this * {@code privilegedThreadFactory} method. A new * {@code privilegedThreadFactory} can be created within an * {@link AccessController#doPrivileged AccessController.doPrivileged} * action setting the current thread's access control context to * create threads with the selected permission settings holding * within that action. * * <p>Note that while tasks running within such threads will have * the same access control and class loader settings as the * current thread, they need not have the same {@link * java.lang.ThreadLocal} or {@link * java.lang.InheritableThreadLocal} values. If necessary, * particular values of thread locals can be set or reset before * any task runs in {@link ThreadPoolExecutor} subclasses using * {@link ThreadPoolExecutor#beforeExecute(Thread, Runnable)}. * Also, if it is necessary to initialize worker threads to have * the same InheritableThreadLocal settings as some other * designated thread, you can create a custom ThreadFactory in * which that thread waits for and services requests to create * others that will inherit its values. * * @return a thread factory * * @throws AccessControlException if the current access control * context does not have permission to both get and set context * class loader / // 特权线程工厂 public static ThreadFactory privilegedThreadFactory() { return new PrivilegedThreadFactory(); } /▲ 线程工厂 ████████████████████████████████████████████████████████████████████████████████┛ / / * 以下定义了各种类型的： * * - 任务执行框架 * - 任务 * - 线程工厂 / /* * A wrapper class that exposes only the ExecutorService methods of an ExecutorService implementation. / // 【任务执行框架代理】，限制只能执行ExecutorService接口内的方法 private static class DelegatedExecutorService implements ExecutorService { private final ExecutorService e; DelegatedExecutorService(ExecutorService executor) { e = executor; } public void execute(Runnable command) { try { e.execute(command); } finally { reachabilityFence(this); } } public void shutdown() { e.shutdown(); } public List<Runnable> shutdownNow() { try { return e.shutdownNow(); } finally { reachabilityFence(this); } } public boolean isShutdown() { try { return e.isShutdown(); } finally { reachabilityFence(this); } } public boolean isTerminated() { try { return e.isTerminated(); } finally { reachabilityFence(this); } } public boolean awaitTermination(long timeout, TimeUnit unit) throws InterruptedException { try { return e.awaitTermination(timeout, unit); } finally { reachabilityFence(this); } } public Future<?> submit(Runnable task) { try { return e.submit(task); } finally { reachabilityFence(this); } } public <T> Future<T> submit(Callable<T> task) { try { return e.submit(task); } finally { reachabilityFence(this); } } public <T> Future<T> submit(Runnable task, T result) { try { return e.submit(task, result); } finally { reachabilityFence(this); } } public <T> List<Future<T>> invokeAll(Collection<? extends Callable<T>> tasks) throws InterruptedException { try { return e.invokeAll(tasks); } finally { reachabilityFence(this); } } public <T> List<Future<T>> invokeAll(Collection<? extends Callable<T>> tasks, long timeout, TimeUnit unit) throws InterruptedException { try { return e.invokeAll(tasks, timeout, unit); } finally { reachabilityFence(this); } } public <T> T invokeAny(Collection<? extends Callable<T>> tasks) throws InterruptedException, ExecutionException { try { return e.invokeAny(tasks); } finally { reachabilityFence(this); } } public <T> T invokeAny(Collection<? extends Callable<T>> tasks, long timeout, TimeUnit unit) throws InterruptedException, ExecutionException, TimeoutException { try { return e.invokeAny(tasks, timeout, unit); } finally { reachabilityFence(this); } } } /* * A wrapper class that exposes only the ScheduledExecutorService * methods of a ScheduledExecutorService implementation. / // 【定时任务执行框架代理】，限制只能执行ExecutorService接口与ScheduledExecutorService接口内的方法 private static class DelegatedScheduledExecutorService extends DelegatedExecutorService implements ScheduledExecutorService { private final ScheduledExecutorService e; DelegatedScheduledExecutorService(ScheduledExecutorService executor) { super(executor); e = executor; } public ScheduledFuture<?> schedule(Runnable command, long delay, TimeUnit unit) { return e.schedule(command, delay, unit); } public <V> ScheduledFuture<V> schedule(Callable<V> callable, long delay, TimeUnit unit) { return e.schedule(callable, delay, unit); } public ScheduledFuture<?> scheduleAtFixedRate(Runnable command, long initialDelay, long period, TimeUnit unit) { return e.scheduleAtFixedRate(command, initialDelay, period, unit); } public ScheduledFuture<?> scheduleWithFixedDelay(Runnable command, long initialDelay, long delay, TimeUnit unit) { return e.scheduleWithFixedDelay(command, initialDelay, delay, unit); } } // 【Finalizable任务执行框架代理】 private static class FinalizableDelegatedExecutorService extends DelegatedExecutorService { FinalizableDelegatedExecutorService(ExecutorService executor) { super(executor); } @SuppressWarnings("deprecation") protected void finalize() { super.shutdown(); } } /* * A callable that runs given task and returns given result. / // 包装Runnable任务 private static final class RunnableAdapter<T> implements Callable<T> { private final Runnable task; private final T result; RunnableAdapter(Runnable task, T result) { this.task = task; this.result = result; } public T call() { task.run(); return result; } public String toString() { return super.toString() + "[Wrapped task = " + task + "]"; } } /* * A callable that runs under established access control settings. / // 包装Callable任务，使用上下文访问权限控制器 private static final class PrivilegedCallable<T> implements Callable<T> { final Callable<T> task; final AccessControlContext acc; PrivilegedCallable(Callable<T> task) { this.task = task; this.acc = AccessController.getContext(); } public T call() throws Exception { try { return AccessController.doPrivileged(new PrivilegedExceptionAction<T>() { public T run() throws Exception { return task.call(); } }, acc); } catch(PrivilegedActionException e) { throw e.getException(); } } public String toString() { return super.toString() + "[Wrapped task = " + task + "]"; } } /* * A callable that runs under established access control settings and * current ClassLoader. / // 包装Callable任务，使用上下文访问权限控制器和当前线程的类加载器 private static final class PrivilegedCallableUsingCurrentClassLoader<T> implements Callable<T> { final Callable<T> task; final AccessControlContext acc; final ClassLoader ccl; PrivilegedCallableUsingCurrentClassLoader(Callable<T> task) { SecurityManager sm = System.getSecurityManager(); if(sm != null) { // Calls to getContextClassLoader from this class // never trigger a security check, but we check // whether our callers have this permission anyways. sm.checkPermission(SecurityConstants.GET_CLASSLOADER_PERMISSION); // Whether setContextClassLoader turns out to be necessary // or not, we fail fast if permission is not available. sm.checkPermission(new RuntimePermission("setContextClassLoader")); } this.task = task; this.acc = AccessController.getContext(); this.ccl = Thread.currentThread().getContextClassLoader(); } public T call() throws Exception { try { return AccessController.doPrivileged(new PrivilegedExceptionAction<T>() { public T run() throws Exception { Thread t = Thread.currentThread(); ClassLoader cl = t.getContextClassLoader(); if(ccl == cl) { return task.call(); } else { t.setContextClassLoader(ccl); try { return task.call(); } finally { t.setContextClassLoader(cl); } } } }, acc); } catch(PrivilegedActionException e) { throw e.getException(); } } public String toString() { return super.toString() + "[Wrapped task = " + task + "]"; } } /* * The default thread factory. / // 默认线程工厂，创建默认线程优先级的非守护线程 private static class DefaultThreadFactory implements ThreadFactory { private static final AtomicInteger poolNumber = new AtomicInteger(1); private final AtomicInteger threadNumber = new AtomicInteger(1); private final String namePrefix; private final ThreadGroup group; DefaultThreadFactory() { SecurityManager s = System.getSecurityManager(); group = (s != null) ? s.getThreadGroup() : Thread.currentThread().getThreadGroup(); namePrefix = "pool-" + poolNumber.getAndIncrement() + "-thread-"; } public Thread newThread(Runnable r) { Thread t = new Thread(group, r, namePrefix + threadNumber.getAndIncrement(), 0); if(t.isDaemon()) { t.setDaemon(false); } if(t.getPriority() != Thread.NORM_PRIORITY) { t.setPriority(Thread.NORM_PRIORITY); } return t; } } /* * Thread factory capturing access control context and class loader. / // 特权线程工厂 private static class PrivilegedThreadFactory extends DefaultThreadFactory { final AccessControlContext acc; final ClassLoader ccl; PrivilegedThreadFactory() { super(); SecurityManager sm = System.getSecurityManager(); if(sm != null) { / * Calls to getContextClassLoader from this class never trigger a security check, * but we check whether our callers have this permission anyways. */ sm.checkPermission(SecurityConstants.GET_CLASSLOADER_PERMISSION); // Fail fast sm.checkPermission(new RuntimePermission("setContextClassLoader")); } this.acc = AccessController.getContext(); this.ccl = Thread.currentThread().getContextClassLoader(); } public Thread newThread(final Runnable r) { return super.newThread(new Runnable() { public void run() { AccessController.doPrivileged(new PrivilegedAction<>() { public Void run() { Thread.currentThread().setContextClassLoader(ccl); r.run(); return null; } }, acc); } }); } } }	{ "pile_set_name": "Github" }
Evaluation of a commercial exoantigen test system for the rapid identification of systemic fungal pathogens. Seventy-nine mycelial-form stock cultures of Blastomyces dermatitidis, Coccidioides immitis, Histoplasma capsulatum, and morphologically similar fungi were extracted and tested by using commercial macroimmunodiffusion exoantigen test kits and the Centers for Disease Control (CDC) reference system for identifying fungal isolates. Results showed 100% correlation between the two systems. Specific exoantigens of C. immitis and H. capsulatum extracted from agar slant cultures (slant extraction method) readily were identified. In eight of 26 cultures of B. dermatitidis, broth culture filtrates (broth-shake-flask method) were required to demonstrate the specific bands of identity. No false-negative reactions or cross-reactivity among the pathogens and other fungi were observed. The commercial test kits provided a rapid and specific method for identifying or confirming suspected fungal pathogens.	{ "pile_set_name": "PubMed Abstracts" }
An XML list of multi-dimensional data is usually associated with a schema to assist in defining the data. However processing a schema and an XML data file to create a XML payload for export to a software application or a web page is very computational intensive. A large amount of computer processing power is consumed in applying the schema to the XML data file. It is very desirable to be able to receive imported XML data or enter XML data, then optionally modify XML data and finally export the data without use a schema during import, modification and export. It is with respect to these considerations and others that the present invention has been made.	{ "pile_set_name": "USPTO Backgrounds" }
183 F.3d 110 (2nd Cir. 1999) UNITED STATES OF AMERICA, Appellee,v.RAYMOND RICHARD STEPHENSON, aka Andrew McCurvin, aka Anthony McCurvin, Defendant-Appellant. Docket No. 98-1490August Term, 1998 UNITED STATES COURT OF APPEALSSECOND CIRCUIT Argued March 1, 1999Decided June 30, 1999 Appeal from a conviction and sentence in the United States District Court for the District of Connecticut (Alfred V. Covello, Judge). We reverse one of two money laundering convictions for legally insufficient evidence of intent to conceal. Otherwise, we affirm. [Copyrighted Material Omitted] ALEX V. HERNANDEZ, Assistant United States Attorney for the District of Connecticut (Stephen C. Robinson, United States Attorney, of counsel), Bridgeport, Connecticut, for Appellee. CONRAD O. SEIFERT, Seifert & Hogan, Old Lyme, Connecticut, for Defendant-Appellant. Before: WINTER, Chief Judge, JACOBS, Circuit Judge, and SAND, District Judge.* WINTER, Chief Judge: 1 Andrew McCurvin, also known as Raymond Richard Stephenson, appeals from his conviction after a jury trial and from a sentence of 336 months' imprisonment imposed by Judge Covello. At issue are convictions for conspiracy to possess with intent to distribute cocaine and cocaine base ("crack"), in violation of 21 U.S.C. §§ 841(a)(1) and 846; of possession with intent to distribute cocaine and crack, in violation of 21 U.S.C. § 841(a)(1); of possession of a firearm by a prohibited person, in violation of 18 U.S.C. §§ 922(g)(1) and (g)(5); of money laundering in connection with the purchase of an Acura Legend, in violation of 18 U.S.C. § 1956(a)(1)(B)(i); and of money laundering in connection with McCurvin's wife's placement of drug proceeds in a safe deposit box, in violation of 18 U.S.C. § 1956(a)(1)(B)(i).1 2 We hold that the government failed to prove money laundering in connection with McCurvin's purchase of a 1992 Acura Legend and therefore vacate the guilty verdict on Count 28. We remand for whatever proceedings are appropriate. Finding no merit in McCurvin's other arguments, we otherwise affirm. BACKGROUND 3 We view the evidence in the light most favorable to the government. See Glasser v. United States, 315 U.S. 60, 80 (1942). In July 1992, FBI Special Agent William S. Reiner, Jr. began a narcotics investigation of McCurvin, a convicted felon and Jamaican national illegally in the United States. Court-authorized wiretaps of his portable cellular and residential telephones played a major role in the investigation and trial. 4 As a result of information provided by a confidential informant, Reiner arranged a meeting between McCurvin and another FBI undercover agent, Juan Jackson, who held himself out as the informant's friend. On February 25, 1993, McCurvin made his first of a total of ten crack sales to Jackson. These sales are not seriously disputed and involved over 1300 grams of crack. On April 29, 1993, Jackson and appellant traveled together to a car dealership called Tri Auto, located in Milford, Connecticut, to negotiate the purchase of an automobile. Jackson was wearing recording and transmitting devices at the time. Appellant told Jackson he could pay cash for the vehicle "without any particular Id. or driver's license." When McCurvin and Jackson arrived at Tri Auto, a car salesman by the name of Greg Mallard explained to Jackson that the dealership was "a big laundromat." 5 On May 7, 1993, Jackson and McCurvin again traveled together to Tri Auto. Jackson was again wearing recording devices. They first discussed the need to conceal drug proceeds. McCurvin explained that he stored his proceeds in a safe deposit box for that purpose. They also talked about the need to avoid triggering the $10,000 cash reporting requirement when purchasing an automobile: 6 JJ: Yeah, cuz there, there's a law they got to do something about a certain amount of money. 7 AM: Yeah, 10,000. 8 JJ: Yeah. 9 AM: But you ain't going to give it at one time. That's when you give it to the person one time. 10 JJ: Right. 11 AM: If you come in today and give me 5 and come tomorrow and give me 5. There's nothing. You know what I mean. But when you just come in one time and hand $10,000. 12 JJ: But that's the way Greg and them do it. They're cool. 13 On May 12, 1993, while conducting surveillance of McCurvin, Special Agent Joseph McTague of the Internal Revenue Service followed McCurvin's wife, Antoinette, to the Bank of Boston in Waterbury, Connecticut. He watched as she descended stairs to the area of the bank that contains safe deposit boxes. Later that day, Antoinette was recorded having the following conversation with a Claudia Pringle: 14 CP: Hello. 15 ANT: This one call has him getting back at me. We had a big fight this morning, you know. Right. 16 CP: That's why you never called back. 17 ANT: Yeah, we had a big fight. I done broke three nails, whatever. He told me to go get his money out of the safe deposit box, so I did. . . . 18 CP: Where you been this morning? 19 ANT: I went to the bank. . . . 20 On May 18, 1993, McCurvin was intercepted discussing the possible purchase of an Acura Legend with someone by the name of Dave: 21 A: Um. Dave, listen now what I'm sayin, now all these cars lists now for 15-5. 22 D: That's what they're callin for. 23 A: Yeah. 24 D: That's a lot of money. 25 A: Lotta money, no, the Legend is a 92 Legend, and light flood. 26 D: Yup. 27 . . . 28 A: They want 17-5 for it. 29 D: Yeah, but you can go down there with 15 and you gotta car. You know what I mean? 30 A: Go down there with 15? 31 D: Yeah. 32 A: But that's what I'm saying. I mean, you know, you can't give them over 10,000, they gotta report it. 33 D: Oh, really. 34 A: You never know that. 35 D. No. 36 A: Yeah, I went to go fuckin look at this 300E. 37 D: Yeah. 38 A: They say once I give them over 10,000, they gotta report it. 39 D: No shit? 40 A: Um hum. So that's what I'm trying to figure. Now how would I do that? You know what I'm saying? That shit is crazy. 41 D: How would you do that? I would buy the car. 42 A: Huh? 43 D: Put the . . . go down there as Gravel's Automotive and buy the car. And then this way, it never hits you then, ah, then we fuckin sell it to you for fucking under ten whatever. 44 That same day, McCurvin was again intercepted discussing the possible purchase of an Acura Legend with a person named Chris: 45 A: Chris? 46 C: Yeah. 47 A: Yeah, um, I'm trying to figure if you still get a 92 Legend . . . . 48 . . . 49 C: Yeah, I have it. 50 A: You got that 92 Legend, light flood? 51 C: No, that has been sold. 52 A: That been sold? 53 C: I have a 91, 91, um, Acura Legend, flood doesn't drive. 54 A: How much you want for that? 55 C: 16-5. 56 A: 16-5? 57 C: Yeah. 58 . . . 59 A: But you basically, listen to what I'm sayin, um, how about like you could use credit card, right? 60 C: No, everything is cash and carry. 61 . . . 62 A: How about the stuff that is like 22,000. I mean if you come up with that 22,000, then you ain't gotta report to the federal government. 63 C: Yeah, that's the law. That or a certified check, whatever easier for you. Cash or certified check. 64 A: Cash or certified check? 65 C: Yeah. 66 A: Damn. All right then, so, um, I think I'm come down later then. 67 On May 19, 1993, McCurvin purchased a 1992 Acura Legend under a financing agreement with Tri Auto. Later that evening, Antoinette was intercepted over her residential telephone discussing with Claudia Pringle how to structure cash payments for an automobile in order to avoid federal cash transaction reporting requirements: 68 ANT: You know how much he told me his car payments are a month? $500 and somethin. Can you fuckin believe that, Claudia? 69 CP: You gotta pay car payments on it? That fuckin car is $37,000. 70 . . . 71 ANT: It's pissin me off but [he said] Antoinette, I'm just gonna pay $2,000 a month and just pay it off until I pay it off. . . . 72 CP: Antoinette, listen, even though Andrew got the money, you see, you know. What the car dealer told me up here? If you fuckin pay $7,000 and over, give them cash, 73 ANT: No $10,000. 74 CP: They tell the Feds on you. 75 ANT: They did, they have to. They have to, so that's why he said couldn't put no more down than what he did that's why the car payments are high. Because you can't give them more than a certain amount of money or they have to call it in. 76 That same day, Antoinette was again intercepted over her residential telephone explaining to her friend: 77 But listen, now, so, what's today, Wednesday. yesterday he beeped Shabba. No called down the store cuz I said I just said I saw Shabba at the bank so he gave me the money back to go put back in the safe deposit box, right. So I told him, look, you can get in an argument with me if you want I'm not going back down there. I'm not running down there every time you get in an argument. You tell me go run and get your money, I'm not doing it. So, I saw Shabba now in the bank when I went down to put the money. 78 On July 13, 1993, the FBI and members of other law enforcement agencie executed a search warrant at McCurvin's residence and arrested McCurvin and Antoinette. During the search, approximately ten ounces of cocaine were seized from the kitchen cabinet. Two microwave ovens, each of which contained trace amounts of cocaine, were seized from the kitchen. The agents also recovered baking soda, an ingredient necessary for the production of crack; an empty box for a portable cellular phone; a triple beam scale; a 64-ounce glass coffee pot containing crack residue; an electronic paging device; two safe deposit keys corresponding to a Bank of Boston safe deposit box located in Waterbury, Connecticut; a photographic identification card with defendant's photograph made out in the name of Anthony McCurvin; identification cards in the name of Antoinette McCurvin; documents reflecting the purchase of a number of automobiles; Western Union wire transfer receipts totaling $3,534; and a receipt made out in the name of Antoinette McCurvin for Bank of Boston safe deposit box number 3557. 79 Later that day, the FBI executed a search warrant at the Bank of Boston in Waterbury and opened safe deposit box number 3557. Inside the box, they discovered $27,800 in cash and a birth certificate for the McCurvins' child. Eighty-one bills totaling $1,710 were identified as prerecorded "buy money" that Jackson had used to purchase crack from McCurvin. 80 On the morning of January 18, 1995, after the case had been submitted to the jury, but before the jury had begun deliberations for that day, Reiner and McTague -- both of whom had testified for the government -- were instructed to carry trial evidence into the jury deliberation room. The agents knocked on the door and, hearing no answer, walked in. Eight jurors were present. When a juror wished them "good morning," the agents returned the greeting and left. They immediately informed the district court and the parties of their interaction with the jury. The court then conducted a Remmer hearing at which it asked each juror if he or she was prejudiced by this encounter. See Remmer v. United States, 347 U.S. 227 (1954). Each juror replied in the negative. Based on this voir dire, the court concluded that it was 81 simply unable to find a factual basis for a conclusion that a private communication, a contact or a tampering with the jury has, in fact, occurred. The bringing of exhibits into a jury room, and the response 'Good morning,' to a salutation made by a juror, just does not, in the Court's view, rise to the level of private communication, contact, or tampering that is contemplated by the cases that have addressed this kind of circumstance. Assuming arguendo that this, in fact, did constitute such a contact, the Court . . . conclude[s] that the presumption [of prejudice] . . . is, in fact, rebutted and that the contact was harmless to the defendants. 82 The jury ultimately convicted McCurvin on all counts but for two money laundering counts involving the purchase of a Honda Accord and a Nissan Maxima from the Tri Auto dealership. The district court later vacated the gun counts relating to narcotics transactions. See Note 1, supra. 83 After holding a Fatico hearing, see United States v. Fatico, 579 F.2d 707 (2d Cir. 1978), the district court concluded that McCurvin was responsible for the distribution of 1,340 grams of crack, warranting a base offense level of 36, see U.S.S.G. §2D1.1(c)(2). The court added four levels pursuant to U.S.S.G. §3B1.1(a) on the ground that McCurvin was a manager and organizer of criminal activity involving five or more persons, and it added two levels pursuant to U.S.S.G. §2D1.1(b)(1) on the ground that a firearm was possessed in connection with the offense. McCurvin's offense level of 42 and Criminal History Category III yielded an imprisonment range of 360 months to life. The court sentenced McCurvin to a prison term of 360 months. 84 On or about April 22, 1998, the government learned that a government witness, one of McCurvin's coconspirators, had lied about his identity. The government promptly notified the district court and defense counsel of this fact. 85 At McCurvin's July 20, 1998 resentencing, new counsel, see Note 1, supra, argued that McCurvin should not have received a four-level upward adjustment for his role in the offense because he did not control or manage those to whom he sold crack. Counsel also maintained that McCurvin should receive a downward adjustment for acceptance of responsibility. Finally, he argued that McCurvin should receive a downward departure because of his status as a deportable alien and because of his post-arrest efforts at rehabilitation. Counsel did not, however, move the court for a new trial based on the perjured testimony of the government's witness. 86 The district court granted McCurvin a two level downward departure based upon his post-arrest rehabilitation and agreed that a four-level upward adjustment based upon McCurvin's role in the offense was not warranted. However, the court found that a two-level upward adjustment was appropriate because McCurvin had managed and directed his wife, Antoinette. The court then denied McCurvin's motion for a downward departure based upon his status as a deportable alien, stating "that on the facts of this case, the requested departure is not warranted." McCurvin's request for an adjustment for acceptance of responsibility was similarly rejected. In light of the adjustment and downward departure, the district court found McCurvin's adjusted offense level to be 38. With McCurvin's Criminal History Category of III, this resulted in an imprisonment range of 292 to 365 months. The court then resentenced McCurvin to 336 months' imprisonment. DISCUSSION 87 On appeal, McCurvin contends that: (i) the district court should have granted his motion for a mistrial because of the interaction between law enforcement agents and the jury; (ii) the perjured testimony of a government witness requires a new trial; (iii) the testimony of coconspirators pursuant to cooperation agreements violated the anti-gratuity statute, 18 U.S.C. § 201(c)(2); (iv) the disparity in the sentences for cocaine and crack under the Sentencing Guidelines is unconstitutional; (v) there was inadequate evidence that McCurvin was involved with 1,314 grams of crack; (vi) the sentence on the conspiracy conviction was miscalculated; (vii) the district court erred in refusing to depart downwardly; and (viii) the evidence proffered by the government did not support either of the money laundering convictions.2 We examine each of these contentions in turn. 88 a) Agents' Interaction with Jury 89 McCurvin contends first that the district court erred in concluding that the jury's interaction with Reiner and McTague was harmless. He maintains that although the jurors might have been sincere in stating that they remained impartial, they were in fact prejudiced. In his view, the agents' act of carrying into the jury-deliberation room a cart containing $27,000 in cash and narcotics improperly enhanced the credibility of their testimony in the jurors' eyes because of their possession of the evidence. Moreover, McCurvin contends that "'[i]t is in the nature of the practices here challenged that proof of actual harm, or lack of harm, is virtually impossible to adduce.'" Appellant Br. At 10 (quoting Peters v. Kiff, 407 U.S. 493, 504 (1972)). We find no merit in this claim. 90 As an initial matter, McCurvin failed to argue in the district court that the voir dire was insufficient to detect juror prejudice. He has, therefore, forfeited this claim, and we may reverse only if there was plain error. See Fed. R. Crim. P. 52(b); United States v. Olano, 507 U.S. 725, 731 (1993). There was not. To be sure, government witnesses should not be used to carry evidence into a jury deliberation room when the jury may be present because of the risk that an improper communication might occur. However, the contact in the instant case was extremely brief and inconsequential. In light of these facts and the district court's voir dire, we fail to see how the brief exchange of "good mornings" could have prejudiced the jurors. Moreover, there was another reason to believe that no prejudice occurred. McTague was, as one of the defense attorneys argued in the trial court, "the man who put on, as a witness, basically the government's case with respect to the money laundering charges." Nevertheless, the jury acquitted McCurvin on two of these charges. These acquittals show the jury's open-mindedness on the counts associated with McTague and bolster the district court's and our conclusion that the brief exchange of greetings was entirely harmless. 91 b) Perjured Testimony of Government Witness 92 Although McCurvin was notified three months before resentencing that one of the government's witnesses had committed perjury by misidentifying himself, he did not move in the district court for a new trial. On appeal, McCurvin claims that a new trial should nevertheless be ordered because the witness's perjury destroyed the fairness of his trial. By not requesting a new trial in the district court, however, McCurvin forfeited this claim. See Olano, 507 U.S. at 731. 93 In any event, there was no error. Where, as here, the government was unaware of a witness's perjury, a court must order a new trial only if it finds that "the jury probably would have acquitted in the absence of the false testimony." United States v. Sanchez, 969 F.2d 1409, 1413-14 (2d Cir. 1992); see also United States v. Locascio, 6 F.3d 924, 949 (2d Cir. 1993) (new trial is required only if newly discovered evidence is "material, non-cumulative, and would probably lead to an acquittal" (internal quotation marks omitted)). Here, the witness's true identity was not material, much less central, to the government's case. Moreover, even without the witness's testimony, the evidence of McCurvin's guilt was overwhelming, consisting of ten hand-to-hand crack sales to an undercover FBI agent, the interception of narcotics-related conversations pursuant to court-authorized wiretaps, other recorded conversations, narcotics and drug trafficking paraphernalia seized from his residence, and the testimony of another coconspirator. 94 c) Anti-gratuity Statute 95 McCurvin next argues that the admission of coconspirator testimony at his trial violated the so-called "anti-gratuity statute," 18 U.S.C. § 201(c)(2), because the government promised these witnesses leniency in exchange for their truthful testimony. We disagree. 96 Section 201(c)(2) provides that "[w]hoever . . . directly or indirectly, gives, offers or promises anything of value to any person, for or because of the testimony under oath or affirmation given or to be given by such person as a witness upon a trial . . . before any court . . . shall be fined under this title or imprisoned for not more than two years, or both." 18 U.S.C. § 201(c)(2) (1994). We agree with the reasoning of the Tenth Circuit's en banc opinion, see United States v. Singleton, 165 F.3d 1297 (10th Cir. 1999) (en banc) cert denied, U.S., 119 S.Ct. 2371,L.Ed.2d (1999), and hold that 18 U.S.C. § 201(c)(2) does not apply to the United States or to any Assistant United States Attorney acting within his or her official capacity. 97 d) Sentencing Disparity Between Crack and Cocaine 98 McCurvin next claims that the disparity in the Guidelines sentences for cocaine and crack is unconstitutional. We have already rejected this argument, see United States v. Canales, 91 F.3d 363, 368 (2d Cir. 1996); United States v. Montoya, 87 F.3d 621, 623 (2d Cir. 1996) (per curiam), and decline to revisit the issue. 99 McCurvin alternatively urges application of the rule of lenity because the distinction between crack and cocaine is, he maintains, inherently ambiguous. However, the record provided the district court with ample evidence to find that McCurvin prepared and distributed crack. Thus, "[n]o ambiguity arose from the manner in which the statute was narrowly applied to" McCurvin. Canales, 91 F.3d at 368 (quoting United States v. Martinez, 49 F.3d 1398, 1404 (9th Cir. 1995)). 100 e) Evidence of Drug Quantity 101 According to McCurvin, the evidence that he was involved with 1,314 grams of crack was legally insufficient because the crack he distributed contained caffeine. However, Section 2D1.1(c) of the Sentencing Guidelines provides that offense levels are to be determined by the weight of the mixture containing the narcotics. Except for certain circumstances not relevant here, the weight of the mixture is determined without regard to the drug's purity. See U.S.S.G. §2D1.1(c), Note A to Drug Quantity Table ("the weight of a controlled substance . . . refers to the entire weight of any mixture or substance containing a detectable amount of the controlled substance"). 102 f) Propriety of Sentence on Conspiracy Conviction 103 McCurvin further argues that we should remand for resentencing because his sentence on the conspiracy conviction was miscalculated. He contends that, under United States v. Orozco-Prada, 732 F.2d 1076 (2d Cir. 1984), and United States v. Barnes, 158 F.3d 662 (2d Cir. 1998), he should have received a ten-year minimum sentence pursuant to 21 U.S.C. § 841(b)(1)(B) (applicable to an offense involving cocaine when defendant has prior drug felony conviction), rather than a twenty-year minimum sentence pursuant to 21 U.S.C. § 841(b)(1)(A) (applicable to an offense involving crack when defendant has prior drug felony conviction), because he was convicted of conspiracy to possess and distribute both cocaine and crack, and the jury returned a general guilty verdict. Both Orozco-Prada and Barnes are, however, inapposite. 104 In Orozco-Prada, the defendant was convicted of conspiracy to distribute cocaine and marijuana. The jury's verdict did not specify whether the defendant had been found guilty of a cocaine conspiracy, which carried a statutory maximum 15-year term of imprisonment, or of a marijuana conspiracy, which carried a statutory maximum 5-year term of imprisonment. We held that, in the absence of a special verdict, the defendant was entitled to the more lenient statutory maximum sentence. Accordingly, we gave the government a choice of having the defendant resentenced to a maximum 5-year term or having his conviction vacated and the case remanded for a new trial on that count. In the instant case, by contrast, the statutory maximum term is lifetime imprisonment regardless of whether McCurvin had been found guilty of a cocaine conspiracy or a crack conspiracy. The nature of the offense of conviction thus has no impact on the maximum term of imprisonment permitted by statute. 105 In Barnes, the defendant was convicted of conspiracies to distribute, inter alia, heroin and crack. Although the district court arrived at a Guidelines sentencing range lower than the 20-year minimum sentence applicable to a conspiracy involving crack, it imposed the 20-year minimum. However, the statutory minimum sentence applicable to a conspiracy involving heroin was only 10 years, and we held that the district court should have "assume[d] that the conviction is for conspiracy to possess the controlled substance that carries the most lenient statutorily prescribed sentence." Barnes, 158 F.3d at 668. Accordingly, we again gave the government "the option of retrying the defendant (and seeking a special verdict if he chooses not to amend the indictment) or having him resentenced . . . for conspiracy to possess heroin, the controlled substance carrying the lowest mandatory minimum and permissive maximum penalty." Id. at 674. 106 Unlike Barnes, the Guidelines imprisonment range in the instant case was 292 to 365 months' imprisonment -- higher than both the statutory 10-year minimum term urged by McCurvin and the statutory 20-year minimum term urged by the government. Thus, regardless of which statutory minimum prison term applies, McCurvin's Guidelines imprisonment range would not be altered. There is, therefore, no need to remand for resentencing on this ground. See Edwards v. United States, 523 U.S. 511 (1998) (jury's understanding of nature of drug conspiracy is irrelevant where sentencing scheme would be same in either event). 107 g) Denial of Motion for Downward Departure 108 McCurvin contends that the district court erred in denying his motion for a one-level downward departure based upon his stipulation to deportation. However, because there is no indication that the court misapprehended its authority to depart, its denial of the downward departure motion is not appealable. See United States v. Brown, 98 F.3d 690, 692 (2d Cir. 1996) (per curiam). 109 h) Money Laundering Convictions 110 McCurvin was charged with violating Section 1956(a)(1)(B)(i) of the federal money laundering statute, which provides that: 111 Whoever, knowing that the property involved in a financial transaction represents the proceeds of some form of unlawful activity, conducts or attempts to conduct such a financial transaction which in fact involves the proceeds of specified unlawful activity . . . knowing that the transaction is designed in whole or in part - (i) to conceal or disguise the nature, the location, the source, the ownership, or the control of the proceeds of specified unlawful activity [shall be guilty of an offense]. 112 One money-laundering count alleged that McCurvin violated this Section by causing his wife to put drug proceeds in a safe deposit box; another alleged that his purchase of the 1992 Acura violated the statute. 113 McCurvin asserts that there was legally insufficient evidence to support the jury's finding that his wife's placement of cash proceeds of narcotics trafficking into a safe deposit box held in her name was part of his design to conceal or disguise the nature, location, source, ownership, or control of the proceeds of specified unlawful activity. We disagree. 114 In reviewing a jury verdict for sufficiency of the evidence, we must uphold the conviction if "after viewing the evidence in the light most favorable to the prosecution, any rational trier of fact could have found the essential elements of the crime beyond a reasonable doubt." Jackson v. Virginia, 443 U.S. 307, 319 (1979) (emphasis in original). A defendant who challenges a jury's findings on the ground of sufficiency of the evidence "bears a very heavy burden." United States v. Gonzalez, 110 F.3d 936, 940 (2d Cir. 1997) (internal quotation marks omitted). 115 The statute provides that covered transactions include "use of a safe deposit box." 18 U.S.C. § 1956(c)(3). The only question, therefore, is whether the use of the safe deposit box was caused by McCurvin and whether he caused it with the requisite intent. A rational jury could easily so find. There was ample evidence that the money in the safe deposit box was the fruit of McCurvin's drug transactions and that Antoinette placed it there at his direction so as to conceal it. Indeed, he was recorded saying just that to Jackson, and the box contained prerecorded money. 116 McCurvin also argues that the evidence was inadequate to establish that his purchase of a 1992 Acura Legend was designed to conceal or disguise drug proceeds. McCurvin was charged only with violating subsection (i) of Section 1956(a)(1)(B), and not subsection (ii) which prohibits transactions intended "to avoid a . . . reporting requirement under State or Federal law." As noted, McCurvin maintains that his purchase of the car was an ordinary commercial transaction and that a money laundering conviction under Section 1956(a)(1)(B)(i) requires more than proof of the spending of the ill-gotten gains. We agree. 117 Joining a number of other circuits, we hold that Subsection (i) of the money laundering statute does not criminalize the mere spending of proceeds of specified unlawful activity. See, e.g., United States v. Dobbs, 63 F.3d 391, 398 (5th Cir. 1995) ("where the use of the money was not disguised and the purchases were for family expenses and business expenses . . . , there is . . . insufficient evidence to support the money laundering conviction"); United States v. Rockelman, 49 F.3d 418, 422 (8th Cir. 1995) (money laundering statuteshould not be interpreted to criminalize ordinary spending of drug sale proceeds); United States v. Garcia-Emanuel, 14 F.3d 1469, 1476 (10th Cir. 1994) (Section 1956(a)(1) "is a concealment statute -- not a spending statute"); United States v. Sanders, 929 F.2d 1466, 1472 (10th Cir. 1991) (money laundering statute should not be interpreted to criminalize ordinary spending of drug proceeds). By its express terms, the statute requires proof that a financial transaction involving drug proceeds was designed "to conceal or disguise the nature, the location, the source, the ownership, or the control of the proceeds of specified unlawful activity." 18 U.S.C. § 1956(a)(1)(B)(i). Thus, absent proof of intent to conceal, an ordinary purchase made with ill-gotten gains does not violate the money laundering statute. 118 The government claims that it established the requisite intent to conceal by showing that McCurvin laundered money through the purchase of the Acura "by employing a bogus payment schedule" with Tri Auto. According to the government's brief on appeal, McCurvin allegedly made a large, cash downpayment in excess of the $10,000 cash reporting requirement in exchange for the automobile. Tri Auto in turn issued two receipts: one for the amount actually paid and one that reflected a payment of less than $10,000. Employment of this phony installment scheme, the government contends, evidences intent to conceal. 119 Had such conduct been shown, it would have been sufficient to support the jury's finding of intent to conceal. See United States v. Kinzler, 55 F.3d 70, 74 (2d Cir. 1995) (upholding money laundering conviction on ground that defendant "did not engage in 'ordinary' commercial transactions that happened to involve the proceeds of [illicit activity], but rather employed an elaborate plan precisely to conceal the unwelcome source of those proceeds from the credit card companies with which he dealt"). However, there is no evidence that McCurvin engaged in any such scheme when he purchased the Acura Legend.3 To the contrary, the record reflects that McCurvin's purchase was "open and notorious," Dobbs, 63 F.3d at 397, that he personally closed the transaction, took title to the Acura in his name, and conspicuously used the car. There is no indication, therefore, that the drug proceeds were spent "to create the appearance of legitimate wealth" or for any purpose other than "present personal benefit." Garcia-Emanuel, 14 F.3d at 1474. 120 McCurvin may have intentionally made a downpayment of less than $10,000 in order to avoid triggering federal transaction reporting requirements. However, we hold that such a purpose is not sufficient to satisfy the "intent to conceal" requirement of Section 1956(a)(1)(B)(i). "Conceal" implies conduct entailing deception that goes beyond merely acting in a way that avoids compulsory disclosure. 121 Moreover, Subsection (ii) expressly criminalizes transactions designed to evade state or federal reporting requirements. A statute should be construed so that all of its parts are given effect, see Mobil Oil Corp. v. Karbowski, 879 F.2d 1052, 1055 (2d Cir. 1989), and "a construction ascribing to two separate statutory provisions the same meaning and scope is [therefore] disfavored." United States v. Yip, 930 F.2d 142, 148 (2d Cir. 1991). In light of these customary guides to statutory interpretation, the government's view that an intent to avoid government reporting requirements by itself establishes intent to conceal must be rejected. To give effect to both subsections 1956(a)(1)(B)(i) and (B)(ii), each must proscribe conduct distinct from the other. See id. Evidence of intent to evade a reporting requirement cannot, therefore, in and of itself satisfy the "intent to conceal" element of subsection (B)(i). The evidence proffered in the instant case thus failed as a matter of law to satisfy the scienter requirement of Subsection 1956(a)(1)(B)(i).4 CONCLUSION 122 For the foregoing reasons, we vacate the money laundering conviction on Count 28 and remand to the district court for proceedings consistent with this opinion. We otherwise affirm in part and dismiss in part. NOTES: * The Honorable Leonard B. Sand, of the United States District Court for the Southern District of New York, sitting by designation. 1 The jury acquitted McCurvin on two counts of money laundering in connection with his purchase of two other automobiles. The district court subsequently vacated, pursuant to Bailey v. United States, 516 U.S. 137 (1995), the guilty verdicts regarding the use and carrying of a firearm during and in relation to a narcotics trafficking offense and, on April 4, 1996, sentenced McCurvin on the remaining counts to 360 months' imprisonment and ten years of court- supervised release. Trial counsel failed to file a timely notice of appeal. On January 27, 1997, McCurvin filed a Section 2255 motion in order to reinstate his right to appeal. See 28 U.S.C. § 2255. Substitute counsel was thereafter appointed to represent McCurvin, and his motion to vacate the sentence was granted. After downwardly departing on the ground of post- arrest rehabilitation, the district court resentenced McCurvin on July 20, 1998, to 336 months' imprisonment and a ten- year term of supervised release. 2 Initially, McCurvin also objected to the Section 3B1.1(a) enhancement, contending that a four-level adjustment was inappropriate. However, in his reply brief, he acknowledged that the district court had in fact imposed only a two-level enhancement. 3 In United States v. Wisniewski, 121 F.3d 54, 56 (2d Cir. 1997), we upheld the money laundering conviction of the owner of Tri Auto because the evidence showed that "the dealership sold cars to a number of drug dealers, who frequently purchased cars with cash, often using names other than their own" and that "Tri Auto routinely substituted checks for the cash payments, apparently in order to avoid cash- reporting requirements." In the instant case, however, the government proffered no evidence establishing either Tri Auto's or McCurvin's employment of such money laundering schemes. 4 We do not reach the issue of whether the evidence in the instant case - - a downpayment below the report-triggering level and installment payment arrangement in an otherwise egitimate consumer purchase - - would be sufficient to support a conviction under subsection 1956(a)(1)(B)(ii).	{ "pile_set_name": "FreeLaw" }
/**************************************************************** MIT License http://www.opensource.org/licenses/mit-license.php Author Mora <qiuzhongleiabc@126.com> (https://github.com/qiu8310) ****************************************************************/ import {execSync} from 'child_process' import as fs from 'fs-extra' import * as path from 'path' import * as JSON5 from 'json5' import * as clog from 'mora-scripts/libs/sys/clog' import {JSON_REGEXP} from '@minapp/common/dist/dev/config' export {JSON_REGEXP} export function code(str: string) { return clog.format('%c' + str, 'yellow') } export function walkDirectory(dir: string, cb: (dir: string, name: string, file: string, stat: fs.Stats) => boolean \| void \| undefined) { fs.readdirSync(dir).forEach(name => { let file = path.join(dir, name) let stat = fs.statSync(file) if (false !== cb(dir, name, file, stat)) { if (stat.isDirectory()) { walkDirectory(file, cb) } } }) } export function getGitUser() { let name = tryExecCmdSync('git config --get user.name', '').trim() let email = tryExecCmdSync('git config --get user.email', '').trim() if (email) email = `<${email}>` return `${name}${email}` } function tryExecCmdSync(cmd: string, fallback: string): string function tryExecCmdSync(cmd: string, fallback?: string): undefined \| string { try { return execSync(cmd).toString() } catch (e) { return fallback } } /** * 从指定的目录中获取指定名称的 json 文件的路径 / export function getJsonFilePath(fromDirectory: string, baseName: string) { let file = fs.readdirSync(fromDirectory).find(n => n.startsWith(baseName) && JSON_REGEXP.test(n) && n.replace(JSON_REGEXP, '') === baseName) return file ? path.join(fromDirectory, file) : undefined } /* * 获取文件不带路径和后缀的名称 */ export function getFileBaseName(file: string) { return path.basename(file, path.extname(file)) } export function getFilePath(fromDirectory: string, baseName: string, extensions: string[]) { let exts = extensions.map(e => e.toLowerCase()) let file = fs.readdirSync(fromDirectory).find(n => n.startsWith(baseName) && exts.includes(n.substr(baseName.length + 1).toLowerCase())) return file ? path.join(fromDirectory, file) : undefined } export function getComponentJson(refFile: string) { let dir = path.dirname(refFile) let name = path.basename(refFile.replace(/\.\w+$/, '')) let foundjson = fs.readdirSync(dir).find(n => n.replace(JSON_REGEXP, '__') === name + '__') let foundjs = fs.readdirSync(dir).find(n => n === name + '.js' \|\| n === name + '.ts') if (foundjson && foundjs) { let jsonFile = path.join(dir, foundjson) let jsFile = path.join(dir, foundjs) let content = fs.readFileSync(path.join(dir, foundjson)).toString() return { jsonFile, jsFile, jsContent: fs.readFileSync(jsFile).toString(), json: JSON5.parse(content) } } return {} }	{ "pile_set_name": "Github" }
Q: How is 'classOf' expression represented in scala AST I'm new to the Scala AST concepts. I need to traverse a Scala code tree that contains an expression such as: classOf[org.apache.commons.lang3.ArrayUtils] I need to be able to identify this case when pattern matching on scala.reflect.internal.Trees.Tree. For instance I know that it is not case _:Apply What is the correct pattern in order to successfuly match this expression? A: A classOf[C] is represented as a Literal(value), where value.tag == ClazzTag, and value.typeValue is a Type representing C. You can match on it as: case Literal(value) if value.tag == ClazzTag => val tpe = value.typeValue // do something with `tpe` See https://github.com/scala-js/scala-js/blob/ec5b328330276b9feb20cccadd75e19d27e887d3/compiler/src/main/scala/org/scalajs/nscplugin/GenJSCode.scala#L2043 for a real-world example.	{ "pile_set_name": "StackExchange" }
On a couple of retreats, I've noticed the odd individual extending a very , very slow walking practice, to other activities (cooking, washing-up.. ),and moving almost robotically.To anyone unfamiliar with this methodology, it looks like "Buddhist " affectation, which I suppose in a way it is Does anyone employ the go slow practice (on or off retreat), and is it worthwhile cultivating as an aid to mindfulness? Mahasi-school teachers recommend maintaining mindfulness continuously, and this is easier to do if you do things slowly and deliberately. Of course, this may not fit well with the method you usually use... Persevering continuity of mindfulness is the third essential factor in developing the controlling faculties. One should try to be with the moment as much as possible, moment after moment, without any breaks in between. In this way mindfulness can be established, and its momentum can increase. Defending our mindfulness prevents the kilesas, the harmful and painful qualities of greed, hatred and delusion, from infiltrating and carrying us off into oblivion. It is a fact of life that the kilesas cannot arise in the presence of strong mindfulness. When the mind is free of kilesas, it becomes unburdened, light and happy. Do whatever is necessary to maintain continuity. Do one action at a time. When you change postures, break down the movement into single units and note each unit with the utmost care. When you arise from sitting, note the intention to open the eyelids, and then the sensations that occur when the lids begin to move. Note lifting the hand from the knee, shifting the leg, and so on. Throughout the day, be fully aware of even the tiniest actions — not just sitting, standing, walking and lying, but also closing your eyes, turning your head, turning doorknobs and so forth. Apart from the hours of sleeping, yogis on retreat should be continuously mindful. Continuity should be so strong, in fact, that there is no time at all for reflection, no hesitation, no thinking, no reasoning, no comparing of one’s experiences with the things one has read about meditation — just time enough to apply this bare awareness. I think its definately a " taste it and see " approach. I too know people who find it useful, and it is certainly widely taught. On an admittedly brief trial though, it didnt do much for me. But the I am quite slow at those type of activities anyway. I can imagine it could be very useful for "speedy ", task orientated , people. The going for refuge is the door of entrance to the teachings of the Buddha. I have found that slowing down definitely increases my mindfulness and I have found it quite beneficial. Some days I have gone nearly every minute of the day with sustained awareness of bodily movements, postures and feelings but I seem to rush a lot lately and am less mindful as a result. It is something I have been thinking about a bit lately, craving for how mindful I was in the past, which of course is pointless since while I am busy craving for past experiences the present moment keeps slipping away. The following Ajahn Chah quote comes to mind: "Try to be mindful and let things take their natural course and your mind will become like a still forest pool". With Metta, Guy Four types of letting go: 1) Giving; expecting nothing back in return2) Throwing things away3) Contentment; wanting to be here, not wanting to be anywhere else4) "Teflon Mind"; having a mind which doesn't accumulate things It can look pretty odd. One thing I noticed on a recent retreat is that I actually slowed down for a little while. I usually walk fast, but uncharacteristically, on this occasion I caught myself walking slowly as others passed me on the path. I didn't really decide to walk slowly, and I don't think I was going so slow that it was odd. But who knows? Maybe the folks around me thought I was "one of them." Any way, this might not relate to your situation at all, but what I figured was that if other folks want to walk slow, eat slow, whatever, I'm not going to assume any more that they're doing it on purpose, or because they're trying to achieve some kind of moment-to-moment awareness. Maybe they're just slow at that particular juncture during the retreat. Bottom line: This is a good question for your teacher. On the retreats I attend, slow-walking is not part of the practice, although of course we're all encourage to be mindful at all times, no matter what we're doing. Rain soddens what is kept wrapped up,But never soddens what is open;Uncover, then, what is concealed,Lest it be soddened by the rain. When I was a kid, I was skiing once. As I climbed back up the hill at one point, a man I did not know called me over to him and said, in essence, "Look, any dummy can ski fast. It takes a good skiier to ski slow." I tried it ... and I can't tell you how many times I ended up on my butt that afternoon. 'Slow' nourishes attention and care and skill. But making a fetish out of it is not much better than the dummy who can ski fast. Jechbi wrote:It can look pretty odd. One thing I noticed on a recent retreat is that I actually slowed down for a little while. I usually walk fast, but uncharacteristically, on this occasion I caught myself walking slowly as others passed me on the path. I didn't really decide to walk slowly, and I don't think I was going so slow that it was odd. But who knows? Maybe the folks around me thought I was "one of them." Any way, this might not relate to your situation at all, but what I figured was that if other folks want to walk slow, eat slow, whatever, I'm not going to assume any more that they're doing it on purpose, or because they're trying to achieve some kind of moment-to-moment awareness. Maybe they're just slow at that particular juncture during the retreat. Bottom line: This is a good question for your teacher. On the retreats I attend, slow-walking is not part of the practice, although of course we're all encourage to be mindful at all times, no matter what we're doing. On retreats were I have seen it done, it was announced before hand that it would form part of the retreat ( Which wasnt Mahasi, but incoporated elememts of that ) for those who wanted to practice that way, it wasnt an individual whimsical choice. I once arrived at the door of a room where everyone was slow walking being led by a Bhikkhu, they all marched forward eyes on the ground more or less in unison and because of the nature of the building they were just above my eye level as I walked up the stairs. It was memorable.... The going for refuge is the door of entrance to the teachings of the Buddha. THREE: UNBROKEN CONTINUITYDo whatever is necessary to maintain continuity. Do one action at a time. When you change postures, break down the movement into single units and note each unit with the utmost care. When you arise from sitting, note the intention to open the eyelids, and then the sensations that occur when the lids begin to move. Note lifting the hand from the knee, shifting the leg, and so on. Throughout the day, be fully aware of even the tiniest actions — not just sitting, standing, walking and lying, but also closing your eyes, turning your head, turning doorknobs and so forth.Apart from the hours of sleeping, yogis on retreat should be continuously mindful. Continuity should be so strong, in fact, that there is no time at all for reflection, no hesitation, no thinking, no reasoning, no comparing of one’s experiences with the things one has read about meditation — just time enough to apply this bare awareness. I don't think I could sustain this practice for very long.. it sounds like real ego-busting stuff. Almost like breaking a horse. Is this why folk are averse to it? And can this "bare awareness" be applied to vedana, citta and dhamma's too? I must admit my own practice is lacking in "attention, care and skill" - though I do "slow" with some panache Also, I agree that people do generally slow down on retreat. Their actions are less driven, less "self" seeking. And just "being" is sufficient A fellow retreatant remarked to me that coming back from a group country walk, "felt" like returning as part of a herd of cows! But that's not quite the aspiration is it? imagemarie wrote:I don't think I could sustain this practice for very long.. it sounds like real ego-busting stuff. Well, that's the point, isn't it? To see through the sense of self... Remember that this is a talk by U Pandita addressing a group of experienced meditators who had done numerous retreats before. I wouldn't advise going straight to that level of intensity. If you listen to a few of Joseph Goldstein's talks interesting little anecdotes about that retreat will pop up. One was, if I recall correctly, that Sharon Salzberg went through a period there where U Pandita would keep asking her about little things that were cleverly designed to be not things that she had paid attention to: "How did you feel brushing your teeth this morning?". "Ummm..." end of interview. Next day she was ready for the teeth question, but the first question was: "How did you feel when you bowed just now when you came in?", "Ummm...". And so on, until she learned to pay attention to everything... My teachers have never been quite so intense, but one of them sometimes asks little things, like if we can remember which finger moved first when we unclasped our hands when moving from walking to sitting meditation. Partly to make clear that there is a lot that we don't notice. Anyway, bear in mind that this is part of a whole package. It doesn't necessarily work to try to pick out bits of different practises and bolt them together... Pay attention to your teacher... Also, after you've spent several days on retreat not talking, just meditating and paying attention, it becomes a lot easier and more natural. This applies to all techniques, of course. Don't judge any of them by what you can do by practising for an hour or two a day... Guy wrote:Hi Marie,The following Ajahn Chah quote comes to mind: "Try to be mindful and let things take their natural course and your mind will become like a still forest pool". Jechbi wrote:It can look pretty odd. One thing I noticed on a recent retreat is that I actually slowed down for a little while. I usually walk fast, but uncharacteristically, on this occasion I caught myself walking slowly as others passed me on the path. I didn't really decide to walk slowly, and I don't think I was going so slow that it was odd. But who knows? Maybe the folks around me thought I was "one of them." This has been my experience too. I have never made a conscious effort to move slowly but I seem to ease into 'slow motion mode' quite naturally when I'm in a contemplative environment like on retreat and sometimes when I'm alone at home. mikenz66 wrote:One was, if I recall correctly, that Sharon Salzberg went through a period there where U Pandita would keep asking her about little things that were cleverly designed to be not things that she had paid attention to: "How did you feel brushing your teeth this morning?". "Ummm..." end of interview. Next day she was ready for the teeth question, but the first question was: "How did you feel when you bowed just now when you came in?", "Ummm...". And so on, until she learned to pay attention to everything... Yeah I've read/heard about this. It's a great anecdote! mikenz66 wrote:Anyway, bear in mind that this is part of a whole package. It doesn't necessarily work to try to pick out bits of different practises and bolt them together... Pay attention to your teacher... Also, after you've spent several days on retreat not talking, just meditating and paying attention, it becomes a lot easier and more natural. This applies to all techniques, of course. Don't judge any of them by what you can do by practising for an hour or two a day... Mike Yes - indeed. Thanks, Mike, that's very helpful. I'm not really advocating a smorgasbord approach to practice. Perhaps sometimes looking at the meals of other diners and thinking..yeah, that looks tasty Maybe my diet is lacking in that As in metabolism perhaps, change happens at the molecular level. And I'm not really lacking anything.As mother's like to say "Your eyes are bigger than your stomach" I do sometimes slow down, but more as an aid to getting my mindfulness back to what im doing, if I have problems for a moment, it is something I would recomend doing as appropriate but cooking isn't one of the situations, as being fast is the virtue in this case, and a safer/easier to wash up, way of doing it, and it is a habit for me while cooking anyway now since I was a chef for a couple of years.I don't go particularly slow, but instead of walking at 2 miles an hour I walk at 1mph just half my spead for a little while and the same goes for slowing down for me as a rule of thumb I employ for it.number one rule for anything is appropriateness, and part of this is safety. This offering maybe right, or wrong, but it is one, the other, both, or neither!Blog,-Some Suttas Translated,Ajahn Chah."Others will misconstrue reality due to their personal perspectives, doggedly holding onto and not easily discarding them; We shall not misconstrue reality due to our own personal perspectives, nor doggedly holding onto them, but will discard them easily. This effacement shall be done."	{ "pile_set_name": "Pile-CC" }
Background ========== Endothelial cell adhesion molecules (\'ECAMs\') play essential roles in the development of chronic inflammation by recruiting leukocytes, especially lymphocytes to tissues. ECAMs support several forms of leukocyte adhesion including rolling, firm adhesion and extravasation \[[@B1]\]. Infiltration of tissues by leukocytes is a common hallmark of many chronic inflammatory states that include the inflammatory bowel diseases (IBD), ulcerative colitis (UC), and Crohn\'s disease (CD). In the setting of IBD, the expression of ECAMs like ICAM-1, VCAM-1, and MAdCAM-1 (mucosal addressin cell adhesion molecule-1) is observed in experimental models of colitis, \[[@B2]-[@B5]\] and also within the inflamed human colon in Crohn\'s disease and ulcerative colitis \[[@B6],[@B7]\]. Among the adhesion molecules up-regulated in IBD, MAdCAM-1, the mucosal cell adhesion molecule, is thought to be preeminent in the development of chronic gut inflammation. MAdCAM-1 is normally expressed in the gut, and its expression is dramatically amplified during inflammation \[[@B2],[@B3]\]. The functional significance of increased appearance of MAdCAM-1 in IBD is supported by several reports which show that immunoneutralization of either MAdCAM-1 or its ligand, the α4β7 integrin, attenuate inflammation and mucosal damage in animal models of colitis \[[@B8]-[@B10]\]. However, since monoclonal antibodies directed against other ECAMs, particularly VCAM-1, can as well reduce disease activity in colitis models \[[@B11]-[@B14]\], the literature suggests that MAdCAM-1 is probably necessary, but insufficient for the maximal penetrance of experimental and probably also clinical IBD. Based on these findings, it is apparent that a better understanding of the mechanisms regulating ECAM expression, especially that of MAdCAM-1, might help to devise improved therapies for colitis. It has been suggested that pathologic activation of the mucosal immune system in response to antigens is a key factor in the pathogenesis of IBD. Furthermore, changes in leukocyte migration and cytokine production appear to contribute the perpetuation of IBD \[[@B15]\]. Based on modern advances, recombinant anti-inflammatory cytokines (i.e. IL-10) treatment is now being developed for experimental colitis and human IBD. IL-10 produced by macrophages and monocytes appears to limit chronic inflammation \[[@B16]-[@B18]\], through a decreased release of inflammatory factors (IL-1, IL-6, IL-12, TNF-α, GM-CSF, GCSF), suppression of adhesive determinants (MHC class II molecule, β7), and by blocking ICAM-1 induction \[[@B19]-[@B24]\]. Conversely, IL-10 gene-knockout mice develop a chronic colitis that is extremely similar to IBD \[[@B25]\]. IL-10 treatment can reduce inflammation in several models of colitis \[[@B26]-[@B30]\] and human IBD \[[@B31]-[@B35]\]. However, the clinical efficacy of systemically administered IL-10 for patients mild to moderately active Crohn\'s disease has not been as effective as hoped \[[@B33]-[@B35]\]. Furthermore the efficacy of IL-10 administration in mouse colitis models is contentious \[[@B36]\]. We have described in vitro that exogenous IL-10 can block the expression of MAdCAM-1 in response to TNF-α, and attenuates lymphocyte adhesion to lymphatic node derived endothelium under cytokine stimulating conditions via NF-kB inhibition \[[@B5]\]. The purpose of the current study was to show that induction of endothelial expression of IL-10 through an IL-10 expression vector attenuates MAdCAM-1 expression in response to TNF-α and optimistically suggests the possibility of targeted Th2-cytokine gene therapy in IBD. Methods ======= Reagents -------- Recombinant mouse TNF-α was purchased from ENDOGEN (Stoughton, MA) amd plasmid containing human IL-10 (phIL-10) was generous gift from Dr. Meng X (Thomas Jefferson University, PA). Cell culture ------------ The SVEC4-10 line is an endothelial cell line derived by SV40 (strain 4A) transformation of murine small vessel endothelial cells, originally isolated from the axillary lymph node vessels of an adult male C3H/Hej mouse \[[@B37],[@B38]\]. These cell types were all maintained in Dulbecco\'s modified Eagle\'s medium (DMEM) with 10% fetal calf serum with 1% antibiotic/ antimycotic. Cells were seeded into 24-well tissue culture plates at approximately 20,000 cells/cm^2^, and cultures were used immediately upon reaching confluence (usually 3--4 days after seeding). Lymphocytes ----------- The mouse CD8^+^T cell lymphoma TK-1 cells (that constitutively expresses the α4β7 integrin \[[@B39]\]) were obtained as a generous gift from Dr. Eugene Butcher (Stanford University, CA). These cells were cultured in RPMI-1640 medium supplemented with 10% FCS and 0.05 mM 2-mercaptoethanol (minus antibiotic/ antimycotic). IL-10 gene transfer ------------------- The pCYIL-10 vector is an expression vector which was established by Dr. Xianmin Meng based on the pCY4B vector \[[@B40]\]. Cultured SVEC endothelial cells seeded in 24 wells were transfected at 70% confluency with SuperFect (Qiagen). Briefly, 1 μg plasmid DNA was diluted with 60 μl DMEM and then 5 μl Superfect (3 mg/ml) was added. After incubation at room temperature for 10 min, the complex was mixed with 350 μl medium and added to the each wells. After 2 h at 37°C, 5% CO2, the complex was aspirated and washed 2 times with medium following replace by 1 ml of medium. After incubation at 37°C for 24 h cells were stimulated with TNF-α. Western analysis of cell lysates -------------------------------- 24 h of IL-10 gene transfer, monolayers were treated with TNF-α (1 ng/ml, 24 h). All cell samples were harvested at 24 hours. Equal quantities of protein (75 μg) from each sample were electrophoretically separated on 7.5% SDS-PAGE gels. Gels were transferred to nitrocellulose membranes (Sigma) and blocked with 5% milk powder in PBS at 4°C (overnight). These membranes were washed twice for 10 min with wash buffer (0.1% milk powder in PBS). Primary rat anti-mouse MAdCAM-1 mAb was added at a concentration of 10 μg/ml and incubated at room temperature for 2 h. These membranes were washed twice with wash buffer. Secondary rabbit anti-rat horseradish peroxidase conjugated secondary antibody (Sigma) was added at a 1:2000 dilution for 2 h. Lastly, membranes were washed 3 times and developed using the enhanced chemiluminescence (ECL) detection system (Amersham, La Jolla, CA). The density of MAdCAM-1 staining was measured by scanning the 60 kD band, using a HP ScanJet™ flatbed scanner. Images were analyzed for density using Image Pro Plus™ image analysis software (Media Cybernetics). The data are expressed as a percentage of TNF-α-induced level of density. In each protocol, treatments were performed at least in triplicate. TK-1 lymphocyte adhesion assay ------------------------------ Briefly, TK-1 cells were suspended in culture medium and fluorescence labeled by incubating TK-1 cells at 2 × 10 ^6^cells/ml with 0.02 mg fluorescein diacetate (FDA) (Sigma) at 37°C for 30 min. The cells were then washed twice with ice-cold HBSS, spun at 250 g for 5 min to remove unincorporated fluorescence and suspended in HBSS. The TK-1 lymphocyte cell line used in this assay expresses high levels of the α4β7 integrin, \[[@B39],[@B41]\] which can interact with multiple ligands including mucosal addressin-1 (MAdCAM-1), as well as VCAM-1, L-selectin and fibronectin \[[@B42]\]. In this system, TNF-α stimulated TK-1 adhesion to SVEC4-10 endothelial cells is at least 50% MAdCAM-1 dependent \[[@B41]\]. SVEC monolayers were grown in 48-well plates as described, and to activate endothelium, the monolayers were incubated with TNF-α (1 ng/ml) for 24 h. Cytokine treated endothelial cells were washed three times with media. Labeled TK-1 cells were then added to the endothelium at a 5:1 lymphocyte to endothelial cell ratio \[[@B43]\] and allowed to bind for 30 min under static conditions. At the end of the incubation period, the supernatant was removed and the monolayers were washed twice with HBSS. Plates were read on a Fluoroskan Ascent (Labsystems, Helsinki, Finland) set for excitation at 485 nm, and emission at 515 nm. Blank wells (0% TK-1 adhesion) were run as controls that did not contain labeled TK-1 cells. The data are expressed as a percentage of TNF-α-induced level of fluorescence. In each protocol, treatments were performed at least in triplicate. Statistical analysis -------------------- All values are expressed as mean ± SD. Data were analyzed using multiple comparisons. Probability (P) values of \< 0.05 were considered significant. Results ======= Secretion of human IL-10 concentration by transfected endothelial cells ----------------------------------------------------------------------- To screen for the efficacy of IL-10 transfected SVEC, we initially measured the IL-10 concentration in the medium prior to gene transfection. There was no detectable human IL-10 signal in the non-transfected cell medium (control), nor any mouse IL-10 (data not shown). However, the medium from the IL-10 transfected SVEC medium showed a large and significant increase in the IL-10 concentration (1209 ± 2 pg/ml) at 48 h after IL-10 gene transfection (Figure [1](#F1){ref-type="fig"}). Importantly, SVEC cells transfected with this vector showed no evidence of toxicity, altered proliferation and morphologically were indistinguishable from mock-transfected and untreated controls. ![Secretion of human IL-10 concentration by transfected endothelial cells.There was no detectable human IL-10 signal in the non-transfected cell medium (control). However, the medium from the IL-10 transfected SVEC medium showed a large and significant increase in the IL-10 concentration (1209 ± 2 pg/ml) at 48 h after IL-10 gene transfection (n = 5). (\# p \< 0.05 from control). One-way ANOVA with Fisher\'s PLSD test.](1471-230X-3-3-1){#F1} MAdCAM-1 expression in IL-10 gene transfected endothelial cells --------------------------------------------------------------- The anti-inflammatory effect of IL-10 gene transfection in endothelial cells was measured by the reduction in the expression of the endothelial cell adhesion molecule MAdCAM-1 induced by TNF-α (1 ng/ml, 24 h). TNF-α strongly induced expression of MAdCAM-1. This effect was significantly reduced by IL-10 gene transfection (Fig. [2](#F2){ref-type="fig"}). Alone, the IL-10 gene transfection had no effect on MAdCAM-1 expression. ![IL-10 gene transfected SVEC is resistant to TNF-α induced MAdCAM-1 expression.TNF-α (1 ng/ml, 24 h) significantly increased expression of MAdCAM-1 and this was significantly blocked by IL-10 gene transfection. Alone, IL-10 gene transfer had no effect on MAdCAM-1 expression (n = 5). (\* p \< 0.05 from TNF-α, \# p \< 0.05 from control). One-way ANOVA with Fisher\'s PLSD test.](1471-230X-3-3-2){#F2} α4β7 integrin lymphocyte adhesion to IL-10 gene transfected endothelial cells ----------------------------------------------------------------------------- Having established that IL-10 gene transfection exerts a significant protective effect against TNF-α stimulated endothelial MAdCAM-1 induction, we next examined the effects of IL-10 gene transfection on the adhesion of α4β7 expressing lymphocytes (using the mouse cell line TK-1) to endothelial monolayers. TNF-α stimulation (1 ng/ml, 24 h) significantly increased the adhesion of TK-1 lymphocytes to SVEC monolayers. IL-10 gene transfection significantly reduced TK-1 adhesion in response to TNF-α stimulation at 24 h (Fig. [3](#F3){ref-type="fig"}). Alone, IL-10 gene transfection did not modify the basal level of lymphocyte adhesion to the endothelium without TNF-α treatment. ![IL-10 gene transfer blocked TNF-α induced lymphocyte adhesion on SVEC.TNF-α stimulation (1 ng/ml, 24 h) significantly increased the adhesion of TK-1 lymphocytes to SVEC monolayers. IL-10 gene transfer significantly reduced TK-1 adhesion in response to TNF-α stimulation at 24 h. IL-10 gene transfer did not modify the basal level of lymphocyte adhesion to the endothelium without TNF-α treatment (n = 7). (\* p \< 0.05 from TNF-α, \# p \< 0.05 from control). One-way ANOVA with Fisher\'s PLSD test.](1471-230X-3-3-3){#F3} Discussion ========== MAdCAM-1 is a 60 kDa endothelial cell surface molecule that is strongly expressed by mucosal endothelial cells, particularly following exposure of these cells to pro-inflammatory cytokines such as TNF-α. Expression of MAdCAM-1 has also been reported in the brain, and in the heart \[[@B44],[@B45]\]; based on these findings, it is now been suggested that MAdCAM-1 might play roles in chronic inflammation of these organs as well. With respect to inflammatory bowel disease, MAdCAM-1 appears to be essential to the lymphocyte homing to the mucosa associated lymphoid tissue (MALT) \[[@B6],[@B37],[@B38],[@B46]\]. Since MAdCAM-1 is normally expressed mainly within the gut microvasculature, and is dramatically amplified during IBD, it has been suggested that increased MAdCAM-1 expression contributes to the etiology of IBD through its ability to direct homing of lymphocytes to the gut. This notion is well supported by several reports that show that antibodies directed against either MAdCAM-1, or its lymphocyte ligand, the α4β7 integrin will significantly attenuate several indices of gut damage in experimental models of colitis \[[@B9],[@B47]\]. Several studies have indicated that T helper (Th1) immune response has important roles in the development of IBD \[[@B48]-[@B50]\]. Moreover, dysregulation of cytokine networks is involved in Th1-dominant immune responses in IBD \[[@B48]-[@B50]\]. Among the Th1 cytokines, TNF-α is thought to be perhaps the most important cytokine responsible for driving the onset and evolution of IBD. Because of this prime role of TNF-α in IBD, anti-TNF-α antibody therapy has been very successfully used in IBD to reduce both colonic injury and expression of ECAMs in IBD \[[@B51]\]. IL-10, a cytokine produced by activated macrophages and Th2-type T cells, has crucial inhibitory effect against several Th-1 type immune responses, such as the antigen-presenting functions of monocytes and macrophages \[[@B52],[@B53]\]. IL-10 may play an important role in preventing the induction of IBD, since animals deficient in IL-10 will develop colitis spontaneously, and low levels of IL-10 are positively correlated with recurrences of Crohn\'s disease \[[@B25],[@B54]\]. However, unlike TNF-α based therapies, the administration of recombinant IL-10 (rIL-10) shows poor clinical efficacy. This may reflect the fact that TNF-α therapies for IBD are aimed at efficiently clearing TNF-α, while IL-10 therapies must increaseIL-10 and recombinant IL-10 is likely too rapidly cleared from the circulation after in vivoadministration to provide a uniform protection \[[@B55]\]. On the other hand, IL-10 gene transfertechnology has been used with some success in models of colitis, however its effectiveness is also variable. One reason for this variability may be that the final serum IL-10 concentration of gene-transfected mice might be below the critical threshold needed for gut protection \[[@B55],[@B56]\]. Therefore targeting of the IL-10 gene to the inflamed colon should ideally exploit tissue (i.e. gut) specific promoters to control selective organ gene transfer technology, endothelial specific promoters and also organ specific intra-arterial injection of vector to activate some genes in specific locations \[[@B57]\]. Administration of IL-10 in vitroprevents TNF-α stimulated expression of MAdCAM-1, and also blocks lymphocyte adhesion to endothelial cells to the same extent as dexamethasone treatment, currently a key therapy in IBD \[[@B5]\]. Interestingly, the low basal levels of MAdCAM-1 expressed by control (cytokine unstimulated) cells were not affected by IL-10 transfection. This suggests that basal expression of MAdCAM-1, is IL-10 independent, while cytokine stimulated MAdCAM-1 ismodulated by IL-10. While we previously showed that delivery of IL-10 to the endothelium in vitrois protective against TNF-α \[[@B5]\], in vivoIL-10 has not been as effective. There are at least two regulating pathways in ECAM expression, one is a cytokine-dependent pathway which is widely studied and the other is cytokine-independent \[[@B58]\]. IL-10 apparently prevents cytokine-induced NF-kB binding activity to the ECAM promoter \[[@B59]\] and blocks the excessive expression of ECAMs in cytokine-mediated inflammatory conditions. In this regard, IL-10 has been used as a treatment in inflammatory diseases, like IBD for precisely this reason: because it has few effects at sites remote from inflammation. Similarly, we found that IL-10 transfection did not affect cell morphology, total protein level, or the expression of actin and vimentin in these cells (measured by Ponceau red S staining density on immunoblots). Therefore methods like endothelial gene transfection/transfer in vivomay effectively maintain adequate IL-10 concentrations near the endothelial cells that finally achieve the protection against cytokines that is not uniformly produced by systemic IL-10 administration. The most important index for how well gene mediated recombinant IL-10 delivery might work in IBD appears to be measurement of the inhibition of lymphocyte-endothelium binding mediated by TNF-α induced MAdCAM-1 expression. In this experiment, IL-10 induction in the endothelium efficiently blocked TNF-α induced MAdCAM-1 expression and α4β7-dependent lymphocyte adhesion on SVEC endothelial cells. IL-10 deficiency in colitis increases expression of several ECAMs including ICAM-1, VCAM-1 and MAdCAM-1 \[[@B60]\]. We performed an experiment, where under non-stimulated conditions only 55.7 ± 5.4% as many of the TK-1 lymphocytes bound to SVEC compared to TNF-α stimulation (100%, or \'maximal\' binding). TK-1 were seen to interact with SVEC through ICAM-1 as well MAdCAM-1, but not VCAM-1, since an antibody against MAdCAM-1 reduced adhesion to 27 ± 4.6% of maximum and an anti-ICAM-1 reduced adhesion to 54.6 ± 8.3 % of maximum; anti-VCAM-1 reduced adhesion to 91% of maximum (blocks lymphocyte adhesion to endothelial cells (data not shown). Therefore we feel that adhesion in this system is mostly MAdCAM-1 dependent. IL-10 transfection of endothelial cells reduced MAdCAM-1 expression by 42% (following TNF-α stimulation) and reduced TK-1 adhesion by 50%. Therefore, these data suggest that the reduction of TK-1 adhesion is approximately 84% (42%/50%) MAdCAM-1 dependent, and that the remaining 16% of adhesion depends on other ECAMs, (such as ICAM-1). Although tissue specific promoters might further increase the organ specificity and transgene delivery of this approach, they have not been evaluated in this report. Our findings suggest that lymphatic or gut endothelial transfection with Th2 cytokines like IL-10 may be an effective method to reduce important clinical symptoms associated with IBD which are mediated by MAdCAM-1 dependent lymphocyte adhesion. Abbreviations ============= MAdCAM-1 (mucosal addressin cell adhesion molecule-1), IL-10 (Interleukin-10), HEV (high endothelial venular), ECAMs (endothelial cell adhesion molecules), IBD (inflammatory bowel diseases), UC (ulcerative colitis), CD (Crohn\'s disease), ICAM-1 (intracellular adhesion molecule 1), VCAM-1 (vascular adhesion molecule 1), NF-kB (nuclear transfection factor kB), TNF-α (tumor necrosis factor alpha), GM-CSF (granulocyte-macrophage colony-stimulating factor), GCSF (granulocute colony stimulating factor), ECL (enhanced chemiluminescence) Competing interests =================== None declared. Pre-publication history ======================= The pre-publication history for this paper can be accessed here: <http://www.biomedcentral.com/1471-230X/3/3/prepub> Acknowledgements ================ This work supported by NIH grants HL47615, DK43785 and DK47663.	{ "pile_set_name": "PubMed Central" }
Percutaneous bypass: subintimal recanalization of peripheral occlusive disease with IVUS guided luminal re-entry. Angioplasty of chronic total occlusions (CTOs) has lower technical success rates with longer procedure times and poorer outcomes. Subintimal recanalization remains limited by the lack of controlled re-entry into the true lumen of the target vessel. We report our experience using a commercially available catheter-based system equipped with an intravascular ultrasound scanner to achieve controlled true lumen re-entry in patients with peripheral CTOs. In a 4-month period, 6 patients with lower extremity (LE) ischemia from CTOs were treated. Occluded segments were crossed subintimally, and controlled re-entry was secured using the CrossPoint TransAccess catheter. This 6.2 F dual-lumen catheter contains an integrated 64-element phased array intravascular ultrasound scanner enabling targeting of structures. Intravascular ultrasound-guided luminal re-entry was achieved by advancing a 24-gauge needle to a desired length and delivering a 0.014" guide wire into the target lumen. The occluded segments were balloon dilated and stented using self-expanding nitinol stents. Effective luminal re-entry and re-establishment of antegrade flow occurred in all 6 patients. Time to recanalization ranged from 5 to 10 minutes. All patients were free of ischemic symptoms at 1 to 5 month follow-up. There were no procedure-related complications. Our preliminary results demonstrate the feasibility of using this catheter system for subintimal recanalization with controlled re-entry in CTOs. This approach can improve the technical success rate, reduce the time of the procedure, and minimize potential complications.	{ "pile_set_name": "PubMed Abstracts" }
Since the 1990s when a Japanese right-wing scholar created the "China Threat" theory, Western scholars have used the theory in analyzing China's rise as a leading player in the international arena. In 2010, the U.S. declared its "return to Asia," balancing power against China in the Asian-Pacific Region. This blog interprets and analyzes news, especially Sino-Japanese, Sino-U.S., and Japanese-U.S. relations in the Asian-Pacific region fairly Book Authored (ISBN-10: 0824821599) Sunday, May 19, 2013 Japan vs. China: The Status of Okinawa in the Cairo Conference/The Diaoyu/Senkaku Islands-XXVIII The movie, Hyde Park on Hudson, starring by Bill Murray and Laura Linney, is good one.It shows the human side of President Roosevelt during the war times.Everyone should see the movie. Also President Roosevelt is the person who finished (in the beginning of the ending) World War II. Recently, geopolitics in the East Asian Region is getting complicated. On May 8, 2013, a mouthpiece of the CCP, People’s Daily, published an article, questioning sovereignty of Okinawa by two Chinese scholars. On the following day, a Japanese spokesman, Suga Yoshihide, protested Beijing’s claim by saying Okinawa is “unquestionably Japan’s territory historically and internationally (BBC News, May 9, 2013).” As soon as the Japanese government complained about Okinawa’s article, the Chinese Foreign Ministry Spokeswoman, Hua Chunying, stated, “China does not accept Japan’s representation or protest. The publishing of the bylined article demonstrates the attention paid to and the research of the Diaoyu Islands and related historical issues (Xinhua News, May 9, 2013).” Source: Jiji Press (Access date: May 15, 2013). Based on the research of historical documents, President Roosevelt, along with Marshall Stalin, recognized that the Liuqiu (Okinawa) was a part of the Chinese territory. For instance, on January 22, 1944 of the post-Cairo conference, at the 36th meeting of the Pacific War Council, which chaired by President Roosevelt in the White House, both Roosevelt and Stalin are “in complete agreement that they (Liuqiu islets) belong to China and should be returned to her (China) (emphasis added).” Among the council members, ambassadors and representatives from the U.K., Netherlands, Canada, Philippine, New Zealand, and Australia attended the meeting. The Chinese Ambassador, Dr. Wei Tao-ming, also joined the Pacific War Council meeting. The major discussions were the territorial issues including the Kurile islets (the Northern territories between Japan and Russia), Manchuria, and others. The Liuqiu Islands was one of major agenda items in the meeting (details in my forthcoming book). Source: Leaders from China, the US, and the USSR in Cairo, PBS (Access date: 19 May 013). If both the U.S.and the U.S.S.R. governments, the winners of the World War II, recognized that the Liuqiu Islands were parts of the Chinese territory, the Diaoyu Islands would not be an issue between Japan and China at all. In other words, Japan might have difficulty claiming any sovereign right of the Diaoyu Islands; history probably is not on Japan’s side.	{ "pile_set_name": "Pile-CC" }
This first appeared in The Libertarian Forum, Volume X, NO.6, June, 1977 As everyone knows, the West, and especially northern California, has been suffering from a year-long drought, leading numerous statists and busybodies to leap in to control, ration, and ordain. The water “shortage” may not be exactly blamed on the private sector, but it is there, supposedly, and surely government must leap in to combat it—not, of course, by creating more water, but by mucking up the distribution of the greater scarcity. The first thing to be said about this is that on the free market, regardless of the stringency of supply, there is never any “shortage”, that is, there is never a condition where a purchaser cannot find supplies available at the market price. On the free market, there is always enough supply available to satisfy demand. The clearing mechanism is fluctuations in price. If, for example, there is an orange blight, and the supply of oranges declines, there is then an increasing scarcity of oranges, and the scarcity, is “rationed” voluntarily to the purchasers by the uncoerced rise in price, a rise sufficient to equalize supply and demand. If, on the other hand, there is an improvement in the orange crop, the supply increases, oranges are relatively less scarce, and the price of oranges falls consumers are induced to purchase the increased supply. The Complete Libertari... Murray N. Rothbard Check Amazon for Pricing. Note that all goods and services are scarce, and the progress of the economy consists in rendering them relatively less scarce, so that their prices decline. Of course, some goods can never increase in supply. The supply of Rembrandts, for example, is exceedingly scarce, and can never be increased—barring the arrival of a Perfect Forger. The price of Rembrandts is high, of course, but no one has ever complained about a “Rembrandt shortage.” They have not, because the price of Rembrandts is allowed to fluctuate freely without interference from the iron hand of government. But suppose that the government, in its wisdom, should one day proclaim that no Rembrandts can be sold for less than $1000—severe maximum price control on the paintings. We can rest assured that, if the decree were taken seriously at all, a severe Rembrandt shortage would promptly develop, accompanied by black markets, bribery, and all the rest of the paraphernalia of price control. If the water industry were free and competitive, the response to a drought would be very simple: water would rise in price. There would be griping about the increase in water prices, no doubt, but there would be no “shortage”, and no need or call for the usual baggage of patriotic hoopla, calls for conservation, altruistic pleas for sacrifice to the common good, and all the rest. But, of course, the water industry is scarcely free; on the contrary, water is almost everywhere in the U.S. the product and service of a governmental monopoly. When the drought hit northern California, raising the price of water to the full extent would have been unthinkable; accusations would have been hurled of oppressing the poor, of selfishness, and all the rest. The result has been a crazy-quilt patchwork of compulsory water rationing, accompanied by a rash of patrioteering ecological exhortation: “Conserve! Conserve! Don’t water your lawns! Shower with a friend! Don’t flush the toilet!” For a New Liberty: The... Murray Rothbard Best Price: $3.99 Buy New $6.49 (as of 05:35 EST - Details) Well, the amusing aspect of all this is that these imbecile exhortations were as manna from heaven to the wealthy liberal elitist ecofreak population of the San Francisco Bay Area. The California water authorities were hoping and shooting for a decline of about 25% in 1977 water consumption as compared to 1976. But, lo and behold, in late June, the figures rolled in and it turned out that Bay Area communities had responded by voluntarily cutting their water consumption by 40-50%. The “morality” of the Bay Area masses had exceeded everyone’s expectations. But what was the reaction to this onrush of patriotic altruism and self-sacrifice? Oddly enough, it was mixed and ambivalent—thereby pointing up in a most amusing way some of the inner contradictions of statism. For suddenly, many of the local governmental water districts, including San Francisco’s, realized that dammit! they were losing revenue! Now, water shortage is all well and good, but there is nothing more important to a bureaucrat and his organization than their income. And so the local California water districts began to scream: “No, no, you fools, you’ve ‘over-conserved.’” (To a veteran anti-ecologist such as myself, the coining of the new term “over-conserving” was music to my ears.) The water districts began to shout that people have conserved too much, and that they should spend more, for which they were sternly chastised by the state water authorities, who accused the municipal groups of “sabotaging” the water conservation program. Meanwhile, other local ecologists and statists got into the act. They groused that the over-conservation had induced people not to water their lawns, which led to the “visual pollution” “unsightly” lawns, and also caused the dried leaves to become fire hazards, which is apparently another ecological no-no. Man, Economy, and Stat... Murray N. Rothbard Best Price: $23.43 Buy New $29.95 (as of 08:10 EST - Details) I can see it now: a debate within the wealthy liberal ecofreak community: Mr. A.: “Dammit, you’ve over-conserved water; your lawns are visual pollutants, and your dry leaves are endangering the environment through fire.” Mr. B.: “You’re a blankety-blank no-good sellout water waster. You guys have been urging me for years to conserve, and now I’m doing it and all I get is hassle.” The culminating irony has been the reaction of the local water districts to the “threat” of “over-conservation” of water and the consequent loss of revenue to the governmental water districts. The response of the Bay Area districts was: “Sorry folks, we have to raise the price of water in order to maintain the beloved revenue of the water district (us.)” So, “over” conservation has led to an increase in the price of water. It is intriguing that raising the price of water in order to ration increased scarcity is universally considered to be reactionary, selfish, and Neanderthal, while raising the price of water in order to keep governmental water district revenues at their former level is considered perfectly legitimate, and barely worth commenting on. And so, the water price goes up anyway, though for the wrong reason and of course not in order to clear the market. The most amusing aspect of this California water caper was the argument of a water district apologist on San Francisco television: Q. But wouldn’t the poor be hurt by the water district raising its water prices? A. No, for since everyone has cut their consumption of water, the total water bill of each poor person will not increase. In short, the poor are not being hurt by the higher price because, being forced to cut their consumption, their total bill has not increased. Thus, a price rise by aprivate firm is always selfish and oppressive of poor people; but when a monopoly governmental agency increases its price, the poor do not suffer at all, since if they cut their purchases sufficiently in response to the higher price, their total dollar payments will not increase. It is this sort of nonsense that our statists and busybodies are now being reduced to. Meanwhile, how is “libertarian” Milton Friedman, now resident in the San Francisco area, taking to the water crisis? Is he advocating privatization, free competition among private water companies? Is he at least advocating the setting of a market-clearing price by the government water company? The answer to all of these is, remarkably, no. In his Newsweek column, Friedman favored keeping government water rationing, but making it more efficient through a typically elaborate scheme for surcharges for consumption over a certain quota of water, to be financing rebates for consuming under the quota. Thus, once again Friedmanism descends to being an efficiency expert for statism. The Best of Murray N. Rothbard	{ "pile_set_name": "OpenWebText2" }
According to a report from The Hollywood Reporter, Apple is objecting to a discovery request in a class action case against Universal Music Group that seeks the release of trial exhibits, expert reports, and depositions from former CEO Steve Jobs and Vice President of Internet Software and Services Eddy Cue. The depositions were originally given in a case between F.B.T. Productions, producers of Eminem records, and Universal Music group division Aftermath Records. That case is about to go to trial, but Apple is filing an objection to the discovery request from the class action that would alter an existing protective order, claiming the depositions and documents are “highly confidential and proprietary trade secrets.” In its objection, Apple apparently referenced the fact that most involved in the case were sent out of the room during the depositions and claimed if released it could lead to “competitive harm”: In support, Apple points to the fact that when the depositions were taken, many individuals, including UMG employees, were sent out of the room. And that when Jobs’ deposition was played before the jury, the judge closed the courtroom, ordered many people to leave, and had the transcripts from the trial sessions filed under seal. The report explained that in the case between F.B.T and Aftermath, the courts previously ruled the “plaintiff was correct in asserting that a contract between the parties should be read as treating digital music as ‘licenses’ rather than ‘sales.'” The case will go to trial in the near future to determine how much that ruling is worth. Meanwhile, the judge in the class action is urging parties to request changes to a protective order on the depositions and documents they are seeking from the F.B.T case. The class action case against UMG was brought by a number of musicians, including Rob Zombie and the Rick James’ estate, and is seeking revenues from music downloads. Related articles 0 0 FTC: We use income earning auto affiliate links. More. Check out 9to5Mac on YouTube for more Apple news:	{ "pile_set_name": "OpenWebText2" }
#! /bin/sh [ -f /usr/bin/input-event ] \|\| exit 0 start() { printf "Starting input-event: " input-event echo "done" } stop() { printf "Stopping input-event: " killall input-event echo "done" } restart() { stop start } # See how we were called. case "$1" in start) start ;; stop) stop ;; restart\|reload) restart ;; *) echo "Usage: $0 {start\|stop\|reload\|restart}" exit 1 esac exit $?	{ "pile_set_name": "Github" }
/* * Generated by class-dump 3.3.4 (64 bit). * * class-dump is Copyright (C) 1997-1998, 2000-2001, 2004-2011 by Steve Nygard. / #import <WebCore/DOMBlob.h> @class NSString; @interface DOMFile : DOMBlob { } - (double)lastModifiedDate; @property(readonly) NSString name; @end	{ "pile_set_name": "Github" }
Analamary, Betroka Analamary is a town and commune in Madagascar. It belongs to the district of Betroka, which is a part of Anosy Region. The population of the commune was estimated to be approximately 4,000 in 2001 commune census. Only primary schooling is available. Farming and raising livestock provides employment for 49% and 50% of the working population. The most important crop is rice, while other important products are peanuts and cassava. Services provide employment for 1% of the population. References and notes Category:Populated places in Anosy Region	{ "pile_set_name": "Wikipedia (en)" }
President Trump Donald John TrumpSteele Dossier sub-source was subject of FBI counterintelligence probe Pelosi slams Trump executive order on pre-existing conditions: It 'isn't worth the paper it's signed on' Trump 'no longer angry' at Romney because of Supreme Court stance MORE’s campaign fired back on Saturday at recent reports that his 2020 reelection campaign was producing its flags in China, denying reports and viral images that suggest the contrary. Reuters reported earlier this week that a factory in eastern China was producing thousands of “Keep America Great!” banners for Trump’s anticipated 2020 reelection bid. Manager Yao Yuanyuan told Reuters that she was worried Trump’s own tariffs would hurt production numbers, but said she did not know if the banners' buyers were officially affiliated with the Trump campaign or the GOP. ADVERTISEMENT Yao said her factory has been making Trump banners since the president was a candidate. But the Trump reelection campaign's chief operating officer, Michael Glassner, said campaign merchandise is "100% made in the USA." "We have made it clear all along that all of our merchandise is 100% made in the USA," Glassner said in a statement to CNN. "Any vendor who claims to have a relationship with us otherwise is lying or violating our protected trademark rights." "This applies to all of the recent fake news about Made in China products for the 2020 campaign," he added. A similar report earlier this month found that another factory in China’s Zhejiang province is reportedly producing small blue and white flags for the reelection campaign. The reports of the factories appear to contradict Trump’s “Buy American, Hire American” agenda amid an escalating trade war with China. Trump in an interview last week said he’s “ready to go” with $500 billion in tariffs on China after already slapping the country with a series of steep tariffs. The White House reportedly used Chinese-made silverware while serving refreshments at its annual Made in America Product Showcase last week, an event meant to show off American-made products.	{ "pile_set_name": "OpenWebText2" }
Q: Cities XL not starting after windows reinstall I have reinstalled my windows XP and now cities XL is giving error "This application has failed to start because the application configuration is incorrect. Reinstalling the application may fix this problem" Is there any solution other then reinstalling the whole game again? I think some registry entries will solve the problem but i don't have them. A: Add registry from here http://www.regfiles.net/file/86/ And install vcredist_x86.exe (Visual C++ Redist) from CitiesXL folder	{ "pile_set_name": "StackExchange" }
	{ "pile_set_name": "PubMed Central" }
Introduction {#S1} ============ Skin with underlying subcutis is armed with neuroendocrine capabilities and represents the largest and one of the most complex organs in the human body ([@R58]). Strategically located at the interface with external environment, skin detects, integrates, and responds to stressors including ultraviolet radiation (UVR) ([@R8]; [@R26]; [@R47]; [@R58]; [@R59]). UVB (290--320 nm) radiation has powerful biological actions not only on cutaneous biology but it also impacts many regulatory pathways involved in immune homeostasis that are both vitamin D-dependent and independent ([@R1]; [@R2]; [@R8]; [@R12]; [@R19]; [@R23]; [@R27]; [@R31]). The mechanisms of UVB-induced immune suppression ([@R63]) are not completely understood. However, evidence is accumulating that DNA damage and other mechanisms such as the photoisomerization of urocanic acid, free-radical formation, and signal transduction-mediated activation of transcription factors and induction of neuroendocrine signaling may also contribute to the resulting pathological conditions as well ([@R8]; [@R23]; [@R39]; [@R58]; [@R63]). The main regulatory algorithm to maintain body homeostasis is the hypothalamic-pituitary-adrenal (HPA) axis, which requires activation of a complex range of responses involving the endocrine, nervous, and immune systems, collectively known as the stress responses ([@R4]; [@R34]; [@R60]; [@R62]). Neural signals encoded by the limbic system as stressors trigger neurons of the paraventricular nucleus (PVN) of hypothalamus to produce and release corticotropin releasing hormone (CRH) into the hypophyseal portal circulation ([@R60]; [@R62]). Next, CRH binds to CRH receptor type 1 (CRH-R1) on pituitary corticotropes, and induces the release of POMC-derived adrenocorticotropic hormone (ACTH) into the systemic circulation. The melanocortin receptor type 2 (MC2R), expressed in the adrenal cortex, stimulates glucocorticoid (GC) synthesis and secretion after binding of ACTH ([@R4]; [@R21]; [@R60]). GC (i.e., cortisol (COR) in humans and corticosterone (CORT) in rodents) maintain metabolic and stress-responses, suppress immune activity and are self-regulated, with negative feedback to the hypothalamus and pituitary to mute the HPA axis ([@R4]; [@R21]). The skin has neuroendocrine capabilities that also encompasses all elements of the "cutaneous HPA axis" that follow the organization of the central HPA axis \[reviewed in ([@R50])\]. This concept was based on the evidence that vertebrate skin expresses CRH with functional CRH-R1 \[reviewed in ([@R59])\] and related POMC macromolecule, which is further processed to ACTH ([@R14]; [@R29]; [@R39]; [@R42]; [@R48]), which, after interaction with MC2R, induces steroidogenesis with the final production of highly adaptable COR or CORT ([@R5]; [@R14]; [@R35]; [@R41]; [@R51]; [@R52]; [@R53]; [@R54]; [@R64]). Furthermore, Hiramoto et al ([@R11]) have demonstrated that exposure of the eye to the UVB increases plasma α-MSH levels with systemic stimulation of epidermal melanocytes. Based on the above we have decided to test the hypothesis that UVB acting on the skin can regulate body homeostasis through activation of central HPA. Using mouse model we evidence that UVB activates the HPA axis both on the local (skin) and systemic (brain, adrenal and plasma) levels, with a latter requiring an intact pituitary. The UVB induced increases in corticosterone production explain immunosuppressive effects of the UVB, while that of β-endorphin could explain a phenomenon of "UV addiction". Results {#S2} ======= General design of UVB exposure {#S3} ------------------------------ To prevent retinal or non-retinal eye signal transmission, the heads including eyes, were covered with aluminum foil, and the skin on the back was irradiated with UVB ([Figure 1](#F1){ref-type="fig"}). Dose and Time Dependent Effects of UVB in the Skin {#S4} -------------------------------------------------- Previously, we have documented that UVB (290--320 nm), but not less energetic UVA (320--400 nm), is effective in stimulating HPA axis elements in human and mouse skin organ culture in vitro ([@R35]; [@R36]; [@R37]). In current experiments we first measured the CORT in the skin in vivo using different doses and time after UVB exposure and found that the dose of 400 mJ/cm^2^ (2.1 minimal erythema doses (MED), [Table S1](#SD1){ref-type="supplementary-material"}) and 12 and 24 h after exposure were most optimal for enhancement of the CORT levels ([Figure 2a,b](#F2){ref-type="fig"}). Lower dose (100 mJ/cm^2^) and shorter times of observation (3 and 6 h) showed significantly lower stimulatory effect. Similarly, markedly stronger stimulation of plasma CORT levels was observed at 400 in comparison to 100 mJ/cm^2^ and at 12 in comparison to 3 h after UVB exposure ([Figure S1](#SD1){ref-type="supplementary-material"}). The histopathological analysis demonstrated that UVB at 400 mJ/cm^2^ did not produce noticeable epidermal necrosis nor trigger marked/moderate inflammatory infiltrate ([Figure 2c](#F2){ref-type="fig"}). However, small increase in infiltrating neutrophils and eosinophils was observed at 1--6 h after UVB exposure, which after 12 or 24 h returned to the control ([Figure 2d](#F2){ref-type="fig"}). Therefore, based on the previous ([@R36]) and current in vivo experiments we have chosen the dose of 400 mJ/cm^2^ (2.1 MED) and a time of 12 and 24 h after UVB exposure for further experiments. UVB effects on cutaneous expression of CRH and Ucn {#S5} -------------------------------------------------- Since the CRH gene is not expressed in C57BL/6 skin ([@R49]; [@R59]), and can be replaced by Ucn in activating HPA axis elements ([@R46]; [@R59]), we examined Ucn cutaneous expression as a potential triggering regulator. We also measured the concentration of CRH since this peptide can be released locally from cutaneous nerve fibers ([@R28]; [@R40]). UVB radiation stimulated the Ucn expression at the gene ([Figure 3a](#F3){ref-type="fig"}) and peptide levels ([Figure 3l](#F3){ref-type="fig"}) with the similar patterns at 12 and 24 h post-radiation. In situ localization studies showed increased expression of Ucn in the main skin compartments including the epidermis, adnexal structures and stratum paniculosum ([Figure 3g](#F3){ref-type="fig"}). There was also an increase in CRH peptide concentration in the skin after UVB exposure, as evaluated by ELISA ([Figure 3k](#F3){ref-type="fig"}). UVB effects on cutaneous expression of POMC, ACTH and β-END {#S6} ----------------------------------------------------------- Next, we checked cutaneous POMC expression, a "pituitary" element of the systemic HPA axis. UVB light stimulated a 2.5-fold increase in expression of POMC mRNA after 12 h, and which was still present after 24 h, although at lower levels ([Figure 3b](#F3){ref-type="fig"}). Immunoblotting with antibodies directed against ACTH, which recognize the 33 kDA POMC precursor, confirmed increased expression of this molecule ([Figure 3e](#F3){ref-type="fig"}). UVB-induced increased ACTH production was also confirmed with quantitative IHC ([Figure 3h](#F3){ref-type="fig"}) as was expression of POMC-derived β-END stimulated by UVB ([Figure 3i](#F3){ref-type="fig"}). UVB effects on cutaneous expression of MC2R, CYP11A1, StAR, 3β-HSD and CORT {#S7} --------------------------------------------------------------------------- The expression of the next crucial element of the HPA axis, the MC2R (responsible for initiation of steroidogenesis upon ACTH activation), was upregulated 1.5 times after 12 h and almost two times after 24 h ([Figure 3c](#F3){ref-type="fig"}). We also investigated StAR gene expression, which is required to transfer cholesterol from the outer to the inner mitochondrial membrane, and showed that its up-regulation occurred after 12 and 24 hrs post-UVB exposure ([Figure 3d](#F3){ref-type="fig"}). Moreover, we evaluated the expression of the rate-limiting enzyme of steroidogenesis, the cytochrome P450scc (CYP11A1), which cleaves the cholesterol side chain to produce pregnenolone, a precursor of all steroids. Western blot analysis revealed high expression of P450scc at 12 h and 24 h post-UVB exposure, compared to appropriate controls ([Figure 3f](#F3){ref-type="fig"}). Furthermore, immunohistochemistry for 3β-HSD, (the enzyme that transforms pregnenolone to progesterone), showed that this antigen is highly expressed in cutaneous adnexal structures and in the stratum paniculosum, but weakly expressed in the epidermis of untreated skin. UVB radiation enhanced 3β-HSD expression, especially in epidermal cells ([Figure 3j](#F3){ref-type="fig"}). The final product of HPA axis activation, CORT was produced at significantly high level at 12 h and increased further at 24 h after UVB irradiation ([Figure 3m](#F3){ref-type="fig"}). UVB effects on CRH expression in the Hypothalamus {#S8} ------------------------------------------------- The area corresponding to the hypothalamus (Bregma \~ −0.34 to −2.70 mm) was dissected out and processed either for CRH mRNA expression or peptide measurements. There was a significant increase of CRH gene expression ([Figure 4a](#F4){ref-type="fig"}) and CRH peptide production ([Figure 4b](#F4){ref-type="fig"}) both 12 and 24 h after UVB exposure. Furthermore, immunohistochemistry showed an increased number of CRH-immunopositive neurons and nerve fibers surrounding the PVN area. The highest immunopositive signal was observed at 12 h after UVB exposure, and its relative values are calculated and presented as an insert to [Figure 4c](#F4){ref-type="fig"}. Changes in Adrenals after UVB exposure {#S9} -------------------------------------- QPCR analyses showed that MC2R mRNA was up-regulated after 12 and 24 h of UVB radiation ([Figure 5a](#F5){ref-type="fig"}). Similarly, StAR mRNA was increased at the same time points ([Figure 5b](#F5){ref-type="fig"}). Expression of the CYP11B1 gene was also up-regulated but only after 24 h of UVB exposure ([Figure 5c](#F5){ref-type="fig"}). Changes in Plasma after UVB exposure {#S10} ------------------------------------ CRH peptide content was highly increased at 12 and 24 h after UVB irradiation, compared to that in sham-irradiated animals ([Figure 5d](#F5){ref-type="fig"}). A similar effect was observed for Ucn ([Figure 5e](#F5){ref-type="fig"}). ACTH concentrations were markedly stimulated at 12 and 24 h after UVB exposure [Figure 5f](#F5){ref-type="fig"}). Interestingly, UVB enhanced plasma concentrations of another peptide, β-END ([Figure 5g](#F5){ref-type="fig"}), that results from POMC cleavage. The final component of the HPA stress-axis in rodents, CORT, was highly elevated after 12 and 24 h post-UVB exposure ([Figure 5h](#F5){ref-type="fig"}). UVB effects in Hypox Animals {#S11} ---------------------------- First, we tested the skin, and showed that both basal and UVB-stimulated cutaneous HPA activity was pronounced in mice with intact pituitary (sham-hypox controls) than in hypophysectomized (lacking the pituitary, hypox) mice ([Figure 6a](#F6){ref-type="fig"}). Histological evaluation showed no significant change in the skin morphology between hypox and sham-hypox mice skin after UVB exposure ([Figure 6b](#F6){ref-type="fig"}). Second, changes evoked by UVB at the plasma level in mice with intact pituitary were markedly different from those of mice lacking the pituitary (hypox). Although, CRH and Ucn followed similar pattern of activation in both animal groups ([Figure 6c,d](#F6){ref-type="fig"}), hypox mice had much lower plasma levels of ACTH and CORT ([Figure 5e,f](#F5){ref-type="fig"}) and UVB failed to stimulate plasma levels of ACTH and CORT ([Figure 6e,f](#F6){ref-type="fig"}). Discussion {#S12} ========== This manuscript shows, that the exposure of the skin to UVB can activate the systemic HPA axis culminating in increased plasma levels of corticosterone, which requires a functional pituitary. These studies parallel an important discovery by Hiramoto's group that exposure of the eyes to UVB stimulates plasma levels of α-MSH and increases number of epidermal melanocytes ([@R11]). Although the mechanism of this stimulation remains to be established (evidence for activation of any the hypothalamic nucleus awaits experimental demonstration), the requirement for an intact pituitary was demonstrated ([@R11]). However, the final product of UVB induced in the eye axis is α-MSH, accompanied by an increased expression of pituitary prohormone convertase 2 ([@R9]; [@R10]), which contrasts the classical HPA axis. In the HPA axis, after pituitary stimulation by hypothalamic CRH, the main product of POMC process is ACTH that acts on the adrenal glands to stimulate glucocorticosteroidogenesis ([@R61]). While Hiramato et al show a novel mechanism of UVB activity at the central level that is different from the HPA axis, our studies demonstrate activation of the classical HPA axis by skin derived factors acting at different entry points [Figure S2](#SD1){ref-type="supplementary-material"}, for detailed discussion see below). We also show that UVB can induce in mouse skin in vivo expression of all the elements of the HPA axis including CRH, POMC and corticosteroidogenic pathway. Since UVB did not induce CRH gene expression in skin cells, CRH must be delivered from nerve endings supplying dermo-epidermal or follicular junctions. This is consistent with previous studies showing increases in skin CRH after trauma1-induced hair cycling in C57BL/6 mouse ([@R25]; [@R28]; [@R40]; [@R45]; [@R49]; [@R56]), and detection of CRH in skin nerve bundles ([@R28]). CRH, together with Ucn (of which both gene and protein expression are up-regulated by UVB), can interact with CRH-R1 and CRH-R2 to promote local POMC activity ([@R59]) followed by the stimulation of local steroidogenesis ([@R51]; [@R57]). Concomitantly, UVB enhanced ACTH and β-END production in the skin, with increased expression of crucial regulators of streoidogenesis such as MC2R (receptor for ACTH), StAR (transporter of cholesterol) and steroidogenic enzymes (CYP11A1/P450scc and 3β-HSD) culminating with the final production of CORT. Thus, UVB activates all elements of the HPA axis in mouse skin in vivo, which is in agreement with previous studies on UVB induction of cutaneous POMC ([@R3]; [@R30]) and of all or selected elements of the HPA axis in skin cells ([@R38]; [@R55]; [@R65]) or skin organ culture ([@R35]; [@R36]). The most striking and previously unreported observations were the stimulation of CRH in the brain localized to the PVN of the hypothalamus and plasma increases of CRH, Ucn, ACTH, β-END and CORT that were accompanied by up-regulation of adrenal MC2R, StAR and CYP11B1. Activation of all of these elements upon skin exposure to UVB clearly indicates that activation of the systemic stress response is centered in the HPA axis and is invoked by skin signals induced by UVB. The crucial role of skin factors in this activation is documented by our experimental design that shielded the head from UVB exposure, preventing retinal signal transmission. The possible mechanisms of this activation are outlined in [Figure S1](#SD1){ref-type="supplementary-material"}, which includes both the neural route and humoral signals sent from the skin to the central regulatory elements. UVB enhancement of the production of CRH mRNA and peptide in the hypothalamus with localization at the PVN supports the hypothesis that cutaneous signals are conveyed via DRG- spinal cord- dorsal column to the PVN, the center where the HPA axis begins ([@R59]; [@R60]). However, the detailed mapping of this routing is beyond the confines of this project and represents a future challenge. The nature of humoral signaling from the skin to increase systemic CORT is more complex because in addition to production of ACTH, Ucn and CRH (see above), UVB stimulates cytokine production (IL1, IL6 and TNFα) and release into circulation ([@R16]; [@R22]; [@R33]), all of which can activate the pituitary POMC ([@R4]; [@R20]; [@R48]; [@R61]). Although dissection of potential contributions of cytokines signals can be difficult or impossible to quantitate in this experimental setting, the most logical explanation would be the activation of CRH-R1 in anterior pituitary by the circulating natural ligands: CRH and Ucn, induced by UVB, to initiate the following cascade of HPA activity: CRH + Ucn→CRH-R1→POMC →ACTH→MC2R→CORT To substantiate this hypothesis, we employed hypophysectomized mice. After UVB exposure, there was significant enhancement of CRH and Ucn peptide levels in the skin and plasma of hypox and sham-hypox animals, with plasma increases of ACTH and CORT seen only in sham-hypox (control) mice. This documents that the pituitary is necessary for UVB activation of a final element of the HPA axis in rodents, CORT. Moreover, the elevated CRH, Ucn and ACTH in the skin after UVB exposure were insufficient for direct (omitting pituitary) humoral activation of adrenals. However, they were capable of stimulating cutaneous CORT but without the corresponding increases in the plasma. Thus, UVB is another trigger of the HPA axis that requires a functional pituitary to stimulate secretion of ACTH and plasma glucocorticoids, while activation of local (skin) HPA activity is restricted to this organ without systemic involvement, as previously predicted ([@R48]). The net phenotypic consequences of these UVB-induced processes will include homeostatic and immunosuppressive effects resulting from the action of glucocorticoids and POMC-derived peptides, consistent with the established role and function of the HPA axis in the regulation of body homeostasis ([@R4]; [@R34]; [@R59]; [@R60]; [@R61]). These activities would explain the powerful systemic UVB immunosuppressive effects ([@R18]; [@R31]) as well as systemic beneficial effects in attenuation of autoimmune processes that are independent of vitamin D3 ([@R1]; [@R15]; [@R32]). Thus, it may be possible to attenuate severity of autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease or scleroderma, by stimulation of endogenous glucocorticoids in an organized fashion through UVB induction of the HPA axis. The stimulation of β-END levels in the skin and plasma offers a mechanistic explanation for the recently described phenomenon of "UV addiction" ([@R17]; [@R24]), as a secondary effect of UVB-induced production of POMC-derived s-END ([@R58]). The above data on β-END are supported by most recent report from Dr. Fisher group showing UVB mediated stimulation of β-END in the skin and serum ([@R7]). In summary, we provide the evidence that UVB can activate the central HPA axis and, based on its organization and function, we propose that this mode of action represents unique mechanism regulating body homeostasis in response to UVB spectrum of solar light. Materials and Methods {#S13} ===================== Animals {#S14} ------- All procedures involving mouse experiments and tissue handling were approved by the IACUC at the UTHSC, Memphis TN. Eighty seven week-old females C57BL/6 mice (n=6) were purchased from the Taconic Farms (Hudson, NY). After arrival, animals were kept for 4 days to avoid transportation stress with free access to standard laboratory chow and water, maintained on a 12:12 light/dark cycle and room temperature (RT) ranged from 20 to 24 C. Eight week-old animals with all hairs at the telogen stage as judged by a lack of skin pigmentation ([@R42]) were used for the experiments. This was further confirmed by histological examination of the hair cycle stage confirming that hairs were at the telogen (resting-quiescence) stage where the expression of neuroendocrine factors is expected to be the lowest ([@R42]; [@R48]) and, therefore, the predicted UVB stimulation would be the highest. To test the role of the pituitary in UVB-induced HPA-activation, hypophysectomized and control (sham hypophysectomized) ninety eight (n=6) B6 females, 7 weeks old, were purchased from Charles River Laboratories (Wilmington, MA) and were kept on 5% sucrose-supplemented water according to the vendor's guidelines. General Experimental Design {#S15} --------------------------- Details of experimental design are in [Figure 1](#F1){ref-type="fig"} and its legend. Shortly, after irradiation, animals (3 animals per cage) were kept for 12 or 24 h, according to the group assignment. Finally, under deep anesthesia (isoflurane 4 %) blood was collected by retro-orbital phlebotomy into EDTA tubes, and animals were euthanized by cervical dislocation. Plasma was obtained by centrifugation (1,600 g, 5 min, 4 C), skin, brain and adrenals harvested and frozen immediately at −80 C or fixed with paraformaldehyde. We repeated experiments 3 times during the spring, summer and winter to avoid confounding effects caused by the seasonal fluctuation of the HPA axis activity ([@R6]). To test the role of the pituitary, we employed the hypophysectomized (hypox) and sham operated controls (sham-hypox) mice. The animals were treated as above. Blood and tissues were collected in the morning (6 -- 7 am, 12 and 24 h after irradiation). Irradiation {#S16} ----------- UVB (290--320 nm) irradiation was performed with a Spectroline XX-15A lamp (Spectronics Corp., Westbury, NY) equipped with a UVB waveband bulb (USHIO G15T8E) from the distance of 2.5 inches (see [Table S1](#SD1){ref-type="supplementary-material"}. The UV dosimetry was described in ([@R37]). During irradiation, the bulb was covered with a cellulose triacetate sheet (Kodacel filter, Kodacel™, Eastman Kodak, Rochester, NY) which cuts-off wavelengths shorter than 290 nm, as described in ([@R37]). The time of UVB irradiation was calculated upon the formula Time (s) = Dose (J/cm^2^)/Intensity (W/cm^2^) and presented as a standard erythema dose (SED) and MED in [Table S1](#SD1){ref-type="supplementary-material"}. One SED is equivalent to an erythemal effective radiant exposures of 100 J/m^2^ (MKS) or 0.01 J/cm^2^ (CGS)([@R13]). Quantitative real time RT-PCR (QRT-PCR) {#S17} --------------------------------------- A detailed description of QRT-PCR is given in Supplemental materials and methods. The list of primers used for amplification with SYBR Green polymerase (Kapa Biosystems, Inc., Woburn, MA) is in [Table S2](#SD1){ref-type="supplementary-material"}. Results are presented as fold change based on the ΔΔ ct method ± SD. ELISA/EIA {#S18} --------- A detailed description is given in Supplemental materials and methods. Commercially available kits used in this study are listed in [Table S3](#SD1){ref-type="supplementary-material"}. Results are presented as mean ± SD in either pg/mL or ng/mL after recalculations by total protein concentration (brain, skin) or dilution (plasma). Immunohistochemistry {#S19} -------------------- Detailed protocols are in supplementary file. Briefly, the hypothalamus was isolated at the level of anterior Bregma +1 mm up to posterior Bregma −2.70 mm, by the use of the Brain Slicer Matrix (Zivic Instrument, Pittsburgh, PA). Region resembling the whole hypothalamus (Bregma \~ −0.34 to −2.70) were characterized under light microscope based on the The Allen Reference Atlas (<http://mouse.brain-map.org/static/atlas>) and 10 µm coronal sections were mounted onto silanized slides (Dako, Carpinteria, CA), and subjected to immunofluorescence protocols described in supplementary file. Western Blot {#S20} ------------ A detailed description is in ([@R35]). Briefly, equal amounts of protein from a combination of 3 skins for each sample was denatured with Laemli buffer, subjected to SDS/PAGE, and proteins were transferred to a PVDF membrane and incubated with antibodies listed in [Table S4](#SD1){ref-type="supplementary-material"}. Next, the membrane was incubated with secondary IgG-HRP, and detection of immunocomplexes was performed with chemiluminescence. Statistics {#S21} ---------- Data are presented as means ± SD and are analyzed using Prism 4.00 (GraphPad Software, San Diego, CA). Statistically significant differences are denoted by \* (Student's t-test for two groups) or \# (one-way ANOVA Tuckey test for more than two groups), where p\<0.05 is considered as statistically significant. Supplementary Material {#SM} ====================== The paper is dedicated to the memory of Dr Wylie Vale. We gratefully acknowledge careful reading of the manuscript and recommendations by Dr Jean Rivier (Salk Institute), Dr John Pawelek (Yale University) and Drs Arnold Postlethwaite and Robert Williams (UTHSC). We also thank Ms Deborah Doan (Salk Institute) for the editing of the manuscript. This study was supported by grants from the National Science Foundation (\# IOS-0918934) and the National Institutes of Health (\#1R01AR056666-01A2 and R01AR052190) to AS. Conflict of interest: The authors state no conflict of interest. ACTH : adrenocorticotropic hormone α-MSH : α-melanocyte stimulating hormone β-END : β-endorphin B6 : C57BL/6 mice CIE : Commission Internationale de L\'Éclairage (International Commission on Illumination) CORT : corticosterone COR : cortisol CRH : corticotropin releasing hormone CRH-R1 : CRH receptor type 1 CYP11B1 : gene coding of Steroid 11β-hydroxylase P450scc : cytochrome P450 side-chain cleavage enzyme DRG : dorsal root ganglia MC2R : Melanocortin receptor 2 POMC : proopiomelanocortin PVN : paraventricular nucleus SED : standard erythemal dose StAR : steroidogenic acute regulatory protein Ucn : Urocortin 3β-HSD : 3-β-hydroxysteroid dehydrogenase ![Outline of the experimental design. Under short (max. 1 min) vapor isoflurane (2 %) anesthesia, the back skin was shaved with animal clippers 12 h before the experimental procedures. The next day, animals were repeatedly anesthetized, eyes covered with aluminum foil (to prevent retinal signal transmission), and the skin on the back was irradiated with UVB (400 mJ/cm^2^ for most experiments), either at 7 am (24 h group) or at 7 pm (12 h group). These optimal doses and times after exposure were based on initial testing of UVB at ranges of 100 -- 400 mJ/cm^2^ vs control and time post-exposure of 3, 6, 12 and 24 hours.](nihms634618f1){#F1} ![Time and dose-dependent changes in CORT production and skin histological evaluation after UVB radiation.\ Dose- (a) and time- (b) dependent increases in CORT production after UVB exposure in C57BL6 shaved mouse skin, evaluated with ELISA. A dose-dependent histological evaluation observed 12 h after UVB irradiation with a dose of 100 and 400 mJ/cm^2^ (c). Time-dependent histological changes evolved after 1, 3 and 6 h followed by UVB exposure of 400 mJ/cm^2^ (d). H&E staining on formalin fixed and paraffin embedded skin representative sections. Data were analyzed using Student's t-test, \* p\<0.05, \\ p\<0.01, and \\\* p\<0.001 or one-way ANOVA, \#\# p\<0.01; \#\#\# p\<0.001. Scale bar = 100 µm.](nihms634618f2){#F2} ![Cutaneous equivalent of the HPA axis in C57BL6 mice is stimulated upon UVB radiation.\ Expression of genes coding Ucn (a), POMC (b), MC2R (c) and StAR (d) after UVB exposure compared to control (shame-treated) animals. Data presented as fold change ± SD. Protein estimation with Western Blot for ACTH/POMC (e) and P450scc (f). In situ expression of Ucn (g), ACTH (h), β-END (i) and 3β-HSD (j) antigens measured by immunofluorescence with corresponding quantification of immunopositive signal intensity (inserts to the subpannels). Arrows indicate examples of positive signals. ELISA evaluation of peptide CRH (k), Ucn (l) and steroid CORT (m) concentrations. Data are presented in pg or ng/mL per 4 µg of total proteins extracted, and analyzed using Student's t-test, \* p\<0.05, \\ p\<0.01, and \\\* p\<0.001.](nihms634618f3){#F3} ![Up-regulation of CRH expression in the murine hypothalamus after exposure of shaved back skin to UVB. CRH gene expression is shown as fold change ± SD (a). CRH peptide was measured by ELISA (b). Data are presented in pg/mL in relation to the same protein concentration (28 µg/µL). CRH immunoreactivity in situ in the PVN was evaluated by immunofluorescence (c). Circled areas show in situ localization of CRH antigen visualized in perikarya and nerve fibers. Calculation of positive signals intensity is presented on the graph in the lower panel c. Data are analyzed using t-test, \* p\<0.05, \\ p\<0.01, and \\\* p\<0.001. Scale bar = 100 µm.](nihms634618f4){#F4} ![UVB stimulates the systemic HPA axis in C57BL/6 mice.\ UVB stimulated expression of gene coding MC2R (a), StAR (b) and CYP11B1 (c) in C57Bl/6 adrenals. Data are presented as fold changes ± SD. UVB enhanced plasma concentrations of CRH (d), Ucn (e), ACTH (f), β-END (g), and CORT (h). Data are presented as pg or ng/mL after appropriate dilutions were performed separately for each assay and analyzed using t-test, \* p\<0.05, \\ p\<0.01, and \\\* p\<0.001.](nihms634618f5){#F5} ![Differential effects of UVB on the HPA axis in hypox (pituitary removed) and sham-hypox (pituitary intact) C57BL6 mice. CORT levels were evaluated with ELISA and presented as ng/mL after adjustment of total protein content to 4 µg/µL (a). Comparison of histological evaluation between hypox and sham-hypox mouse skin after UVB (400 mJ/cm^2^) exposure (b). Plasma levels of peptide CRH (c), Ucn (d), ACTH (e) and CORT (f) after exposure of shaved back skin to UVB. Data presented as pg or ng/mL after prior dilution performed separately for each assay, and analyzed using t-test, \\ p\<0.01, and \\\* p\<0.001.](nihms634618f6){#F6}	{ "pile_set_name": "PubMed Central" }
Share: The Pokémon Pop Parody Medley You Need to See Share: We all know that Professor Oak keeps track of Pokémon near and far with his handy-dandy Pokédex, but until now there was no corresponding songédex for everyone’s favorite pocket monsters. Luckily, the Nerdist Alliance members/Gym Leaders of Screen Team Show are here to both save the day and the Pokémon from Team Rocket in their latest video. “Pokémon Parody Medley” combines cameos by Charmander, Snorlax, Espurr, and an evolving Timburr/Gurdurr (which itself can and should be the name of a Pokémon dating app) with reworked versions of huge pop hits like Ellie Goulding’s “Burn” and Miley Cyrus’s “Wrecking Ball,” which we think is much improved in Screen Team’s version, “Pokéball”. BRB, gonna catch ‘em all. Meanwhile, let us know which of the video’s parody pair-ups is your favorite in the comments. Why is this on Nerdist? It’s just her dressed as different pokemon but re-imagined to have massive cleavage. This is the kind of pandering low quality stuff that the nerd community needs to be trying to shake the perception of, not celebrate. If you’ve seen any of Screen Team’s videos, this is what they do. It’s their thing, they do a song and she dresses up in Cosplay with big cleavage. If it’s not your cup of tea, then go ahead and move on, but it’s not like they’re particularly deceptive. The video is pretty much exactly what you see in the still. I’m amazed how people always seem to get angry that a hot girl would dare to dress up and show off her figure, as if somehow that’s some sort of nerd sacrilege. Isn’t that half the point of Cosplay in general (for which Nerdist has a weekly column)? Stop resenting and enjoy!	{ "pile_set_name": "Pile-CC" }
Q: jquery showing related xml categories I have an xml file like this: <?xml version="1.0" ?> <scketchit> <categories> <category title="MANGA" /> <category title="MARVEL" /> </categories> <comics> <comic title="Comic number 1"> <date>21/02/2011</date> <category>MANGA</category> </comic> <comic title="Comic number 2"> <date>13/02/2011</date> <category>MARVEL</category> </comic> <comic title="Comic number 4"> <date>12/02/2011</date> <category>MANGA</category> </comic> </comics> </scketchit> and i want to convert the categories items into links and when i click in this categories show in a div the corresponding comics I'm new to jquery and this is the jquery i'm writting: $(document).ready(function(){ $.ajax({ type: "GET", url: "comics.xml", dataType: "xml", success: xmlParser }); }); function xmlParser(xml) { $(xml).find('categories').eq(0).find('category').each(function () { $("#categories-data1").append('<div class="title"><a href="#" class="CategoryTab">' + $(this).attr('title') + '</a></div>'); }); var nav_link = $('.CategoryTab'); nav_link.click( function() { alert( $(xml).find("category:contains('" + nav_link.html() + "')").closest('comic').html() ); }); } I don't know if iwhat i'm doing is well done and i cant show the comic items for every category. How would you do all this? Thanks in advance. A: i have it working now but i'm sure it can be done in another simple and clean way ¿? $(document).ready(function(){ $.ajax({ type: "GET", url: "categories.xml", dataType: "xml", success: xmlParser }); }); function xmlParser(xml) { $(xml).find('categories').eq(0).find('category').each(function () { $("#categories-data1").append('<div class="title"><a href="#" class="CategoryTab">' + $(this).attr('title') + '</a></div>'); }); var nav_link = $('.CategoryTab'); nav_link.click( function() { var cat = $(this).html(); $("#posts").empty(); $(xml).find('comic').each(function() { var comic = $(this).attr('title'); var category = $(this).children('category').text(); if(category == cat) { $("#posts").append('<p>' + comic + '</p>'); } }) }); } May anyone tell me what of what i've done should be done in another way? Thank you very much.	{ "pile_set_name": "StackExchange" }
# coding=utf-8 # * WARNING: this file was generated by the Pulumi Terraform Bridge (tfgen) Tool. * # * Do not edit by hand unless you're certain you know what you are doing! * import warnings import pulumi import pulumi.runtime from typing import Any, Mapping, Optional, Sequence, Union from .. import _utilities, _tables __all__ = ['TargetGroupAttachment'] class TargetGroupAttachment(pulumi.CustomResource): def __init__(__self__, resource_name: str, opts: Optional[pulumi.ResourceOptions] = None, availability_zone: Optional[pulumi.Input[str]] = None, port: Optional[pulumi.Input[int]] = None, target_group_arn: Optional[pulumi.Input[str]] = None, target_id: Optional[pulumi.Input[str]] = None, __props__=None, __name__=None, __opts__=None): """ Provides the ability to register instances and containers with an Application Load Balancer (ALB) or Network Load Balancer (NLB) target group. For attaching resources with Elastic Load Balancer (ELB), see the `elb.Attachment` resource. > Note: `alb.TargetGroupAttachment` is known as `lb.TargetGroupAttachment`. The functionality is identical. ## Example Usage ```python import pulumi import pulumi_aws as aws test_target_group = aws.lb.TargetGroup("testTargetGroup") # ... other configuration ... test_instance = aws.ec2.Instance("testInstance") # ... other configuration ... test_target_group_attachment = aws.lb.TargetGroupAttachment("testTargetGroupAttachment", target_group_arn=test_target_group.arn, target_id=test_instance.id, port=80) ``` ## Usage with lambda ```python import pulumi import pulumi_aws as aws test_target_group = aws.lb.TargetGroup("testTargetGroup", target_type="lambda") test_function = aws.lambda_.Function("testFunction") # ... other configuration ... with_lb = aws.lambda_.Permission("withLb", action="lambda:InvokeFunction", function=test_function.arn, principal="elasticloadbalancing.amazonaws.com", source_arn=test_target_group.arn) test_target_group_attachment = aws.lb.TargetGroupAttachment("testTargetGroupAttachment", target_group_arn=test_target_group.arn, target_id=test_function.arn, opts=ResourceOptions(depends_on=[with_lb])) ``` :param str resource_name: The name of the resource. :param pulumi.ResourceOptions opts: Options for the resource. :param pulumi.Input[str] availability_zone: The Availability Zone where the IP address of the target is to be registered. If the private ip address is outside of the VPC scope, this value must be set to 'all'. :param pulumi.Input[int] port: The port on which targets receive traffic. :param pulumi.Input[str] target_group_arn: The ARN of the target group with which to register targets :param pulumi.Input[str] target_id: The ID of the target. This is the Instance ID for an instance, or the container ID for an ECS container. If the target type is ip, specify an IP address. If the target type is lambda, specify the arn of lambda. """ if __name__ is not None: warnings.warn("explicit use of __name__ is deprecated", DeprecationWarning) resource_name = __name__ if __opts__ is not None: warnings.warn("explicit use of __opts__ is deprecated, use 'opts' instead", DeprecationWarning) opts = __opts__ if opts is None: opts = pulumi.ResourceOptions() if not isinstance(opts, pulumi.ResourceOptions): raise TypeError('Expected resource options to be a ResourceOptions instance') if opts.version is None: opts.version = _utilities.get_version() if opts.id is None: if __props__ is not None: raise TypeError('__props__ is only valid when passed in combination with a valid opts.id to get an existing resource') __props__ = dict() __props__['availability_zone'] = availability_zone __props__['port'] = port if target_group_arn is None: raise TypeError("Missing required property 'target_group_arn'") __props__['target_group_arn'] = target_group_arn if target_id is None: raise TypeError("Missing required property 'target_id'") __props__['target_id'] = target_id alias_opts = pulumi.ResourceOptions(aliases=[pulumi.Alias(type_="aws:elasticloadbalancingv2/targetGroupAttachment:TargetGroupAttachment")]) opts = pulumi.ResourceOptions.merge(opts, alias_opts) super(TargetGroupAttachment, __self__).__init__( 'aws:lb/targetGroupAttachment:TargetGroupAttachment', resource_name, __props__, opts) @staticmethod def get(resource_name: str, id: pulumi.Input[str], opts: Optional[pulumi.ResourceOptions] = None, availability_zone: Optional[pulumi.Input[str]] = None, port: Optional[pulumi.Input[int]] = None, target_group_arn: Optional[pulumi.Input[str]] = None, target_id: Optional[pulumi.Input[str]] = None) -> 'TargetGroupAttachment': """ Get an existing TargetGroupAttachment resource's state with the given name, id, and optional extra properties used to qualify the lookup. :param str resource_name: The unique name of the resulting resource. :param pulumi.Input[str] id: The unique provider ID of the resource to lookup. :param pulumi.ResourceOptions opts: Options for the resource. :param pulumi.Input[str] availability_zone: The Availability Zone where the IP address of the target is to be registered. If the private ip address is outside of the VPC scope, this value must be set to 'all'. :param pulumi.Input[int] port: The port on which targets receive traffic. :param pulumi.Input[str] target_group_arn: The ARN of the target group with which to register targets :param pulumi.Input[str] target_id: The ID of the target. This is the Instance ID for an instance, or the container ID for an ECS container. If the target type is ip, specify an IP address. If the target type is lambda, specify the arn of lambda. """ opts = pulumi.ResourceOptions.merge(opts, pulumi.ResourceOptions(id=id)) __props__ = dict() __props__["availability_zone"] = availability_zone __props__["port"] = port __props__["target_group_arn"] = target_group_arn __props__["target_id"] = target_id return TargetGroupAttachment(resource_name, opts=opts, __props__=__props__) @property @pulumi.getter(name="availabilityZone") def availability_zone(self) -> pulumi.Output[Optional[str]]: """ The Availability Zone where the IP address of the target is to be registered. If the private ip address is outside of the VPC scope, this value must be set to 'all'. """ return pulumi.get(self, "availability_zone") @property @pulumi.getter def port(self) -> pulumi.Output[Optional[int]]: """ The port on which targets receive traffic. """ return pulumi.get(self, "port") @property @pulumi.getter(name="targetGroupArn") def target_group_arn(self) -> pulumi.Output[str]: """ The ARN of the target group with which to register targets """ return pulumi.get(self, "target_group_arn") @property @pulumi.getter(name="targetId") def target_id(self) -> pulumi.Output[str]: """ The ID of the target. This is the Instance ID for an instance, or the container ID for an ECS container. If the target type is ip, specify an IP address. If the target type is lambda, specify the arn of lambda. """ return pulumi.get(self, "target_id") def translate_output_property(self, prop): return _tables.CAMEL_TO_SNAKE_CASE_TABLE.get(prop) or prop def translate_input_property(self, prop): return _tables.SNAKE_TO_CAMEL_CASE_TABLE.get(prop) or prop	{ "pile_set_name": "Github" }
The Hum on the Shore	{ "pile_set_name": "OpenWebText2" }
Q: How to set color for first row in Datagrid I have a datagrid on a wpf (mvvm) project. the datagrid sort is showing the last item added to the collection as the first row. i want to color the first row (in order to highlight new item added to the collection) I've seen some similar questions about this manner but none of them are really related to what i am looking for. i have tried to use a IValueConverter but it doesnt seems to be the right path for me as i need to get a unique identifier for the first row and change all the rest of the rows in order to classified it as a "First Row". my object model for the items in the collection looks like this: public class Messages { public string Date {get; set;} public string Sender{get; set;} public string Content{get; set;} } *EDIT Forgot to add the converter code... of course this will color all rows to red, as i dont know how to affect the other rows when the collection changes. class DateToColorConverter : IValueConverter { object IValueConverter.Convert(object value, Type targetType, object parameter, System.Globalization.CultureInfo culture) { if (Convert.ToDateTime(value) >= DateTime.Now.AddMinutes(-1)) { return "Red"; } else return "Yellow"; } object IValueConverter.ConvertBack(object value, Type targetType, object parameter, System.Globalization.CultureInfo culture) { throw new NotImplementedException(); } } A: You can use RelativeSource with Mode set to PreviousData to identify whether dataGrid row is first one or not. For first row PreviousData will return null. Apply DataTrigger on DataGridRow in ItemContainerStyle: <DataGrid> <DataGrid.ItemContainerStyle> <Style TargetType="DataGridRow"> <Setter Property="Background" Value="LightBlue"/> <Style.Triggers> <DataTrigger Binding="{Binding RelativeSource={RelativeSource Mode=PreviousData}}" Value="{x:Null}"> <Setter Property="Background" Value="Green"/> </DataTrigger> </Style.Triggers> </Style> </DataGrid.ItemContainerStyle> </DataGrid>	{ "pile_set_name": "StackExchange" }
[Discussion on randomized controlled trials about clinical researches of acupuncture and moxibustion medicine]. The characteristics of clinical tests of acupuncture and moxibustion were analyzed by studies of the literature about clinical evidence-based trials of acupuncture and moxibustion medicine at present and on the basis of full analysis on the cause of insufficient evidence of clinical researches of acupuncture and moxibustion, in combination with the authors' experiences of clinical studies, and it is put forward that future clinical researches of acupuncture and moxibustion medicine should actively search for new research methods, insist evidence-based acupuncture and moxibustion medical researches, pay attention to retaining own researching characteristics of the acupuncture and moxibustion medicine, accumulate experiences, gradually establish and perfect the assessment system conforming with clinical research methods of acupuncture and moxibustion medicine, elevate the position of acupuncture and moxibustion medicine and develop the acupuncture and moxibustion medicine.	{ "pile_set_name": "PubMed Abstracts" }
SIRT1 regulates the histone methyl-transferase SUV39H1 during heterochromatin formation. In contrast to stably repressive, constitutive heterochromatin and stably active, euchromatin, facultative heterochromatin has the capacity to alternate between repressive and activated states of transcription. As such, it is an instructive source to understand the molecular basis for changes in chromatin structure that correlate with transcriptional status. Sirtuin 1 (SIRT1) and suppressor of variegation 3-9 homologue 1 (SUV39H1) are amongst the enzymes responsible for chromatin modulations associated with facultative heterochromatin formation. SUV39H1 is the principal enzyme responsible for the accumulation of histone H3 containing a tri-methyl group at its lysine 9 position (H3K9me3) in regions of heterochromatin. SIRT1 is an NAD+-dependent deacetylase that targets histone H4 at lysine 16 (refs 3 and 4), and through an unknown mechanism facilitates increased levels of H3K9me3 (ref. 3). Here we show that the mammalian histone methyltransferase SUV39H1 is itself targeted by the histone deacetylase SIRT1 and that SUV39H1 activity is regulated by acetylation at lysine residue 266 in its catalytic SET domain. SIRT1 interacts directly with, recruits and deacetylates SUV39H1, and these activities independently contribute to elevated levels of SUV39H1 activity resulting in increased levels of the H3K9me3 modification. Loss of SIRT1 greatly affects SUV39H1-dependent H3K9me3 and impairs localization of heterochromatin protein 1. These findings demonstrate a functional link between the heterochromatin-related histone methyltransferase SUV39H1 and the histone deacetylase SIRT1.	{ "pile_set_name": "PubMed Abstracts" }
Great to see you guys, and despite all the excitement, it was alot of fun. Hope that you made it back safely. Couple of things: I'd like to talk to several vineyard consultants, so if it ain't too much trouble, and you've got a name, I'd love to check around. Can I order two cases of coastal zin? What about the champagne? How much per magnum is it? Best, Jeff	{ "pile_set_name": "Enron Emails" }
Sporting Wood Now that carbon frames are ubiquitous, that super-light frame of yours just isn’t turning heads like it used to. Lucky for you, my narcissistic friend, several companies’ new high-tech composite frames are sure to turn the tables back in your favor, and there’s little danger of wide adoption. I am of course referring to wooden frames.	{ "pile_set_name": "Pile-CC" }
Associated with worry, stress, paranoia, fear, irritability, moodiness, anger. Connected to weakened health and immune system. Fully awake and alert. Nervousness, depression, and anxiety. People spend most of their time in the beta state.The beta brainwave is the predominant frequency when we are fully awake and alert. Active awareness directed to the outer world. Beta brainwaves are present during stress, paranoia, worry, fear, and anxiety. They are also present during hunger, depression, irritability, and moodiness. Insomnia is the result of producing excessive beta brainwaves. Associated with "mental chatter” and self-destructive impulses. Too much time in the beta state weakens the immune system. Beta brainwaves make up much of our conscious mind. The alpha state is where meditation and relaxation begins. We start to encounter the wealth of effortless creativity flowing just beneath our conscious state. Awake but deeply relaxed.Studies have shown the alpha state has been associated with “peak performance.” Elite athletes produce alpha brainwaves prior to concentrated performance (shooting a free throw, hitting an important golf shot). Amateur athletes produce more of the anxious beta brainwaves. In the alpha state we learn, process, memorize and recollect large sums of information fast and with peak effectiveness. Highly creative people have been shown to have “bursts” of alpha brainwaves when they have good ideas Alpha brainwaves are thought to make the brain “act young” again. In the alpha state fears, habits, and phobias begin to melt away. Alpha brainwaves bring an effortless sense of comfort, peace, and harmony. Best for “super learning”. The alpha state is the first layer of our subconscious mind. A gateway to deeper states of awareness. Theta Brainwave Entrainment Benefits: 4-7 Hz Insight, intuition, inspiration. Answers to important questions can be found. Feels like you are floating. A wonderful realm to explore. Dream like imagery. Good for problem solving. Feel more connected to others.Theta brainwaves become prominent when we go deeper into meditation and relaxation — “almost trance-like”.Here, brain activity decelerates to the threshold of the sleep stage. One of the more indescribable and wonderful realms we can explore. The theta state produces flashes of creative visualization through vivid imagery. In this state we feel much more open and connected to other people. People often report a feeling of floating while producing theta brainwaves. Theta brainwaves are thought to bring out a person’s dormant extrasensory perception (ESP) skills. The theta state heightens problem-solving skills. Having dominant theta brainwaves are correlated with insight and intuition. Theta brainwaves bring inspired thought and increased motivation. Sometimes long-forgotten memories come to the surface. Children have strong theta brainwaves, which helps to explain their superior ability to learn. Theta is briefly experienced as we climb out of the depths of delta upon waking, or when falling asleep. The theta state is the deeper sub-conscious to super- conscious part of the mind. Delta Brainwave Entrainment Benefits: 0-4 Hz Renewal, healing, rejuvenation. Deep, dreamless sleep. Very rewarding. Said to be the entrance to non-physical states of reality. Best state for immune system function, restoration, and health. The deepest level of meditation. The delta state is associated with “no thinking” during deep, dreamless sleep. Delta brainwaves are very rewarding. Delta is said to be the entrance to non-physical states of reality. A crucial state for renewal, healing, and rejuvenation. The immune system strengthens in the delta state. The delta state is the unconscious/super-conscious part of our mind. Many scientists believe this state to be the most beneficial. AUGUST 1 Lammas - the festival of the wheat harvest, is the first harvest festival of the year. On this day it was customary to bring to church a loaf made from the new crop, the loaf was blessed to produce magic. In many parts of England, tenants were bound to present freshly harvested wheat to their landlords on or before the first day of August, this was called “THE FEAST OF THE FIRST FRUITS". FIRST FRUITS are a religious offering of the first agricultural produce of the harvest. In classical Greek, Roman, Hebrew and Christian religions, the first fruits were given to priests to offer to God. First Fruits were often a primary source of income to maintain the religious leaders and the church. In the Canonical Gospels, the concept of the harvest of FIRST FRUITS is used metaphorically and allegorically. In the Gospel of Matthew, Jesus is described as stating that “in the time of harvest” he would instruct the harvesters (i.e., the angels) to gather the “tares”, bind them into bundles, and burn them, and they were to "gather the wheat into His barn”. Some argue that this teaching is about the Last Judgment, the “tares” being sinners or unbelievers of God and the “wheat” being the believers of God. In medieval times the feast was sometimes known in England and Scotland as the “GULE OF AUGUST” The origin of the word GULE is similar to “gullet”; from Old French “goulet”, meaning “THROAT, NECK," from Latin “gula” meaning "THROAT". In Ancient Rome the "Goddess of HOPE" was called SPES.She was worshipped on August 1 Hope is an optimistic attitude of mind based on an expectation of positive outcomes related to events and circumstances in one's life or the world at large. As a verb, its definitions include: "expect with confidence" and"to cherish a desire with anticipation". Among its opposites are dejection, hopelessness and despair. Interestingly, Barack Obama’s run for the Presidency was basedon a promise of "HOPE". I am curious if Obama, or someone else will bestow the feeling of HOPE on the world this August 1st. Or will the same lame mantra of “no hope” reel across the news feeds today? Today is the Pagan feast of LAMMAS, the Feast of the First Fruits.It is also the ancient Holy day of the Goddess "HOPE". The First Fruits have been Sacrificed...... The World has been mourning the death of CECIL the LION. And now today, August 1, 2015, Lammas, Cecil's brother JERICHO has been killed in Africa. CECIL means BLIND SIXTH JERICHO means FRAGRANT MOON The two brothers were the: BLIND SIXTH FRAGRANT MOON Jericho is a city located near the Jordan River in the West Bank of ISRAEL. It is an ancient city famous in the Bible as the site of the battle of JERICHO. According to the Book of Joshua, the Battle of Jericho was the first battle of the Israelites in their conquest of Canaan. According to Joshua 6:1-27, the WALLS of JERICHO fell after Joshua's Israelite army marched around the city blowing their TRUMPets. I am reminded of Donald TRUMP recently in the news saying he was prepared to build a WALL between the United States and Mexico. The story of JERICHO is told in Joshua 6:1-27. The first five books of the Hebrew Bible tell how Noah cursed Canaan to become a slave, and how God gave the land of the Canaanites to Abraham and his descendants. The children of Israel (descendants of Abraham) themselves became slaves in Egypt, but through Moses God brought them out of Egypt and to the borders of the promised land of Canaan. There Moses instructed them to seize the land by conquest, and placed them under the command of Joshua. Joshua sent spies to Jericho, the first city of Canaan to be taken, and discovered that the land was in fear of Israel and their God. The Israelites marched around the walls once every day for six days with the priests and the Ark of the Covenant. On the seventh day they marched seven times around the walls, then the priests blew their ram's horns, the Israelites raised a great shout, and the walls of the city fell. Following God's law of herem the Israelites took no slaves or plunder but slaughtered every man, woman and child in Jericho, sparing only Rahab, a Canaanite prostitute who had sheltered the spies, and her family. JERICHO and again became famous in the New Testament when JESUS healed several BLIND men as he passed through. I am reminded that JERICHO is not only the site where Jesus allowed the BLIND to SEE but.... CECIL means BLIND as well and his brother is JERICHO the second murdered Lion. ++++ On the ceiling of the US Capitol Dome is the Greatest Alchemical painting in America. The Father of the country, George Washington is displayed in his Rainbow Light Body form, surrounded by five Pagan Gods representing the Five Elements-	{ "pile_set_name": "Pile-CC" }
Feds OK $4B to boost coastal levees amid questions about... 1of19Francisco Martinez helps clean up Eleanor Tinsley Park after the floodwaters receded Thursday. near the Freedom Over Texas main stage while taking down the setup at Eleanor Tinsley Park on Thursday, July 5, 2018, in Houston. The Freedom Over Texas concerts were canclled due to the flood. ( Yi-Chin Lee / Houston Chronicle )Photo: Yi-Chin Lee, Staff / Houston Chronicle 2of19An Army Black Hawk helicopter, carrying U.S. Army Corps of Engineers officials, flies over the ship channel Wednesday, September 7, 2016. A dike, called the "Ike Dike," is being proposed to protect Galveston, Bolivar and the Galveston Bay area from storm surges. ( Michael Ciaglo / Houston Chronicle )Photo: Michael Ciaglo, Staff / Houston Chronicle 3of19Texas asked for $12 billion for the Galveston County Coastal Spine project, part of the so-called "Ike Duke." The federal government on July 5, 2018 announced $3.9 billion in funding for the coastal barrier. 4of19The letters spelling H-O-U-S-T-O-N that floated away from the Bud Light beach volleyball court with Buffalo Bayou floodwater during the July 4th flood is seen back to the Eleanor Tinsley Park on Thursday, July 5, 2018, in Houston. The Freedom Over Texas concerts were canclled due to the flood. ( Yi-Chin Lee / Houston Chronicle )Photo: Yi-Chin Lee, Staff / Houston Chronicle 5of19The Buffalo Bayou floodwater has receded near downtown Houston but remains in brown color after the July 4th flood on Thursday, July 5, 2018, in Houston. The Freedom Over Texas concerts at Eleanor Tinsley Park were canclled due to the flood. ( Yi-Chin Lee / Houston Chronicle )Photo: Yi-Chin Lee, Staff / Houston Chronicle 6of19Production crew members take down the Freedom Over Texas CITGO Main Stage at Eleanor Tinsley Park on Thursday, July 5, 2018, in Houston. The Freedom Over Texas concerts were canclled due to the flood. ( Yi-Chin Lee / Houston Chronicle )Photo: Yi-Chin Lee, Staff / Houston Chronicle 7of19The Buffalo Bayou trail at Eleanor Tinsley Park is covered in mud after the July 4th flood on Thursday, July 5, 2018, in Houston. The Freedom Over Texas concerts were canclled due to the flood. ( Yi-Chin Lee / Houston Chronicle )Photo: Yi-Chin Lee, Staff / Houston Chronicle 10of19A worker's boots are covered in mud while taking down the setups near the Freedom Over Texas main stage at Eleanor Tinsley Park on Thursday, July 5, 2018, in Houston. The Freedom Over Texas concerts were canclled due to the July 4th flood. ( Yi-Chin Lee / Houston Chronicle )Photo: Yi-Chin Lee, Staff / Houston Chronicle 11of19Ernesto Baeza, from left, Francisco Martinez and a worker load a decoration plant onto a truck near the Freedom Over Texas main stage while taking down the setups at Eleanor Tinsley Park on Thursday, July 5, 2018, in Houston. The Freedom Over Texas concerts were canclled due to the flood. ( Yi-Chin Lee / Houston Chronicle )Photo: Yi-Chin Lee, Staff / Houston Chronicle 12of19Francisco Martinez wheels the decoration plant in a mud-covered walkway near the Freedom Over Texas main stage while taking down the setup at Eleanor Tinsley Park on Thursday, July 5, 2018, in Houston. The Freedom Over Texas concerts were canclled due to the flood. ( Yi-Chin Lee / Houston Chronicle )Photo: Yi-Chin Lee, Staff / Houston Chronicle 13of19Direct Scaffold Supply crew Diego Romero, front, and Alexander Garcia take down the fences for the Freedom Over Texas main stage at Eleanor Tinsley Park on Thursday, July 5, 2018, in Houston. The Freedom Over Texas concerts were canclled due to the flood. ( Yi-Chin Lee / Houston Chronicle )Photo: Yi-Chin Lee, Staff / Houston Chronicle 16of19The Buffalo Bayou floodwater has receded near downtown Houston but remains in brown color after the July 4th flood on Thursday, July 5, 2018, in Houston. The Freedom Over Texas concerts at Eleanor Tinsley Park were canclled due to the flood. ( Yi-Chin Lee / Houston Chronicle )Photo: Yi-Chin Lee, Staff / Houston Chronicle 17of19A walkway at Eleanor Tinsley Park is covered in mud after the July 4th flood on Thursday, July 5, 2018, in Houston. The Freedom Over Texas concerts were canclled due to the flood. ( Yi-Chin Lee / Houston Chronicle )Photo: Yi-Chin Lee, Staff / Houston Chronicle 19of19Jared Wilson takes his dog, Benji, to the Johnny Steele Dog Park on Buffalo Bayou for some fun only to find out it is covered in thick mud after the July 4th flood on Thursday, July 5, 2018, in Houston. The family visits the dog park often because is it the closest dog park that is close to their Midtown home. The dog park recently reopened for the first time since Hurricane Harvey. ( Yi-Chin Lee / Houston Chronicle )Photo: Yi-Chin Lee, Staff / Houston Chronicle Even as residents await a long-discussed plan to create a 60-mile barrier, known as the “Ike Dike,” to protect Texas’ Gulf Coast from major hurricanes, the U.S. Army Corps of Engineers said Tuesday it would provide nearly $4 billion toward part of the larger barrier system. One day after an Independence Day rainstorm stirred memories of past Houston floods and underscored how the Houston-Galveston area remains vulnerable to natural disasters, the Corps announced nearly $5 billion in funding for high-priority disaster recovery projects in Texas, much of it designed to spur flood mitigation and continued recovery from Hurricane Harvey. The biggest item by far is $3.9 billion for the Sabine Pass-to-Galveston Bay Coastal Storm Risk Management and Ecosystem Restoration, a series of upgrades and improvements to 30 miles of existing coastal levees in Port Arthur and Freeport, and the construction of nearly 27 miles of coastal levees in southern Orange County. "The [Sabine Pass to Galveston Bay] study is done, the money that we're gonna get from the [federal] Bipartisan Budget Act, that will allow us to go into the design phase and then go into construction," said Sharon Tirpak, deputy chief of project management for the Galveston District of the U.S. Army Corps of Engineers. The Sabine Pass to Galveston Bay project has a long history, initially conceived in 2004 as a way to shore up aging levee systems along the coastline. The Army Corps of Engineers was in the midst of studying the project when Hurricane Ike hit in 2008, devastating parts of the Texas coast and halting the study indefinitely. The Texas General Land Office signed on to sponsor a new study of the project in 2013, and by the end of 2017 the Corps had narrowed the scope of the project to Freeport, Port Arthur, and Orange County. U.S. Rep. John Culberson hailed the allocation as “an important step in developing a comprehensive coastal spine to protect the Texas coast," but Tirpak made clear to draw a distinction between the levee project and the long-awaited "Ike Dike" study. "If you look at the entire Texas coast, that's a portion of the coast that we have answered the questions on, 'How do you protect that upper southeast Texas coast?'" Tirpak said. "So, if you look at it comprehensively, that's taking care of that portion, but it does not include what everyone considers the coastal spine or the Ike Dike solution." Jim Blackburn of Rice University's Severe Storm Prediction Education and Evacuation from Disasters (SSPEED) Center said the amount allocated to the levee project is not nearly enough to fund the “Ike Dike," the estimated cost of which runs upwards of $12 billion. "It is irregular to appropriate funds before the internal Corps review is completed," Blackburn said. The Army Corps of Engineers has not yet approved a design for the Ike Dike, but it did allocate $1.9 million for the continued study of a coastal spine barrier. Tirpak said a draft report of that study and an environmental impact statement would be released by the end of September, followed by a series of public meetings, likely beginning in November. Several meetings are being planned for the Houston-Galveston area, one in League City, one in Galveston, and one in Winnie, with other meetings planned farther down the Texas coast. The final Ike Dike study is expected to be completed by the spring of 2021. There remained a lot of uncertainty about the Houston area’s preparedness for the next big storm after 7 inches of rain fell on parts of Harris County on Wednesday before tapering off in the early afternoon. The 6 inches recorded at Hobby airport set a record for the July 4th holiday, putting nerves on edge in a region still recovering from Harvey’s catastrophic flooding. Those totals fell short of the rainfall during the Tax Day and Memorial Day floods of 2015 and 2016, which each dumped more than a dozen inches on the area, and well short of Harvey’s 30 to 50 inches. Still, the rain fell hard and quickly Wednesday morning, flooding streets, stranding motorists, spurring Harris County to open its emergency operations center and forcing Houston to cancel its Freedom Over Texas celebration for the first time ever. Skies did clear in time for an evening fireworks show near downtown Houston. "This was a relatively minor storm that almost reached catastrophic proportions," Blackburn said. "I don't think it's really sunk in that these types of storms will occur more and more often." National Weather Service data shows rainfall in Houston from 5 a.m. to 5 p.m. on Wednesday, July 4. Source: NWS \| Created by Rachael Gleason/Houston Chronicle Harris County Judge Ed Emmett said the July 4th flooding, from a mere 4 to 6 hours of rain, highlighted the need for a $2.5 billion flood infrastructure bond that will go before voters on Aug. 25, the one-year anniversary of Harvey making landfall. Some of the bond proceeds would go toward reducing street flooding in extreme rain events, according to the Harris County Flood Control District’s website. Officials from Houston and Harris County said Wednesday that the preparedness level of first responders is the same or better than when Harvey hit, thanks to the addition of rescue boats and high-water vehicles to several agencies. But most of the flood infrastructure damaged by that historic storm has yet to be repaired, and it weakens each time a new system batters the region. “I would expect to see that where there were previous damages, they probably start to get incrementally worse,” said Alan Black, director of engineering for the flood control district. “Anytime you’ve got exposed slopes, the erosion just keeps on going.” Blackburn said just 5 percent of the $150 million in needed infrastructure repairs has been completed. He estimated that crews will need until the end of 2019 to complete the rest. The projects that the flood control district has completed so far, at a cost of $6 million, have focused on damaged infrastructure that posed the greatest risk to public safety. The “Ike Dike” funding came in response to a state request for $12 billion for what the governor’s office called the “Galveston County Coastal Spine Project,” according to a state presentation on post-Harvey needs. “This project is part of a larger coastal spine proposal also known as the ‘Ike Dike,’” the presentation said. “The Ike Dike is a coastal barrier that, when completed, would protect the Houston-Galveston region including Galveston Bay from hurricane storm surge.” A spokesman for Emmett said Thursday that the county judge “was pleased with the coastal spine funding announcement, and looks forward to learning how it can be spent.” Follow-up calls to Abbott and Culberson were not immediately returned. Galveston County Judge Mark Henry, who has been an advocate for the Ike Dike project, did not immediately respond to a request for comment late Thursday. Gov. Greg Abbott said in a written statement that the bulk of this third round of flood mitigation funds would “go a long way toward future-proofing Texas against another hurricane and strengthening our infrastructure to withstand dangerous flooding.” The funding includes $295 million for a Clear Creek flood damage reduction project; $75 million to complete construction of the Brays Bayou flood damage reduction project, plus $1.75 million to repair damages to the project; $65 million to complete construction of the Hunting Bayou flood damage reduction project; $45 million to finish the White Oak Bayou flood damage reduction project, plus $1.75 million to repair damages to the project; and $30 million for maintenance dredging of the Houston Ship Channel. Other allocations include $11.7 million to repair damage to Buffalo Bayou and its tributaries, plus $6 million to study options to reduce the bayou’s flooding risk, including making changes to the Addicks and Barker dams, as well as $1.5 million to complete the Addicks and Barker dams safety project; $3 million apiece to study flood risk management options in Houston, excluding Buffalo Bayou, and the Brazos River; and $1 million to repair damages to the Sims Bayou flood damage reduction project. A day after Wednesday’s downpour, workers cleared tree limbs from roadways and towed flooded vehicles. They also trudged through the vast green space of Eleanor Tinsley Park on the south bank of Buffalo Bayou, still muddy and submerged in areas, to deconstruct tents, fencing and a main concert stage. For the second consecutive year, floodwaters had canceled concerts planned for the site near downtown Houston. Just upstream, the Johnny Steele Dog Park was swamped for the first time since Harvey and less than a month after it reopened following renovations. Each of the next seven days carries a chance of more rain, the National Weather Service predicts. Blackburn questioned the logic of continuing to hold events in places like Eleanor Tinsley Park, a popular recreational space near downtown that nevertheless has a documented history of flooding. “There is a very real risk there,” Blackburn said. “We all still think we can play the odds and we’ll win, and right now we’re not winning.” Susan Christian, Houston’s director of special events, said the city estimates a loss of several hundred thousand dollars of revenue due to the cancellation of Freedom Over Texas. Still, she said organizers are not considering relocating. “We’ve produced this event there for 31 years,” Christian said. “Our intention is to move forward at this point in the manner that we have.” Blackburn said he believes Houston and Harris County leaders need to more aggressively oppose development in flood plains, and said they should consider buyouts of tens of thousands of homes. The flood bond, as proposed, includes funding for around 3,600 buyouts. Their sneakers caked with mud, Gianna Maggiani, from near Cypress, and Kristen Washington of Austin walked along Buffalo Bayou on Thursday morning. When they saw heavy rain in Wednesday’s forecast, they knew to steer clear of the Fourth of July celebrations near downtown. Message therapist Claudine Yao lives with her family in a townhouse near Buffalo Bayou park. She had planned to attend Freedom Over Texas, and said she has learned that storms far weaker than Harvey can force the bayou out of its banks. Though her townhouse stayed dry during the August storm, she knows the streets in her neighborhood can quickly become impassable, and she often worries when forecasts call for wet weather.	{ "pile_set_name": "Pile-CC" }
Ten years ago, Formula One nearly wrote itself and everyone involved off from one of the biggest markets it always wanted to conquer - driven by ego and self-interests. Here is what (probably) happened. [image source] In 2000, Formula One was - generally speaking - more than welcome at the precious circuit, as the series and the legendary 500-mile race at the track had had shared history during the early years of the ‘continental circus’. The - more or less - only discrepancy emerging during the introduction of the United States Grand Prix to Indianapolis was the need to erect a road course in the infield of the track, which some people felt to be a sacrilege and pointed at the groin area of the newcomers, ridiculing the assumed lack of reproductive male organs for not racing on the classic oval. Due to the inherent design of F1 cars, this was never to be a plan, but the new circuit made up for some of the magic the circuit had to offer.Formula One is heading to Texas with Lewis Hamilton more than likely clinching the world title for a third time. There is much anticipation about the event, one could also say it is the most looked forward to since Formula One set a foot on the Indianapolis Motor Speedway in 2000, following a near-decade-long absence from the country. [image source] The winding, slightly unimaginative infield section ran clockwise - as opposed to the oval version -, but it finished off by merging with the original track for its final turn (i.e. no. 13 - the first one on oval configuration), running amok on the main straight in the ‘wrong direction’, only to engage in heavy breaking to leave the ‘outer rim’ on a 90-degree right turn. The effect was spectacular. It wasn’t as if it was unprecedented for American audiences, but it was slightly new to (modern) Formula One. Circuits with only slightly similar features included the Autódromo Hermanos Rodriguez in Mexico, the Autodormo Nazionale Monza in Italy and the Autódromo José Carlos Pace in Brazil. All of them feature(d) long, fast, slightly cambered turns (funnily enough, the final one in all three cases), but the 9-degree banking of Turn 13 at the Indianapolis Motor Speedway was something Formula 1 had not seen in a very long time - yet it was considered relatively flat by US-standards. [image source] Needless to say, the 2000 US Grand Prix was a massive hit. It drew the largest-ever crowd in all of F1’s history, instantly becoming a fan-favourite and a permanent fixture on the calendar. A shocked world was watching the race the following year, less than three weeks after the terrorist attack on the World Trade Center on September 11th, with the cars running very little - if no - advertisement [EDIT: at Monza]. [image source] By 2005, the game was very different from the first race. There was much inner battle going within F1 to gain control over the series’ management by the teams, all of which failed - thanks to the de facto owner’s, Bernie Ecclestone’s impeccable survival instincts. In 2001, Michelin became the second tyre-supplier of the series next to the established Bridgestone, instantly spurring rivalry between the two. Moreover, the FIA introduced a new rule for 2005 that disallowed tyre-changes during races, forcing the manufacturers to run harder compounds, which still lead to some dramatic punctures towards the end of some races earlier in the season. To further complicate matters, the oval track was resurfaced in 2004 - after that year’s F1 race - featuring a brand new, high-grip, diamond-cut asphalt. As IMS was not an allocated venue for testing, the two tyre-manufacturers used previous year’s data as reference coming into the race for 2005, which proved to be disastrous for the French Michelin. [image source] The three teams using Bridgestone tyres (Ferrari, Jordan and the backmarker Minardi) turned up with a - traditionally - more conservative mixture. Also, one cannot discount the fact that Firestone, the sister company of the Jaapnese, was a regular in the Indy Racing League and they just scored a win at the 500-mile race a few weeks earlier - already on the new surface. Therefore it is possible that Bridgestone wasn’t completely in the dark when heading into the F1 race. The rest of the teams (all seven of them), who were sporting Michelin rubber, quickly hit a wall - quite literally - when going out for the first of the Friday free practices. One of the Toyotas - driven by Ralf Schumacher - suddenly veered off from the racing line in Turn 13 and kissed the outside barrier, slowly drifting towards the pit wall on the inside - not unlike what he managed to do in the previous year. The German was visibly unhurt, putting the blame on the car with an aimed kick at the nose cone, but it was apparent he was very much shaken by the accident. He was replaced by Ricardo Zonta for the rest of the weekend, but the problems revealed something much worse than that. [image source] The Michelin tyre collapsed under the heavy load in the turn, only after a short stint of competitive driving. The biggest problem seemed to be that it wasn’t unique to the German’s accident. As a matter of fact, several failures on left-rear tyres were reported during the session. Every single one of the 14 cars with Michelin rubber was in jeopardy through Turn 13. Trying to avoid catastrophe on what seemed to be a collision course, Michelin flew new tyres in from its headquarters in France to Indianapolis, all of which turned out to be the very same compound the teams had already been using. They were screwed. Nevertheless, in a crude twist of irony, Ralf Schumacher’s team-mate, Jarno Trulli put his Toyota on pole position during Saturday’s qualifying. This is where one of Formula One’s biggest scandals started. Michelin notified the FIA - with Max Mosley sitting at home, in Monaco - about the situation and advised a chicane to be implemented just before Turn 13 to slow the cars down and to lessen tyre-load around the corner. Ferrari quickly shrugged off the matter and refused to take part in any further negotiations, claiming that it was only Michelin’s problem, but they adopted a neutral stand on the question of the chicane per se. [image source] Somebody else opposed the modification of the track, though. The FIA itself. Bernie Ecclestone already ordered the chicane to be built on Sunday morning, which was stopped by FIA’s race director, Charlie Whiting. The official standpoint of the FIA was that they couldn’t assist to last-minute changes to the layout of the track for safety reasons. Therefore if the teams went on with the idea of the chicane, the FIA would be forced to remove all of its staff from the race and would exclude it from the World Championship. Ferrari’s Jean Todt didn’t like the idea at all as they were very much in battle for the Constructors’ title and this was their strongest chance to bag a win for the season, finally. The rest of the teams initially agreed to proceed with the chicane and the non-championship race - even without Ferrari if it came to that -, but an alleged threat from Max Mosley signaled that the act would put all FIA-sanctioned races in jeopardy in the US in the future. F1 and the Michelin teams - lead by Renault’s Flavio Briatore - weren’t left out in the cold, though. Cooking up a brand new Michelin compound was already ruled out the day before, therefore the only solutions left were the reintroduction of tyre-changes for the race - as the rules permitted changing in case of fearing terminal failure -, but it was downvoted by the teams. The same way the idea of enforcing a speed limit through the corner or a drive-through the pits - with the compulsory speed limit - was dismissed at the meetings where the Bridgestone-riding Jordan and Minardi was present as well. In effect, it turned into a political struggle with all the teams - minus Ferrari, regardless of tyre-manufacturers, gravitating around Flavio Briatore and Bernie Ecclestone - apparently uniting against the sanctioning body, the FIA, not unlike in the early 80s. The only difference being this time is that Max Mosley took the other side. A widespread boycott was announced literally within the hour of the start of the race that would have meant that either a chicane was installed and all the teams - but maybe not Ferrari - would go out and race for zero points or everything was left as it had been and it would only be Ferrari starting the race. As the start of the race was approaching at a rapid pace, the Jordan team announced they would make it to the grid, which was followed by Minardi’s similar announcement - despite team leader Paul Stoddart being very much vocal on siding with the Michelin teams - citing the Jordan precedent and pressure from Bridgestone when making the decision, and perhaps the guaranteed points - when not failing the race - for the last team on the grid was too attractive. Approaching the top of the hour, all the teams went out to make the grid for the start of the race. With still too much confusion in the air, no one was willing to give a straight answer, citing only the chicane issue. Minutes after the signal was given for the formation lap (with two, former Indy 500 winners in the field), the - second - worst scenario unfolded. All Michelin-equipped cars peeled off into the pits, leaving the six Bridgestone-riding vehicles on the grid. The lights were off and the strangest F1 race was a-go. [image source] Those in the grandstands and the many millions around the world couldn’t believe their eyes. A laughable amount of six cars were lapping the gigantic venue, four of them being no match for the front-runner Ferraris. The audience was furious, the live feed was showing people throwing bottles and beer cans on the track with brave marshals running in, collecting as much as they could. Makeshift transparents were made, wishing the FIA and Formula One hell, while others were leaving the track midway through the ‘race’. The cherry on the cake was when the two Ferraris nearly collided following a pit stop, which was quickly followed by a team radio message that set the order between the two cars. The podium ceremony’s only positive moment was Jordan’s Tiago Monteiro’s brief, but honest celebration, spraying champagne, as the two Ferrari drivers quickly left the stage after receiving their respective awards. [image source] The political self-interests between Michelin, Bridgestone, Ferrari and the FIA resulted in one of the biggest blowbacks in Formula One’s history. Later that month, all Michelin teams were found guilty by the World Motorsport Council on the counts of failing to present suitable tyres for the race - with mitigating circumstances - and that they allowed the cars to race (by not notifying the stewards on NOT starting the race beforehand while going out to the formation lap, they technically started the race). This would be the only race during the season where Ferrari or Bridgestone won. The FIA reinstated tyre-changes for the following season. Michelin left Formula one at the end of the following season. Brigestone would follow suit at the end of 2010, to be replaced by Pirelli as the sole tyre-manufacturer. The Indianapolis Motor Speedway hosted two more US Grands Prix, then the event dropped from the calendar until the newly-built Circuit of the Americas picked up the race in 2012. The road course at Indy was reconfigured to circumvent the banked corner and it would be used for IndyCar and MotoGP races. Flavio Briatore was temporarily banned from all Formula 1 race tracks and activities following the race-fix-by-crashing scandal at the 2008 Singapore Grand Prix, damaging Renault’s reputation, eventually pulling out of the sport as a manufacturer. Both the Jordan and Minardi teams were sold, they are currently running as Force India and Toro Rosso, respectively. Max Mosley did not run for the FIA presidency again, he resigned in 2009. His successor currently is Jean Todt, former Scuderia Ferrari team leader. Bernie is still Bernie and not a fan of the US.	{ "pile_set_name": "OpenWebText2" }
Multiple-unit dental restorations (i.e., bridges or pontics) have for many years been made by preparing a metal base or coping and then adding several layers of dental porcelain over the metal to simulate, as closely as possible, the appearance of natural teeth. The metal base for the bridge is usually assembled on a master cast and the individual units (teeth) are fastened together with wax containing rosin, known in the dental profession as "sticky wax". The assembly of individual units bonded together with wax is then carefully removed from the master cast and is embedded in a unitary mass of refractory cement ("soldering investment"), with only the portions of the units that are to be joined to the adjacent units exposed. After the cement has hardened, the wax is removed, as by flushing with boiling water. Next, the units are soldered together. After the soldering operation, the assembly is removed from the investment and is ready for the addition of the porcelain layers. Recently, all-ceramic dental restorations have become commercially available. Because no metal is used in their fabrication, all-ceramic restorations can be made to more closely resemble natural dentition. Such all-ceramic dental restorations are disclosed, for instance, by Starling et al. in U.S. Pat. No. 4,265,669. Naturally, the techniques for producing an all-ceramic dental restoration must differ in some respects from those used to produce a metal-based restoration. For instance, in the preparation of an all-ceramic multiple unit restoration, the individual units cannot be soldered together as they are in a metal-based restoration. This invention is directed to a procedure that is particularly applicable for joining the individual units to each other in the production of an all-ceramic multiple unit dental restoration, although the invention is more widely applicable to the joining of all types of ceramic components that must be joined in precise spatial relationship.	{ "pile_set_name": "USPTO Backgrounds" }
Aβ43 is the earliest-depositing Aβ species in APP transgenic mouse brain and is converted to Aβ41 by two active domains of ACE. Amyloid-β protein (Aβ) varies in length at its carboxyl terminus. The longer Aβ species, Aβ43 and Aβ42, are highly amyloidogenic and deposit more frequently than Aβ40 in the brain of Alzheimer disease (AD) patients. However, the characterization of Aβ43 deposition in the brain and the relationship between Aβ43 and Aβ42 or Aβ40 remain unclear. We provide evidence that Aβ43 deposition appears earlier than Aβ42 and Aβ40 deposition in the brain of mutant amyloid precursor protein transgenic (APPtg) mice, suggesting that Aβ43 is the earliest-depositing species. In addition, we found increased Aβ43 levels and Aβ43/Aβ42 ratios in the serum of AD patients, suggesting their use as diagnostic blood biomarkers for AD. We further show that angiotensin-converting enzyme (ACE) converts Aβ43 to Aβ41. Notably, this Aβ43-to-Aβ41 converting activity requires two active domains of ACE. Inhibition of ACE activity significantly enhanced Aβ43 deposition in APPtg mouse brain. Our results suggest that Aβ43 is the earliest-depositing species in brain parenchyma and that Aβ43 may trigger later Aβ42 and Aβ40 deposition or may be converted to Aβ42 and Aβ40 plaques. Activities of both ACE domains may be important for reducing Aβ43 levels in serum and reducing brain Aβ43 deposition.	{ "pile_set_name": "PubMed Abstracts" }
Q: Precession in the vector model of angular momentum - quantum mechanics? The vector model of angular momentum in quantum mechanics says that, for example, the angular momentum vector $\mathbf{L}$ precesses about its projection on the $z$ axis, like this: We can add $\mathbf{L}$ and $\mathbf{S}$ to make $\mathbf{J}$, so that $\mathbf{L}$ and $\mathbf{S}$ precess about $\mathbf{J}$, like this: NOW: 1) Does the direction of precession (clockwise or anticlockwise) matter? 2) This is just a model, $\mathbf{L}$ and $\mathbf{S}$ do not actually precess, right? So why do use this model? Is it a way to take into account the fact that we don't know $L_x$ and $L_y$? A: My quantum mechanics teacher, always say to me, that those models for "see" the spin and the angular momentum, are not correct. the reason is that the picture of an electron precessing associated with the spin in't correct because the spin is'nt associated with any spacial coordinate. in quantum mechanics is better abandon those pictures, the important are the properties of L and S and the measure.	{ "pile_set_name": "StackExchange" }
FIELD OF THE INVENTION The field of this invention relates to household appliances and, more particularly, to controlling the performance of household appliances.	{ "pile_set_name": "USPTO Backgrounds" }
IN THE UNITED STATES COURT OF APPEALS FOR THE FIFTH CIRCUIT _____________________ No. 01-50232 _____________________ MARTIN ALVAREZ; PETE ALVAREZ; SERGIO ARMENDARIZ; ANDREW BROOKS; TAYLOR BARKLEY; GARY CADD; HECTOR JESUS CANO; PEDRO A. CHAVEZ; BRUCE A. CRUMP; MARIO D’AGOSTINO; ROBERTO FLORES; RAUL GARCIA-FLORES; DAVID GONZALEZ; GREG HERNANDEZ; MARIO HERNANDEZ; RICHARD HOLGUIN; MARK KLINE; LORENZO MARQUEZ; ANTONIO MURO, JR.; MICHAEL NELIGH; CARLOS A. PIEDRA; ERIC SODEMANN; MICHAEL A. STUBBLEFIELD; DANIEL TARIN; JOSEPH A. TELLEZ; MIGUEL A. TORRES; DAVE VALERO All individually and on behalf of all other employees similarly situated, Plaintiffs - Appellants, versus CITY OF EL PASO, Defendant - Appellee. _________________________________________________________________ Appeal from the United States District Court for the Western District of Texas No. EP-00-CV-103-H February 14, 2002 Before GARWOOD, JOLLY, and DAVIS, Circuit Judges. PER CURIAM:1 Martin Alvarez and twenty-seven other firefighters brought 1 Pursuant to 5th Cir. R. 47.5, the court has determined that this opinion should not be published and is not precedent except under the limited circumstances set forth in 5th Cir. R. 47.5.4. suit against the City of El Paso based on the Fair Labor Standards Act (FLSA). They claimed that the City had violated the FLSA, 29 U.S.C. § 207(a)(1), by refusing to pay compensation for their lunch hour. They argued that, because the City placed so many restrictions on the firefighters’ activities during lunch, it was impossible to derive any personal benefits from the lunch hour. Thus, because the lunch hour did not qualify as a bona fide meal period under the FLSA, they were entitled to be compensated for the hour. The district court granted the City’s motion for summary judgment. Alvarez now appeals. We have studied the briefs, heard the argument of the parties, and considered the issues raised in this appeal. It is now clear to us that the finding and conclusions of the district court are not reversible. In deciding whether a lunch hour qualifies as a bona fide meal period, the courts apply a “predominant benefit test.” See Bernard v. IBP, Inc. of Nebraska, 154 F.3d 259, 264 (5th Cir. 1998). “The critical question [under this test] is whether the meal period is used predominantly or primarily for the benefit of the employer or for the benefit of the employee.” Id. at 264-65. In resolving this question, we must decide whether the employee can use the time during lunch for his or her own purposes. Id. at 266. The restrictions placed here on the employees’ dress and use of city-owned automobiles were more in the nature of inconveniences than restrictions on the free use of the time at 2 issue. The district court therefore did not err when it determined, as a matter of law, that the firefighters could use the lunch hour time primarily for their own personal benefit. Accordingly, the judgment of the district court is AFFIRMED. 3	{ "pile_set_name": "FreeLaw" }
This article is from the archive of our partner . Always one to detest the TSA's intrusion on people's privacy, Sen. Rand Paul has been detained himself by officials with the agency at Nashville's airport this morning, according to Paul spokesperson Moira Bagley. As CNN and Politico report, Paul, ever the libertarian, refused to be patted down when asked by airport officials in Nashville. "Paul went through a scanner at the airport and set off an alarm, Bagley said. He wanted to go through the body scan again instead of getting a pat-down, but officers of the Transportation Security Administration refused," says CNN. This isn't the first time Paul's been irked by the TSA's pat-down procedures. The Daily Caller reported in June how Paul criticized TSA head John Pistole for the pat-down of a 6-year-old Kentucky girl, chosen at random per TSA policy. "It makes me think you’re clueless, if you think she’s going to attack our country and you’re not doing your research on the people who want to attack our country," he said in Congress at the time. So presumably, Paul believed he (white, male, U.S. senator) wasn't enough of a threat to be patted down either. Update 11:45 a.m.: The TSA is now coming forward with its version of the agency's standoff with Paul when he tried to fly from Nashville to D.C. for a session of Congress today, saying that Paul was not detained but rather escorted to the airport's exit. "The passenger triggered an alarm during routine airport screening and refused to complete the screening process in order to resolve the issue," reads a TSA statement. "Passengers, as in this case, who refuse to comply with security procedures are denied access to the secure gate area. He was escorted out of the screening area by local law enforcement." Maybe being "escorted" and being "detained" are tomato, tomahto for Paul. Paul, in his defense, says that his setting-off of the body scanner is "clearly a glitch." This article is from the archive of our partner The Wire.	{ "pile_set_name": "OpenWebText2" }
Starks was an aspiring rapper who performed under the stage name "Booley Boo". (Photo : Twitter Photo Section). The community of Savannah State University is in mourning after a shooting that has left one of its students dead. SSU junior Christopher ... Cinderford's Elliot Booley is likely to miss the start of the new National One season as he recovers from double shoulder surgery over the summer period. The Foresters prop will go under the knife for the third time in his career within the next ... Daredevil Dot Booley, of Holton, jumped from a plane in the skies above Beccles to raise money for Halesworth Community Nursing Care Fund (HCNCF) while marking the sixth anniversary of her husband Peter's death. The only downside from the day was ... Bullish Elliott Booley has enjoyed his first team return. Rested and refuelled, second team rugby has done him the world of good, he says, and is now paying dividends. The 26-year-old tight-head has spearheaded a Cinderford scrum that has found some ... Elliot Booley returns to the front row for Cinderford as they welcome Blaydon to Dockham Road on Saturday (2.30pm). He replaces Chris Bundy who has been rested for this fixture. Jake Caulfield will turn out for the United set who travel to Worthing ... But officials said confirmation of closure came from business owner and NHS contract holder, dentist Abdul-Basit Booley, who has issued a heartfelt apology for his departure. It is understood Mr Booley left the practice and moved abroad to Texas early ...	{ "pile_set_name": "Pile-CC" }
1. Field of the Invention The present disclosure relates generally to healing of wounds and wound-treatment therapies. More particularly, but not by way of limitation, the present disclosure relates to modified materials, for example, silyl modified polyurethane foam for the reversible binding of factors in a wound bed. 2. Background Information Clinical studies and practice have shown that providing a reduced pressure in proximity to a tissue site augments and accelerates the growth of new tissue at the tissue site. The applications of this phenomenon are numerous, but application of reduced pressure has been particularly successful in treating wounds. This treatment (frequently referred to in the medical community as “negative pressure wound therapy,” “reduced pressure therapy,” or “vacuum therapy”) provides a number of benefits, including faster healing and increased formulation of granulation tissue. One of the major clinical benefits of negative pressure wound therapy is its ability to effectively eliminate wound exudate, thereby reducing edema and allowing tissue decompression. Negative pressure wound therapy may not always be able to differentiate between harmful and beneficial factors removed from the wound. Coating used to address this such as collagen, PVA, PEG, and fibrinogen often suffer from not being covalent, uniform, or target specific. Typically they cannot bind proteins at a specific site and present them to cells in a manner that allows the active site to retain its function. Improvements that would allow the binding of molecules in a covalent manner, specify the types of compounds that could be bound, the chemical reactions with which to bind them, and/or the orientation with which the protein is presented to the cells, e.g., for use in a dressing, wound insert, pad, etc., would therefore be highly desirable.	{ "pile_set_name": "USPTO Backgrounds" }
Oak Hill, Wisconsin Oak Hill is an unincorporated community located in the town of Sullivan, Jefferson County, Wisconsin, United States. Notes Category:Unincorporated communities in Jefferson County, Wisconsin Category:Unincorporated communities in Wisconsin	{ "pile_set_name": "Wikipedia (en)" }
1. Field of the Invention The present invention relates to an internal combustion engine having a nutating member. The engine also has provision for continuously varying engine parameters such as displacement, compression ratio, valve timing, and valve lift. 2. Description of the Prior Art It has been known in the art that the traditional fixed-geometry internal combustion engines cannot perform optimally over their entire operational rpm and torque range. For this reason, many designs have been proposed in the prior art that allow the variation of one or several of the more important engine parameters such as compression ratio, displacement, and valve timing. U.S. Pat. No. 5,165,368, issued to Schechter, shows a variable compression ratio engine where the compression ratio is varied by varying the crank radius using a mechanical and hydraulic mechanism responsive to the torsional impulses applied through the connecting rod. The Schechter system cannot vary the compression ratio independent of the piston stroke. U.S. Pat. No. 5,136,987, issued to Schechter et al., shows a variable piston stroke engine where the piston stroke is varied by varying the length of an arm extending between the connecting rod pivot, distal from the piston, and the engine block. Again the Schechter et al. system does not permit the independent variation of the compression ratio and the piston stroke. U.S. Pat. No. 4,270,495, issued to Freudenstein et al., shows a variable stroke engine where the stroke is varied by changing the pivot point of a rocker arm extending between the connecting rods of two adjacent cylinders. U.S. Pat. No. 4,131,094, issued to Crise, shows a variable stroke engine where the stroke is varied by varying the crank radius. Again the Crise system does not permit the independent variation of the compression ratio and the piston stroke. U.S. Pat. No. 4,100,815, issued to Kemper, shows a variable displacement engine where the displacement is varied by the rotation of an eccentric sleeve relative to a nutating member. The Kemper engine suffers from the serious drawback that the nutating member is constrained from rotation about the output shaft only by the forces exerted on the pistons by the cylinder walls. Thus the reaction torque on the nutating member is borne entirely by the piston sides and cylinder walls. For this reason the Kemper engine would suffer from rapid wear damage to the cylinder walls and piston sides resulting in their premature failure. Further, in the Kemper engine the forces of the pistons act at a distance from the axis of the output shaft, which is greater than the distance, from the axis of the output shaft, of the forces between the nutating member and the rotating support member. The greater moment arm of the piston forces greatly amplifies the forces on the bearing surfaces of the nutating member and the rotating support member, thus leading to faster wear and consequent mechanical failure. U.S. Pat. No. 4,066,049, issued to Teodorescu et al., shows a variable displacement engine where the displacement is varied by moving the bracket supporting the nutating member relative to the cylinder block. The Teodorescu et al. engine suffers from the same drawbacks enumerated with respect to the Kemper engine. In addition, there are no discernable means in the Teodorescu et al. engine for counteracting the torque on the output shaft of the engine. Although Teodorescu et al. do not explicitly state how the connecting rods attach to the pistons, the geometric constraints imposed by nutation of the equatorial band of the Teodorescu et al. engine would dictate that the piston rods should be ball-jointed at both ends. Therefore, the only rotational constraint on the equatorial band of the Teodorescu et al. engine would be the piston rods crashing into the bottoms of the cylinder bores. It should be readily apparent that such an arrangement would lead to rapid wear and consequent premature mechanical failure of the piston rods and the cylinder bore bottoms. French Patent Document Number 2 647 508, by Jurkovic, shows a variable compression ratio engine where the compression ratio is varied by moving the axis of rotation of the crank shaft relative to the cylinder block. German Patent Document Number 27 53 563, by Zeilinger, shows a variable compression ratio engine where the compression ratio is varied by varying the connecting rod length. Netherlands Patent Document Number 8901197, by Van Hoeven, shows a variable compression ratio engine where the compression ratio is varied by moving the pivot point of a rocker arm extending between the piston rod and a connecting rod engaging the throw of the crankshaft. United Kingdom Patent Document Number 2 219 836 A, by Heniges, shows a variable stroke engine where the stroke is varied by changing the crank radius using an eccentric mounted on the crank throw. United Kingdom Patent Document Number 286,075, by Myers, shows a variable stroke engine where the stroke is varied by a pivoting plate extending between the piston rod and a rod connected to the crankshaft throw. The Myers design does not allow for dynamic control of the piston stroke and compression ratio in response to engine load conditions. None of the above inventions and patents, taken either singly or in combination, is seen to describe the instant invention as claimed.	{ "pile_set_name": "USPTO Backgrounds" }
Pages Saturday, February 21, 2009 Under the Mountain I just have to get through a mountain of things this week and then next weekend is Artexpo New York. I'll be posting details on that this Monday so stay tuned. Then, after the weekend and all the hard work...Italy! We're leaving for 12 days on March 2nd. We are finally making it there after canceling the original trip in October. I cannot wait. In the meantime, while I'm trying to focus on the today and the here and now, my mind is on faraway places.	{ "pile_set_name": "Pile-CC" }
Q: How do I call a method from another class within a listbox? In my listbox form I want to make it possible to call a method from a class in a different folder. Here is what I thought I was meant to do: public void ListBox_SelectedIndexChanged(object sender, EventArgs e) { SharedClasses.Form.FormConsole newFormConsole = new SharedClasses.Form.newFormConsole(); } A: You are creating a new instance of the FormConsole class, which I'm guessing is probably not what you wanted to do. What you probably want to do is have the form that contains your ListBox have a reference to an existing instance of FormConsole. Then you can call methods on that instance. So, somewhere in the class that contains your ListBox: private FormConsole _myForm; You can set that in the constructor for your class, or provide a getter and setter: public FormConsole MyForm { get { return _myForm; } set { _myForm = value; } } // and/or... public ListBoxForm(FormConsole myForm) { MyForm = myForm; } Then you can call (public) methods on myForm: public void ListBox_SelectedIndexChanged(object sender, EventArgs e) { MyForm.MyMethod(); }	{ "pile_set_name": "StackExchange" }
Toxic nodular goiter and cancer: a compelling case for thyroidectomy. Recent American Thyroid Association guidelines call for thyroidectomy or (131)I (Recommendation 31) in managing hyperthyroidism due to toxic nodular goiter (TNG). Concern for concomitant malignancy favors surgery. A 3 % thyroid cancer incidence in TNG patients has been reported, yet recent studies suggest this rate is underestimated. This multi-institutional study examined cancer incidence in TNG patients referred to surgery. Patients referred for thyroidectomy at three tertiary-care institutions were included (2002-2011). Patients with concurrent indeterminate or malignant diagnosis by fine-needle aspiration (FNA) were excluded. Cancer incidence in TNG patients was determined. Fisher's exact and chi-square tests and nonparametric t tests were used. Among 2,551 surgically treated patients, 164 had TNG (6.4 %). Median age at presentation was 49.7 years, and 86 % were female. Overall cancer incidence was 18.3 % (30 of 164), and rates were not significantly different between institutions. A significantly greater cancer rate was noted in toxic multinodular goiter versus single toxic nodule patients (21 vs. 4.5 %, P < 0.05). Mean tumor size was 0.71 cm (range 0.1-1.5 cm; 23 % ≥1 cm). Most patients underwent total or near-total thyroidectomy. There were no significant differences in tumor sizes among institutions (P > 0.05). No significant cancer association was noted with age, preoperative dominant nodule size, lymphocytic thyroiditis or preoperative FNA (P > 0.05). These data demonstrate a higher than expected incidental cancer rate in TNG patients compared to historical reports (18.3 vs. 3 %). This higher cancer incidence may alter the risk/benefit analysis regarding TNG treatment. This information should be provided to TNG patients before decision making regarding treatment.	{ "pile_set_name": "PubMed Abstracts" }
Q: How to get table using relationships in Entity Framework I am using EF Core 2.1 and i'm trying to get Profile from Authentication but every time i get it i found it null and i don't now where is the problem. And for authentication i can get profiles. Entities: [Table("USER_AUTHENTICATION")] public class Authentication { public int ID { get; set; } //...some code [ForeignKey("ProfileID")] public Profile Profile { get; set; } public virtual int ProfileID { get; set; } } [Table("USER_PROFILE")] public class Profile { public Profile() { Authentication = new HashSet<Authentication>(); } public int ID { get; set; } //... some code public virtual ICollection<Authentication> Authentication { get; set; } } DataContext public DataContext(DbContextOptions<DataContext> options) : base(options) { } public DbSet<Authentication> Authentications { get; set; } public DbSet<Profile> Profiles { get; set; } public Profile GetById(int currentUserId) { var user = _context.Authentications.Find(currentUserId); Console.WriteLine(user.Profile); //<--- here is the probelm null// return _context.Profiles.Find(user.ProfileID); } How can i use relations with correct way A: You need use include for sub-entity and change Find to SingleOrDefault. Add Include var user = _context.Authentications.Include(p => p.Profile).SingleOrDefault(currentUserId); return user.Profile;	{ "pile_set_name": "StackExchange" }
The Diamond Awards, presented for credit union marketing and business development by CUNA's Marketing and Business Development Council, feature 34 categories, ranging from direct mail and website marketing to public relations and political action.This year, five credit unions in Missouri took home prizes, including? Judges reviewed entries with a different focus than in the past. They were asked to identify entries that deserved to be recognized with a Diamond Award and determine the entries that were the best in each category. This year, new awards: "Brilliance" for brilliant use of art; "Cut" for the most edgy; "Carat" for the greatest impact; and, "Clarity" for the most sentimental, were also added. Also honored was the Best Use of Humor, and, of course, the Diamond Award Best of Show. CUNA's Marketing & Business Development Council offers exclusive benefits that will help members with career growth, connect with others at credit unions nationwide, and provide tools, resources, and education that will help them in their job. For more information, click here.	{ "pile_set_name": "Pile-CC" }
The approvals could also assist Apple shares, which have fallen 14 percent from their all-time high of $644 set on April 10. At midday Monday, they were at $554.42, down $10.47. China's Telecommunications Equipment Certification Center said the new iPad is compatible with China Unicom's (NYSE: CHU) 3G wireless services. The approval removes the last obstacle to selling the products. Apple sold 11.8 million iPads last quarter, bringing cumulative sales to about 55 million. The China regulatory approval came around the same time the same agency approved the acquisition of Motorola Mobility by Google (Nasdaq: GOOG), the No. 1 search engine. Google closed the $12.5 billion acquisition of the Motorola Android smartphone maker on May 22. China Unicom had been Apple's exclusive iPhone seller until recently, when the company added China Mobile Ltd. (NYSE: CHL), the No. 3 carrier. Last quarter, China accounted for $7.9 billion of Apple's overall revenue, or 20 percent of the total. We had an incredible quarter in China, Cook said, when he discussed results with investors. But Apple's primary contractor, Foxconn, a unit of Taiwan's Hon Hai Precision Industries (Taipei: 2317), couldn't meet initial consumer demand: Before the Year of the Dragon began in late January, consumers rioted over iPhone shortages in Shanghai. Cook visited Apple retail stores in Beijing and Shanghai during his tour, his first as Apple CEO. Besides boosting Apple sales, analysts believe the company sells the iPhone 4S at a higher margin than in the U.S. Apple's overall gross margin, or sales less costs of revenue, rose to a record 47.1 percent last quarter from only 41.4 percent a year earlier. For earnings, that could also add more to Apple's bottom line. Jefferies analyst Peter Misek estimates Apple will report third-quarter net income around $9.38 billion, or $10.02 a share, compared with $7.3 billion, or $7.89 a year ago. Meanwhile, Misek and other analysts expect Apple to refresh the iPhone 4S before long with a successor, an iPhone 5 or whatever monicker Apple decides, which will be an improved product with better displays and features, a higher retail price and resulting higher margins. Based on Monday's market, Apple's market capitalization is $516.2 billion.	{ "pile_set_name": "Pile-CC" }
The purpose of this study is to investigate the mechanisms by which oncostatin M (OSM) promotes vascular endothelial cell growth factor (VEGF) in human breast cancer. Oncostatin M is a member of the interleukin-6 (IL-6) family of cytokines and is produced by many immune cells and some tumor cells. Preliminary studies on human breast cancer cells indicate that OSM promotes expression of the potent proangiogenic factor VEGF. OSM also induces expression of the alpha subunit of hypoxia-inducible factor 1 (HIF1), a critical transcription factor for VEGF gene regulation. Our recent data and other published studies suggest that OSM may promote angiogenesis, tumor progression, and metastasis in vivo. In this grant, we propose to determine the multiple mechanisms by which OSM promotes VEGF expression in human breast cancer. To accomplish this, we will investigate OSM's induction of HIF11 in breast cancer cells and other cell types and confirm that OSM-induced VEGF expression is dependent on HIF11. Additionally, we will study the mechanism behind and the signaling pathway utilized by OSM to induce HIF11. We will also determine why, in contrast to OSM, another IL-6 family cytokine, leukemia inhibitory factor (LIF), induces HIF11 but does not promote VEGF expression. Results demonstrating that OSM activates multiple pathways to upregulate VEGF would provide insight into cytokine-induced angiogenesis in tumor cells and supply rationale for the design of breast cancer therapies that inhibit OSM expression, function, or signaling. The potential to develop experimental anti-OSM therapeutics is limitless: to date, there has been no attempt to inhibit OSM for the purpose of cancer therapy. PUBLIC HEALTH RELEVANCE: The proposed work could establish an important role for oncostatin M (OSM) in breast cancer progression and metastasis. This research could provide the rationale for the development breast cancer therapeutics that target OSM to prevent metastatic spread of the disease. In addition, this project represents the opportunity for undergraduate students at Boise State University to participate in biomedical research and gain a deeper understanding of the molecular and cellular events involved in breast cancer.	{ "pile_set_name": "NIH ExPorter" }
In the formation of integrated circuits (IC's), thin films containing metal and metalloid elements are often deposited upon the surface of a substrate, such as a semiconductor wafer. Thin films are deposited to provide conductive and ohmic contacts in the circuits and between the various devices of an IC. For example, a desired thin film might be applied to the exposed surface of a contact or via hole on a semiconductor wafer, with the film passing through the insulative layers on the wafer to provide plugs of conductive material for the purpose of making interconnections across the insulating layers. One well known process for depositing thin metal films is chemical vapor deposition (CVD) in which a thin film is deposited using chemical reactions between various deposition or reactant gases at the surface of the substrate. In CVD, reactant gases are pumped into proximity to a substrate inside a reaction chamber, and the gases subsequently react at the substrate surface resulting in one or more reaction by-products which form a film on the substrate surface. Any by-products remaining after the deposition are removed from the chamber. While CVD is a useful technique for depositing films, many of the traditional CVD processes are basically thermal processes and require temperatures in excess of 1000.degree. C. in order to obtain the necessary reactions. Such a deposition temperature is often far too high to be practically useful in IC fabrication due to the effects that high temperatures have on various other aspects and layers of the electrical devices making up the IC. Particularly, certain aspects of IC components are degraded by exposure to the high temperatures normally related to traditional thermal CVD processes. For example, at the device level of an IC, there are shallow diffusions of semiconductor dopants which form the junctions of the electrical devices within the IC. The dopants are often initially diffused using heat during a diffusion step, and therefore, the dopants will continue to diffuse when the IC is subjected to a high temperature during CVD. Such further diffusion is undesirable because it causes the junction of the device to shift, and thus alters the resulting electrical characteristics of the IC. Therefore, for certain IC devices, exposing the substrate to processing temperatures of above 800.degree. C. is avoided, and the upper temperature limit may be as low as 650.degree. C. for other more temperature sensitive devices. Furthermore, such temperature limitations may become even more severe if thermal CVD is performed after metal interconnection or wiring has been applied to the IC. For example, many IC's utilize aluminum as an interconnection metal. However, various undesirable voids and extrusions occur in aluminum when it is subjected to high processing temperatures. Therefore, once interconnecting aluminum has been deposited onto an IC, the maximum temperature to which it can be exposed is approximately 500.degree. C., and the preferred upper temperature limit is 400.degree. C. Therefore, as may be appreciated, it is desirable during CVD processes to maintain low deposition temperatures whenever possible. Consequently, the upper temperature limit to which a substrate must be exposed precludes the use of some traditional thermal CVD processes which might otherwise be very useful in fabricating IC's. A good example of one such useful process is the chemical vapor deposition of titanium. Titanium is typically used to provide ohmic contact between the silicon contacts of an IC device and a metal interconnection. Titanium may be deposited from TiBr.sub.4, TiCl.sub.4 or TiI.sub.4 by using CVD methods such as unimolecular pyrolysis or hydrogen reduction. However, the temperatures necessary for these thermal processes are in excess of 1000.degree. C., and such a deposition temperature is much to high to be practically useful in IC fabrication. Therefore, the deposition of titanium and titanium-containing rims presents a problem in formation of integrated circuits. There are low temperature physical techniques available for depositing titanium on temperature sensitive substrates. Sputtering is one such technique involving the use of a target of layer material and an ionized plasma. To sputter deposit a film, the target is electrically biased and ions from the plasma are attracted to the target to bombard the target and dislodge target material particles. The particles then deposit themselves cumulatively as a film upon the substrate. Titanium may be sputtered, for example, over a silicon substrate after various contacts or via openings are cut into a level of the substrate. The substrate might then be heated to about 800.degree. C. to allow the silicon and titanium to alloy and form a layer of titanium silicide TiSi.sub.2). After the deposition of the titanium layer, the excess titanium is etched away from the top surface of the substrate leaving TiSi.sub.2 at the bottom of each contact or via. A metal interconnection is then deposited directly over the TiSi.sub.2. While physical sputtering provides deposition of a titanium film at a lower temperature, sputtering processes have various drawbacks. Sputtering normally yields very poor step coverage. Step coverage is defined as the ratio of film thickness on the bottom of a contact on a substrate wafer to the film thickness on the sides of the contact or the top surface of the substrate. Consequently, to sputter deposit a predetermined amount of titanium at the bottom of a contact or via, a larger amount of the sputtered titanium must be deposited on the top surface of the substrate or the sides of the contact. For example, in order to deposit a 200 .ANG. film at the bottom of a contact using sputtering, a 600 .ANG. to 1000 .ANG. film layer may have to be deposited onto the top surface of the substrate or the sides of the contact. Since the excess titanium has to be etched away, sputtering is wasteful and costly when depositing layers containing titanium. Furthermore, the step coverage of the contact with sputtering techniques decreases as the aspect ratio of the contact or via increases. The aspect ratio of a contact is defined as the ratio of contact depth to the width of the contact. Therefore, a thicker sputtered film must be deposited on the top or sides of a contact that is narrow and deep (high aspect ratio) in order to obtain a particular film thickness at the bottom of the contact than would be necessary with a shallow and wide contact (low aspect ratio). In other words, for smaller device dimensions in an IC, corresponding to high aspect ratio contacts and vias, sputtering is even more inefficient and wasteful. The decreased step coverage during sputter deposition over smaller devices results in an increased amount of titanium that must be deposited, thus increasing the amount of titanium applied and etched away, increasing the titanium deposition time, and increasing the etching time that is necessary to remove excess titanium. Accordingly, as IC device geometries continue to shrink and aspect ratios increase, deposition of titanium-containing layers by sputtering becomes very costly. On the other hand, using a CVD process for depositing a titanium-containing film layer may be accomplished with nearly 100% step coverage. That is, the film thickness at the bottom of the contact would approximately equal the thickness on the top surface almost regardless of the aspect ratio of the contact or via being filled. However, as discussed above, the temperatures necessary for such CVD processes are too high and would degrade Other aspects of the IC. Consequently, it would be desirable to achieve titanium CVD at a temperature less than 800.degree. C., and preferably less than 650.degree. C. Further, it is generally desirable to reduce the deposition temperature for any CVD process which is utilized to deposit a film in IC fabrication. One approach which has been utilized in CVD processes to lower the reaction temperature is to ionize one or more of the reactant gases. Such a technique is generally referred to as plasma enhanced chemical vapor deposition (PECVD). While it has been possible with such an approach to somewhat lower the deposition temperatures, the high sticking coefficient of the ionized plasma particles degrades the step coverage of the film. That is, ions of the reactant gases are highly reactive and have a tendency to contact and stick to the walls of the vias or contacts in the substrate. The ion particles do not migrate downwardly to the bottom surface of the contact where the coating is desired but rather non-conformally coat the sides of the contact. This results in increased material usage, deposition times and etch times. Therefore, PECVD using ionized reactant gases has not been a completely adequate solution to lowering traditional high CVD temperatures and achieving good step coverage and film conformality. Additionally, when using a CVD process to apply a film, it is desirable to uniformly deposit the film. To do so, such as to apply a uniform film of tungsten (W), for example, a uniform supply of reactant gases must be supplied across the surface of the substrate and the spent gases and reaction by-products should be removed from the surface being coated. In this respect, prior art CVD processes have again performed with limited success. Specifically, in known CVD processes, turbulence in the flow of reaction gases inhibits the efficiency and uniformity of the coating process and aggravates the deposition and migration of contaminants within the reaction chamber. In tungsten CVD processes, tungsten hexafluoride (WF.sub.6) is employed as a reactant gas. Tungsten hexafluoride is very costly and thus, when reactant gas utilization efficiency is low, as it is in prior art CVD processes, the overall process costs are significantly increased. Accordingly, there is a need for CVD processes which have improved gas flow and reduced gas flow turbulence to more efficiently and more uniformly supply reaction gases to and remove reaction by-products from the surfaces of the substrate being coated. Therefore, CVD processes which may be accomplished at lower effective temperatures are desired. It is further desirable to have a low temperature deposition which provides good step coverage. It is still further desirable to have a PECVD process which produces uniform film thickness and effective utilization of reactant gases. Accordingly, the present invention addresses these objectives and the shortcomings of the various CVD and PECVD processes currently available. Further, the present invention, particularly addresses the difficulties associated with depositing titanium and titanium-containing films using CVD.	{ "pile_set_name": "USPTO Backgrounds" }
Q: Using sqlalchemy scoped_session in theading.Thread I'm having problems using sqlalchemy together with threading. import queue import threading import sqlalchemy from sqlalchemy import create_engine, Column, Integer, String, Sequence from sqlalchemy.ext.declarative import declarative_base from sqlalchemy.orm import sessionmaker from sqlalchemy.orm.scoping import scoped_session engine = create_engine('sqlite:///:memory:', echo=False) Base = declarative_base() class User(Base): __tablename__ = 'users' id = Column(Integer, Sequence('user_id_seq'), primary_key=True) name = Column(String) fullname = Column(String) password = Column(String) def __repr__(self): return "<User(name='%s', fullname='%s', password='%s')>" % ( self.name, self.fullname, self.password) Base.metadata.create_all(engine) sessionfactory = sessionmaker(bind=engine) # called by each thread def write_name(q, name, sessionfactory): session = scoped_session(sessionfactory) ed_user = User(name=name, fullname='Power', password='edspassword') session.add(ed_user) session.commit() q.put(name) names = ["Max", "Austin"] q = queue.Queue() for u in names: t = threading.Thread(target=write_name, args = (q, u, sessionfactory)) t.daemon = True t.start() s = q.get() This results in: sqlalchemy.exc.OperationalError: (sqlite3.OperationalError) no such table: users [SQL: 'INSERT INTO users (name, fullname, password) VALUES (?, ?, ?)'] [parameters: ('Max', 'Power', 'edspassword')] but it works fine to add and read data in the main thread. Furthermore I assume I need to use threading over multiprocess because scoped_session uses thread local storage. A: The main problem is that you can't have multiple connections to a SQLite database that only exists in memory, because each connection will create a new empty database. See the SQLAlchemy docs on this. In short, you need to create the engine like this to make sure that is only one instance that can be shared across threads. from sqlalchemy.pool import StaticPool engine = create_engine('sqlite://:memory:', connect_args={'check_same_thread': False}, poolclass=StaticPool, echo=True) Once you do that, you don't need scoped_session, because the point of scoped_session is to create one connection per each thread and you specifically can't do that here. Also, note that you should have only one scoped_session instance if you want it to work correctly (with a non-SQLite engine). You should treat it as global variable and then it will be able to handle the thread-local stuff.	{ "pile_set_name": "StackExchange" }
Q: How to use ngModelChange with Pipe Here is the follow Html input : <input matInput [ngModel]="myDates[i][month]\|number:'1.2-2'" (ngModelChange)="myDates[i][month]=$event" (blur)="singleUpdate('cargo', j + 1, myDates[i][month], i)"> in this case, when I input 1, the result become 1.00 However when I input 12, the result become 1.002 not 12.00 how can i fix this issue ? A: Technically the output you are getting is correct, because the number pipe tries to format the input as soon as it gets the value within the ngModel. And also ngModelChange will not help you in this case. It will output the same. You got to utilize blur event and DecimalPipe. Also you can use two way binding for ngModel with [()] syntax. template <input [(ngModel)]="myDates" (blur)="formatNumber()"> component.ts import { DecimalPipe } from '@angular/common'; constructor(private decPipe: DecimalPipe) {} formatNumber() { this.myDates = this.decPipe.transform(this.myDates, '1.2-2'); } Demo	{ "pile_set_name": "StackExchange" }
Q: If then command yielding string as output in r I am trying to calculate after-tax income for each household in a data frame like this: id hhinc 1 1 53880 2 2 49501 3 3 37525 4 4 28791 5 5 91049 6 6 133000 7 7 12299 8 8 23000 9 9 58100 10 10 9764 where hhinc is household income. I then created the following function to calculate the taxes paid by each household: taxpaid = function(hhinc) { if (hhinc > 0 & hhinc <= 19999) {tax = 0} else if (hhinc > 20000 & hhinc <= 49999) {tax = (hhinc - 20000).15} else if (hhinc > 50000 & hhinc <= 199999) {tax = 4499.85 + ((hhinc - 50000).25)} else if (hhinc > 200000 & hhinc <= 999999) {tax <- 37499.75 + ((hhinc - 200000).39)} else if (hhinc > 1000000) {tax <- 311999.61 + ((hhinc - 1000000).85)} return(tax) } Since this function only works for a scalar input, I vectorized the function: taxpaid_vec = Vectorize(taxpaid, vectorize.args = "hhinc") However, when I use this function to calculate the taxes paid, I receive non-numeric outputs. I therefore cannot subtract the taxes paid from each household's income to determine the after-tax income. I would like to know how to fix my code so that get a numeric output for taxes paid. A: Replace if/else to ifelse to make your function vectorized. taxpaid = function(hhinc) { ifelse(hhinc > 0 & hhinc <= 19999, 0, ifelse(hhinc > 20000 & hhinc <= 49999, (hhinc - 20000).15, ifelse(hhinc > 50000 & hhinc <= 199999, 4499.85 + ((hhinc - 50000).25), ifelse(hhinc > 200000 & hhinc <= 999999, 37499.75 + ((hhinc - 200000).39), ifelse(hhinc > 1000000, 311999.61 + ((hhinc - 1000000).85), NA))))) } Apply the function df$tax_income <- taxpaid(df$hhinc) df # id hhinc tax_income #1 1 53880 5469.85 #2 2 49501 4425.15 #3 3 37525 2628.75 #4 4 28791 1318.65 #5 5 91049 14762.10 #6 6 133000 25249.85 #7 7 12299 0.00 #8 8 23000 450.00 #9 9 58100 6524.85 #10 10 9764 0.00 You might also look in to ?dplyr::case_when for handling such nested conditions.	{ "pile_set_name": "StackExchange" }
Chancey Williams and the Younger Brothers Band Chancey Williams (born August 24, 1981) is an American country music singer-songwriter and former saddle bronc rider. He and fellow Wyoming artist and rodeo cowboy Chris LeDoux are the only two individuals to compete in the rodeo and perform on the main stage of Cheyenne Frontier Days. Chancey Williams and the Younger Brothers Band's newest single "Fastest Gun in Town" released December 13, 2019. Early life Chancey Williams was raised on a ranch near the small town of Moorcroft, Wyoming. Williams followed his dad as a saddle bronc rider, going to the National High School Rodeo Finals, the College National Finals and won two rounds at Cheyenne Frontier Days. Williams has a total of four degrees, including a Bachelor's degree in Political Science and a Master's Degree in Public Administration from the University of Wyoming. Career Williams and his drummer, lifelong friend Travis DeWitt, started the Younger Brothers Band with the initial goal of entering a high school talent contest. In 2008 they were joined by Wyatt Springsteen (lead guitar and vocal harmonies) and Brooke Latka (fiddle and vocal harmonies). In 2012 Jack Robbins (bass) joined the band. The studio album Honkey Tonk Road was released in 2008, Highway Junkie in 2011 and, recently, the Billboard charting Echo. Chancey Williams and the Younger Brothers Band have sold, between digital downloads and CD sales, more than 40,000 records. In the Fall of 2013, Williams signed with HomeSlice Artist Management, a subsidiary of the HomeSlice Group, an entertainment and media company that is the worldwide exclusive licensing agent of the Sturgis Motorcycle Rally. Williams signed with WME, the industries premier booking agency in Fall of 2019. Discography Studio albums HonkyTonk Road Released 2008 Label: Self-Released Highway Junkie Released 2011 Label: Self-Released Echo Released 2013 Label: Self-Released Peaked at #10 on Billboards Mountain-Heatseeker Chart Rodeo Cold Beer Released 2017 Label : Younger Brothers Records Singles "Six Figure Job" (2008) "She Loves me Anyway" (2011) "Worth the Whiskey" (2013) "Down with That" (2015) "Silhouette" (2016) Music videos References Category:American country music groups Category:Musicians from Wyoming Category:People from Crook County, Wyoming	{ "pile_set_name": "Wikipedia (en)" }
Politician asks for local support October 5, 2012 ST. CLAIRSVILLE - Ohio Senate Minority Leader Eric Kearney talked "friendship" with Belmont County Democrats Thursday and encouraged them to support his family friend - President Barack Obama - and other friends seeking office in Belmont County. Kearney, D-Cincinnati, was the keynote speaker for the annual Belmont County Jefferson-Jackson Democrat Dinner at Undo's West. Before joining the Ohio Senate in December 2005, Kearney founded and built one of the largest African-American owned publishing companies, Sesh Communications. He is a graduate of Dartmouth College and the University of Cincinnati College of Law. Kearney spoke of how in 2006 he saw a newspaper article about a state senator seeking a U.S. Senate seat in Illinois and how he had been impressed enough with what he read to ask his wife, Jan-Michele, if they should support him. She immediately recognized him as a good friend and former college classmate, Barack Obama, and reminded Kearney they had attended the Obama's wedding in Chicago. Kearney said he next began to make calls and arrange a fundraiser in Ohio, and he noted people frequently asked him why they should support a candidate in Illinois. "I'll tell you why - issues aren't local," he said. "Issues that are important in Belmont County are important in Washington, D.C., and they're important in Columbus. You need to have people who have a voice wherever they are - the voice is important. To get the issues out is the important thing." A friendship next evolved between him and Obama, Kearney said. He added he also formed a bond with Charlie Wilson, then an Ohio senator. Wilson would move on to the U.S. House, but was defeated in 2010 after two terms. Among other things, Wilson taught him "you have to make tough votes" as a lawmaker. "The way I understand it, the only reason we're not calling him 'congressman' here tonight, is that he took a tough vote" in favor of health care reform legislation," Kearney said. "He stood by his friend, the president of the United States, and people punished him for that. Frankly, I would rather have somebody who will stand up, take the tough vote, and do what is right." Other candidates speaking briefly at the dinner were Wilson, Democrat nominee seeking election in the 6th Congressional District; Ohio Sen. Lou Gentile, D-Steubenville, seeking re-election in the 30th Senate District; and Charles Daniels, a Democrat seeking election in the 95th Ohio House District.	{ "pile_set_name": "Pile-CC" }
I started 1998 with Amateur Radio as DB2PK and I was using this callsign about 4 weeks. After that I renewed my licence and got the call DH5PK. My QTH is near the french border, directly on the River RHEIN. I am also a member of the legendere 10 - 10 Club. DOK K23 . Z09; LOC:JN49DD Club-member: DARC, 10-10 -> 70812; GDXF-> 375; FIH-> 759FL My Rig: IC 756 . SM 8 . small PA with 600W . SP 23 . SCS PTC II TS 950 SD . MC 85 . SM 230 . SP 950 YAESU FT - ONE, SP8 OptiBeam 9 - 5, W3DZZ, Vertical for 28Mhz Look for me also on 29070.00 on AM and 29470.00 on FM. Best regards from Oliver Please enjoy my QSL cards Here on this place, you can see some Pics from my vacation on the Island of Kauai OC-019, Hawaii. Many thanks to Jim, W6KPI ( ex KH7M ) for giving me the chance to using his station. Now some Pics from Rathlin Island EU - 122. Thanks a lot to these Hams. It was great for me, to met you.	{ "pile_set_name": "Pile-CC" }
--- abstract: \| A pair is a holomorphic map from a Riemann surface to $S^2$ with additional properties. A dessin d’enfants is a bipartite graph with additional structure. It is well know that there is a bijection between pairs and dessins d’enfants. Vassiliev has defined a filtration on formal sums of isotopy classes of knots. Motivated by this, we define a filtration on formal sums of Belyĭ pairs, and another on dessin d’enfants. We ask if the two definitions give the same filtration. author: - \| Jonathan Fine\ Milton Keynes\ England\ `jfine@pytex.org` date: 28 September 2009 title: A filtration question on Belyĭ pairs and dessins --- Introduction ============ First, we recall some definitions [@Belyui; @Dessins]. A Belyĭ pair is a Riemann surface $C$ together with a holomorphic map $f:C \to S^2 = \C \cup \{\infty\}$ to the Riemann sphere, such that $f'(p)$ is non-zero provided $f(p)$ is not $0$, $1$ or $\infty$. (Belyĭ proved that given $C$ such an $f$ can be found iff $C$ can be defined as an algebraic curve over the algebraic numbers.) A dessin d’enfants, or dessin for short, is a graph $G$ together with a cyclic order of the edges at each vertex, and also a partition of the vertices $V$ into two sets $V_0$ and $V_1$ such that every edge joins $V_0$ to $V_1$. Necessarily, $G$ must be a bipartite graph. Traditionally, the vertices in $V_0$ and $V_1$ are coloured black and white respectively. It is easy to see that a Belyĭ pair gives rise to a dessin, where $V_0=f^{-1}(0)$, $V_1 = f^{-1}(1)$, and the edges are the components of the inverse image $f^{-1}([0,1])$ of the unit interval in $\C$. The cyclic order arise from local monodromy around the vertices. A much harder result, upon which our definitions rely, is that up to isomorphism every dessin arises from exactly one Belyĭ pair, or in other words that there is a bijection between isomorphism classes of Belyĭ pairs and dessins. Definitions =========== A Belyĭ object $B$ consists of $((B_C, B_f), B_D)$ where $(B_C, B_f)$ is a Belyĭ pair and $B_D$ is the associated dessin (or vice versa for the dessin and the pair). The Vassiliev space $V=V_\C$ (for Belyĭ objects) is the vector space over $\C$ which has as basis the isomorphism classes of Belyĭ objects. Clearly, when an edge is removed from a dessin then it is still a dessin. Suppose $D$ is a dessin, and $T$ is a subset of its edges. We will use $D \setminus T$ to denote the dessin so obtained. This same operation can also be applied to a Belyĭ object $B$, even though computing the associated curve $(B\setminus T)_C$ from $B_D$ and $T$ might be hard. We will now define one or two filtrations of $V$. Let $D$ be dessin and $S$ a $d$-element subset of $D$. Each subset $T$ of $S$ determines a dessin $S\setminus T$ and hence a object $B_{S\setminus T}$. Let $\|T\|$ denote the number of edges in $T$. Use $$B_S = \sum\nolimits _{T\subseteq S} (-1)^{\|T\|}B_{S \setminus T}$$ to define a vector $B_S$ in $V$, which we call the expansion of a dessin with $d$ optional edges. Let $V_{D,d}$ be the span of the expansions of all dessins with $d$ optional edges. The sequence $$V = V_{D, 0} \supseteq V_{D, 1} \supseteq V_{D, 2} \supseteq V_{D, 3} \ldots$$ is the dessin filtration of $V$. We can also think of a Belyĭ object as a map $f:C\to S^2$ (with special properties). Let $(C_1, f_1)$ and $(C_2, f_2)$ be Belyĭ pairs. Then there is of course a map $$g: C_1 \times C_2 \to S^2 \times S^2 \>.$$ Let $\Delta \subset S^2 \times S^2$ denote the diagonal, and let $C$ denote $g^{-1}(\Delta)$, and $f$ the restriction of $g$ to $C$. In general $$f: C \to \Delta \cong S^2$$ will not be a Belyĭ pair. There are two possible problems. The first is that $C\subset C_1\times C_2$ might have self intersections or be otherwise singular. If this happens, we replace $C$ by its resolution, which is unique. The second problem is more interesting. It might be that $f$ has critical points not lying above the special points $0$, $1$ and $\infty$. This problem cannot be avoided. However, the above discussion does show that there is product, which we will denote by ‘$\circ$’, on holomorphic branched covers of $S^2$. Let $W$ be the vector space with basis isomorphism classes of branched covers of $S^2$. We set $W_n$ to be the span of all products of the form $$(A_1 - B_1) \circ (A_2 - B_2) \circ \ldots \circ (A_n - B_n)$$ for $A_i$ and $B_i$ basis vectors of $W$. Clearly, the $W_n$ provide a filtration of $W$. The induced filtration of $V$ defined by $V_{B,n} = W_n \cap V$ is called the filtration of $V$. Questions ========= Are the two filtrations $V_D$ and $V_B$ equal? If so, then we have also answered the next two questions. The absolute Galois group acts on pairs, and preserves the filtration. Does this action also preserve the dessin filtration? Because the dessins with $d$ edges, all of which are optional, span $V_d/V_{d+1}$, the dessin filtration has finite dimensional quotients. Does the filtration have finite dimensional quotients? Investigating the last two questions might help us answer the first. They might also be of interest in their own right. [9]{} D. Bar-Natan, On the Vassiliev knot invariants, Topology 34 (1995), 423–472 G. V. , Another proof of the three points theorem, Subornik: Mathematics 193 (2002), 329–32. Leila Schneps, ed, The Grothendieck Theory of Dessins d’Enfants, London Math. Soc. Lecture Note Ser., vol 200, Cambridge Univ. Press 1994.	{ "pile_set_name": "ArXiv" }
Sorry but you have missed the cutoff for submission of a poem to this project (see first post). But you are welcome to submit this recording to our Short Poetry Collection (one is always ongoing). And I hope you will participate in a future Weekly or Fortnightly Poetry project, both great places to familiarize yourself with the recording/editing/uploading process followed at Librivox. Links to these projects are listed in our Readers Wanted: Short Works forum, here: viewforum.php?f=19 Meanwhile I recommend you submit your 1-Minute test for review. This is NOT an audition, but a way to check to make sure all your technical settings are correct, your volume loud enough, etc. You will find the information for the 1-Minute Test Recording here: http://wiki.librivox.org/index.php/1-Minute_Test. The instructions also tell you how to upload your test and then post in the Listeners and Editors Wanted forum so someone can give you feedback on it. Bill, please forward this to Flora, who I understand is having trouble with her password so you submitted the link for her. If she continues having trouble with that, post in the Need Help forum and someone will come along to help you. Alas, I know nothing about it. Michele Fry, CCMy Projects"Success is not final, failure is not fatal: it is the courage to continue that counts." ~Winston Churchill	{ "pile_set_name": "Pile-CC" }
Anabolic-androgenic steroid and adrenal steroid effects on hippocampal plasticity. Anabolic-androgenic steroids (AAS) are synthetic androgen-like compounds which are taken in high doses by athletes with the intention of enhancing muscular appearance, strength and/or athletic performance. Recent research indicates that high doses of AAS may influence the functions of the hippocampus. This evidence led us to explore the extent to which chronic AAS treatments influence spatial memory and the integrity of the hippocampus in the rat. Gonadally intact adult male Long-Evans rats were treated with either the AAS methandrostenolone, a steroid 'cocktail' (TNB; testosterone cypionate, boldenone undecylenate and nandrolone decanoate), or the oil vehicle daily for 12 weeks. A group of male rats treated with corticosterone (CORT; 10 mg/day) was also examined. Spatial memory was assessed in the Morris water maze after 10 weeks of hormone treatment. At 12 weeks, the animals were sacrificed, blood collected and the brain sectioned to assess hippocampal cell number. There were no impairments in the acquisition or retention of the Morris water maze in any hormone treatment group. Although serum testosterone levels were elevated in rats treated with TNB relative to the oil controls, neither the TNB or methandrostenolone treatments produced changes in hippocampal cell number. Serum CORT levels were significantly elevated in the rats treated with CORT and cell loss (15%) was detectable in the CA3b subfield in this group of animals. These results indicate that the AAS administered in the present study were not detrimental to hippocampal spatial memory or cell survival and that, while chronic CORT may produce mild hippocampal cell loss, this loss is not accompanied by deficits on a spatial memory task.	{ "pile_set_name": "PubMed Abstracts" }
Q: Improve performance of ggplotly when plotting time-series heatmap I'm building an interactive time-series heatmap in R using Plotly and Shiny. As part of this process, I'm re-coding heatmap values from continuous to ordinal format - so I have a heatmap where six colours represent specific count categories, and those categories are created from aggregated count values. However, this causes a major performance issue with the speed of the creation of heatmap using ggplotly(). I've traced it to the tooltip() function from Plotly which renders interactive boxes. Labels data from my heatmap somehow overload this function in a way that it performs very slowly, even if I just add a single label component to the tooltip(). I'm using a processed subset of COVID-19 outbreak data from Johns Hopkins CSSE repository. Here is a simplified heatmap code, which also uses The Simpsons colour theme from ggsci: #Load packages library(shiny) library(plotly) library(tidyverse) library(RCurl) library(ggsci) #Read example data from Gist confirmed <- read_csv("https://gist.githubusercontent.com/GeekOnAcid/5638e37c688c257b1c381a15e3fb531a/raw/80ba9704417c61298ca6919343505725b8b162a5/covid_selected_europe_subset.csv") #Wrap ggplot of time-series heatmap in ggplotly, call "tooltip" ggplot_ts_heatmap <- confirmed %>% ggplot(aes(as.factor(date), reorder(`Country/Region`,`cases count`), fill=cnt.cat, label = `cases count`, label2 = as.factor(date), text = paste("country:", `Country/Region`))) + geom_tile(col=1) + theme_bw(base_line_size = 0, base_rect_size = 0, base_size = 10) + theme(axis.text.x = element_text(angle = 45, hjust = 1),legend.title = element_blank()) + scale_fill_manual(labels = levels(confirmed$cnt.cat), values = pal_simpsons("springfield")(7)) + labs(x = "", y = "") ggplotly(ggplot_ts_heatmap, tooltip = c("text","label","label2")) Performance improves once tooltip = c("text","label","label2") is reduced (for instance to tooltip = c("text")). Now, I know that delay is not "massive", but I'm integrating this with a Shiny app. And once it's integrated with Shiny and scaled with more data, it is really, really, really slow. I don't even show all variables in tooltip and its still slow - you can see it in the current version of the app when you click on 'confirmed' cases. Any suggestions? I've considered alternative interactive heatmap packages like d3heatmap, heatmaply and shinyHeatmaply but all those solutions are more intended for correlation heatmaps and they lack customisation options of ggplot. A: If you rewrite it as "pure" plotly (without the ggplotly conversion), it will be much faster. Around 3000 times even. Here's the result of a very small benchmark: Unit: milliseconds expr min lq mean median uq max neval a 9929.8299 9929.8299 9932.49130 9932.49130 9935.1527 9935.1527 2 b 3.1396 3.1396 3.15665 3.15665 3.1737 3.1737 2 The reason why ggplotly is much slower, is that it doesnt recognize the input as a heatmap and creates a scatterplot where each rectangle is drawn separately with all the necessary attributes. You can look at the resulting JSON if you wrap the result of ggplotly or plot_ly in plotly_json(). You can also inspect the object.size of the plots, where you will see that the ggplotly object is around 4616.4 Kb and the plotly-heatmap is just 40.4 Kb big. df_colors = data.frame(range=c(0:13), colors=c(0:13)) color_s <- setNames(data.frame(df_colors$range, df_colors$colors), NULL) for (i in 1:14) { color_s[[2]][[i]] <- pal_simpsons("springfield")(13)[[(i + 1) / 2]] color_s[[1]][[i]] <- i / 14 - (i %% 2) / 14 } plot_ly(data = confirmed, text = text) %>% plotly::add_heatmap(x = ~as.factor(date), y = ~reorder(`Country/Region`, `cases count`), z = ~as.numeric(factor(confirmed$`cnt.cat`, ordered = T, levels = unique(confirmed$`cnt.cat`))), xgap = 0.5, ygap = 0.5, colorscale = color_s, colorbar = list(tickmode='array', title = "Cases", tickvals=c(1:7), ticktext=levels(factor(x = confirmed$`cnt.cat`, levels = unique(confirmed$`cnt.cat`), ordered = TRUE)), len=0.5), text = ~paste0("country: ", `Country/Region`, "<br>", "Number of cases: ", `cases count`, "<br>", "Category: ", `cnt.cat`), hoverinfo ="text" ) %>% layout(plot_bgcolor='black', xaxis = list(title = ""), yaxis = list(title = ""));	{ "pile_set_name": "StackExchange" }
Q: Launcher icon in Android not showing Are there any special guidelines to put launcher icon in Android 7.1.1 ? Because I added a logo in manifest file and its showing in all Android versions but not in my phone. Anyone got a clue? A: In Manifest.xml, please check have to set icons for both android:icon="@mipmap/ic_app_icon" and android:roundIcon="@mipmap/ic_app_icon": Here is the full code : <application android:allowBackup="true" android:icon="@mipmap/ic_app_icon" android:label="@string/app_name" android:roundIcon="@mipmap/ic_app_icon" android:supportsRtl="true" android:theme="@style/AppTheme">	{ "pile_set_name": "StackExchange" }
It seems I’m constantly on the lookout for things that will stimulate my mind. Or that will possibly stimulate the minds of others. (Sometimes this tends to get me in a little bit of trouble.) Well, today I found a little gold nugget poking out of the dirt in the form of an excellent post by Lot’s Cave publisher Pheadrus T. Wolfe, which is presented below. Perusing through various author forums at times, one of the most common questions that comes up (after “Will Amazon ban me for this book?”) is, “How do I be successful as an author?” Lots of people offer lots of advice, but this article really hits it on the head, at least for me. The ultimate answer is, you first have to decide your OWN definition of “success”! Phaedrus’ article presents many forms of criteria to consider, not just one (tons of money!). Personally, there are actually a number of ways I judge my own “success”… It is, of course, gratifying to receive a check from my publisher every month, no matter how big or small. I’m notified almost immediately by Boruma Publishing and Smashwords whenever someone makes a purchase of my books. It’s always a nice little thrill, even if it happens multiple times in a day. I have also been fortunate enough to receive a handful of very complimentary reviews, which is very rare in this genre, especially considering the taboo subjects I indulge in. More than that, though, I gauge my success in how many imaginations I’ve stimulated… how many minds I’ve opened… how many different ways of thinking were sparked by my words. Yes, I would like to make money doing this. I know there’s a lot of “free” stuff out there in the genre I write in. Most of it is crap. And even that’s being generous at times. Charging a fee may not get me as many readers.. but knowing that I’m putting a price on my stories forces me to be a better writer. I received a personal note one time from a guy who said his hand was constantly in his pants during every page of reading If The Door Is Open. What higher praise could an erotica writer ask for? Ultimately, the main criteria for my “success” is, how many orgasms have I caused? Anyway, thanks Phaedrus, for hitting the nail so delightfully on the head: In today’s erotic market, it can be tough to measure an author’s individual success. Part of the problem authors face is the question of how to remain motivated to do well. Authors repeatedly pour their heart and soul into their erotic books. Whether the story is short or long, takes a day or a month to write, an author still wants the book to succeed. It’s worth noting that this urge to do well drives every author in every book he or she publishes. An author’s success is not measured overall, but rather on an individual per book basis. The definition of a book’s success, while a personal one, often transfers into a greater overall opinion of the erotic market. Every author views the market differently and therefore measures success differently, various similarities remain standard for the majority of authors. High Sales – The most obvious measure of success for authors is the concept of high sales. This metric poses numerous problems, especially for controversial erotica. Many erotica authors hear grandiose stories of riches and wealth from other authors bragging (sometimes falsely) about their book’s latest success. Claims of making $5,000 dollars in a single month is not unheard of. For an author trying to make a living and barely getting by, this is immensely discouraging. The truth is, many authors would be considered successful just to make a meager living from their royalties. Perceptions do not change easily in authors’ minds however, causing many successful authors to quit early just because they don’t see insane profits as quickly as they’d like. Reader Feedback – Reader feedback is perhaps a less obvious measure of success which authors rely on heavily. Nothing excites an author more than seeing a positive book review raving about his or her writing skill and efforts. These reviews many times are the only measurement of a reader’s happiness. In the erotic market however, book reviews are rare occurrences, as readers often do not want their name connected permanently with erotica on Internet. Even so, in today’s market, many authors give away free copies of their books by the hundreds just to receive this feedback. The truth is, we live in an age where many reviews are faked, paid for, or insincere. Because of this, many readers have stopped looking at reviews, not to mention even reading them. For erotica authors, reviews should not be a measure of success in any form. On the bright side, a bad review doesn’t make an author’s work bad either, as so many erotica authors find their books under attack by religious zealots. Fan Base – Another less obvious measure of success worth noting is the idea of a fan base. Many authors just starting out want to see a fan base, or an instant number of guaranteed sales. While this may actually be a justified measurement of success, this metric is the hardest to judge. Fan bases change depending on time of year, individual financial situations, and book platform availability. It’s worth noting that just because an author sees a disproportionate number of readers to actual sales doesn’t mean those “fans” don’t exist. In actuality, it takes several months, if not years, to build a good steady fan base. While a fan base isn’t a good way to measure success, it can be a rewarding undertaking for authors to consider. Keeping the reader in mind will often turn out to be a better experience for authors. Getting Discovered – The worst metric of success in the mind of many authors is a fantasy of “getting discovered.” Fifty Shades of Grey, left many erotic authors with sudden hopes of their book taking off. While the Fifty Shades Trilogy has done enormously well in multiple regards, authors should not use this as a tool of measurement. Many authors have compared their own writing to that book, finding their own better. Authors begin wondering why his or her books haven’t taken off. Getting discovered is a lengthy, painful, and not always beneficial process–much depends on chance. Authors should instead focus on writing their books, enjoying the freedom they have to do so. This is especially true for authors of more controversial works; consider the likelihood of such books taking off in the public mindset. While getting discovered isn’t impossible, it should NEVER be a metric for new authors to gauge success in any form. With so many traps to measure success, accurate judgments of success may seem impossible. Authors will find that multiple ways to judge success do exist, however. These methods will be very individual, but each author should try to be adopt them in some form. Try replacing any of the above traits with the following positive ways to judge success: Positive Ways To Judge Success Writing Goals – Every author has things they’d like to work on. Whether it’s about writing better blurbs, or changing the overall length of stories, writing goals can be extremely productive. Setting small goals that enhance the quality of an author’s writing will lead to outside feelings of accomplishment. In time, authors will feel less defensive of their writing opting to actually share selections of their work. Being able to take a step back from your writing will also help the feelings of anxiety and nervousness at publishing a new book. Feeling proud of your work as an author is more important than feeling successful by society’s standards. At the end of the day, an author has to answer to themselves about their writing first. Small writing goals is certainly the way to go. If an author wants to be successful, then keep writing writing writing and do not stop to play with marketing, making book covers, or become distracted by other facets of publishing. Quarterly Sales – While I mentioned above that high sales rates are a bad measure of success, that doesn’t mean sales are a completely negative measurement tool. Taking a step back, and looking at your personal sales report can be highly productive. Please do not use this on a monthly basis, as some months are not good sale months… ever. The right unit of measurement seems to be somewhere around every four months. A four month’s span seems to be just enough time to find an overall sales pattern. By comparing four months at a time with another 4 month segment, authors can see increases based on the number of new books an author has for sale. Looking at these subtle increases, an author will most likely find only a positive notion of success from these overall spans of time while looking at it month by month doesn’t cut it at all. Knowledge of the Market – An author hardly ever considers their knowledge of the market as a measure of success. This is one of the biggest mistakes made, especially by authors just starting out. Knowledge of the market seems to correlate to an author’s success. Think about it; the more an author can navigate the market, the more an author knows how to judge their books. Taking into consideration how successfully an author can navigate their potential sales, an author quickly changes their writing. Not always, but usually these changes are for the better. Authors that take time to understand how the market works learns to improve the writing of their blurbs, their story content, and even to set the titles of their book. In order to truly be successful, an author simply must learn how the market works. Trademark Writing – Part of understanding the market and improved authorship skills results in trademark writing. This takes a couple different forms, depending on the author. Some authors like their cover to have a certain design quality specific to them. Other authors tend to write only within a certain sub-genre. Being able to lock yourself within a specific sub-genre really allows author success. While some authors hesitate to pick one sub-genre for fear of not appealing to the vast majority of people. successful authors know their audience. Writing for five different sub-genres creates confused readers who will, never really know what they’ll get. Trademarking turns into a positive way to measure success. Fan Outreach – Differing from trying to measure a fan base, an author’s fan outreach doesn’t focus on numbers. Fan outreach is an author’s ability to be found online by their readers. Taking time to utilize social media is the sign of a successful author. Not getting trapped in an endless social media marketing loop authors that have fan outreach know when to quit. Taking time to be searchable, but not overwhelming, successful authors have the ability to self promote. While this may not seem important to success, it is. If an author takes time to look at their appeal to readers, they can gauge some fan feedback. All in all, fan outreach can be good or bad. It can get real bad if an author spends time blogging that would be more productive in getting a new book out. Taking time to measure success can be painful for authors who don’t know any better. Realizing that some gauging methods are more successful than others, authors keep from getting too discouraged. Judging the various methods for their effectiveness, some authors may find individual ways of feeling successful. So many author experiences are unique, as each genre can be measured differently. Feedback from readers may be more likely for example, or sales higher than in a separate genre. Whatever method an author uses, it’s important to remember everything should be taken with a grain of salt. Feedback won’t always be positive, but that doesn’t mean all books are poorly written. Take time to enjoy being an author, whether or not you feel successful. In any case, for an author to be successful, just keep on writing and do not waste too much time gauging. Write!	{ "pile_set_name": "OpenWebText2" }
Quentin Tarantino’s had to defend violence in his films, mainly through the aestheticization of violence. He’s made some great points in doing so, but – let’s be honest – it’s bullshit to some degree. Given that his most recent film is in some way his most violent, he’s clearly convinced he’s right. Whether or not you agree with his view or his argument, chances are that you’re watching his films in spite of this fact. His movies are entertaining – and wildly so – which makes it easy to look past the bloodshed. You’re not necessarily agreeing with him by watching his films, you’re being entertained. Speaking of self-proclaimed righteousness, A$AP Rocky obviously thinks he’s one of the – if not the – best rappers alive. And on his major label debut, Long.Live.A$AP, he makes a pretty great case for it by sheer force of belief. A$AP doesn’t have a whole lot to say beyond what he’s already discussed ad nauseum (sex, money, being awesome), but he finds slightly new ways of saying it. He talks a lot of shit, basically. “Goldie,” for example, contains the line “Niggas talk shit ‘til they get lockjaw” which seems hypocritical when coming from him. But that’s Rocky just being Rocky. The key to A$AP’s success goes beyond his charismatic awesomeness – not that he doesn’t have a seemingly infinite amount of it (he does) – to a place where it makes total sense that a New York rapper borrows from every hotbed of hip-hop of the entire country. That is to say, he’s the incarnation of a Gen Y’ers iTunes collection: anything and everything goes together. Fuck trends. Fuck East vs. West. Given that he’s from NY, fuck the Five Boroughs. You see, being awesome means you can do what you want and make it work despite it not making any sense on paper. On “PMW,” A$AP double-times it about sex, money and drugs over a half-time, screwed-esque beat for no reason other than because he can. Elsewhere, he’s got a six-minute posse cut (“1 Train”) featuring as many guests because why the fuck not? To Rocky, it makes perfect sense precisely because it doesn’t Not only that, he believes that he belongs alongside rappers who rap circles around him (Kendrick and Yelawolf) because he’s one of the best himself. And he’s got a quasi-Wiz Khalifa, Euro-trash song in “Fashion Killa” that sits comfortably next to current Top 40. It has what could be called lyrics, but are actually just a list of expensive brands. Think Watch The Throne meets keeping up with the Johnsons and you’re close. But that’s the intent: When you’re the best rapper alive making the best rap album of 2013, you can use the everything-and-the-kitchen-sink approach and make it work. You can even use second-tier Lil Wayne puns successfully: “My mama always told me keep your mind on your money/ Boy, you better pay attention.” And while paying attention may not seem like something A$AP ever does, he’s got an amazing ear for cohesiveness. While Live.Love.A$AP was mostly filled with Clams Casino haze, Long.Live has an impressive guest list of rappers and producers. With a major label budget, the two Clams beats here are definite upgrades. The foamy whitewash he perfected in 2011 is given a sonic overhaul, allowing all the lushness to truly float to the top and the dark underbelly to sink to the bottom. There’s finally enough space for Rocky to run around in. Drake appears as both guest and producer, giving a hand to 40 with “Fuckin’ Problems” under the name C. Papi. A$AP even makes Skrillex production listenable on “Wild for the Night” by reducing the obnoxious metallic shrieks and skwonks to a minimum. But it’s Hit-Boy’s two contributions that are the true standouts. The aforementioned “Goldie,” isn’t his best post-“Niggas in Paris” beat (that’d be Kendrick’s “Backseat Freestyle”), but it is his most memorable: The hi-hats and snare pogostick around a spirally ascending synth. His other credit, “1 Train,” has none of his copywritten flash; instead, it’s pretty basic boom-bap with a drunkenly staggering string loop and minor key piano plinking in the background. Yet, it works because the point of the song is to act as a vehicle for as many of A$AP’s friends as possible to brag and bullshit. Yet, in the end, this is Rocky’s show. A$AP’s entire career thus far has been to give a “middle finger to the critics,” as he states on “Wild.” He opens Long.Live with, “I thought I’d probably die in prison/ expensive taste in women/ Ain’t had no pot to piss in, now my kitchen full of dishes,” demonstrating the bizarre dichotomy of his existence and effectively asserting he made it, despite any obstacle in his life. But this could also be a fuck-you to the critics who’ve argued Rocky isn’t worthwhile because he has little to say. True enough, but they’re missing the point: A$AP got here regardless of that. Simply ask Jules Winnfield: “personality goes a long way.”	{ "pile_set_name": "Pile-CC" }
LG G Pro 2 preview — even bigger, even better Everything you loved in the smaller LG G2, and then some, is in the G Pro 2 The game that is the oversized Android smartphone — don't say "phablet," we beg you — has become one of leapfrog in the past couple years. Consider: The original Samsung Galaxy Note in 2011 was a surprise hit. Turns out folks do want phones that big. Then LG rolled out the forgettable Optimus Vu. Samsung continues on in 2012 with the Note 2. But then LG — seemingly (ahem) inspired — fires back in early 2013 with the original Optimus G Pro, sleeker and slimmer than its competitor. Last fall sees the Galaxy Note 3. And now we have the LG G Pro 2. Even bigger. Even better. Unburdened by the "Optimus" name, which LG tells us didn't really do that much in terms of brand recognition anyway. If things look familiar, they should. Much of what you'll see here is present in the LG G2 (and some of the additions will make their way back to the G2). Let's take a walk through this oversized phone, shall we? Why a 'preview,' and not a full LG G Pro 2 review? Using a Korean phone on U.S. networks doesn't do much for battery life. As was the case last year, we've come into possession of the Korean version of the G Pro 2, and that means a few things. First and foremost is that we've got a sweet TV antenna for watching television over the air, but only in Korea. Then there's the plethora of software that we'll never see in a U.S. release. (Yes, Korea has more than its share of carrier bloatware, too.) And finally there's the issue of network and battery life. One directly affects the other more than anything else in a smartphone, and so there's no good way to get a feel for real-world battery life. (Theoretical testing is fine for what it's worth, but we prefer real-world stats.) So think of this preview as one of our "casual" reviews. We'll get more into the nuts and bolts when we've got a proper U.S. version. But there's still a lot to see here — and we like what we're seeing. The LG G Pro 2 hardware LG's hardware prowess continues to shine. The G Pro 2 is further proof that LG has finally come into its own with hardware design. What started back with the Optimus G and the Nexus 4 continues here. Let's start with the basics. The G Pro 2 sports a 5.9-inch display at 1080x1920 resolution. It's powered by a Snapdragon 800 processor (quad-core at 2.26 GHz) and has an Adreno 330 GPU. It's running a full 3 gigabytes of RAM, has a 13-megapixel camera out back (2.1MP in the front) and comes with a 3,200 mAh battery. A 1080p display on a 5.9-inch phones works just fine — and LG makes displays as good as anyone. On paper, the only one of those specs that raises an eyebrow is a 5.9-inch display at 1080p. But do the math, and that's still some 373 pixels per inch — still more dense than the magical "retina" threshold. And in actuality, the display looks great. There's basically no gap between the glass and the display itself, so images seem to almost float above the phone. Simply put, LG Display (LG Mobile's sister company that provides the panels) continues to outdo itself here. The phone's design helps some here as well. The bezels on the outside of the display are down to just 3.3 mm, and the glass is flat instead of chamfered, giving everything a really sleek look. The physical home button and capacitive buttons are gone, the LG logo's been moved to the bottom, and anything that's not display has a subtle but noticeable shiny pattern. Not as cool as the "crystal reflective process" used in the Nexus 4 and Optimus G, but still attractive. The flatness of the front also helps accentuate what's going on out back. Gone is the glossy plastic of yesteryear, replaced by a matte gray with a sort of crosshatch texture. And while we wouldn't call the original G Pro boxy by any means, this year's model has a much nicer slope to it, where the back heads outward to the edges. It's not flexible or bendable like the G Flex, but between the slope and the texture it's definitely easier to hold. The G Pro 2 switches to on-screen buttons, but LG still makes them more difficult than they need be. And, of course, there's the matter of the buttons. The volume keys and power button are out back, just like on the G2 and the G Flex. All three serve their intended functions as you'd expect, and they also have secondary uses. The power button serves as a notification light when the phone is face-down (there's an LED on the front of the phone for when it's resting on its back), long-pressing volume-down fires up the camera app (and also serves as a shutter button), and long-pressing volume-up opens Quick Memo. As we mentioned at the outset, we can't get a real feel for battery life until we get U.S. versions of the G Pro 2. But sitting here on Wifi, the Snapdragon 800 platform acts as expected — fast. We've got a spare battery in our retail box; it's unknown whether any potential U.S. versions will include that extra nugget. The LG G Pro 2 software A few cool new features added onto LG's workmanlike user interface. Ah, and then there's the software. A bit of good news here — the G Pro 2 is running Android 4.4.2 out of the box. We'll have to see how LG does with updates this year — historically it's not been great. The original G Pro still languishes on Android 4.1.2. LG's user interface hasn't changed all that much, and we're still not huge fans of it. But there are some new features worth noting. Add in your own recent apps button Now that the physical buttons are gone from the phone (the G2 killed them off for good, actually), you've got proper on-screen buttons. The layout is back-home-menu — yes, a legacy menu button. You can add in a proper recent apps (multitasking) button, but the menu button remains. There also are button options for the notifications pulldown (so that you don't have to reach all the way up top to get to them), QMemo and QSlide. You can have up to five buttons visible at any time. Knock Code Knock Code is the big deal for LG this year, and rightfully so. With the G2, LG introduced the ability to "knock" — tap twice, really — on the display to wake the phone. Using it as a pattern unlock mechanism is a great continuation. The gist is that you've got a 2x2 grid, in which you tap as few as four and as many as eight times, in any combination you want. That gives (and we'll trust LG's math here) some 86,367 potential unlock codes. Just as important is that it's quick and easy to use, and the phone walks you through setting it up at first boot. And, yes, you'll have to set a backup PIN code for when you forget your knock code. Also: the traditional Knock-on works fine, even without a code. But set up a code. Protect ya neck. Mini View So you bought yourself a 5.9-inch smartphone but find yourself wishing it were smaller. (That's known as "phablet remorse," by the way.) LG's added in Mini View. Swipe through the on-screen buttons and your screen will shrink to a size that's just a bit bigger than the iPhone. Swipe to the right to put it on the right edge of the screen, and left for left. You can extend the window to make it larger, and hit the X to close. Or, you know, just buy a smaller phone that you can use one-handed. The LG G Pro 2 camera OK, there's a lot going on here, too. LG's traditionally had pretty good cameras, and that trend appears to continue with the G Pro 2. By default you're shooting at a 16:9 aspect ratio, or 4160x2340. The full 13MP resolution takes things to 4160x3120, or a 4:3 aspect ratio. LG's cameras have always been pretty good — but Magic Focus just isn't necessary. The usual modes are here — HDR, panorama, bust mode, beauty shots, the ability to erase people, etc. — but the one new one LG's talking about is "Magic Focus." Basically that takes five shots at different focal points, then allows you to choose where on the image you want to focus — or to put the entire scene in focus. It works, but it's going to be a bit complicated for most folks, and simply retaking a picture with the proper focal point might be quicker. It's certainly not as cool as what Lytro's doing, but it's something different. There's also something new when it comes to selfies. (When is there not?) LG's calling it a front-facing flash, but really it just shrinks the preview window when you're using front facing camera and replacing the space with a white background — that's your "flash." It doesn't seem to do all that much unless you're in a pretty dark space, though, but at the same time it doesn't seem to hurt any. (Well, maybe except for your battery.) The bottom line (for now) If the Note 3 just isn't your thing, the G Pro 2 absolutely will deserve a look. There is a whole lot to like in the LG G Pro 2. (Even if the name is still a mouthful.) The display is bigger and as beautiful as ever. The design shows that LG's got the chops to hold its own. The software? Well, there's still some room for improvement. On the other hand, it's completely functional. The world "utilitarianism" comes to mind, still, and maybe that's not the worst thing in the world. But neither is it the most friendly. Knock Code is a great addition. The camera looks like it should be a keeper — we're going to keep testing it. And a 3,200 mAh battery — replaceable, at that — means not having to say you're sorry. It is very Astonishing to see Antenna in this Era of mobile, But Good To see this Feature this Features Will Leap Android Application Development Company to enhance features in providing Apps for LG mobiles Htc one has something no other phone has. Software partnership with netgear Mira cast. You can cast while talking on phone or having screen off. That's a real good feature. Lg g3 might have 2k screen and z2 is all around good. I have a blog which contains a lot of movie which you can download. My Planning is make this blog will a Professional website. You can download any good movie from my blog / web (FREE). Help me to improve my web by visit my blog and comment for your opinion. Everyday my film collection will be updated by me. You can request film that you want to watch by comment on my blog, than I will find the movie for you.. All OK except for the ugly skin.. why would anyone want to buy this cartoon looking phone? LG make your skin flatter, cleaner and simpler. And yeah you suck at updates even though few people buy the phone with the argument that they buy for the features that exist now. Get on with the game. I have a G2 and I love it... dare I say even more so then my Nexus 4, if only for the fact that its just works. Its great looking and it has features I use. I used to be a purest and wanted my stock android with all the latest updates, but what I didn't get was features.. With the G2 I do. Will the new G pro be an upgrade, I think so.. New display, bigger display, knock code, and maybe a few others thrown in later, of course this would be a worth upgrade. I used to skawk at the people with their huge note phones until I got my G2, and now, it only makes me want a G2 even bigger, which this phone would provide. Personally I could care less about what Android version its running if it works well, and so far I have not been disappointed with LG. I got KitKat, and it has not made me hate or love the phone any less. If TMo gets this phone I will use Jump to switch to it.. Unless something mindblowing comes along in the next 4 -5 months. This is a fail as a successor to the G Pro. While the slide to shrink feature is nice, the physical phone doesn't fit in one hand any more. The best thing about the G Pro was that it was smaller than the Note 2 with a bigger screen, better screen. They should have stuck to that. 5.6 inch with even slimmer bezels with the same overall dimensions would have made this a true successor. Now it's just a stupid big phone. With the G continually growing, I guess I will wait for the G3 to grow to 5.5" to replace my G Pro. Well my last LG was a cookie or a snap can't remember and wow it was so unresponsive and tiny at around 3" I think lol Anyway this G Pro 2 looks great and by the sound of things it's a vast improvement as was the G2, which I was nearly tempted with but opted for the Nexus 5 instead. In terms of design I like the G2 and I like this G Pro 2 with that Matt back yup it works atleast by what I can see in the pictures, and I like the fact that LG tried something different with the button placement but not for all and one thing is a guarentee "you can please some people some of the time, but you can't please all of the people all of the time" Posted via Android Central App Anyone else prefer physical home button instead of on screen buttons? Physical Nd capacitive buttons were what tipped the scales for me to choose the G Pro over the G2. I must be in the minority on these forums, I wonder what the regular Joe prefers. I'm not your typical mobile user (I guess I'm called a "power user" and a tech enthusiast), but I still prefer the physical home and back buttons. it gives the phone the sleek look on the front (i.e. the black nexus 5) and i like it. honestly the fact that it takes up some space on the screen doesn't bother me. I came from phones with physical buttons and switching to soft keys was not a deal breaker for me. I like it since I prefer the tactile feel and I can't accidentally press the home button like I can the on screen buttons. Also, when watching movies or playing a game, I don't want to have to do any gesture or action to hide or toggle the on screen buttons. I like knowing the physical home button is there , away from the screen, whenever I need it without hindering the video or game experience. That's the issue. They should have released this in November or with the g2. They would have made waves. The knock on code is cool, but I wonder how well it will work after hearing about issues with knock on. Then, you wonder about lg and updates. That's a whole other story. Well, truth be told, I don't care for updates that much. Don't get me wrong: I get as giddy as the next person, when I see an update pushing out that might include some cool new features. But, they're definitely not as necessary as they used to be. I like the Note 3. But, I'm always in the market for something new. And, I've never had an LG device. But, this release cycle is killing me. I feel like this phone would be better served, if it debuted and was released during the summer. I liked getting updated to Kit Kat, but yeah, my G2 was sweet already on 4.2. It was just a nice bonus, and I was surprised it could run even faster. That "17% faster" was no BS. The thing was already fast, lol. I agree it seems like the G Pro 2 ran late. They need to tweak the cycle. After seeing the difference between Sammy's S4 and S5, I'm really interested to see what LG does with the G3. And I do think I keep the Z2 I liked the Z1 but the Z2 as of now is probably the best phone on the market followed by the G2. To make it short. I love the Z2. Sony improved everything that needed to be improved from the almost perfect Z1s. The smartphone is going through that SUV phase, where you had that monstrous Hummer vehicle as the "ultimate SUV", only to find out that it was too big, too gas guzzling, too awkward .... At some point the "larger" smartphone is going to hit that ceiling, where bigger is more a hindrance than an asset. I think 6" is getting there, but unless the market stops buying bigger phones (more than 5.5"?) the manufacturer will keep making them bigger. Yeah, I had the original Note. It was a 5.3" but with a screen ratio that made the phone extra wide in your hand. I got tired of such a bulky phone, but I was still loving the large screen. Then, the G2 came out, with a 5.2" 16:9 screen. Same screen height, but so much sleeker and lighter. Just the right size. I'm fine with companies making two separate categories. Flagship and Phlabship, lol. SUVs are still around. They have become more efficient. Much like phablets. I think your megas and your xperia z ultras will go by the wayside, but the notes and others will still be around. They will always be popular with business people and people with large hands. And much like jeans, the trend will change and phones will get smaller, but you will still have a demand for the baggier jeans and bigger phones. Posted via Nexus 7 AC App i have wanted one of these since the G2 came out a few months back. dat bezel. the possibility of a phone this big with bezels that thin and even a sense of style... oh i drool. im usually reserved for HTC but boy do i want one of these G Pro 2s! Tru dat. I'm in favor of any manufacturer that pushes our phones forward. Right now, I like LG the best, but that could easily change before my next purchase. I just wish LG, HTC, etc had Samsung sized advertising budgets, so Joe Schmoe would know about 'em. The G2 is perfect as it is. Even if the software didn't get updated, it wouldn't really matter with the Optimus UI. It's not like you would be able to tell the difference between 4.0/4.1/4.2/4.3/4.4. The Optimus G's UI looks exactly the same as the G2's. If it's not a vanilla Android phone, the updates are almost meaningless, unless there's some type of bug that needs to be fixed on the phone. Well, I'd welcome an update if it not only fixed bugs, but also added features or increased performance. But, I do agree, the necessity of the updates has decreased dramatically; and the differences between versions are almost indistinguishable, aside from the version numbers in the Settings menu. So a leaked is came out...so? Official support...nope. Its classic LG through and through...support the new...answer people with year old device languishing with out of date software that they should upgrade.... Next you're going to defend them with "Is doesn't matter now that Google.services gets updated..." What about the galaxy ace, mega, etc etc there not the only ones not updating there whole line of phones, Samsung released 80+ different phones/variants last year guess how many of those actually will see KitKat? Am I alone in wishing oems would stop making phones bigger? I'm not saying there isn't a niche market for the phablet, but Samsung seems to have that guy on lock. How about working on other innovation like battery life or better yet, new hardware materials that render the need for a case obsolete? It seems a shame that everyone makes beautiful devices with attention to ergonomics, but then we have to cover them up to protect them, thus rendering design obsolete. Lets see. N5, KK doesnt run that great as far as I see. MotoG update buggy, HTC One update stopped pending a review, S4 update, buggy and needed a patch. KK is buggy crap, im glad LG is taking its time to fix Googles mess. you are because they don't just make one phone. There's a market for every size phone and stay in this business you need to cater to all of them. Even if Samsung seems to have that market on lock, competition is always good. Well, I'm a fan of the bigger devices. I don't want any OEM to stop making the bigger smartphones. Sure, tech can be improved. But, I shouldn't lose my choice of smartphone, simply because you don't like it. For a long time I refused to even consider any smartphone that didn't have a physical keyboard, but finally, I accepted that OEMs weren't going to make any high-end devices with physical keyboards. Clearly some people want high-end QWERTY phones -- I did and so did a lot of other commenters -- but the overall perceived demand was low. Likewise, despite the many comments from people who say they want small phones with high-end specs, the OEMs seem convinced that this market is too small to care about. Small phone lovers may have to also come to accept that the minimum size for high-end specs is 5" and likely to get larger. In any case, last month, I decided to upgrade from a Droid 4 to a Galaxy Note 3, and I'm very happy with it. I had to give up my QWERTY, but the big screen makes up for it, and at least typing on a virtual keyboard is a more pleasant experience with a large screen. I'm all for choice, but unless Ara succeeds, small market niches may continue to be underserved. Though personally, I'd love to see a high-end phone with a 5" screen AND a good physical keyboard. Actually, I think a 12-inch "phone" would be a great idea. In fact, I was arguing for that ten years ago. That is, I was hoping that someone would add telephony features to my laptop then and tablet now. Again, I think it is a great idea but as long as people expect heavily subsidized phones from their phone companies, (at least US) manufacturers have very little incentives to actually build and market them. I actually tend to agree -- me personally, I think the "Note"-series is Samsung's flagship line and their "G"-series is rapidly becoming their "mainstream" or even midrange product line -- but until the Note 4 is actually introduced, we won't know for certain. And giving credit where credit is due, I think that spec-wise, the LG G Pro 2 looks like a fairly formidable phone. As you mention, it gives the Note 3 "a run for the money" and I would even add the Samsung G5 to that list. In fact, although I think the G5 is a definite even if only an incremental improvement over the G4, I think the Note 3 is still the better Samsung phone; but I digress. I had the original Note. Used the S-Pen for two days. It was kinda cool at first, but my finger was perfectly fine for everything I do on my phone, and happens to always be "at hand". Not everybody wants a big phone for the purpose of using a stylus. The spen isn't just for replacing your finger. If that's all you used it for then yes, that wasn't the phone for you. Unfortunately not everyone with a note uses the stylus just to replace their finger. They actually use the features that come with it. I can definitely understand. I had the Note 2 since it came out. Tried other phones just to see and I kept coming back to my spen which I use more and more. Just yesterday I used it to write a note then I needed to share that note so I did a multi window so I could see the Note and type at the same time. It was priceless. Although I would love to end up using this phone as my main phone the spen feature on the Note line will just never be beaten, yet. Why on earth would you want either this or the Gflex? Both are stupidly large without serving a purpose...notice how the Galaxy Note is shrinking over time...at least there's a reason that screen is so big... Okay, here's something constructive...without stylus support (and I mean real note taking support...not "we support snub nosed stylus's that succeed in replicating your finger)...this is a bigger waste of time and money than the Gflex. Not as fast as a Galaxy S5, with a worse display, and LG's track record of software updates....and likely to cost as much if not more than the S5 (if anyone bothers bringing it stateside) Hey genius, a Big phone serves the purpose of people who want a Big phone. Can't make it any simpler than that. I'm not a fan of stupid curvy phones whether it's made by LG or Samsung. Software updates? Old news, guy. LG has stepped it up. "After his smartphone was returned to him, he discovered that it was now running Android 4.4.2 already. The person who worked on the device then revealed that an official update would be making its way out to device very soon, probably in a month." - It's not a guarantee, but it looks pretty good to me. I'm just wondering if a family member was killed in a tragic phone accident, and it happened to be manufactured by LG? Well, I haven't seen a Pro 2 yet in the flesh unsurprisingly, but I still consider the G Pro 1 the sleeper hit of 2013 and the best phone of the first half of 2013. it was just crushed by AT&T exclusivity in the States and, of course, the wicked combo of LG's rotten skin & horrible update policy. Now, a proper G Pro 2 rolled out to ALL the carriers by early summer Stateside would be absolutely fantastic, especially if they don't gimp it by removing the microSD slot and the removable battery. What's missing? I don't care for styli or the S-Pen at all, so I don't consider that a loss. I'd like to see the Pro 2 bumped up to a Snapdragon 801 for the US launch and maybe receive a 64GB storage variant. USB 3.0 is also a truly nice addition that no one but Samsung seems to take seriously . So yeah, my dream phone for 2014 would be a refreshed Pro 2 GPE edition with 64GB, 801, and USB 3.0. Barring that, I could live with a GPE Pro 2 just fine. This is actually very comparable to the s5, the G pro 2 has its advantages over the s5 and vice versa it has a larger display, and much larger battery that is also removable and better speakers, they both have SD card, the difference in speed most likely won't be noticeable and we havnt seen any comparisons on the cameras yet. The only advantages I see is the dust/water resistance of the s5. Well I dunno about you but I'm much more impressed with the g pro 2 than the s5. Its an interesting device,and as much as I hate to say it LG seems to be the only ones bold enough to be creative(for better or worse). Then I guess this is not the phone for you. People said the Note 2 was stupid and too big and just look at how famous it was and still is. I still love my Note 2. I'm waiting for this phone before I decide on Note 3 but on the end I think the spen will keep bringing me back to the Note. But I have high hopes for this phone. If you don't like big phones it's easy, DON'T BUY IT.	{ "pile_set_name": "Pile-CC" }
20 reasons to go to the London Design Festival Mathieu Lehanneur at the V&A As the hub of the entire festival, the V&A is always the place to go to find outstanding works of design art and immersive installations. Check out French designer Mathieu Lehanneur's piece Liquid Marble: a surreal representation of the sea which both looks and feels like rippling water, realised in black marble using the latest 3D software. The structure will be on a 45cm-high pedestal in the museum's Norfolk House Music Room, where visitors are invited to touch it, sit on it, and have 'a contemplative experience'.	{ "pile_set_name": "Pile-CC" }
Wavelet PCA for automatic identification of walking with and without an exoskeleton on a treadmill using pressure and accelerometer sensors. Nowadays portable devices with more number of sensors are used for gait assessment and monitoring for elderly and disabled. However, the problem with using multiple sensors is that if they are placed on the same platform or base, there could be cross talk between them, which could change the signal amplitude or add noise to the signal. Hence, this study uses wavelet PCA as a signal processing technique to separate the original sensor signal from the signal obtained from the sensors through the integrated unit to compare the two types of walking (with and without an exoskeleton). This comparison using wavelet PCA will enable the researchers to obtain accurate sensor data and compare and analyze the data in order to further improve the design of compact portable devices used to monitor and assess the gait in stroke or paralyzed subjects. The advantage of designing such systems is that they can also be used to assess and monitor the gait of the stroke subjects at home, which will save them time and efforts to visit the laboratory or clinic.	{ "pile_set_name": "PubMed Abstracts" }

Subsets and Splits

No community queries yet

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