Last night we left Kappadokia. Kappadokia is one of nice city in my travel. I really want to come back here when I have girlfriend or wife.
8:00pm The bus departed. As it didn't have toilet inside bus, several times stopped kind of SA.
One time I was left before I came back. Then I had nothing even Phone 📱.
Heeeeyyy !! Where is my bus!!!
I asked one worker. He explained me that my bus just went to take gasoline.
Finally bus came back and picked me up. And 6h later it arrived Pamukkale.
Pamukkale also one of famous sightseeing point. In summer, people come to swim. Coz here is hot spring.
Before gate open, We walked around bus station.
Absolutely I'm not in Japan.
It is increasing step by step. You should come as soon as possible.
As I walked more long time , gradually hot water appeared!!
After this point, we walked other places.
Not only white place but also others places are nice!!!
When we came back bus station, these girls saw us and called. They explained their school.


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Say hello to the experts who help The Lawyer Portal provide the best information to aspiring lawyers!
Rachel Davis is managing director of The Lawyer Portal and a qualified solicitor. After graduating from the University of Leeds with her law degree, she joined international law firm Dentons. Rachel then moved to BPP Law School, before joining TLP. Her breadth of experience both in practising and teaching law has helped in the creation of TLP's comprehensive resources.
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As one of the co-founders of The Medic Portal, Dr Ricardo Tavares completed his prize-winning pre-clinical Medicine degree at Oxford University and finished his clinical training at UCL. He is also a Fellow of the Higher Education Academy. At The Lawyer Portal, he oversees business development and our partnerships with hundreds of schools globally.
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George Rendel is a co-founder of The Medic Portal as well as The Lawyer Portal, where he oversees marketing, technology, content and e-commerce. He has plenty of blue chip business experience at home and abroad, having worked for both Pearson in North America and Accenture in the UK.
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Cloquet senior Aidan Ripp skis in the classic portion of the Section 7 pursuit race Feb. 7 at Giants Ridge. Ripp took second in both legs of the pursuit race, good enough for second overall. Ripp and teammates Benjamin Bauer and Josh Sanders made it to the state meet, which was scheduled for Thursday, Feb. 14, after this issue of the Pine Knot News went to press.
Despite less than ideal conditions, Cloquet-Esko-Carlton's Aidan Ripp took second place at the Section 7 Nordic Ski Meet held in Biwabik at Giants Ridge Thursday, Feb. 7. Garrett Beckrich of Grand Rapids claimed the overall boys top spot with Gretchen Haggenmiller of Duluth East taking first place in the girls race.


Posted on July 9, 2018 · As we wait to find out who the President selects, we learn more about how justices are chosen in the first place.
Posted on July 26, 2017 · With guest Professor Bret Wells.
Posted on October 18, 2016 · A federal judge has sided with the University of Houston for a preliminary injunction against what was formerly known as the South Texas College of Law.
Posted on July 29, 2016 · The South Texas College of Law changed its name to Houston College of Law. The name change brought a lawsuit from the University of Houston Law Center. Now Houston College of Law has filed a counterclaim.
Posted on June 30, 2016 · It all started when South Texas changed its name and logo last week.
Posted on December 11, 2015 · Pfizer's merger with Allergan is only the latest, and largest, example of "corporate tax inversion." Houston companies helped pioneer the practice.


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Remains of the Day: Google Announces its First High-End Chromebook, Pixel
Utah Judge Rules It's 'Lewd' for a Woman to Be Topless in Her Own Home
Joshua Rivera
Filed to:For What It's Worth
Google shows off a premium Chromebook, Netflix updates its iOS app, Google search now includes improved weather info, and Coursera adds a large number of new courses.
Google Debuts Pixel, a Premium Touchscreen Chromebook Today Google announced the Chromebook Pixel, a premium version of their budget laptop running Chrome OS. The Pixel comes with a high pixel density touchscreen comparable to Apple's Retina display but with a 3:2 aspect ratio. The higher-end laptop will retail for $1,300 for a Wi-Fi-only model with a 32GB SSD or $1,450 for the Wi-Fi-and-LTE model that includes a 64GB SSD. The Pixel is now available for pre-order through Google Play and Best Buy, and will ship the first week of April. [Wired]
Netflix for iOS Hits Version 3.0 with UI Improvements Netflix has updated its iOS app with a few UI tweaks for video playback. The app will now display the title of what you're currently watching with a tap and shifts the placement of the playback controls for ease of use. For those of you who missed it, the zoom button has returned as well. [Mac Life]
New Google Weather OneBox for Desktop Google has updated it's weather results OneBox in desktop search to look more like it does on tablets. Desktop users will now see an eight-day forecast with precipitation and wind conditions whereas before the desktop results only displayed a four-day forecast and current conditions. [Google Operating System]
Coursera Adds 29 Schools, 90 Courses And 3 New Languages To Its Online Learning Platform Free online course provider Coursera has just announced that it has added 90 new courses from 29 universities to its course offerings. Some of the Universities new to Coursera include CalArts, Northwestern University, and the University of Geneva [TechCrunch]
Flickr for iOS Updated With Tagging, Faster Uploading, and Features You Were Missing An update to Flickr's iOS app comes with a bunch of small tweaks like improved upload speeds and auto-saving original photos before you edit them. It will also finally let you take photos using the volume up button. [Gizmodo]
3.5m Downloads On, CloudOn Takes its Microsoft Office Editing Suite to Android Smartphones CloudOn, the mobile app that lets you use Microsoft Office and syncs to the cloud, has just been released for Android phones. Previously only on iOS and Android tablets, the smartphone version of the app is now available on the Google Play store. [The Next Web]
Photo by photastic (Shutterstock), a2bb5s (Shutterstock), and Feng Yu (Shutterstock).


If your order is not in stock at the time of purchase , your credit card or Paypal account will not be charged. Buy the Universal Audio UAD-2 Satellite USB - QUAD Custom online in Hong Kong at the best price of HKD $12,072. Serviced cities in Hong Kong (香港) include Kowloon , Tsuen Wan and Yuen Long.


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A site is comparable to a digital store, and the purpose of placing a big investment into making a website is to ultimately aid boost the profits of your service. Lots of people, specifically the startups and the business owners who are new to the online service world focus too much on the looks of the style to think about whether it is efficient enough to really make a sale.
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Drawing in brand-new visitors to the website is the very first and one of the most vital tasks that a sales funnel does. This is the mouth of the funnel. This stage is narrower and also in the following step of the funnel as well as ought to be well maintained considering that they are most likely to make a purchase how to set up clickfunnels cname in the next couple of phases as long as you keep them satisfied.
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Celebrities Caught In Groupie Scandals
Jon Kopaloff/Getty Images
By Daryl Nelson/April 5, 2021 1:22 pm EST
While several celebrities have been accused to being caught with groupies, public perception of these admirers of the rich and famous has shifted over the span of decades, particularly in the wake of the #MeToo movement. As Flare put it in 2020, while "groupies have always held a divisive — and misunderstood — role," back during the '60s and '70s, "the heyday of groupies was a time of cultural, spiritual and sexual revolution." Indeed, back in the day, it might not have seemed like too big of a deal to hear of a celeb hooking up with groupies — especially since there wasn't much proof to show for it, apart from claims churned out in the rumor mill.
But thanks to a little thing called technological advances, stars eventually started getting photographed or filmed by alleged groupies, with the images and videos subsequently being put up on social media for all to see. It seems that many of these reported incidents coincided with the rise of cell phones and social media engagement — leading to a learning curve for those same celebs, whose likeness was captured seemingly without their knowledge or consent. So while some of these groupies' hookup stories may not even be true, their accusations still made headlines when the photos inevitably went viral.
These are the celebrities who found themselves caught in groupie scandals.
James Harden was allegedly caught having 'sleepy time'
Jim Mcisaac/Getty Images
Oftentimes, when James Harden's name is in the headlines, it's for making some poor soul look like a novice on the basketball court while defending him. That's because Harden is considered to be one of the NBA's most prolific scorers. But in June 2015, he made headlines after being photographed in bed by a woman whose Instagram handle is @gvngstvxboo. She then posted the pic to her page, along with the caption, "#Lilsleepytime @jharden13."
Harden stayed quiet about the image, but he was teased about it by people like Bow Wow, who claimed he should have known better. "I see yall boys still young rich and DUMB," the rapper wrote in a since-deleted Instagram post (via The Source). "Now James is my boy but let me say this now. This is how I use to do it. Its called 'leaving no evidence' if you was chilling w me, my security takes phones and you signing papers." Bow Wow continued, "I give credit to the ladies because most of us are just that rich and stupid so yall know how to get us. I been caught up too before not knowing, being a rookie."
As for @gvngstvxboo, she pretty much disappeared from headlines once shock of the photo subsided, and she hasn't posted anything to her Instagram page since 2016.
Justin Bieber might've hooked up with a woman in Brazil
On Nov. 5, 2013, it's safe to say that not many people knew who Tatiana Neves Barbosa was. But that changed just one day later after a short video of Justin Bieber sleeping in bed surfaced on YouTube ... which the Brazilian model supposedly filmed, per E!. Barbosa also shot herself blowing a kiss to the "As I Am" singer in the clip — so right away, the general assumption was that JBiebs allegedly had a tryst with a groupie.
Unsurprisingly, the video instantly got millions of hits, but Bieber and his team never publicly addressed it. However, Barbosa — who was also a part-time actor at the time — did talk about it to The Sun (via Page Six) days later. According to Barbosa, Bieber and his team reportedly rented a villa in Brazil, and one of his handlers asked Barbosa to attend a party there. Afterward, she reportedly went to the singer's hotel room.
Claiming that she and Bieber had a one-night fling, Barbosa told The Sun that she didn't mean for the clip to get out and had only sent it to a friend to show that she was really with the pop star. But the leak didn't seem to take away from how she felt about her alleged night with Bieber, as she stated, "It was one of the best moments in my life. It was marvelous and unforgettable."
Snoop Dogg was supposedly outed by a famed groupie
Ethan Miller/Getty Images
Instagram celeb Celina Powell has been called hip-hop's most famous groupie, as she's claimed to have hooked up with several rappers. In 2018, for example, Powell alleged that she was carrying the child of Offset from Migos, but later admitted to lying about it (via Urban Islandz). Not to mention that, in January 2021, she tried to convince Drake that he gave her his number in the past, but the Canadian rapper said he wanted nothing to do with her. Drake then shared their text exchange to prove that he turned her down cold.
Snoop Dogg may have considered Drake's move when it came to Powell — especially since he's been married to his high school sweetheart, Shante Broadus, since 1997. After Powell claimed that he'd cheated with her by sharing their alleged text messages in July 2018, Snoop seemed to respond on Instagram, saying he'd be starting a TV show called Clout Chasers, the slang term used for those who try to get fame by piggybacking off another person's celebrity.
Not that this deterred Powell, who later shared explicit details of her alleged tryst with the "Gin and Juice" rhymer in a YouTube video posted in December 2019. The following September, Powell implied that she and Snoop were seeing each other again on Instagram, captioning a photo of him with, "Snoop dogg isn't leaving me lol no matter what I do ... FYI, him and his girl are separated living in different houses." That claim is also yet to be confirmed.
Conor McGregor may have been exposed by a rap-loving brunette
Steve Marcus/Getty Images
In February 2020, a woman reportedly named Kim Hendrick posted a video that showed someone looking a lot like UFC fighter Conor McGregor sleeping in what appeared to be a hotel room. In the clip, AceShowbiz reports, Hendrick danced and rapped along to Tyga's "Girls Have Fun," featuring G-Eazy and Rich the Kid.
Right away, accusations surfaced that the mixed martial artist had cheated on his longtime girlfriend and mother of his children, Dee Devlin. But for the record, it was never proven whether or not the guy in the grainy clip was even McGregor, so others expressed doubt at the time about whether or not he'd actually engaged in infidelity.
Meanwhile, the couple — who actually got engaged in August 2020, mere months after the supposed scandal — never addressed the rumor, and as of Feb. 14, 2021, it looks like they're still going strong. "My Valentine," Devlin captioned an Instagram photo of herself and McGregor, complete with crown and red heart emojis.
Usain Bolt: 'There is no way to tell the difference between a groupie and a good woman'
Ian Macnicol/Getty Images
There was one particular week in 2016 when Kasi Bennett's phone must have been buzzing with text messages. Who is Kasi Bennett, you might ask? She's sprinter Usain Bolt's longtime girlfriend and mother of his child. Your second question might be: Why was her phone blowing up back then? Well, because photos of the famed Jamaican athlete appearing to be in bed with a woman named Jady Duarte went viral while he was in Rio, Brazil for the Olympics.
Duarte detailed their alleged encounter in a 2016 interview with The Sun, in which she claimed that she met Bolt at a nightclub after he sent his security guard to set up an introduction. When she turned the request down, he reportedly lifted his shirt to show off his six-pack abs, which led to her joining him in his Olympic Village living quarters, which is where they supposedly engaged in a little hanky-panky. Duarte went on to explain that she took photos of herself and the runner and uploaded them to WhatsApp as a way to prove to her friends that she was really with him.
For his part, Bolt didn't respond to Duarte's interview, but during a 2017 chat with Page Six, he expressed confusion about some of the women he meets. "I think I have gotten better over the years when it comes to women, but there is no way to tell the difference between a groupie and a good woman," Bolt stated.
Ezekiel Elliott started his NFL career with a groupie scandal
Mitchell Leff/Getty Images
NFL running back Ezekiel Elliott was seen getting some Zs as an unnamed woman took a photo of two while they appeared to be in bed together. The woman was seen in the photo wearing a pink shirt while holding up her phone to snap the shot while puckering her lips. She also let everyone know who was supposedly in the picture with her, just in case there was any confusion. And according to Bossip, she put the pic on Snapchat right after Elliott was selected by the Dallas Cowboys in the fourth overall pick of the 2016 draft that May.
Of course, the photo went quickly viral for two reasons. One, Elliott was already a household name after having massive football success at Ohio State, and second, he went incredibly high in the 2016 NFL draft. As for the woman in question, she's since done a stellar job of keeping her name out of the press. For his part, Elliott has kept silent about the photo, which seemed to help people eventually stop talking about it so much — and he hasn't been caught up in a similar alleged situation since.
Julian Edelman was reportedly seen with a woman after a Super Bowl win
Abbie Parr/Getty Images
A Massachusetts woman named Sabrina Dudish might've thought that taking a photo with New England Patriots star Julian Edelman would improve her life on some level, but it did the opposite and got her banned from Boston nightclubs. We'll explain. Back in February 2015, Dudish took a picture of someone who appeared to be the wide receiver and posted it to Tinder — just one day after his team won the Super Bowl, per Deadspin. If the photo of a sleeping Edelman wasn't enough to cause shock, what Dudish claimed in the caption sure did the trick: "Just f**ked Edelman no lie."
The image in question rubbed nightclub owner Michael Winter the wrong way, and he quickly ripped Dudish on Facebook, before apologizing after some thought his message was too harsh. "In many years I haven't BLACK LISTED anyone from the nightclubs. YOU ARE BLACK LISTED 86'd so stay in Metro West. Putting Edelman on Blast during celebration," wrote Winter, according to TMZ. "... Btw you're a 5 if that and he was blackout. I'm sure I speak on behalf of many Boston Industry ppl to not show your face in this city."
The celebrity news site later reported that Dudish apologized for taking the photo and expressed regretted. "I made a mistake. I feel really bad about it ... He passed out and I was bored I guess," she said. "I was drunk ... and I made a mistake and I feel terrible about it."
Klay Thompson was accused of cheating with a groupie
Ezra Shaw/Getty Images
NBA Player Klay Thompson isn't an athlete who's associated with a lot of off-the-court shenanigans, but in 2015, his name was all over the place — and it had nothing to do with his super sweet jump shot. Thompson made headlines because his girlfriend at the time, model and social media star Hannah Stocking, accused him of committing a personal foul.
"So I guess he really wanted that tag to get his numbers up," Stocking wrote in multiple since-deleted tweets, which were captured by Yahoo!News. "When you catch ur man naked in bed with a groupie ... lol @KlayThompson." For his part, Thompson remained silent about the accusation, but according to Married Biography, Stockings reportedly broke up with him shortly after.
Since then, both parties have moved on. In 2020, rumors started to spread Stocking was dating TikTok star Ondreaz Lopez, but the couple later split, which she confirmed in February 2021 while talking to The Hollywood Fix. As for Thompson, he began dating actor Laura Harrier in 2018, as Yahoo!Sports reports.
Trace Adkins flirted with a groupie on Twitter — and then married her
Country singer Trace Adkins married his second wife, Canadian actor Victoria Pratt, in October 2019 — but years earlier, Pratt admitted to being his groupie and flirted with him on Twitter. In fact, it was reported by Radar at the time that the flirting reportedly led to the singer's then-wife of 17 years, Rhonda Forlaw, to divorce him in 2014.
But Pratt and the Dreamin' Out Loud artist didn't keep their attraction for each other online, because Pratt seemed to imply that they'd hooked up while filming The Virginian, which is where they met. "Gave Trace Adkins a sponge bath at work today ... just another day at the office," tweeted Pratt in March 2013. "I owe the universe big time! #Bestjobever." When Adkins won Celebrity Apprentice that May, Pratt tweeted in all caps, "YAY!! CONGRATS, YOU HANDSOME DEVIL!!" In response, the singer wrote, "Thanks gorgeous! MWAH."
According to Radar, Pratt later gave an emphatic "yes" when someone asked if she was Adkins' groupie while watching him perform at California's Stage Coach music festival that year. As a source cited by the outlet claimed the following year, "Rhonda was totally humiliated. When Trace told her that he had fallen in love with Victoria Pratt, she completely flipped out."
For their part, Pratt and Adkins exchanged vows in a New Orleans ceremony that was officiated by fellow country singer Blake Shelton.
Lil Wayne was photographed by a Miami dancer
Throughout Lil Wayne's long and successful career, fans have seen him in various fashion styles, whether it was the baggy look of the early 2000s or the more fitted look that came years later. But in July 2012, Weezy appeared to be seen in just his boxer shorts and eyeglasses after a woman named Saralyn Rivera was accused of taking a photo of him while he was sleeping, per VladTV.
Many also assumed the pic was taken following an alleged romantic episode between the two, and the photo instantly went viral. However, model-dancer Rivera claimed it wasn't her who put it online. "Woke up 2 craziness," she wrote in a series of tweets (via VladTV). "[I'll] say this, it wasn't a 'groupie' situation at all ... [It's] between me n wayne actually, but I would never send anything to blogs. Whoever did is a lame. Lol."
For his part, Wayne didn't respond to the chatter surrounding the photo, but he later made headlines for being with other women, like singer Christina Milian, before they split in 2015 (via ET). In regards to Rivera, it's not clear whether she and Lil Wayne continued their alleged relationship after that photo went viral, but she later promoted the video to his 2020 song "2 Diamonds" in her Instagram bio.


This traditional and classic men's wedding band is sleek. The domed body features a brushed satin finish and slightly raised polished edges providing a unique depth that is stylish and handsome. It is made of solid 10k gold and is made in the USA.


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Jugoslawien nahm erstmals an den Olympischen Spielen 1920 teil. Zuvor traten viele Athleten Jugoslawiens für Österreich-Ungarn an. Eine kleine Mannschaft serbischer Athleten nahm an den Olympischen Sommerspielen 1912 teil.

Jugoslawien nahm unter drei verschiedenen Mannschaften teil:

 Königreich Jugoslawien (offiziell: Staat der Slowenen, Kroaten und Serben bis 1929) von 1920–1926
 SFRJ von 1948-Olympischen Winterspielen 1992
 Serbien und Montenegro (gegründet nach dem Zerfall von Jugoslawien) 1996–2002

Kroatien und Slowenien traten bei den Winterspielen 1992 erstmals als unabhängige Mannschaft an, Bosnien und Herzegowina bei den Sommerspielen 1992. Bei den Olympischen Sommerspielen 2008 waren alle ehemaligen Mitglieder Jugoslawiens vertreten, bis auf die ehemalige autonome Provinz Kosovo, welche ihr Debüt bei den Olympischen Sommerspielen 2016 gab.

Geschichte

Ausgetragene Spiele
Jugoslawien war lediglich einmal Gastgeber von Olympischen Spielen.

Medaillen
Ewiger Medaillenspiegel der Olympischen Spiele

Medaillen bei Sommerspielen

Die Bundesrepublik Jugoslawien gewann bei den olympischen Spielen 1996 und 2000, 2× Gold, 2× Silber und 3× Bronze und kommt so insgesamt auf 28× Gold, 31× Silber und 31× Bronze.

Medaillen bei Winterspielen

Weblinks

 Sportnet Bernard Jurišić: Tuđe nećemo - svoje ne damo (von Kroaten gewonnene Medaillen), 1. April 2008, abgerufen am 4. Mai 2017

Olympische Spiele (Jugoslawien)

redpajama_set_name: RedPajamaWikipedia


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Робърт Майкъл Уайт () (6 юли 1924 – 17 март 2010 г.) е американски тест пилот и генерал-майор от USAF. Участник в Програмата X-15.

Образование
Робърт Уайт завършва Нюйоркския университет през 1951 г. с бакалавърска степен по електроинженерство. През 1966 г. придобива магистърска степен по бизнес администрация от The George Washington University.

Военна кариера
Той постъпва на активна военна служба през ноември 1942 като курсант в United States Army Air Forces. През февруари 1944 г. завършва курса на обучение за бойни пилоти и е произведен в чин младши лейтенант. По време на Втората световна война служи в 355-а Бойна група на Европейския театър на военните действя. Извършва 52 бойни полета над германска територия на изтребител P-51 Mustang. През декември 1945 г. е върнат в САЩ, в авиобазата Мичел, близо до Ню Йорк. От следващата година започва да следва електроинженерство и преминава в резерва. След дипломирането си, отново се връща на активна служба. През февруари 1952 г. е назначен за командир на 40-а бойна ескадрила на USAF, базирана в авиобазата Джонсън, Япония. Взима участие в Корейската война, а след нея е изпратен в школата за експериментални тест пилоти Грифитс, Ню Йорк.

В Програмата Х – 15
Робърт Уайт е избран за космически полети в 1958 USAF Man In Space Soonest group. В тази селекция той заменя трагично загиналия Айвън Кинкелоу. На X-15 лети от 1960 г. През февруари 1961 г., Уайт поставя световен рекорд по скорост 2 275 мили в час (3660 км/час), след това в продължение на осем месеца става първия човек в света достигнал Mах 4 и Mах 5. На 9 ноември 1961 г. по време на Полет 45 той достига скорост от 4093 мили в час (6590 км/час), ставайки първия пилот в света достигнал Mах 6. На 17 юли 1962 г., майор Уайт по време на Полет 62 достига височина на полета 96 км, трето постижение в цялата програма и съобразно действащите нормативи му е присвоено званието "астронавт на USAF". През 2005 г. Робърт Уайт получава званието "астронавт" и почетния знак "астронавтски крила на НАСА", но неговия Полет 62 не е признат за космически полет.

Награди
  Кръст за заслуги на ВВС;
  Медал за отлична служба на ВВС;
  Сребърна звезда (с три дъбови листа);
  Легион за заслуги;
  Летателен кръст за изключителни заслуги (с четири дъбови листа);
  Бронзова звезда;
  Медал на ВВС (с шестнадесет дъбови листа);
  Награда за изключителни заслуги.

В Аерокосмическата зала на славата е приет през 1992 г.

Източници

 Thompson, Milton O. (1992) At The Edge Of Space: The X-15 Flight Program, Smithsonian Institution Press, Washington and London. ISBN 1-56098-107-5

Външни препратки
 Air Force biography
 Personal website of MGEN Robert M. 'Bob' White
 NASA Images: Major Robert M. White is seen here next to the X-15 aircraft after a research flight
 First Flight Society: Major Robert M. White
 Veteran Tributes biography: Robert M. White
 "A Place called the Doumer Bridge", AIR FORCE Magazine, February 1988

Американски генерали
Американски летци-изпитатели


Its recent strength notwithstanding, gold isn't a great hedge against an escalation of geopolitical tensions, writes MarketWatch columnist Mark Hulbert.
Hulbert compiled a list of the most momentous geopolitical events of the 1980s and 1990s. During these 18 crises, gold bullion fell 11 times—or 61% of the time. Its average return across all 18 was a loss of 1.8%.
"About the only consolation a gold investor can draw from these results is that gold didn't perform as poorly as the Dow Jones Industrial Average which fell an average of 4.9% during those same crises," Hulbert writes.
This result echoes a National Bureau of Economic Research study several years ago. The researchers looked at big declines in the S&P 500, which would indicate some sort of trouble. They found that gold fell almost as often as it gained during the months of big S&P losses. Specifically, they found that gold fell during 47% of the months when the S&P experienced those declines, and rose 53% of the time.


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text:
Pauly, Louis W.
Browse by Discipline
Before entering the academy, Louis W. Pauly held management positions in the Royal Bank of Canada and served on the staff of the International Monetary Fund. He is currently the J. Stefan Distinguished Professor of Political Economy in the Department of Political Science and the Munk School of Global Affairs and Public Policy at the University of Toronto. With Emanuel Adler, from 2007 to 2012 he edited International Organization, the top-ranked journal in the fields of international relations and international political economy. He is a Fellow of the Royal Society of Canada and in 2015 received the Distinguished Scholar Award in International Political Economy from the International Studies Association. He has published many articles in the field's leading journals, and his books and edited volumes include Global Ordering: Institutions and Autonomy in a Changing World (UBC Press); Complex Sovereignty: Reconstituting Political Authority in the Twenty-First Century (University of Toronto Press); and Democracy beyond the State? The European Dilemma and the Emerging Global Order (University of Toronto Press).
Current position(s), Institution
Professor of Political Economy, Department of Political Science, University of Toronto
Economic and Monetary Union in Europe
Publications related to European/EU Studies
Pauly, L. (2020). EU Fiscal Policy Coordination in Hard Times: Free Riders on the Storm. By Charlotte Rommerskirchen. Oxford: Oxford University Press, 2019. 240p.
Open to media contact
University of Toronto, Centre for International Studies
munkschool.utoronto.ca/pauly/
Other important publications
Pauly, L. W. (2019). Opening Financial Markets. Ithaca: Cornell University Press
Pauly, L. (2020) "Financial Openness and the Challenge of Global Governance," in Global Political Economy, Sixth Edition, edited by John Ravenhill, Oxford: Oxford University Press, pp. 222-246.
Deibert, R. J., & Pauly, L. W. (2019). Mutual entanglement and complex sovereignty in cyberspace. Data Politics, 81-99.
Earnest, D. C., Pauly, L. W., Rosenau, J. N., Lawton, T. C., & Verdun, A. C. (2018). Reflections: Blurring the Boundaries and Shaping the Agenda. In Strange Power: Shaping the Parameters of International Relations and International Political Economy (pp. 431-442). Routledge.
Education and professional achievements
Ph.D. Cornell University, Department of Government, 1987.
M.A. Cornell University, Department of Government, 1984.
M.Sc. The London School of Economics and Political Science,
Department of International Relations, 1977 (awarded with a mark of distinction; with course work at the School of Oriental and African Studies).
M.A. Fordham University, Department of Economics, 1975.
B.A. Fordham University, Department of Philosophy and Department of Economics, 1974 (awarded with honors).
International Political Economy, undergraduate and graduate levels
Fluent spoken languages
Fluent written languages


text:
Japan's INPEX pursues giant CCS hub as part of clean energy future in Australia
By Damon Evans
Carbon capture and storage (CCS) will form a key plank in INPEX's (TYO:1605) efforts to progressively decarbonise its Ichthys liquefied natural gas (LNG) operations in Australia's Northern Territory. It will also help Japan's biggest energy company establish the foundations for the next generation of clean fuels.
Shell's troubled Prelude LNG project restarts again in Australia
By Energy Voice
The first liquefied natural gas (LNG) tanker to berth at Shell's (LON:SHEL) Prelude floating LNG (FLNG) project off Western Australia since it was shut down after a fire has started loading, Refinitiv data shows.
Inpex targets ramping up LNG output in tight market
By News Wires
Inpex, Japan's biggest oil and natural gas explorer, plans to accelerate its expansion of production and sales of liquefied natural gas (LNG) as it expects the LNG market will remain tight in the mid-term.
Japan's Inpex expands Indonesia geothermal footprint
Japan's Inpex has announced that it has joined the Rajabasa geothermal project in Indonesia's Lampung province in the southeast area of Sumatra island.
Norway dishes out dozens of oil and gas licences
Norway has handed out nearly 50 oil and gas exploration licences in a "gratifying" display of interest in the sector.
Japan taps Oman, US for LNG supplies
Japanese companies have struck a number of LNG deals, as the government pushes to lock in future energy supplies.
Pertamina starts negotiations with Shell to buy Masela stake in Indonesia
Indonesia's state-backed energy company Pertamina has started official negotiations with Shell (LON:SHEL) to acquire the Anglo-Dutch supermajor's 35% share of the undeveloped Abadi LNG project in the Masela Block offshore Indonesia.
Inpex gives investment nod for Japan's first clean hydrogen and ammonia CCUS project
Inpex has taken a final investment decision for Japan's first demonstration project that will produce clean hydrogen and ammonia in association with carbon capture utilisation and storage (CCUS).
Petronas and ExxonMobil show interest in Shell's Masela LNG divestment
Malaysia's Petronas is the latest company tipped to be interested in acquiring a stake in the proposed Abadi liquefied natural gas (LNG) project in the Masela Block offshore Indonesia that is led by Japan's Inpex (TYO:1605)
Adnoc Drilling claims longest well record
Adnoc Drilling has drilled a new world record for the longest well, at the Upper Zakum concession.
Inpex extends LNG supply talks for Masela in Indonesia, eyes hydrogen opportunities
Japan's Inpex and joint venture partner Shell have extended a memorandum of understanding (MOU) with Indonesian utility PLN concerning long-term liquefied natural gas (LNG) supply. They have also expanded the MOU to incorporate joint studies in hydrogen, as well as ammonia, and CCS in relation to the proposed Abadi LNG project at the Masela Block offshore Indonesia.
Santos' Barossa could face two year delay leaving Darwin LNG empty
The development of the Santos-led (ASX:STO) Barossa gas project offshore Australia that will backfill the Darwin liquefied natural gas (LNG) export plant could be delayed by up to two years after a Federal Court ordered the operator to stop drilling at the US$3.6 billion project on 21 September.
Smoke and mirrors in Indonesia as giant gas projects struggle
Indonesia has an ambitious target to almost double natural gas production from 6.5 billion cubic feet per day (cf/d) to 12 billion cf/d by 2030. Hitting that goal means giant undeveloped gas projects, such as Inpex's Masela and Chevron's IDD, must proceed rapidly.
Medco interested in acquiring stake in Inpex-led Masela as Shell seeks divestment
Indonesia's Medco Energi (IDX:MEDC) is open to the possibility of joining the Indonesian government consortium that is considering acquiring Shell's (LON:SHEL) 35% share in the Abadi liquefied natural gas (LNG) project in the Masela Block offshore Indonesia that is led by Japan's Inpex (TYO:1605).
Indonesia may form consortium to buy Shell's stake in Masela LNG project
Indonesia may form a consortium to buy Shell's (LON:SHEL) 35% equity in the proposed Abadi liquefied natural gas (LNG) project in the Masela Block offshore Indonesia that is led by Japan's Inpex (TYO:1605), the country's investment minister said Thursday.
Santos and Chevron win Australia CCS permits and commit $136m
Australia's Santos (ASX:STO) and US giant Chevron (NYSE:CVX) have committed to spending around A$200 million (US$136 million) to assess the geological potential for carbon capture and storage (CCS) projects offshore Australia after winning two greenhouse gas (GHG) acreage permits.
Australia officially awards offshore CCS acreage, more to come
Minister for Resources and Northern Australia, Madeleine King, said greenhouse gas (GHG) storage permits have been awarded to two areas offshore the Northern Territory and Western Australia. Three more permits are expected to be awarded later this year.
Inpex and TotalEnergies win acreage for key CCS hub offshore Australia
Japan's Inpex (TYO:1605) and partner TotalEnergies (LON:TTE) have won a key greenhouse gas storage (GHG) permit offshore Australia that could help a plan to bury emissions from liquefied natural gas (LNG) export projects in northern Australia.
$1.3bn price tag for CCS at Inpex and Shell's Masela project
The cost to add carbon capture and storage (CCS) to the proposed Abadi liquefied natural gas (LNG) project in the Masela Block offshore Indonesia that is owned by Japan's Inpex (TYO:1605) and Shell (LON:SHEL) is expected to cost over $1 billion.
Japan offers loan to Indonesia to buy Shell's Masela LNG stake
Japan has reportedly offered to give Indonesia a loan to buy Shell's (LON:SHEL) 35% equity in the proposed Abadi liquefied natural gas (LNG) project in the Masela Block offshore Indonesia that is led by Japan's Inpex (TYO:1605). The move is aimed at kickstarting the long delayed development.
Inpex repeats Abadi LNG start-up eyed in early 2030s
Japan's Inpex has reiterated that it is targeting start-up of the stalled Abadi LNG project in the Masela Block offshore Indonesia in the early 2030s.
Inpex seeks $975m compensation from Korean yard over Ichthys FPSO
Japan's Inpex (TYO:1605) has filed a claim for $975 million against South Korean yard Daewoo Shipbuilding & Marine Engineering (DSME) relating to the construction of a floating production storage & offloading (FPSO) vessel for its Ichthys LNG project in Australia.
Indonesia's Pertamina pushed to buy Shell's stake in Masela LNG project
The Indonesian government is directing national oil company Pertamina to buy Shell's (LON:SHEL) 35% equity in the proposed Abadi liquefied natural gas (LNG) project in the Masela Block offshore Indonesia that is led by Japan's Inpex (TYO:1605).
Japan's Inpex signs another carbon neutral LNG deal
Japan's Inpex and Japanese gas distributor Sakata Natural Gas have signed an agreement that will see Inpex supply carbon neutral liquefied natural gas (LNG) to Sakata.
Inpex to boost Ichthys LNG output and lead CCS hub
Japan's Inpex has signed a statement of commitment to a net zero emissions future with the government of Australia's Northern Territory, where the Ichthys liquefied natural gas (LNG) project's onshore gas liquefaction plant is located.


settings. In addition, if more than 10 percent of people are picking up their antiretroviral drugs after their previously dispensed antiretroviral drugs run out, this may indicate that an underlying programmatic problem that affects the quality of services provided (such as the cost of drugs or clinic appointments, transport, clinic hours or a combination of issues) should be addressed.
been associated with more rapid disease progression and death.
-the date antiretroviral therapy stopped after the baseline pick-up (that is , a recorded decision by the person receiving antiretroviral therapy or physician that no more antiretroviral drugs should be dispensed) if two antiretroviral pick-ups were not recorded after the baseline pick-up.


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A seventeenth century house and 9 acre garden, used as a college garden. It has terraces, a sunken garden, a walled garden and a range of demonstration beds.
The gardens exceed 10 acres and include a large collection of unusual trees, shrubs, herbaceous and ornamental borders. The Victorian Walled Garden has something for everyone and contains a variety of mixed borders, fruit, vegetables and flowers for cutting.
Kirkley Hall offers guided tours of the beautiful gardens, during which experienced staff will be on hand to answer your questions and offer practical tips and advice.
The garden tours are available for groups (max 40)and can be tailored to meet your needs.
The gardens are also used by Northumberland College's Horticulture students to enrich their learning experience.
Among the gardens is also the National Fagus collection, an array of beeches, which is unique to Kirkley. The only other person who has such a collection is Prince Charles!
Opening times All year. Monday to Friday. Open 10am to 5pm (10 am to 3pm October to March).


text:
Pancreatic Neuroendocrine Neoplasms (pNENs)
by Massimo Falconi
Massimo Falconi, Angela Maurizi, Stefano Partelli and Stefano Crippa
Ospedali Riuniti-Università Politecnica delle Marche, Ancona, Italy & Ospedale San Raffaele-Università Vita e Salute, Milan, Italy
m.falconi@univpm.it
Version 1.0, January 23, 2015
Falconi, Massimo. Maurizi, Angela. Partelli,Stefano. Crippa,Stefano. (2015). Pancreatic Neuroendocrine Neoplasms (pNENs).
Pancreapedia: Exocrine Pancreas Knowledge Base, DOI: 10.3998/panc.2015.4
Pancreatic Neuroendocrine Neoplasms (pNENs) 862.98 KB
Pancreatic neuroendocrine neoplasms (pNENs) are relatively rare lesions that have been increasing in incidence over the past few decades largely because of the diagnosis of pancreatic incidentalomas on cross-sectional imaging. Most of these tumors are nonfunctioning presenting with symptoms secondary to mass effect, metastatic disease or as incidental findings. Diagnostic work-up aims to assess the stage and the grade of the disease as these parameters represent the main driver for treatment choice. The treatment of pNENs varies from conservative management to extensive surgical resection. Different medical treatments have been recently validated in large randomized clinical trials.
According to a population–based study, malignant pancreatic neuroendocrine neoplasms (pNENs) account for approximately 1% of pancreatic cancers by prevalence (55). An estimated 40% to 91% of pNENs are non-functioning. The remainder exhibit clinically evident hormonal symptoms (32). In the last decade, three different classifications have been proposed by the World Health Organization (WHO) (45). In the last classification, pNENs are divided according to tumor grading that is still the most powerful predictor of survival in these tumors. Recent years have seen a dramatic increase in interest and effort in conducting large randomized trials in order to explore different treatments. In this chapter, we focus on the current status of clinical and pathological aspects of pNENs.
2. Epidemiology
pNENs are relatively rare as their incidence is below 1 case per 100,000 inhabitants representing approximately 8-10% of all pancreatic neoplasms (19). The reported incidence of pNENs is about 0.32 per 100,000 inhabitants per year, which is lower than the incidence of lung, ileal and rectal NET (i.e. 1.35, 0.67, 0.86 per 100,000 respectively) (55). In the largest and most recent series of pNENs, including gastroenteropancreatic, thoracic and unknown primary NEN, the age adjusted incidence has risen from 1.1 to 5.2 per 100,000 inhabitants per year over the years 1973-2004 (20). Several factors may have contributed to this rise, including the improvement in classification of NENs, the widespread use of endoscopy for cancer screening and of other sensitive imaging procedures such as endoscopy ultrasound (EUS) and computed tomography CT (50). As a direct consequence, the incidence of pNETs <2 cm in the United States has increased by 710% over the last 22 years (20).
3. Classification and staging
The WHO 2010 classification (7, 45) distinguishes between well- or moderately-differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas (NEC) of small or large cell type. This classification is mainly constructed on a grading scheme based on mitotic count or Ki67 index. pNENs are then classified into three categories: NET-G1 (with a mitotic count < 2 per 10 high-power fields (HPF) and/or < 2% Ki67 index), NET-G2 (with a mitotic count 2–20 per 10 HPF and/or 3–20% Ki67 index) and NEC-G3 (with a mitotic count > 20 per 10 HPF and/or > 20% Ki67 index) (Table 1).
The grading requires mitotic count in at least 50 HPFs (1 HPF = 2mm) and Ki67 index using the Dako MIB-1 antibody as a percentage of 500-2000 cells counted in areas of strongest nuclear labeling ("hot spots") (Figure 1). If grade differs for mitotic count compared with Ki67 index, it is suggested that the higher grade must be assumed (45).
The tumor-node-metastasis (TNM) system, proposed by the European Neuroendocrine Tumor Society (ENETS), is based on the evaluation of the following parameters: size, extra pancreatic invasion, lymph-node and liver metastasis. In this classification, pT1tumors are < 2 cm, pT2 are between 2 cm and 4 cm and pT3 are > 4cm (44). In 2009 an additional TNM staging classification for pNET was suggested in the seventh edition of the AJCC/UICC TNM classification (47). The AJCC/UICC and ENETS classifications differ in the definitions of the T stages although a cut-off of 2 cm to distinguish pT1 from pT2 is used in both. On the contrary, the AJCC/UICC system requires recognition of peripancreatic soft tissue invasion in order to distinguish pT2 from pT3 whereas the ENETS classification based this distinction on tumor size using a cut-off of 4 cm. (Table 2).
Figure 1. Non-functioning pNET: well-differentiated solid tumor cell nests with immunostaining for Ki67 (Ki-67: 6%)
A large retrospective multi-institutional study that included 1072 patients affected by pNENs demonstrated that the ENETS TNM staging system is superior to the AJCC/UICC 2010 TNM staging system (43).
4. Pathology
pNENs are usually solitary and solid masses with rounded borders. The most common pNEN is rich in small vessels and has little fibrotic stroma. Evident features of malignancy after macroscopic examination include involvement of perivisceral fat, invasion of duodenal wall or adjacent organs (2). Microscopically, the majority of pNENs are well-differentiated tumors, which grow as solid nests or arranged on trabecular patterns (Figure 2).
Figure 2. Example of the most common form of a pNEN, a well differentiated tumor.Architectural patterns included nesting and micro trabecular, with numerous small vessels. Nuclear features show the coarsely clumped, "salt and pepper" chromatin pattern
Glandular, acinar and cribriform features are also observed. A rich vascularization is typical. Immunohistochemistry is used to differentiate a pNEN from other neoplasms using antibodies to at least one general endocrine marker such as synaptophysin or chromogranin A (CgA). pNEN may express normally produced pancreatic hormones (i.e. insulin, glucagon, somatostatin, pancreatic polypeptide), hormones of ectopic origin (i.e. gastrin, vasoactive intestinal polypeptide, adrenocorticotrophic hormone) and bioamines (i.e. serotonin).
Clinical suspect of PNEN should be considered in one of the following conditions:
presence of a clinical endocrine syndrome, which pushes the patient to seek medical care. In this case, diagnosis is considered "early" and allows the identification of the endocrine neoplasm when it is still small;
presence of clinical symptoms related to the growth of the neoplasm or to the presence of pain related to retroperitoneal infiltration. Those cases usually involve a non-functioning pNEN (NF-pNEN) and do not lead to early symptoms, also they are diagnosed by symptoms caused by the increase in tumoral mass;
incidental diagnosis of a pancreatic mass, which is the most common way these lesions are diagnosed.
If patients have symptoms, the most common presenting symptoms are abdominal pain (35-78%), weight loss (20-35%), anorexia and nausea (45%). Less frequent signs are intra-abdominal haemorrhage (4-20%), jaundice (17-50%), or a palpable mass (7-40%) (10, 11, 27, 29, 54).
There are generally two types of laboratory analyses. First, measurement of specific hormones in the case of functioning-pNEN, which include glucagon, somatostatin, serotonin, gastrin, insulin, etc. in baseline conditions and after stimulation using respective clinical-laboratory tests (12, 48). Secondly, dosage of generic neuroendocrine markers such as chromogranin A (CgA) and neuron-specific enolase (NSE). The former is a glycoprotein localized inside secretory vesicles of endocrine cells as well as neuronal cells of the central and peripheral nervous system. It is the most important generic neuroendocrine marker with sensitivity between 60-90% (39). Nevertheless, plasma levels of CgA can be falsely positive in the presence of altered renal function, atrophic chronic gastritis, and during therapy with proton pump inhibitors. The latter (NSE) is found at the cytoplasmic level in endocrine cells and neurons (37).
Radiological examinations such as abdominal computed tomography (CT) and ultrasound, especially with contrast medium, are able to localize the neoplasm and obtain complete preoperative assessment in about 60% of cases (46). Hyper vascularization of endocrine tumors, present in 60-70% of patients (30, 35), can be observed by both CT (Figure 3) and ultrasound with contrast medium, and can localize the lesion and provide other information regarding its nature. Recently, there has been a dramatic technical improvement in MRI assessment of pancreatic disease using diffusion-weighted imaging (DWI) (14). DWI has been used for years in brain MRI but it has only recently been extended to abdominal imaging. Recent reports have suggested that high b-value DWI may be helpful in the detection and characterization of pancreatic tumors (25, 28).
Figure 3. CT scan demonstrating a hypervascularized lesion of the pancreatic tail associated with multiple liver metastase
It has been reported that a reduced apparent diffusion coefficient (ADC) is observed in most malignant lesions related to the histopathological features of the tumor (33). Endoscopic ultrasound (EUS) can be useful when it is difficult to localize the neoplasm as well as other techniques such as venous sampling during angiography. As EUS offers excellent visualization of the pancreas from the duodenum or stomach and can produce high-resolution images of the pancreas. It has been considered one of the most accurate methods for the detection of a pancreatic focal lesion, especially in patients with small tumors of 3 cm or less, but is operator dependant (41, 53). EUS also has the unique ability to obtain specimens for histopathological diagnosis using EUS-guided fine-needle tissue acquisition (EUS-FNTA). Ki-67 determination can be assessed in the 87% of patients with a concordance of 83% with postoperative Ki-67 (22).
The presence of prominent molecular biomarkers makes pNENs attractive for functional imaging with PET and SPECT. Over the past few years the gold standard for functional imaging of pNENs has been somatostatin receptor scintigraphy (SRS) with 111In-diethylenetriaminepentaacetic acid octreotide (6). More recently the introduction of 68Ga-DOTA-peptide PET/CT has significantly improved the diagnostic work-up in the evaluation of pNENs (3) (Figure 4). In comparison to scintigraphy, positron emission tomography (PET) has a 2- to 3-fold higher spatial resolution (3–6 vs. 10–15 mm) and facilities quantification of tracer uptake.
Figure 4. 68Gallium PET/CT of a pNET with liver metastases
Several different DOTA-peptides (DOTATOC, DOTANOC, and DOTATATE) have been used in the clinical setting for both pNENs diagnosis and peptide receptor radionuclide therapy (PRRT). The major difference among these compounds relies on a slightly different affinity to somatostatin receptor subtypes (3). The sensitivity and specificity of 68Ga PET/CT in detecting NET is 93 and 91%, respectively (49). Moreover, this technique provides relevant information for pNET patients' clinical management (3). 18F-FDG PET/CT is of value for tumors with a high proliferation index (pNEC), whereas the diagnostic sensitivity seems to be low for pNETs with a low proliferation index, slow growth rate, and low glucose consumption (6). Usually, 18F-FDG PET/CT had a sensitivity of 92% for tumors with a proliferation index of above 15% (6). Dual tracer
PET/CT can be performed on a single day owing to the short half-life of 68Ga and can be superior to histopathology by demonstrating tumor heterogeneity especially for patients with multiple metastases (18).
6. Treatment
Incidental diagnosis of pancreatic NENs is associated with a significantly better survival after curative resection, compared to patients with symptoms (9). Moreover, Bettini et al. (4) demonstrated that patients with an incidental diagnosis associated with a tumor size < 2 cm, had a 5-year overall survival of 100% with a minimal risk of recurrence. On the basis of these experiences, the European Neuroendocrine Tumor Society (ENETS) guidelines now recommend a wait and see policy in selected patients with asymptomatic sporadic pancreatic NENs, when the possibility of surgical cure has to be weighed against the operative morbidity, mortality and long-term complications associated with pancreatic surgery (15). Preliminary reports have demonstrated the safety of this conservative approach (9, 17, 24). On the other hand, surgery still represents the treatment of choice for pancreatic NENs > 2 cm and/or for symptomatic forms. Pancreatic resections differ according to tumor site: lesions of the pancreatic head are treated with a pancreaticoduodenectomy while lesions of the body and tail with a distal pancreatectomy. Role of lymphadenectomy for patients with a pancreatic NEN is still unclear (40). Lymph node metastases occur only in the 30% of patients affected by these tumors (40) but the association between node metastases and poorer survival is still debated (5). Laparoscopic procedures play an important role in the treatment of pancreatic endocrine tumors. It was demonstrated that laparoscopic distal pancreatectomy and enucleation are safe and feasible in patients with pancreatic endocrine tumors (16). Whenever a resection leaves no residual disease, an aggressive approach, including liver resection, is recommended. The conditions that have to be assessed preoperatively are (23) the absence of extra-abdominal disease, (30) the presence of a low proliferative index (Ki67), and (34) the existence of somatostatin receptors in order to deliver radiolabelled therapies, as they have been effective after cytoreductive surgery (15). The type of hepatic resection depends on the number of liver metastases, site and hepatic reserve itself. It can range from simple enucleation to segmental resection or to hepatectomy. In those patients with bilobar metastases or more than 75% of liver involvement, radical surgery can be rarely performed. In this light, medical, ablative and embolizing techniques can be provided in order to allow radical resection. There are valid palliative options in patients with pancreatic NETs with liver metastases which are not candidates for surgical resection. These mainly include trans arterial embolization (TAE), trans arterial chemo-embolization (TACE) and radiofrequency ablation (RFA). Such procedures can be used as loco-regional ablative therapy per se or as an adjunct to palliative surgery. Liver transplantation may be an option in a patient without extrahepatic metastases, and low proliferation rate when all other therapeutic options have failed (15).
Anti-tumoral treatments
A number of potential therapeutic targets have been identified and investigated for treating advanced pNENs. Recently, three large randomized clinical trials have been published (Table 3).
The mTOR pathway
The mammalian target of rapamycin (mTOR) is a serine-threonine kinase that stimulated cell growth, proliferation, and angiogenesis. Autocrine activation of the mTOR signaling pathway mediated through insulin-like growth factor 1, has been implicated in the proliferation of pancreatic neuroendocrine tumor cells. Consistently with this observation is the finding that inhibition of mTOR has a significant antiproliferative effect on PNET (56).
RADIANT-3 compared the efficacy of daily everolimus 10 mg versus placebo in 410 patients with advanced low- or intermediate-grade PNET (56). Everolimus significantly increased median PFS (progression-free survival) by 6.4 months compared with placebo (11 vs. 4.6 months, respectively; HR 0.35; 95% CI 0.27-0.45, p<0.001).
VEGF pathway
Vascular endothelial growth factor (VEGF) is a key driver of angiogenesis in PNET. Tissue from pancreatic neuroendocrine tumors shows widespread expression of platelet-derived growth factor receptors (PDGFRs) α and β, stem-cell factor receptor (c-kit), and VEGF receptor (VEGFR)-2 and VEGFR-3 (42). Sunitinib malate inhibits these kinases. In a phase III, double-blind, placebo-controlled trial, sunitinib was compared with placebo in patients with advanced, well-differentiated PNET (42). Patients in the sunitinib group (37.5 mg/d) had a median PFS of 11.4 months compared with 5.5 months for the placebo group (HR 0.42; 95% CI 0.26-0.66; np<0.001).
Somatostatin Receptor Pathway
Somatostatin is a hormone that targets transmembrane G-protein-coupled somatostatin receptors. There are 5 known types of somatostatin receptors (SST1, SST2, SST3, SST4, and SST5). The use of somatostatin analogues (SSAs) in the treatment of patients with neuroendocrine neoplasms is a well-established practice (38). SSAs include octreotide/octreotide LAR, Lanreotide, and Pasireotide. Lanreotide was compared with placebo in a recent randomized, double-blind, multinational study (8). This study included neuroendocrine tumors originating in the pancreas, midgut, or hindgut or of unknown origin. Lanreotide, as compared with placebo, was associated with significantly prolonged PFS (HR 0.47; 95% CI 0.30-0.73, P<0.001). Nevertheless, therapeutic effect in the subgroup of PNET was not demonstrated (HR 0.58; 95% CI 0.32-1.04) (8). Peptide receptor radionuclide therapy (PRRT) is a new modality that uses radiolabelled peptides for treating unresectable or metastasized NENs. The rationale for such therapy is to convey radioactivity inside the tumor cells, where the sensitive targets, such as DNA, can be hit as a result of internalization of the somatostatin receptor and radiolabelled analogue complex (21). However, the exact role of this treatment in the management of NET remains to be defined. One trial comparing PRRT with high-dose SSA therapy has been launched (1).
Chemotherapy is recommended in PNET-G2 when other treatments failed and in PNEC-G3 (15). Most important regimens include the combination of streptozotocin (STZ) + doxorubicin or 5-fluorouracil (5-FU), cisplatin + etoposide and dacarbazine (13). The main indication for the use of cisplatin+etoposide is treatment of poorly differentiated neuroendocrine tumors. The combination has been reported to produce objective response in about 50% of anaplastic or poorly differentiated neuroendocrine tumors (31).
7. Functioning PNET
Insulinomas are the most common functional pNETs with an incidence of 4 cases in one million people per year. Insulinoma should be suspected in the presence of Whipple's triad (symptoms or signs consistent with hypoglycemia; glucose level <50 mg/dL; relief of symptoms after administration of glucose). Insulinomas usually appear as small neoplasms, and are smaller than 1 cm in about 85% of cases (51); in 10-20% of cases they cannot be localized. In the majority of cases, however, ultrasound with contrast medium, abdominal CT and EUS are sufficient to localize the neoplasm. Surgery is the treatment of choice for localized lesions. A laparotomy is preferable because it allows meticulous manual exploration of the pancreas (36).
Gastrinomas are the second most frequent functioning endocrine tumor of the pancreatic area. Gastrinomas are malignant in 60-90% of cases and have a very aggressive behaviour in about 25% of cases. Similar to other functioning endocrine neoplasms, a gastrinoma is suspected when patients exhibit clinical symptoms, known as Zollinger-Ellison syndrome. The diagnosis is confirmed based on laboratory tests of acid secretion and gastrin levels before and after secretin stimulation. Gastrinomas are generally malignant tumors and are often associated with unrecognized nodal metastases (52). A pancreaticoduodenectomy is the treatment of choice (26).
PNENs are rare neoplasms of the pancreas with a disease course considerably different from pancreatic ductal adenocarcinoma. Aggressive and extensive surgery may be an option for some patients suffering from locally advanced and even metastatic disease. In select cases this may involve resection of multiple organs to achieve a significant reduction of the tumor mass. The multidisciplinary approach is always mandatory in the management of these lesions. Since most pNENs exhibit indolent behavior, both the preservation of quality of life of the patient and the personalization of the therapy according to tumor's and patient's features are needed.
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text:
Their status for this Saturday's 7 p.m. game at No. 2-ranked Clemson (10-0, 7-0) remains uncertain.
Duke also saw reserve defensive tackle Ben Frye suffer a torn ACL in practice last week. Reserve linebacker Koby Quansah is limited as he plays on a foot he broke in practice on Oct. 10.
Duke has seen 15 players with starting experience miss at least one game this season, including defensive players Giles-Harris, Quansah, Carter II, Gilbert, Singleton, Cerenord, linebacker Ben Humphreys, safeties Jeremy McDuffie and Jordan Hayes and defensive end Drew Jordan.
"This just kind of continues," Duke coach David Cutcliffe said. "We've got a lot of fight left in us. Somebody is going to step up. I believe that in my heart. I couldn't be more proud of players and staff and everybody that's involved with Duke."
Injured starters
Fight and pride might not be enough this week. Duke hasn't played a team ranked in the top two spots of the Associated Press poll since 2013, when the Blue Devils lost 45-7 to top-ranked and eventual national champion Florida State in the ACC championship game.
Duke last played a top-10 team in 2016, a 24-14 loss at No. 7 Louisville.
The Blue Devils head to Clemson's Death Valley after almost as many reserves played on defense as starters in the second half against UNC.
With Giles-Harris, Duke's leading tackler, out after spraining his MCL against Miami on Nov. 3, sophomore Brandon Hill got his first start and recorded a team-best 10 tackles.
Singleton entered the game Duke's second-leading tackler. He was injured in the first half, meaning Hayes took over. Hayes had played in only four games previously this season, taking part in 47 snaps.
He played well enough, recording five tackles with a tackle for loss, that Cutcliffe awarded him a game ball.
"We just stuck together and played as a team," Hayes said. "We did our 1/11th, knowing that at the end of the day we can all do this together."
Safety Lummie Young had played in 91 snaps over seven games before playing the entire second half against the Tar Heels.
Senior Jeremy McDuffie, a third-team all-ACC player last season, has missed two entire games and been limited in the seven games he has played after suffering a torn ACL last November.
McDuffie started against UNC in place of redshirt freshman Leonard Johnson. But it was Johnson who returned to play the second half.
Redshirt freshman Josh Blackwell played cornerback when Carter was injured. He recorded a key tackle during UNC's final possession in the last 53 seconds, keeping Tar Heels receiver Anthony Ratliff-Williams in bounds to keep the clock running.
Redshirt junior cornerback Brandon Feamster moved up the depth chart due to Gilbert's September injury. He batted away UNC's final desperation pass into the end zone as time expired.
Clemson looms
"It's been tough to endure all the of the change and all of the people out," Cutcliffe said. "I hate it for players, particularly those who are facing surgeries and all the rehab associated with it. But this will ultimately help our program. As I look at depth charts for 2019, it's just going to be a lot of people on those depth charts who have played a lot of football. That's never a bad thing."
There are more immediate challenges with two regular-season games before a bowl game.
Clemson looms large on the horizon.
"It's going to be a great opportunity," Cutcliffe said on Sunday. "Certainly a big challenge. They basically have steamrolled a lot of good football teams. We'll dive into this to prepare. We'll dive into this schematically. We've got to prepare exceptionally well. I think our team will embrace that."
Duke safety Brandon Feamster (30) and cornerback Antone Williams (35) celebrate in the second quarter. Duke defeated UNC 42-35 at Wallace Wade Stadium In Durham, N.C., Saturday, Nov. 10, 2018 Chuck Liddy cliddy@newsobserver.com
USBA owner hopes for full house in Raleigh
Luke Kuechly still runs Panthers defense, but what about the linebackers around him?
By Brendan Marks
Pro Bowl linebacker Luke Kuechly of the Carolina Panthers will have a somewhat different role as the team uses more 3-4 defensive schemes. Kuechly and Shaq Thompson will need other linebackers to step up.
Ron Francis, forced out by the Hurricanes in 2018, is heading back to the NHL
SC Pro-Am releases roster, schedule. AJ Lawson, PJ Dozier highlight field
What to make of South Carolina's quirky early bowl projections
Dabo, Clemson preparing for different type of challenge in 2019
Coastal Division preview: Is it Virginia's turn?


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Raipur: Chhattisgarh Chief Minister Raman Singh says there is no anti-incumbency against his government despite being in power for over 14 years and that the ruling BJP is poised for a fourth successive victory in Assembly polls later this year.
"The BJP is in power since December 2003 and there is still no anti-incumbency. I have travelled widely to urban pockets and rural belts this year during various public interaction programmes and clearly saw in people's eyes that they wish to see the BJP regime to continue," Raman Singh, the longest-serving BJP Chief Minister, told IANS in an interview.
"Everyone, even the opposition Congress, knows in the state that anti-incumbency is nonexistent. People had some grievances in certain areas against local officials, not against the state government. The government has reached out to these people through public interaction drives such as Lok Suraj Abhiyan, Gram Suraj Abhiyan and Vikas Yatra.
"It's people's desire in Chhattisgarh that the BJP deserves a fourth successive term. It speaks volumes about the development works and the kind of governance I have delivered in the state," the ayurvedic doctor-turned-politician said.
Raman Singh predicted 65-plus seats for the Bharatiya Janata Party (BJP) in the 90-member Assembly in the upcoming polls in the mineral-rich state.
"The state has witnessed a sea change during the BJP regime. You will find a network of quality roads in all 27 districts. Schools and hospitals have been opened even in forested areas," the 66-year-old politician said.
He revealed that his government would be launching the world's largest free mobile smart phones distribution scheme in a month to women and college going students under Sanchar Kranti Yojana (SKY).
Chhattisgarh has a history of bipolar contest between the BJP and the Congress. In the last Assembly polls held in 2013, the BJP won 49 seats while the Congress bagged 39. The Bahujan Samaj Party (BSP) and an independent got one seat each.
But the vote percentage difference between the BJP and the Congress was less than one per cent and the overall vote difference was just 92,000 in the entire state.
Chhattisgarh is now set to witness triangular contests this year as the state's first Chief Minister Ajit Jogi has deserted the Congress and floated his own outfit to nurture his dream of becoming the H.D. Kumaraswamy of Chhattisgarh if there is a hung verdict.
Raman Singh acknowledged that there would a three-way fight in the state on certain seats in 2018 and the third player's entry into the electoral fray could spice up poll battle.
Political analysts say that the wheelchair-bound Jogi has developed some closeness with the BJP in recent months as he has a pathological hatred for Chhattisgarh Congress President and potential Congress Chief Ministerial candidate Bhupesh Baghel.
The Jogi-led Janta Congress Chhattisgarh (JCC) is said to have the capability to walk away with considerable percentage of traditional Congress votes in at least 20-22 Assembly segments.
Some analysts say he could away with 5 to 6 per cent of all votes, primarily that of the Congress. Knowing his abilities, BSP leader Mayawati has opened talks with him. But the BSP is also being wooed by the Congress which is desperate to end the BJP innings.


1. You and your group members decided upon and set up a still life using the supplies provided for you in the classroom. You must have chose at least 6 different items, looking for a variety of sizes and textures.
2. A viewfinder was made and a section of the still life was chosen from the view of your assigned seat. You chose your view by looking through the hole in the viewfinder and drawing what you saw through that space.
4. Your drawing was done in a thoughtful manner and you took your time, seeing the different sizes and placements of the objects in your still life. The scale and proportion in your drawing was relative to the scale and proportion in the actual still life. You shaded your drawing using the 10 values on the gray scale. You also drew in the shadows on/around your objects.
5. Your still life drawing was done neatly and considerately, and you used your time wisely. Your paper was kept clean and neat with no eraser marks showing.


text:
CAMK4 () – білок, який кодується однойменним геном, розташованим у людей на короткому плечі 5-ї хромосоми.  Довжина поліпептидного ланцюга білка становить 473 амінокислот, а молекулярна маса — 51 926.

Кодований геном білок за функціями належить до трансфераз, кіназ, серин/треонінових протеїнкіназ, фосфопротеїнів.
Задіяний у таких біологічних процесах як адаптивний імунітет, імунітет, запальна відповідь, поліморфізм.
Білок має сайт для зв'язування з АТФ, нуклеотидами, молекулою кальмодуліну, іоном кальцію.
Локалізований у цитоплазмі, ядрі.

Література

Примітки

Див. також
 Хромосома 5

Протеїнкінази


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