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There are around 15,000 CrossFit gyms in more than 120 countries worldwide. Approximately 7,000 of them are affiliate gyms.
- 1 How many CrossFit boxes are there?
- 2 How many CrossFit gyms are there around the world?
- 3 How many CrossFit gyms are there in the world in 2020?
- 4 How big is the CrossFit market?
- 5 Why are CrossFit boxes so expensive?
- 6 How many CrossFit affiliates are there 2021?
- 7 Is CrossFit losing popularity?
- 8 How many CrossFit gyms are there in the UK?
- 9 Is CrossFit still popular 2021?
- 10 How much do CrossFit athletes make 2020?
- 11 How many gyms did CrossFit lose?
- 12 How much is CrossFit worth 2020?
- 13 How popular is CrossFit now?
- 14 How much revenue does CrossFit generate?
How many CrossFit boxes are there?
CrossFit has 13,000 gyms in more than 120 countries. That’s more than the 12,521 Starbucks locations in the United States. Its direct rival, Planet Fitness, has just 1,124 locations. Over the years, CrossFit has been described as a fitness cult, something that its CEO and founder, Greg Glassman, laughs at now.
How many CrossFit gyms are there around the world?
Global CrossFit Statistics There are more than 15,000 CrossFit affiliate gyms around the world, according to CrossFit.
How many CrossFit gyms are there in the world in 2020?
Glassman then began to develop a curriculum to train and certify coaches and gym owners using his methodology. There were 13 gyms by 2005, and in 2016 there were more than 13,000. By 2020, there were approximately 15,000 CrossFit affiliates around the world.
How big is the CrossFit market?
Today, there are over 12,000+ CrossFit boxes worldwide and the brand generates some $4 billion in annual revenue with Glassman as sole owner of the company (Ozanian, 2015).
Why are CrossFit boxes so expensive?
#2- CrossFit Owners pay more for space per member and more for training and other maintenance costs. Also, more square foot per person is required to do CrossFit and as a result, our commercial rent per member is much higher than the traditional gyms or non-CrossFitgyms.
How many CrossFit affiliates are there 2021?
Today, with over 15,000 affiliates worldwide, we see ourselves as part of a larger war between the methods, outcomes, and principles of big-box franchisors such as the Gold’s, Bally’s, and 24-Hour Fitnesses versus those of our small-box facilities.
Is CrossFit losing popularity?
In less than a year (the last Open was in February), CrossFit has lost more than a third of its participants. In money terms, that’s a loss of over 2.5 million in revenue for CrossFit Inc. Open registrations peaked in 2018 when 415,000+ athletes participated. So, what’s driving the decline in participation?
How many CrossFit gyms are there in the UK?
At the time of writing, there are currently over 500 CrossFit affiliates in the UK, almost 3000 in larger Europe and approximately 13,000 worldwide.
Is CrossFit still popular 2021?
CrossFit hasn’t released the official numbers yet, but from our calculations, it looks like total registrations for 2021 are 245,914. While participation is slightly higher than last year’s, you’d still have to go back to 2015 (209,585) to find worse numbers.
How much do CrossFit athletes make 2020?
Individual. The marquee events at the CrossFit Games are the men’s and women’s individual competitions. The first place prize for each paid out $300,000 in 2020, with that amount set to increase to $310,000 in 2021.
How many gyms did CrossFit lose?
Around 500 gyms around the world have announced that they are dropping their CrossFit affiliation in the last three days, in response to a racist tweet from CrossFit CEO Greg Glassman.
How much is CrossFit worth 2020?
The value of the Crossfit business, which is based on a branded exercise regimen focused on high intensity workouts, has previously been estimated at about $4bn (£3.1bn). It is affiliated with about 13,000 gyms in 158 countries worldwide.
How popular is CrossFit now?
So is CrossFit still popular? Yes, CrossFit is still very popular with approximately 13,000 affiliated gyms remaining worldwide.
How much revenue does CrossFit generate?
There are now 11,000 CrossFit gyms, or “boxes” worldwide, up 22-fold from nine years ago. Its adherents have turned CrossFit into a cult whose brand generates some $4 billion in annual revenue and CrossFit, Inc.


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Russia and China are in discussions about stepping up cooperation between the two countries in the film area, a Russian official stated.
“Currently, we are in talks about joint production of movies with our Chinese partners, about sales of Russian TV series to China, as well as adaptation rights and film exhibition issues,” Alexei Volin, Russia’s deputy communication minister, was quoted as saying by the Russian news agency RIA Novosti.
One of the main obstacles for Russian films’ exhibition in China are restrictions on foreign releases that are in place there.
According to Volin, the two countries are currently negotiating quotas for Russian films on top of other foreign releases, which would increase the number of Russian films released in China.
Two Russian features, Soulless 2 and Battle for Sevastopol, are to take part in Beijing International Film Festival this coming April, which Volin said was a sign of Russian films’ rising profile in China.
A special section is to be devoted to business contacts between China and Russia during the two countries’ business forum, scheduled to be held in Beijing on April 21-22.
The idea of closer cooperation between Russia and China in the area of film production was first discussed last year.
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Nicola Roberts has revealed that recording her solo album made her ill.
The Girls Aloud singer told The Sun that she put herself under a lot of pressure while recording Cinderella's Eyes.
She said: "I came down with a cold and was like, 'I'm making myself ill'. I've never felt stress like that."
Nicola added that she had no qualms about arguing with her producer over the sound of the tracks.
She said: "If a track's slightly changed it doesn't give me the same feeling. So when the producer's like, 'It's not changed, I haven't done that,' I'm like, 'You have. I don't feel the same as when I first heard it. So we either argue all day or you just admit you've changed it and change it back'."
The singer also said she didn't know if Girls Aloud would make another album.


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Tokyo, August 29, 2012 – Hitachi, Ltd. (TSE: 6501, “Hitachi”) today announced that Hitachi Rail Europe Ltd. has received an order for a prototype traffic management system from Network Rail Infrastructure Limited (“Network Rail”) in England, Scotland and Wales. Network Rail will test and evaluate prototypes ordered from Hitachi and two other companies, and based on the outcome, it will make a decision regarding the future roll-out of traffic management across the entire rail network in Great Britain.
Network Rail currently owns and manages railway infrastructure that includes railway stations and tracks throughout Britain, and controls railway operations from more than 800 signalling locations. Network Rail is planning to implement centralised management at 14 operating centres, including new centres scheduled to be built in the near future, and to introduce a new traffic management system as part of efforts to increase efficiency and reduce costs. This traffic management system, which is expected to be rolled out from 2014, will eventually cover all parts of Britain’s rail network. Network Rail has placed orders for prototype systems with three companies including Hitachi, and will use these prototypes to test and evaluate the systems’ performance and reliability.
Hitachi’s railway traffic management systems create railway operation plans that can be reconfigured flexibly in keeping with passenger demand, manage and control railway operations based on those plans, and support the rapid recovery of operations in the event of a delay or disruption. In Japan, these systems have been used on high-density commuter networks, as well as Shinkansen high speed lines and other main lines for over 30 years, and support the Japanese railway operation, which has gained a high reputation for its punctual and high-density operations. By providing traffic management systems, Hitachi will ensure reliable railway operations in Great Britain.
This is a remarkable achievement for Hitachi rail system business in the UK, following the successful introduction of the Class 395 high speed trains in 2009 and the Intercity Express Programme contract signed in July 2012. With this new order for railway system products, Hitachi will continue to strengthen its railway-related business on a global scale.
- End -

domain: economics


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How To Tell If Your Dog Loves You Quiz. 4 years ago by rachel mcvey ∙ 1 min read. 9 questions | by semraa0209 | last updated:
All dog owners are familiar with this scene. Anticipate when he is going to jump up and firmly say sit, rewarding him for doing so.
30 DIY Projects And Crafts For Dogs DIY Dog Hammock
Being a dog, it’s often difficult to. Cats get a bad rap for being standoffish and selfish, but any cat lover knows that they just have their own way of showing their love for us…right?
How To Tell If Your Dog Loves You Quiz
Even litters born at the same time can represent every color of the doggy rainbow!Give him a lengthy lecture on social etiquette.He wags his tail and eats whatever i
put down.Here are some ways you can tell if your pup is showing some love:
He’s happy and excited to see you.His/her favourite spot is right on my lap.If you could read his mind what would he say?If you have a pet and you can’t speak dogs language, you may not be sure how does your hairy friend feel about you.
If you know of any dog owners, be sure to share this quiz with them, so that they can find out more about their own pets as well.If you’re undecided about a new love interest, introduce.In the end you were escorted back home after you threatened to call the police since the people who attacked you were still out there, however, when you.Jul 8, 2020 | total attempts:
Jump on your dog to show him how it feels.Keep interesting toys in the yard to keep your dog busy when you’re not around.Last time you met the 4 boys, but it wasn’t a warm welcoming as they all wanted you out.Looks at me then eats like two bites.
My dog jumps up on the couch and cuddles with me.My dog sits or lays at my feet, unless i.My dog stays under the chair, which appears to be his/her favourite spot.Now, if your dog’s tail wags more to the right side of his rear, it just might be an even better sign he loves you.
Once you share your love for dogs with us, we will be able to tell you if your guardian is red like a setter or black like a lab.Pet him and push him down gently.Please 5 star if you like it!Signs your dog loves you.
Stacker put together a list of clues and answers about dog breeds using a.Take this quiz and tell me what you think about it!Take this quiz to find out how well bonded you and your dog are.Take this quiz to find out who that is!.
Teach your dog a few commands or tricks… take a training class with your dog and practice what you learn daily.That’s okay i like those treats too.These hairy, messy, goofy creatures have been at mankind’s side for tens of thousands of years, ever since they first shared the warmth of our fires on the prairies and savannas of old, and paid us for.They like nothing more than playing fetch and getting patted on the head by their favourite human (you).
They’re very patient though, and never snap or complain, even when you make them pose for silly pictures.They’re excited to see you.This quiz reveals the strength of your bond!This test is also suitable for cats.
Unless you’re a bond villain, or you had a bad experience with the neighbor’s angry guard dog, that is.Walk your dog at least twice daily… play with them using active toys (balls, flying disks) as often as possible.Well, fear no more, because this quiz will let you know if he really loves you or just something happens to fade away in time questions and answers remove excerptWhat is your true love’s name?
When you go and sit on the couch, what does your dog do?Whether you and your kitty are friends furever or you sometimes wonder if your cat just puts up with you to avoid starvation, this quiz will show you where you.While white dogs might work for some of you, others will need something more colorful to do the deed.Yell get down and throw him off you.
Yes, my dog definitely smiles at me.You can never tell if they like you or not.You open your front door to a.You run out of your dogs favorite treats.
You’re a big ball of fluff with a big smile.You’re also great at playing video games.You’re laid back and love a good movie.Your dog generally feels secure in its surroundings, but sometimes harsh training techniques may end up causing a display of aggression.
Your dog loves you!.but that doesn’t mean they don’t get annoyed with you sometimes.Your results suggest you’re loyal and fun to be around!

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Bill Summary & Status
102nd Congress (1991 - 1992)
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Latest Title: To amend title I of the Omnibus Crime Control and Safe Streets Act of 1968 to ensure an equitable and timely distribution of benefits to public safety officers.
Sponsor: Rep Manton, Thomas J. [NY-9] (introduced 8/12/1992) Cosponsors (27)
Latest Major Action: 10/25/1992 Became Public Law No: 102-520.
|All Information (except text)||Text of Legislation||CRS Summary||Major Congressional Actions
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Obama 'humbled' to visit jail cell and walk in footsteps of his hero Madiba
Barack Obama has spoken of how he and his family had been "deeply humbled" to stand in the cell where Nelson Mandela was held for 18 years as South Africa's most dangerous political prisoner.
The US president and his wife Michelle took daughters Sasha and Malia to the museum created from the former prison island off the coast of Cape Town for what he said he hoped would be "an experience they would never forget".
They were guided by Mr Mandela's close friend and former co-detainee, Ahmed Kathrada, through the bleak stone quarry where they and the 32 other anti-apartheid activists were forced to work before being taken in to Prisoner 46664's tiny cell.
Standing in the darkened room where Mr Mandela was kept hidden away from the world for so long, Mr Obama gazed through the barred window before picking up a small metal bowl he would have eaten from and looking down to the thin straw mat on the floor where he would have slept.
Afterwards, he and his wife wrote a tribute in the museum visitor's book to Mr Mandela, who now lies critically ill in a Pretoria hospital, and his fellow prisoners.
"On behalf of our family we're deeply humbled to stand where men of such courage faced down injustice and refused to yield," their entry read.
"The world is grateful for the heroes of Robben Island, who remind us that no shackles or cells can match the strength of the human spirit."
In a recreation yard paved with concrete and dotted with shrubs, the Obamas were shown where Mr Mandela buried pieces of the manuscript of his autobiography, 'Long Walk to Freedom'. The manuscript was eventually smuggled out of Robben Island by Mac Maharaj, another jailed political activist who now serves as President Jacob Zuma's spokesman, delivering updates to the nation about the fading health of his old friend Mr Mandela.
There have been no updates on Mr Mandela's condition since Mr Zuma said he remained "critical but stable" during a joint press conference with Mr Obama on Saturday morning. He is now entering his fourth week in the hospital where he was rushed early on Saturday June 8, suffering from a recurring lung infection.
Embarking on the main speech of his long-awaited Africa tour at the University of Cape Town later, Mr Obama said he had visited Robben Island before when he was a senator but his latest visit held far more resonance.
"There was something different about bringing my children, Malia is now 15, Sasha is 12," he said.
"Seeing them stand within the walls that once surrounded Nelson Mandela, I knew this was an experience they would never forget, that they now appreciated a little bit more the sacrifices Madiba and his contemporaries made for freedom.
"Mandela's spirit could never be imprisoned because his legacy is here for all to see . . . (he) shows us that one man's courage can move the world."
As the Obamas toured Robben Island, it was noted on Twitter that it was "ironic" the US president should lament the cruelty of that institution while America's own prison island, Guantanamo Bay – which he pledged to close before his election – remains functional.
As Mr Obama visited a HIV centre later, the point was made more forcefully by Archbishop Desmond Tutu. "We pray you will be known as having brought peace to all the regions where there has been strife and peace and no need for Guantanamo Bay," the former Archbishop of Cape Town told him.
He said the arrival on the continent of Mr Obama, who moves on to Tanzania today, held a "special joy" for him.
"When you became the first black incumbent of the White House you don't know what you did for our psyche," he said. "My wife sat in front of a TV with tears running down her face . . . So welcome home, even if you're about to go." (© Daily Telegraph, London)


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Want to know How to pass PMP without reading PMBOK guide? Many aspirants find it difficult and boring to read the PMBOK Guide.
It might be true because PMBOK guide concepts are somewhat hard to understand. That doesn’t mean you can’t understand it at all. It is a guide to Project Management, which defines many concepts about project management processes and techniques. As it is introduced by PMI, which is the authority behind PMP so this makes it more logical to study PMBOK guide.
What Is the PMBOK Guide?
PMBOK (A guide to the project management body of knowledge). This is the PMP exam guide which aspirants generally used during their preparation. PMBOK Guide explains every concept of project management. It tells about the project management techniques in a systematic way. And clear every concept to the deep. Generally, it is advisable to read the PMBOK guide atleast once during your PMP exam preparation.
PMBOK explains the 10 knowledge areas of the project management they are:-
- Integration Management
- Scope Management
- Time Management
- Cost Management
- Quality Management
- Human Resources Management
- Communications Management
- Risk Management
- Procurement Management
- Stakeholder Management
Each knowledge area is explained in detail. Tools and techniques used in project management. PMBOK guide evolves with time. It’s the latest edition is the 6th edition. Although the knowledge areas and process groups are still the same. It changes some concepts and some updates are also there in the 6th edition from the 5th edition. In 6th edition, some tools and techniques are grouped together based on their purpose. To reduce the number of tools and techniques.
The new groups are:-
- Data Analysis
- Data Gathering
- Decision Making
- Interpersonal & Team Skills
Can You Pass PMP Without Reading The PMBOK Guide?
Many aspirants find it difficult to read the PMBOK guide. There are many other handbooks available in the market for PMP exam preparation. Some of them are mentioning here which are widely used and are very famous Andy Crowe, Headfirst and Rita, Cornelius Fichtner, Christopher Scordo. Choose any of the handbooks which you like for your PMP exam preparation.
All of them are recommendable to read during your preparation. And it is advisable also while during your preparation use two reference books so to make the concepts more clear. Also, do practice with the practice exams available online. This will helps you in your preparation a lot. Boost your confidence and give you the fell of the real exam before going for the main exam.
If you have time in your preparation do read PMBOK guide also as it covers all the concepts which are explained in all these handbooks. It is not necessary that you need to read the PMBOK guide cover by cover. You can read it with your handbook chapter by chapter. This makes you understand the concepts very well. And helps you in solving the questions in the exam quickly.
If you want to be fully prepared for your PMP exam it is advisable to read PMBOK guide also. Yes, definitely you can use other handbooks. But with them reading PMBOK guide is a plus. It is introduced by PMI so it has a systematic approach to every project management techniques. Rather than other handbooks which somewhere and somehow depicts the author’s perspective.
So decide your plan of study and go for it. All the best with your preparation.
Over To You
What is your point of view is it necessary to read PMBOK guide or not? Does it really help in your preparation? Let us know in the comment section.


Allentown High School opened up its field hockey season in dominant fashion with a 6-0 victory over Hamilton High School West.
That home game on Sept. 7 featured a hat trick by Allentown’s Mary Bellotti and two-assist games for both Sierra Wojcik, and Brielle Uher, who also scored a goal. MacKenzie Hultberg and Alex Pritchard both found the back of the net once as well.
Goalkeeper Katie White only had to make one save for the shutout.
The rout was not surprising for Allentown. Last year, the Lady Redbirds won the Valley Division of the Colonial Valley Conference (CVC) with a 12-5 record and made it to the semifinals in the NJSIAA Central Jersey, Group 3 tournament. The team also made it to the Mercer County Tournament semifinals.
The Redbirds hoped to eclipse their success from last year, and that triumph against division rival Hamilton West was a great start to the 2017 campaign.
Allentown’s second game of the season was a memorable one as well, albeit it in a much tougher match.
In Allentown, the Redbirds were locked in a battle with Shore Regional High School on Sept. 9.
Fourth-year Shore Regional coach Kelly Koenig was matched up against Allentown coaching legend Mary Ellen McCarthy, who returned to the sidelines this year after retiring in 2014. Allentown coach Dana Wells is on maternity leave this year.
In a tightly contested bout, the Blue Devils were able to come away with a narrow 1-0 victory. Shore Regional forward Talia Cantaffa scored off a corner from midfielder Abby Kopec. White made 20 saves in the losing effort in goal for Allentown.
For Allentown, the loss dropped the Redbirds to 1-1 on the young season. McCarthy’s expectations remained the same, even after the loss.
“The goal is always to improve on what you did last year,” McCarthy said. “They made it to the [semifinals] last year, so we want to be able to compete for the division again, Mercy County Tournament championship and then make it far into the Central Jersey tournament. They won the Mercer County Tournament in 2014, so they want to win that again. We want to win the Central Jersey tournament, so if they can make it to the final, that’s a successful season.”
The Redbirds will continue to try to build on the highs and lows of last week’s games as the season rolls on. Allentown is still a favorite to win the Valley Division.
Allentown’s next two games are on the road. It faces Steinert High School on Sept. 15 at 4 p.m. and Toms River High School North the following day at 10 a.m.


The 2022 version of the Michelin Information will launch on Tuesday, with organisers vowing to have fun the range of French cooking and the business’s resilience after two difficult years brought on by the Covid-19 pandemic. The yearly rankings are hotly anticipated by cooks and gourmets, and this 12 months the well-known red book is
The 2022 version of the Michelin Information will launch on Tuesday, with organisers vowing to have fun the range of French cooking and the business’s resilience after two difficult years brought on by the Covid-19 pandemic.
The yearly rankings are hotly anticipated by cooks and gourmets, and this 12 months the well-known red book is being unveiled in Cognac in southwest France, the primary time in its 122-year historical past that the ceremony has taken place exterior of Paris.
“However it’ll additionally make room for a brand new era of cooks who’ve taken the chance of embarking on this journey despite the difficult context,” he stated.
“Regardless of the disaster, the occupation has proven nice resilience. It was a possibility for professionals to reinvent themselves, to go additional, and that is what we need to help.”
Final 12 months’s ceremony, within the midst of a months-long shutdown brought on by the pandemic, was a low-key affair with just one chef – Alexandre Mazzia – promoted to 3 stars, the very best distinction.
Whereas Poullennec stated the judges’ standards remained the identical, there was an elevated deal with extra minimalist, sustainably sourced eating places which have come to dominate the meals scene.
Suicides and lawsuits
Controversies have lengthy swirled across the guidebook and the strain it locations on cooks.
A handful of French restaurateurs have relinquished their Michelin standing due to the stress of being judged by its inspectors, together with Joël Robuchon (1996), Alain Senderens (2005), Olivier Roellinger (2008) and Sébastien Bras (2017).
The 2003 suicide of chef Bernard Loiseau was linked, amongst different causes, to hints that his restaurant was about to lose its three stars.
Star Swiss chef Benoît Violier took his life in 2016, a day forward of the discharge of the Michelin Information, though his restaurant maintained its three-star score.
A 12 months earlier, Marc Veyrat became the first to sue the guidebook, after shedding the third star for his Alps restaurant La Maison des Bois only a 12 months after it was awarded.
He lost the case and stated he by no means once more desires to see a Michelin inspector in his eating places.
However Poullennec stated demotions have been important if the guidebook was to “stay related to prospects”.
Total, nonetheless, the French meals scene is again in wonderful type. After a protracted interval throughout which French eating places have been accused of rising stale and lazy, the previous 15 years have seen an inflow of younger cooks who’re extra open to world influences and new approaches, stated Paris-based meals author Lindsey Tramuta.
The Michelin Information has typically struggled to maintain up, she added.
“When you might have one thing as structured as Michelin, it is vitally difficult to include all of the issues which can be occurring within the meals scene – issues which can be high-calibre, however perhaps aren’t as formal,” she stated, including that feminine cooks remained poorly represented.
“However Michelin remains to be essential for cooks and house owners. If it motivates their kitchen employees and group, and brings extra diners and curiosity, then it has worth.”
From motorist support to wonderful eating standard-bearer
The crimson information was created in 1900 by tyre producers André and Édouard Michelin as a journey support for motorists that included maps, directions on the right way to change tyres, and lists of mechanics and resorts alongside the route. The primary run of 35,000 copies was so successful that guides for Belgium, Germany, Portugal and Spain adopted.
Michelin started together with restaurant listings in 1920, when it additionally began charging for the publication. The corporate additionally started dispatching undercover inspectors and beginning in the early Thirties launched its well-known star rankings.
Michelin says it points its stars based mostly on the standard of the elements used; mastery of flavour and cooking methods; the persona of the chef in his delicacies; worth for cash; and consistency between visits.
One star signifies “Excessive-quality cooking, value a cease”; two stars is for “Glorious cooking, value a detour” and the coveted three stars are reserved just for “Distinctive delicacies, value a particular journey”.
Of about 20,000 worldwide eating places listed, solely round 130 have attained this highest distinction.
The information now has editions throughout Europe, Asia, and North and South America. In 2005, the Michelin Information branched out of Europe with a New York information adopted by editions for San Francisco, Las Vegas and Los Angeles in 2007.
It moved to Asia with a Tokyo model in 2008 when 90,000 copies, in English and Japanese, flew off the cabinets in 48 hours.
Michelin revealed its first Shanghai information in 2016 and at the moment there are variations for a number of Asian cities.
Having lengthy been criticised as biased in the direction of formal eating, the information in 2016 awarded a star to a Singapore road meals outlet identified for a braised rooster dish.
A famed Tokyo sushi restaurant, the place former US president Barack Obama is claimed to have loved the most effective sushi of his life, was dropped in 2019 after it stopped accepting reservations from most of the people.
Michelin introduced in March that it was suspending operations in Russia as a result of struggle in Ukraine, only a few months after launching its first guide in Moscow.
(FRANCE 24 with AFP)


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HBO’s hit series Game of Thrones caused an uproar last week with a scene which wasn’t in the books, and one episode later, it still seems to have the internet divided.
(Warning: Spoilers up to episode 7 The Gift follow. Also, all views contained within are mine and not representative of any other Geek Crusade writers/the site as a whole. Just in case you wanna yell at someone.)
Sansa Stark (Sophie Turner), once bethrothed to Joffrey Baratheon (Jack Gleeson) and then married to Tyrion Lannister (Peter Dinklage), found herself saying her vows with the next person the viewers can’t wait to send their regards to, the recently unbastardised Ramsay Bolton (Iwan Rheon).
What happened after, when Ramsay forced himself on Sansa while making Theon Greyjoy (Alfie Allen) watch, led to an outcry on the interwebs.
Many (including US senator Claire McCaskill) said they would stop watching the show because of that scene, so they wouldn’t have stuck around to see that things haven’t got better this week.
Ok, I'm done Game of Thrones.Water Garden, stupid.Gratuitous rape scene disgusting and unacceptable.It was a rocky ride that just ended.
— Claire McCaskill (@clairecmc) May 19, 2015
Sansa has been confined to her room, abused and bruised, her only “friend” in Winterfell flayed after Theon once again failed to be a decent human being (why is anyone surprised, though).
Her situation is clearly horrific, and anyone who says otherwise has issues (and needs help).
But this is where I start to disagree with some of what’s being said online. Some publications such as The Mary Sue, which decided that it would not be “actively promoting” Game of Thrones after that scene last week. (As opposed to inactively promoting?)
First of all, let’s just look at the scene alone. There’s no nudity in the scene, but we know Sansa is in pain. The close ups of her face and Theon’s clearly convey the message that the show wanted to deliver, without being overly sexualised. I think that hardly qualifies as “gratuitous”.
For comparison, recall Daenerys Targaryen’s (Emilia Clarke) wedding night with future Aquaman Khal Drogo (Jason Momoa), full frontal nudity and all.
Of course, one could argue Emilia Clarke was a lot older than Sophie Turner is now. However, there was this episode’s prison scene in Dorne with Bronn and Tyene Sand, played by Rosabell Laurenti Sellers, who is 19 like future Jean Grey (and that was a pointless sexualised scene *cue Jessica Henwick’s Nymeria Sand rolling her eyes*).
If we’re looking past non-wedding night sexual abuse, there’s that scene where Ros (Esmé Bianco) is forced to beat another prostitute on Joffrey’s orders, or the Night’s Watch mutineers abusing Craster’s wives
And for violence against women, the examples are many – Ros’ death at hands of Joffrey and a pregnant Talisa Stark (Oona Chaplin) stabbed repeatedly in her stomach at the Red Wedding are some of the more horrific ones that come to mind.
Why then, among all the scenes I’ve listed above, has Sansa’s been the one to generate so much outrage that it made George RR Martin feel he had to issue a response on Livejournal?
While Sansa hasn’t had such a fate in the books, it did befall a character named Jeyne Poole, who was wed to Ramsay under the guise of Arya Stark. So the moment the show’s producers decided that Sansa would be going to Winterfell and marrying Ramsay, it seemed predictable that she would follow Jeyne’s storyline.
I can understand people getting upset about the books not staying to source material (though we were warned about it), but to get upset about such scenes being in a medieval fantasy show in the first place?
Some people argue that the scene does nothing to show that Ramsay is evil incarnate, or that Sansa is in trouble. I agree.
But, to me, the scene wasn’t pointless, and it wasn’t supposed to be all about Ramsay or Sansa. The major development belonged to the character the episode ended with – Theon Greyjoy, forced to tears as he perhaps considers what he has become (albeit all for naught at the moment as the next episode proved).
If anything, such scenes are conversation starters. Let’s not pretend we live in a perfectly civilised world where none of this happens.
In Singapore, for example, marital rape isn’t considered an offence unless under certain conditions, such as divorce proceedings having started or the couple agreeing to separation and living apart. And that’s after the law was amended from a previous one where there weren’t these exceptions.
And in Britain, fewer than half of the top universities recorded sexual violence against their students, meaning that many victims don’t get a proper investigation and the figures released to the public are sorely inaccurate.
Also, if we’re going to demand that shows sanitise themselves, should we be telling Game of Thrones to stop with the beheading because it offends some of us?
I’ll tell you what offends me, that real people in the real world are executed (and sometimes unjustly) in this day and age by beheading. I’m not just talking about ISIS, by the way. Saudi Arabia’s looking for prospective Ilyn Payne wannabes.
The Sansa scene in Game of Thrones serves as a reminder of how uncomfortable we feel when faced with such situations. We’re meant to see the scene through Theon’s eyes, himself a victim of Sansa’s abuser.
We’re meant to feel uncomfortable. We’re meant to feel helpless. We’re meant to sympathise with Sansa and wish we could jump into the TV screen and throttle Ramsay or stab him with the nearest pointy object (I have to give credit to how good an actor Iwan Rheon is to make me want to do that).
We’re meant to hope against all odds that Brienne of Tarth (Gwendoline Christie) bursts through the door in Chrome Trooper garb and cleaves Ramsay in half.
Instead of trying to demand that fictional shows not use such plots, we should be channelling that rage and demanding that more be done for victims of sexual abuse, male and female alike, in our societies, whether in the form of legislature or otherwise.
The media’s attention span is severely short in this day and age, and when pop culture offers an opportunity for such conversations to be raised among a wider audience, we should do more than “this is offensive, get it off my screen”.
It’s not as if such incidents in real life will go away once they’re out of our TV shows. They won’t. It’s not out of sight, out of mind.
Let’s be honest, Ramsay will get his just deserts, sooner or later, and justice will be served, and the interwebs will rejoice. After all, there is a precedent.
Those who didn’t read the books may have thought Game of Thrones’ most-hated character for three seasons running, Joffrey, “had to survive”. But like Tyrion reminds us: “He ain’t in the credits for season five.”
Numerous victims of sexual abuse in the real world may not, and as things stand, will not, be as fortunate to get justice for themselves.
And if that’s not enough to get my point across… we live in a world where Fifty Shades of Grey is a best-selling book and movie series. At least Game of Thrones is set in Westeros and in a different time period.

domain: entertainment


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“When did we get this chicken? you yell at your roommate or partner as you squat deep in front of the fridge. You look over your shoulder, tilt your head, wait for an answer and hear nothing. You hold the container of cooked chicken up to the light, looking at all four corners, before bringing it back to your heart center, opening the lid, and sniffing it. It doesn’t necessarily smell bad, but something is wrong.
“Is it safe to eat this for lunch?” you ask yourself, hoping to avoid having to cook something new on an already busy workday. “What if I shred it and toss it with mayonnaise and celery for a quick chicken salad? Is that okay? What if I shred it and cook it in chicken broth with vegetables and noodles with eggs for a quick soup?”
As you ponder life’s most pressing question – how long does cooked chicken actually last in the fridge? – let’s take a deeper look at the facts.
According to the Food and Drug Administration (FDA), cooked chicken, whether in its whole form (such as roast chicken) or in pieces, such as chicken breast or thighs, will last three to four days in the refrigerator, or four at six months in the freezer; the longest is if you freeze a chicken dish like chicken soup or coq au vin, rather than chicken pieces. After this time, it’s safe to say that the chicken has probably gone bad and bacteria may begin to grow.
Besides the weather, here are some obvious signs that it is no longer safe to eat cooked chicken: if it has a slimy texture, an obvious pungent odor, or if you remember the chicken was kept in the fridge for longer of a week.
This is a question that our own community has discussed at length:
Community member LeBec F. recommends “keeping meats, fish, and poultry in the back left corner of your refrigerator. [It] has a remarkable impact on extending their shelf life, both before and after cooking.” The back of your refrigerator is always the coldest and safest place for meat, dairy and products; this way, the products will be located farther from the airflow caused by the opening and closing of the refrigerator door. Community member Chef Ono says, “Every time you wear a dish at pasteurization temperature, the clock is reset”, which means that if you prepare a new batch of chicken broth three days after you precook chicken, you gain a few extra days of consumption.
And so you never have to ask yourself the question “When did we have this for dinner? Tuesday? Wednesday?” make a habit of labeling all your food containers. Simply write the item and cook date on a strip of painter’s tape or duct tape and stick it to the container like an industry professional to protect you and your loved ones from food poisoning.

domain: food


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Lahaina film ‘My Partner’ to screen at Lahainaluna High School, March 28
Lahainaluna High School will hold a free public screening of “My Partner” on Thursday, March 28 at the Lahainaluna Sue D. Cooley Football Stadium. Gates open at 6:30 p.m., with the screening to begin promptly at 7 p.m.
Set in Lahaina, “My Partner” is Hawaiʻi’s first Boys’ Love drama and follows the story of two Lahainaluna high school senior boys whose separate worlds collide in a journey of self-awakening.
Admission is free by registration and is required through GoFan: https://shorturl.at/duHQ5. Concessions will be available. No drugs, alcohol or tobacco are allowed on campus.
“My Partner” has screened around the world earning numerous film festival awards such as the Audience Award at the LA Asian Pacific Film Festival, Grand Jury Award at the Honolulu Rainbow Film Festival, Best Foreign Film at the Mpumalanga (South Africa) International Film Festival and the Lily Tomlin Memorial Award for Best Comedy at the San Antonio QFest International Film Festival.
Directed by Native Hawaiian visual storyteller Keliʻi Grace and written by Maui’s Lance D. Collins, the film focuses on the lives of Edmar (Jayron Munoz), a high achieving Filipino student, and Pili (Kaipo Dudoit), a Native Hawaiian student athlete stand-out, as their seemingly separate worlds enter into a collision course when they are assigned to work on a class project together despite coming from rival friend groups.
“My Partner” was shot in Lahaina and is believed to be the last production to film Lahaina town before the destructive Aug. 8 fire. The film has a PG rating from the Philippine MTRCB.

domain: artistic


Jorge Ballesteros is an electronic music and techno/minimal producer from Spain. His professional career stared as a songwriter and music adapter in 1987, when he began to work at ibymusic with his father D. Ignacio Ballesteros Diaz, an international recognized songwriter and music adapter.
Playing in clubs all around the world like Pacha in Spain, Italy and the Dominican Republic, Jorge Ballesteros is definitely not new to the electronic dance music scene. Helping artists like Italian pop star Laura Pausini, An international hit who topped the charts in Italy, the Netherlands and Belgium, and has sold more than 70 million records in her career. Jorge has also worked with Negramaro, Nek, and latin pop star Alejandro Sanz; who has won fifteen Latin Grammy Awards, and three Grammy Awards.
INTO THE NIGHT Vol.2; The night is like another dimension of life full of fascinating stories: In this album is 16 tracks, some complex, some simple, some dark, and some bright, and others are simply weird!
Introducing: INTO THE NIGHT Vol.2 the second volume of a collection with exclusives tracks from e-tracks records, specially selected to soundtrack your night and the stories your about to experience by yourself. Just let the music play!


For most people, the ultra-expensive gold Apple Watch, retailing for $10,000 (£8,000) and upwards, is an unobtainable dream. But if you’re the son of China’s richest man, it’s no big deal to buy two. For your dog.
A wealthy man has come forward to claim a luxury boat that has been floating in a Swedish harbour for at least two years, after he apparently forgot all about it.
The boat’s Norwegian owner says he intended to sell the vessel in 2012 – and was under the impression that he had, Expressen GT newspaper reports. The boat, said to be worth as much as $108,000 (£65,000), was moored in the Swedish town of Stromstad, close to Norway’s southern border. The keys were tied to the railings for all to see.


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What does a catering server do?
A banquet server is a member of a wait staff that serves food for catered events. Banquet servers set the table and buffets for service. During service, banquet servers take food and drink orders at tables, replenish buffet food, refill beverages, and help facilitate a smooth service.
What are the duties and responsibilities of a waitress?
Waiter/waitress duties and responsibilities
Some of their common daily duties include: Taking orders from customers. Answering questions about menu items, food sensitivities and food substitutions. Giving customers suggestions for food and drinks and telling them about any special menu items.
What are the responsibilities of a restaurant server?
Restaurant Server duties and responsibilities
- Welcoming and sitting diners comfortably in the dining section.
- Taking customers’ food and drink orders.
- Collaborating with the kitchen and bar staff for prompt and correct delivery of orders.
What skills do you need to be a caterer?
What Makes a Good Caterer?
- Cooking. At its most basic level, catering is all about food. …
- Food safety. …
- Customer Service. …
- Flexibility & Creativity. …
- Leadership. …
- Motivation. …
- Financial planning. …
- Business Management.
Do catering servers get tips?
Banquet servers often earn tips. A service fee or gratuity may also be included on the bill and may either get distributed to the staff or factored into the hourly wage of a banquet server. … According to Pascal, banquet servers can earn between $0.34 and $19.88 per hour in tips.
What are the qualities of a waitress?
Top Qualities of a Great Restaurant Waiter!
- Appearance: Waiters are the face of a restaurant. …
- Punctuality: …
- Cordial & Hospitable: …
- Profound knowledge of menu: …
- Inspect the item before serving: …
- Observant & attentive: …
- Quick post meal service: …
- Tip accepting manners:
What are the skills of a waitress?
Skills to include on waiter/waitress resume include:
- Point-of-sale systems.
- Food safety.
- Alcoholic beverage regulation.
- Effective communication.
- Active listening.
- Positive language.
- Problem solving.
How do you put waitressing on a resume?
Focus on Your Skill Sets
- Exceptional, personalized customer service.
- Attention to detail.
- Dispute resolution.
- Interpersonal communication.
- Multilingual (if applicable)
What are four duties a server may do?
What Are the Duties of a Server?
- Make guests feel welcome and accommodated.
- Take orders from guests and input them into the point of sale.
- Make menu recommendations to guests.
- List ingredients or common allergens for guests from memory.
- Sell menu specials or limited time offers.
What skills does a server need?
Soft Skills for a Server Resume
- Customer service.
- Physical stamina.
- Neat appearance.
- Memory for patrons and their orders.
- Conflict resolution.
What do you do as a server?
21 server tips and tricks
- Write “thank you” on your guest’s checks. …
- Speak to your guests, learn their preferences and suggest drinks, appetizers, entrees and desserts. …
- Always stay positive and approach guests with a smile.
- Offer recommendations to guests based on their preferences and your experiences.
How do you describe catering on a resume?
A caterer is a person who provides food and beverages to a group at a remote location, including tables, equipment, and providing service. A catering resume must show the event director that you have the food handling skills, customer service attitude, and physical stamina to do the job right.
How can I be a good catering manager?
Here are the ten keys to manage catering staff at large events:
- Prioritize Training.
- Get to Know Your Staff.
- Prepare Your Rush Strategy.
- Improve Your Customer Service Experience.
- Model Behavior in Your Leadership.
- Give Rewards Early and Often.
- Have a Comprehensive Back-Up Plan.
- Use Top-Notch Scheduling Tools.


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Mixing & Mastering Engineers, Producers & Songwriters who worked with Alberta Ferretti
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Hi, I am an Audio Engineer from Portugal. My expertise is Mixing and Mastering and I would love to help you with your tracks! I specialize in Classical Music and Jazz, but also love to mix and master all styles of music !!
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"Easy to work with, polite, and caught the vision of my record. This is the second engineer that I could say, knows what he is doing. God willing I will be sending him more records to mix and master for future projects."
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"Music has to be mixed and mastered by a professional engineer. Sefi Carmel should be your engineer of choice, no matter what your genre is. He took extra good care of my song "When A Man Loves Another" Listen for y..."
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"Very impressed with the level of professionalism and the priority on turning out great results that guarantee client satisfaction. Very pleasant to work with, friendly and attentive! Would certainly work with Alex Mor..."


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Plant extracts can be used as the raw materials of feed additives, deodorants, and natural antibiotics for dogs, cats, pigs, cattle, broilers, horses and aquatic animals. Like human foods, plant extracts are widely believed (or proven) to have benefits for animal health, such as immunity enhancement, brightening and softening the fur, improved the health of mouth&tooth, joint & bone & muscle, digestive and urinary system protection, fecal odor removing, weight & muscle gain, etc.
Plant extracts used in animal nutrition include yucca, rosemary, parsley, nettle, chamomile, marigold, thyme, dandelion, chlorophylla, green tea, turmeric, etc. Yucca extract is rich in the steroid yucca saponin, which is an excellent natural intestinal cleaner and surfactant to reduce volatile nitrogen compounds in the intestinal tract and remove fecal odor.
Rainbow® biotech serves animal producers and animal feed manufacturers operating in the poultry, pork pig, ruminants, and aquaculture sectors. Our all-natural ingredients allow them to develop more nutritional products and maintain the health of the animals and increase the quality of such end products as meat, milk, or eggs and reduce feed costs.


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SorafenibR HCC cells display improved viability, enhanced migration and reduced apoptosis after transient sorafenib treatment
To gain insights into the mechanisms of sorafenib resistance, we initially modeled the response of HCCHep3bandHuh7cells tosorafenibby continuously culturing them with a step-wise increase of drug dosages for 8 weeks. The final concentration ofsorafenibwas 2 µM, which exerted sufficient inhibitory action and was in the range of clinically achievable levels.23,24 To characterize these sorafenib-selected cells, we first measured the proliferation of parental and resistant (sorafenibR) cells upon transient exposure to 2 µM sorafenib. Although all parental controls displayed significant decreases of cell proliferation, thesorafenibR cells did not show obvious difference in cell proliferate (Fig. 1a and Fig. S1a), upon exposure to sorafenib. This was further confirmed by the enhanced wound-healing capability insorafenibR versus parental Hep3bandHuh7cells (Fig. 1b and Fig. S1b). Second, flow cytometry analysis revealed that transient sorafenib treatment does not have obvious alterations in cell apoptosis and cell viability insorafenibR Hep3b and Huh7 cells, but significantly promotes cell apoptosis and impairs cell viability in parental controls (Fig. 1c and 1d). We did not see obvious changes in cell cycles in both parental andsorafenibR Hep3b and Huh7 cells when exposed to 2 µM sorafenib (Fig. S1c). Third, we observed that,as compared with parentalcells,the oncosphere formationis enhancedinsorafenibR with less affected by sorafenib treatment (Fig. 1e; Fig. S1d), and resistant cells exhibit a higher rate of cell proliferation in drug free medium (Fig. 1f; Fig. S1e). These findings are in line with our previous data showing that lung cancercells resistant to tyrosine kinase inhibitors (i.e., midostaurin)migrate andgrow at a faster pace than parental cellsin vitro, and possess higher tumorigenic potential in vivo.9
As sorafenib discontinuation is a frequent event in HCC patients, we mimicked sorafenib “holiday”by culturingsorafenibR cells in drug-free medium for 14 days (released cells). Interestingly, the released cells displayed proliferation impairment, which is supported by a reduction of cell proliferation, and increase of cell apoptosis in the presence of sorafenib, when compared with parental and sorafenibR cells(Fig. 1g; Fig. S1f). These results indicate that partial re-acquisition of sensitivity to sorafenib leads to a transient proliferation arrest upon drug withdrawal, phenocopying the drug holiday effect seen in the clinic. This is consistent with our recent findings in leukemia that resistance to TKIs (i.e., nilotinib, imatinib) displays reversible features or a transient proliferation arrest upon exposure to the same drug.21 Finally, we performed sequencing for epigenetic regulators, for example, DNMT3a and TET2 that are frequently mutated in cancers, insorafenibR Hep3b and Huh7cells. We did not find any acquired mutations in these genes. Taken together, these results suggest that non-genetic mechanisms could be essential in sorafenib resistance, and although generated in vitro, our drug-resistant HCC cell line derivatives faithfully recapitulate clinical drug resistance.
HCC cells with sorafenib-acquired resistance have activation of pathways involved in DNA methylation
To identify critical molecules that promote sorafenib resistance, first we examined the expression of DNA methyltransferases (DNMTs) in parental and sorafenibR Hep3b and Huh7cells, because epigenetic aberration (i.e., DNA hypermethylation) is becoming increasingly important in the development of TKI resistance.9,21 The results from qPCR and Western blotting disclosed that expression of DNMT3a and DNMT3b, two de novo DNA methyltransferases,7 is increased at both RNA and protein levels, but expression of DNMT1, a maintenance DNMT,25 as well as HDAC2 and HDAC3, histone protein modifiers, is not obviously changed (Fig. 2a and 2b). As DNA methylation is installed by DNMTs via adding a methyl group to C-5 position of cytosine residues yielding 5-methylcytosine (5mC), we proceeded to determine whether 5mC amount is changed in sorafenibR cells. The DNA dotblotting by anti-5mC antibody10,26 revealed that 5mC production is significantly elevated in sorafenibR Hep3b and Huh7cells compared with parental counterparts (Fig. 2c and 2d). These results extend previous findings showing that 5mC amount is markedly increased in leukemia cells resistant to nilotinib10 and in lung cancer cells resistant tomidostaurin.9
It has been shown thatthe TET methylcytosine dioxygenases catalyze the conversion of 5mC to 5hmC, resulting in DNA demethylation.8,27-29 To further understand the role of DNA methylation in sorafenib resistance, we performed qPCR and Western blot for changes of TETs, and found that expression of TET1, TET2 and TET3 is significantly upregulated at both RNA and protein levels insorafenibR compared with parental cells (Fig. 2e and 2f). Dotblotting analysis using anti-5hmC antibody revealed that 5hmC level is much higher insorafenibR Hep3b and Huh7 cells than that in parental counterparts (Fig. 2g and 2h), in agreement with the methylcytosine dioxygenase activities of TET1, TET2 and TET3. Collectively, these findings suggest that long-term exposure to sorafenib alters the functions of DNA methylation machinery in HCC cells.
Knockdown of DNMT3a and TET2 impairs sorafenibR HCC cell growth
Having demonstrated the upregulation of DNMT3a, a de novo DNA methyltransferase,7 in sorafenibR HCC cells, next we sought to determine the biological functions of DNMT3a aberrations. SorafenibR Hep3b and Huh7 cells were infected with DNMT3a shRNA or scrambled vectors for 24 hours and further selected by 2 µM puromycin for additional 96 hours. First, the efficacy of virus infection was verified by the high rate of GFP/fluorescent cells (Fig. S2a). The shRNA-3, which showed the most DNMT3a reduction, was used for further investigations. As shown in Fig. 3a and 3b, both RNA and protein expression of DNMT3a was markedly decreased in DNMT3a shRNA compared with control group. The specificity of DNMT3a knockdown was supported by the unchanged expression of DNMT1, DNMT3b and TET2 in DNMT3a shRNA versus control cells. Second, the results from dotblotting showed that 5mC production is much lower in DNMT3a-depleted cells than that in control groups (Fig. 3c and 3d). Interestingly, DNMT3a knockdown led to a decrease of 5hmC abundance even when TET2 protein levels are not changed. This may result from the reduction of 5mC amount, the original substrate of TET2. Third, these DNMT3a depleted cells were subjected to proliferation and wound-healing assays. We observed that cells with DNMT3a knockdown could proliferate and migrate at a much lower rate, in a time-dependent manner, than that in control counterparts (Fig. 3e and 3f; Fig. S2a and Fig. S2b). These findings support an important contribution of DNMT3a to sorafenibR cell growth.
Having shown that TET2 is upregulated in sorafenibR compared with parental cells, next we sought to examine whether TET2 expression is essential for sorafenibR cell growth. To this end, sorafenibR Hep3b and Huh7 cells were infected with TET2 shRNA or control vectors for 24 hours followed by puromycin selection for additional 96 hours. The high rate of GFP/fluorescent cells indicated the high efficacy of virus infection (Fig. S2c). The results from qPCR and Western blot demonstrated the efficient knockdown of TET2 gene, and the specificity of TET2 knockdown was supported by the unchanged levels of TET1, TET3 and DNMT3a in TET2 shRNA-transfected cells (Fig. 3g and 3h). As TET2 is a methylcytosine dioxygenase, we speculated that TET2 ablation may decrease 5hmC production. Indeed, the results from dotblotting using 5hmC antibody support that sorafenibR Hep3b and Huh7 cells have much lower levels of 5hmC than parental cells (Fig. 3i and 3j). Notably, TET2 knockdown led to an increase of 5mC abundance even when DNMT3a protein expression are not changed. This may be attributed to the downregulation of TET2, leading to less conversion of 5mC to 5hmC.
To investigate the biological outcomes of TET2 knockdown, the sorafenibR Hep3b and Huh7 cells with TET2 depletion were subjected to proliferation and wound-healing assays. We found that, compared to those with scrambled controls, the cells with TET2 knockdown proliferate at a much slower rate (Fig. 3k, Fig. S2c) and migrate at a much shorter distance (Fig. 3l, Fig. S2d), which occurs in a time-dependent manner. These findings suggest that TET2 is required for the aggressive proliferation and migration of sorafenibR HCC cells.
CSCs with upregulation of DNMT3a and TET2 are more tolerant to sorafenib-induced cell death
Given the highly heterogeneous of HCC cells and the role of oncospheres in developing drug resistance, we performed oncosphere-forming assays in HCC Hep3b and Huh7 cells, and found that about 6% and 5% cells(ratio: Onco/total) can form oncospheres, respectively (Fig. 4a). To examine the drugsensitivity of oncospheres, we replated oncospheres and treated them with different doses of sorafenib. As shown in Fig. 4b, the replated oncosphere cells displayed IC50 values to sorafenib much larger than those exhibited by their parental counterparts, suggesting that oncospheres may mediate, at least partially, the development and maintenance of sorafenib resistance. In line with this, sorafenibR Hep3b and Huh7 cells had a greater tendency to form oncospheres than parental cells (Fig. 4c). To identify essential regulators for oncosphere formation, we examined the levels of DNMTs and TETs. We found that expression of DNMT3a and TET2 at RNA and protein levels is highly elevated in oncosphere compared to parental cells (Fig. 4d and 4e). To assess the involvement of DNMT3a and TET2 in oncosphere formation, we used shRNA lentiviruses to knock down them, and found that DNMT3a or TET2 knockdown inhibits the oncosphere growth supported by reduction of oncosphere number without obvious changes of oncosphere sizes (Fig. 4f). Further, we found that oncosphere cells express elevated levels of stem cell makers like CD133, CD25, CD44 and c-KIT (Fig. 4g). Therefore, we propose that upregulation of DNMT3a and TET2 in CSCs is essential for the development of sorafenib resistance.
Dysregulation of DNMTs and TETs is linked to sorafenib responses and survivals in HCC patients
To explore the clinical implications of DNMT upregulation insorafenibR HCC cells, we sought to determineif DNMT3a expression can predict HCC patient responses receiving sorafenib therapy. We first analyzed DNMT3a mRNA levels in public datasets GDS4887, GSE45267 GSE54236 and GSE109211, and found that DNMT3a is significantly upregulated in HCC tumors compared to non-tumor tissues (Fig. 5a). Importantly, sorafenib non-responders (n = 21) had higher levels of DNMT3a expression than responders (n = 40) (Fig. 5b). Notably, we also found that DNMT1 and DNMT3b expression is higher in HCC tumors than non-tumor tissues as well as in sorafenib non-responders than responders (Fig. S3a). To validate prognostic implications for DNMT3a overexpression, we analyzed the survival of HCC patients from GSE54236, GSE109211 or used online tools (protein atlas, Gepia2) to examine the association between patient outcomes and DNMT3a levels. We observed that HCC patients with higher DNMT3a expression have significantly shorter survival time than patients with lower levels (Fig. 5c and 5d). Importantly, sorafenib non-responding patients, who have higher DNMT3a expression, had a shorter survival time than responders carrying lower DNMT3a expression (Fig. 5e). We also assessed the association of patient outcomes with the expression of DNMT1 and DNMT3b, and found that upregulation of DNMT1 and DNMT3b corresponds with short overall survival in HCC patients as well as in sorafenib non-responders (Fig. S3b and 3c). Given that DNMT3a is a de novo DNA methyltransferase, these findings suggest that DNMT3a upregulation followed by 5mC increase is more essential in sustaining sorafenib resistance.
To demonstrate the clinical significance of TET2 upregulation in HCC patients, we analyzed public datasets GSE45267, GSE54236 and GSE109211 for TET2 mRNA levels. We found that, in general, TET2 expression has a trend toward upregulation in HCC tumors compared to normal tissues (Fig. 5f), which is required to be validated in a larger cohort of patients. Importantly, sorafenib nonresponders (n = 21) had significantly higher levels of TET2 (p < 0.05) than responders (n = 40) (Fig. 5g). Notably, we also found that TET1 is higher in HCC tumors than non-tumor tissues and in sorafenib non-responders than responders (Fig. S3d). To explore the prognostic implications of TET2 overexpression, we analyzed the survival of HCC patients from GSE54236, GSE109211 or used online tools (protein atlas, Gepia2) to examine the association between patient outcomes and TET2 levels. We observed that HCC patients with higher TET2 have significantly shorter survival time than those with lower TET2 (Fig. 5h). Importantly, sorafenib non-responding patients, who have higher TET2 expression, had a small survival probability than responders carrying lower TET2 expression (Fig. 5i). We also assessed the association of patient outcomes with the expression of TET1 and TET3, and found that upregulation of TET1 and TET3 corresponds with short overall survival in HCC patients (Fig. S3e and S3f). These findings extended the previous studies showing that TET2 is upregulated in HCC cells and may be important for HCC cell growth.14 Collectively, our data suggest that TET2 is an essential regulator of HCC sorafenibresistance.
Pharmacological targeting of TET2 impairs sorafenibRcell growth
The findings, which TET2 is upregulated in sorafenibR cells, and TET2 gene knockdown inhibits resistant cell growth, imply that TET2 could be a pharmacological target. To test this, we treated sorafenibR Hep3b and Huh7 cells with bobcat339, a selective cytosine-based TET enzyme inhibitor.30 Western blotting revealed that exposure to bobcat339 does not change protein expression of either TET2 nor TET1 and TET3 (Fig. 6a), and dotblotting analysis showed that bobcat339 treatment reduces DNA 5-hmC abundance (Fig.6b and 6c) without obvious changes of 5mC amount (Fig.6d and 6e), in line with the concept that bobcat339 does not inhibit de novo methyltransferase DNMT3a.30
To assess if exposure to bobcat339 inhibits sorafenibR cell growth, we performed flow cytometry and observed that cell apoptosis is significantly increased in the presence versus absence of bobcat339 (Fig. 6f and 6g). Further, proliferation and wound-healing assays found that sorafenibR cells treated with bobcat339 proliferate and migrate at a much lower rate than untreated cells (Fig. 6h and 6i; Fig. S4a and Fig. S4b). Furthermore, combination of sorafenib with bobcat339 resulted in more pronounced inhibition of sorafenibR cell proliferation than the treatment with single reagents (Fig. 6j; Fig. S4c). Collectively, these results support that TET2 inhibitors may be promising therapeutic reagents in overcoming sorafenib resistance, which merits thorough investigations in vivo.
DNMT3a and TET2 regulate sorafenib sensitivity and coordinately modulate sorafenibRcell proliferation
Given that both DNMT3a and TET2 are upregulated in resistant cells, and as knockdown of DNMT3a or TET2 suppresses resistant cell growth, we speculated that DNMT3a or TET2 expression may be associated with sorafenib sensitivity. To this end, DNMT3a or TET2 was knocked down in sorafenibR Hep3b and Huh7 cells having their overexpression. These cells were treated with 2 µM of sorafenib for indicated time points. Cell proliferation assays revealed that depletion of DNMT3a or TET2 sensitizes sorafenibR cells to sorafenib-inhibited cell proliferation (Fig. 7a and 7b), and wound-healing studies uncovered that DNMT3a or TET2 knockdown enhances sorafenib-impaired cell migration (Fig. 7c and 7d). These findings suggest that DNMT3a or TET2 expression is required to maintain sorafenib-resistant phenotypes of HCC cells.
To establish the role of DNMT3a and TET2 interaction on sorafenibR cell growth, we knocked down either DNMT3a and TET2 alone or both. The cell proliferation assays revealed that concurrent knockdown of DNMT3a and TET2 leads to more robust inhibition of cell proliferation and migration than that of a single gene change (Fig. 7e and 7f), suggesting that DNMT3a and TET2 have functional cooperation in sustaining proliferation and migration of sorafenibR HCC cells.
DNMT3a physically interacts with TET2, but does not form a regulatory loop, to enhance sorafenibR resistant phenotypes
Because DNMT3a and TET2 are upregulated simultaneously in sorafenibR HCC cells, we first determined if DNMT3a regulates TET2 transcription or vice versa. By using online tools (GEPIA 2) and analyzing public data GDS4887, GSE45267 and GSE54236, we did not find an obvious correlation between DNMT3a and TET2 (Fig. S5a and S5b). These findings, together with the observations that DNMT3a knockdown does not change TET2 protein expression or vice versa (Ref. Fig. 3b and 3h), suggest that DNMT3a and TET2 don’t transcriptionally regulate each other. We then examine if DNMT3a and TET2 have protein interactions in HCC cells. Co-IP assays revealed that DNMT3a forms a complex with TET2 and HDAC2 in both sorafenibR and parental HCC cells with a slight increase of their interaction potential in sorafenibR cells (Fig. S5c and S5d). The protein interaction among DNMT3a, TET2 and HDAC2 was further confirmed by the results from string-interaction assays (Fig. S5e; https://string-db.org), which was consistent with previous studies showing that HDAC2 and TET2 are co-transcription factors of DNMT3a.31-33 Given the dual function of TET2 in cancers,33 these findings suggest that a transcriptional complex of DNMT3a, TET2 and HDAC2 exists in sorafenibR HCC cells.
Tumor suppressor genes are further silenced in sorafenibR HCC cells by DNMT3a- mediated promoter DNA hypermethylation
To define the mechanisms that DNA methylation aberrations contribute to faster growth of sorafenibR cells, we examined the changes of epigenetically silenced tumor suppressor genes (TSGs), for example, p15, p16, p18, FHIT, SOCS1 and SOCS2, which are frequently silenced by promoter DNA methylation and their downregulation predicts worse prognosis in HCC patients. The results from qPCR showed that expression of p15 and SOCS2 is largely decreased in sorafenibR compared with parental Hep3b and Huh7 cells, but no obvious changes were detected in the expression of p16, p18, FHIT, and SOCS1 (Fig. 8a). These results suggest that further TSG silencing is required for the survival and faster proliferation of sorafenibR cells.
As epigenetic regulators TET2 and DNMT3a are upregulated in sorafenibR cells, we reasoned that overexpression of TET2 and DNMT3a may account for TSG silencing. To test this, we knocked down DNMT3a or disrupted TET2 activity via bobcat339 in sorafenibR Hep3b and Huh7 cells, and assessed expression of these TSGs. As expected, DNMT3a ablation significantly increased the levels of p15 and SOCS2, but genetic or pharmacological inactivation of TET2 did not obviously change their expression. Notably, co-knockdown of TET2 and DNMT3a led to more pronounced upregulation of p15 and SOCS2 (Fig. 8b), suggesting that TET2 and DNMT3a coordinately silence TSGs in sorafenibR cells.
To investigate the methylation status of p15 and SOCS2 promoters, genomic DNA from sorafenibR and parental cells was digested with the restriction enzyme HpaII cutting only nonmethylated sites or BstUI cutting only methylated sites. Decitabine-treated cells were used as positive controls. Following digestion, DNA was analyzed by qPCR using primers specific to p15 or SOCS2 gene promoter containing CpG islands. Efficient digestion by HpaII or BstuI leads to stronger amplification in hypomethylated or hypermethylated p15 and SOCS2 promoters, respectively, in sorafenibR cells compared to parental controls. Consistent with the silencing data (see Fig. 8a) and opposite to decitabine-treated controls, these data provide the evidence that the p15 and SOCS2 promoters are more hypermethylated in sorafenibR cells than that in parental controls (Fig. 8c). To precisely measure the alterations of promoter methylation, we performed MeDIP assays, in which methylated DNA was enriched by 5mC antibody and quantified by qPCR. Consistent with the findings from enzyme digestion (see Fig. 8c), the levels of 5mC in the promoters of p15 and SOCS2 were significantly increased in sorafenibR cells compared to parental controls (Fig. 8d).To address how TSG promoters become hypermethylated, we performed ChIP assays, and found that both DNMT3a and TET2 bind the promoters of p15 and SOCS2 (Fig. 8e), which are in line with the physical protein interactions between DNMT3a and TET2, leading to DNA hypermethylation that interacts with HDAC2 in the promoter to further silence TSGs.
DNMT3a and TET2 activate cell proliferation genes through promoter binding in a DNA methylation-independent manner
To further understand how sorafenibR cells more aggressively proliferate and migrate, we first examined the expression of certain oncogenes, like CDK1, CCNA2 and RASEF. We found that these oncogenes are highly elevated in sorafenibR compared to parental cells (Fig. 8f). These results suggest that, in addition to TSG silencing, oncogenic upregulation may contribute to the survival and faster proliferation of sorafenibR cells. Second, inactivation of either TET2 or DNMT3a led to a decrease of oncogene expression, but we did not see a synergistic effect on oncogenic downregulation upon knockdown of both TET2 and DNMT3a (Fig. 8g). Third, the assays of enzymatic digestion from bulk DNA did not see obvious changes of DNA methylation in the promoters of oncogenes CDK1, CCNA2 and RASEF (Fig. S6a). Instead, MeDIP assays revealed a slight decrease of 5mC in the promoters of CDK1 and CCNA2, but not RASEF (Fig. S6b). Fourth, ChIP analysis disclosed thatDNMT3a, TET2 and HDAC2 are enriched in the promoters of oncogenes CDK1, CCNA2 and RASEF (Fig. S6c), although such binding did not increase the levels of DNA methylationin sorafenibR cells.These findings strongly support that both DNMT3a and TET2 have DNA methylation-independent functions.34,35

domain: literature


text:
Littoral Press, 2006 - £5.00
MUCH OF THIS COLLECTION, winner of the 2006 Littoral Magazine Poetry Pamphlet Competition, carries a definite pastoral flavour, sometimes refracted through the lens of art. There’s some use of rhyme, most notably for ‘In Memoriam’, but generally Ackroyd sticks to free verse. One complaint would be the occasionally erratic use of punctuation, but generally it’s well controlled.
The second poem’s opening line—“There is a gap in the hedge” –immediately calls to mind R S Thomas, albeit without the cantankerous edge that the great Welsh poet cultivated. Perhaps that’s not surprising, given that Ackroyd was born in Cardiff and now lives in Shropshire, and she is generally at her best when dealing with clear-eyed glimpses of the natural world, occasionally with spiritual or even overtly religious overtones.
She also acknowledges, with lines such as “My thought, outside the orbit of your art”, the difficulties for any art form in articulating the essentially abstract. A few pages further on, in a poem actually called ‘R S Thomas’, she defines this aesthetic well: “words”, she says, “have been earth, stones, bread”.
She’s far less engaging when she lapses into the overly ‘poetic’, such as in ‘Rising To The Occasion’, where the phrase “The sky invites/ excavation of its radiance” lets sentimentality creep in; or when she decides to ‘tell’ rather than ‘show’. ‘Committal’ is probably the worst offender on that count, with the last stanza’s epiphany feeling particularly contrived. Ackroyd’s poems work best when, in her own words, she leaves her writing “open to the wind’s sting” and bears in mind the lines that give the collection its title (“Affinity is deepest in memory/ Poetry what sticks like lichen”) and lets sharply observed detail and precise language do all the hard work.
Pamphlet available from author at 21 Lucifelde Rd, Shrewsbury, Shropshire SY3 7LB


text:
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Study visit to Hedmark/V?rmland. Cross border labour market and combating Youth unemployment
The study tour started with a visit to Morokulien – a six-hectare area on the border between Norway (municipality of Eidskog) and Sweden (Eda Municipality).
In 1910 the Nordic Peace Congress in Stockholm decided that a peace monument should be raised on the border between Sweden and Norway to celebrate 100 years of peace between the countries. The building of the peace monument was finished in 1914, just several days after the 1st World War broke out. The Border Info Service operating in Morokulien is divided into two; the borderline is marked on the roof and the floor. The border can be crossed without a passport.
Upon arrival to the Border Info Service participants of the study visit listened to presentations describing how problems related to youth unemployment are tackled in the border area:
- “Grensetjensten - How to facilitate a cross border labour market for businesses and individuals” (by Kikki Lindset)
- “Border opportunities – a project aiming at integrating Norwegian and Swedish business- and labor market“ (by Mikael Sondell)
- “NAV (Norwegian social service)” (by Unni Dalsegg)
- “Arbetsf?rmedlingen (Swedish job agency)” (by Christian Kling and Anna Tv?r?na)
The presentations were followed by a Q&A session, where the participants had an opportunity to further clarify some aspects of combating youth unemployment in the border area between Norway and Sweden.
At the end of Day 1 the group moved to Karlstad, where a meeting with Mr. Kenneth Johansson, Governor of V?rmland was organized. Mr. Johansson invited the participants of the study visit to the top floor of his residence and held a tour of the building, as well as described how his working day is organized. The meeting was held in an informal manner.
The second day of the study tour was dedicated to the visit to Karlstad Innovation Park at Karlstad University.
|Study visit to Hedmark/V?rmland - final programme (as of 09.02.2017)||377 KB|


text:
The Healthcare Information and Management Systems Society (HIMSS) recently submitted suggestions to improve the proposed Centers for Medicare & Medicaid Services (CMS) prior authorization rule, with a focus on bolstering interoperability and patient access.
The current CMS proposal aims to simplify the prior authorization process, minimize administrative tasks, and enhance patient outcomes. However, HIMSS identifies areas that require further refinement to achieve these goals.
A key concern highlighted by HIMSS is the necessity for improved interoperability, which refers to the smooth exchange of data between distinct electronic health record (EHR) systems. Enhanced interoperability would allow healthcare providers to retrieve patient information more effectively, leading to well-informed decisions and shorter wait times.
HIMSS proposes that the CMS rule align with existing interoperability standards, such as Fast Healthcare Interoperability Resources (FHIR). Implementing FHIR would help healthcare providers adopt a consistent approach to data exchange, fostering efficient communication and collaboration.
Another critical aspect emphasized by HIMSS is the improvement of patient information access. The organization urges the CMS to reinforce provisions that support patients’ ability to access their health data. By granting patients access to their medical records, healthcare providers can encourage shared decision-making and enable individuals to actively participate in their health management.
Addressing privacy and security concerns related to data exchange is vitally essential. The organization suggests that the CMS implement robust privacy and security measures for data exchange under the prior authorization rule. This would protect patients’ personal health information and instill trust in the healthcare system.
HIMSS also advocates for provisions that encourage the utilization of Application Programming Interfaces (APIs). APIs facilitate the integration of various software applications, allowing healthcare providers to efficiently access and share patient data. By incorporating APIs into the prior authorization process, healthcare providers can optimize workflows and alleviate the administrative load related to prior authorizations.
Finally, HIMSS underscores the importance of continuous stakeholder engagement in the development and execution of the CMS prior authorization rule. Collaborating with healthcare providers, patients, and other stakeholders, the CMS can tailor the rule to address the healthcare community’s needs and enhance patient outcomes.
HIMSS presents valuable suggestions aimed at refining the proposed CMS prior authorization rule. By concentrating on interoperability, patient access, privacy and security, API incorporation, and stakeholder involvement, the CMS can improve the rule to effectively serve healthcare providers and patients.
Read More: HIMSS Written Comments

domain: medical


text:
Everyone loves a good villainess. We love it when developers go out of their way to design characters that give us the creeps. Especially since we'll get to eventually destroy them, which hopefully makes the ensuing nightmares a bit easier to bear.
But sometimes, these character designs can be a little confusing. While these horrifying antagonists are absolutely terrifying, sometimes they're also a little bit... sexy? Let's look back at some of the frightening freaks who are also maybe, possibly, kind of somewhat alluring in their own way.


text:
At the core of Artspace's mission lies an unwavering commitment to supporting creativity and cultural communities.
In an era marked by rapid change and significant challenges, we are refocusing our efforts on what has always been our foundation: building affordable housing for artists, developing inclusive workforce housing, and crafting spaces that not only nurture entrepreneurialism and creativity but also ensure the long-term viability and resilience of these communities.
Deepening Our Roots for Lasting Impact
Artspace's journey is propelled by a belief in the transformative power of art and the need for artists and entrepreneurs to have spaces where their creativity can thrive. Recognizing the growing challenges creatives face in securing affordable living and working spaces, we are redoubling our efforts. Our strategic realignment is geared towards enhancing our ability to provide solutions that not only meet immediate needs but also ensure the sustainability of entrepreneurs' and artists' careers and communities in the long run.
Expanding the Canvas: Workforce Housing
Understanding that a vibrant creative ecosystem benefits from diversity, Artspace is broadening its scope to include workforce housing. This initiative aims to embrace a wider spectrum of creatives and individuals who, while not traditionally labeled as artists, play a crucial role in enriching our cultural landscape. By fostering inclusive communities, we are laying the groundwork for a sustainable future where creativity and collaboration can flourish.
Sustainability as Longevity
When we speak of sustainability, we envision a future that holds enduring opportunities for artists and creatives. This means not only implementing environmentally responsible practices in our projects but also ensuring these spaces support the long-term growth, stability, and resilience of the creative community. Our commitment to sustainability is twofold: reducing our environmental impact while building a foundation for the lasting success of creatives and their contributions to society.
Empowering Through Programs: Pathways and Immersion
To further our mission, Artspace has launched innovative programs like Pathways and Immersion, designed to directly support artists, entrepreneurs, and cultural organizations in realizing their space-related aspirations. Pathways is a program of sharing real estate learning and resources among Indigenous leaders and communities that can lead to the development of new or renovated spaces where Indigenous culture and education can thrive. In a similar way, the Immersion Program provides hands-on support and mentoring to help creative entities advance their space-related projects from concept to reality. These programs underscore our commitment to empowering the creative sector, ensuring they have the tools and knowledge to succeed.
The Power of Partnership
Achieving our vision of sustainable, affordable creative spaces relies on the strength of collaboration. Engaging with local governments, the private sector, and community organizations allows us to navigate the complexities of real estate development and community engagement with a unified purpose. These partnerships are essential for creating spaces that are not just physically enduring but also integral to the cultural and economic vitality of their communities.
The Road Ahead
As Artspace embarks on this path of renewed focus, we are filled with optimism about the potential to make a meaningful difference in the lives of artists and the broader creative community. By prioritizing long-term sustainability in all its forms, we aim to create a legacy of vibrant, inclusive communities where creativity is a cornerstone of longevity and prosperity.
We invite you to join us in this endeavor. Together, we can build a future where creatives have the support they need to succeed over the long haul, where creativity is a catalyst for community resilience, and where cultural and entrepreneurial communities are recognized as essential to the sustainable development of society.

domain: sociology