text:
1997 Nissan King Cab - Bag'n It
Beyond Slammed
After Anthony Tyminski finished his '86 Nissan 720, he wanted to stick with the same brand (since he already considered himself a Nissan nut) but roll something newer. In late 1996, Tyminski bought a brand-new '97 Nissan King Cab and threw himself into building what would eventually become one of the East Coast rides that constantly vie for Best of Show trophies.
Anthony began this project with subtle changes, making the truck more of what he had always wanted in a custom mini. Since Anthony is a body repairman at a local body shop, this part of his buildup was a no-brainer. After work and on weekends, he slowly shaved and molded his way toward the perfect Nissan Hardbody. Anthony soon found himself wanting more and more, and his Nissan rapidly changed to reflect the leaps and bounds being made. The more he became involved with the mini-truckin' scene and realized what he wanted, the faster Anthony worked to make his truck a piece of rolling artwork.
At some point, Anthony caught the bug that compells mini-truckers to lay their trucks as close to Mother Earth as possible. With this new fever, he decided that his truck needed to be body-dropped. Anthony didn't just do a shallow 2- or 2-1/2-inch body drop - he went all out. His body drop was full-tilt at a whopping 4 inches of total body slam. Since he was working with the only mini-truck to sport tons of interior room, his body drop made the truck exceptionally low and still afforded him the ability to drive it comfortably.
Since day one, Anthony made sure he had a direct hand in all the craftsmanship of his Nissan. We feel this is the best way to build a custom truck since no one will care as much as you do about your body-dropped baby. In three years of total build time, Anthony created a clean Hardbody that any other mini-truck would have a tough time beating. Because of this, we're kinda glad that Mr. Tyminski doesn't live on the left side of the nation. Then again, maybe it would get some people off their cans and into the garage more often. In any case, Anthony's ride serves as a shining example of what can be accomplished if you put your mind to something and keep at it until your dream is finally realized. We hope you enjoy poring over the images of Anthony's incredible Hardbody. No matter how kick-ass you think the truck is by looking at the images, you must see this truck in person to appreciate how incredibly detailed and visually pleasing it truly is.
The Lowdown
Wheels/Tires 17x7-inch Budnik Scissor Six billet wheels with 5-1/4-inch backspacing and 205/40R17 BFGoodrich tires.
Suspension: Installed by owner and Jeff Zalfino / AIM Industries 2-inch dropped spindles / Firestone airbags all around / Belltech shocks / Pete & Jake's four-link / smoothed and painted frame using VW Silver
Body Modifications: 4-inch body drop / '92-'95 Toyota 4Runner front bumper, headlights, and grille / 4x4 Nissan Hardbody front fenders / chrome electric side mirrors / shaved door handles / shaved hood squirters / shaved emblems / shaved cowl panel / shaved fuel filler door / shaved marker lights / shaved tailgate handle / molded tailgate / rolled rear pan to bed and tailgate / shaved taillights / shaved third brake light / suicide doors / Hi-Tech LED taillights / custom-rolled rear fenders / bodywork by the owner
Paint: House of Kolor Organic Green by Frank Bratoli in Pompton Plains, New Jersey
Stereo: Pioneer head unit / Phoenix Gold 350-watt midrange amplifier / Phoenix Gold 600-watt subwoofer amplifier / two 10-inch Kicker Solo-Baric subwoofers in King Cab enclosure / Pioneer tweeters mounted in-dash / Pioneer midrange speakers mounted in the doors / wiring and installation by owner
Interior: Stock seats, dash, headliner, and door panels wrapped in sandstone tweed / fiberglass center console (houses air gauges and air controls) painted to match Organic Green exterior / billet dash vents / sliding ragtop / installation by the owner and Tom's Upholstery in Butler, New Jersey
Engine/Performance: Engine dropped 1-1/4 inches / ceramic-coated headers / polished engine pulleys / chromed valve cover / chromed power steering tank / polished brake lines / painted brake booster / painted battery box and miscellaneous accessories
Miscellaneous: The truck has made appearances all over the East Coast and taken trophies everywhere it's been. Anthony has enjoyed wins at the Carlisle All-Truck Nationals, the Magnetic Minis Bash, the Garden State Nationals, and the Sullen Creations and Low Rollers' End of Summer Bash.
Special Thanks: Frank Bratoli / Anthony's parents / Jeff Zalfino / Anthony Cetani / Anthony's girlfriend / the members of Down and Dirty
MotorTrend Recommended Stories
Trending Pages
Why the Lucid Air Is the Best and Worst Car We've Ever Had
2024 MG ZS EV First Drive: A Cheap EV Done the Old-Fashioned Way
Bonkers Ford F-150 Lightning Race Truck to Strike Pikes Peak Hillclimb
Most Reliable SUVs: Which Dependable Brands Dominate?
Fisker Says It Could Go Bankrupt and Pear Prospects Bruised


text:
President Obama's answer shows wrong-headed U.S. attitude
This article was originally on a blog post platform and may be missing photos, graphics or links. See About archive blog posts.
I'd like to add a few things to my take on the voting for the 2018 and 2022 soccer World Cups, which appeared in Friday's print and online editions of the Chicago Tribune.
1. What was President Obama thinking when he said, 'I think it was the wrong decision'' when asked by reporters Thursday for a comment on Qatar having won the right to host the 2022 World Cup over the United States?
I understand this was a chance encounter between the president and the White House press corps, so he couldn't have prepared an answer. But his reaction smacked of the attitude -- a combination of entitlement, superiority and sour grapes -- that has made the United States terra non grata in the international sports world.
Couldn't the president simply have congratulated Qatar on its historic triumph while expressing disappointment that the U.S. bid had failed? What he actually said, effectively belittling Qatar with a wrong-headed answer, can do future U.S. bids for the World Cup no good, as the people who vote for these things have long memories.
President Obama also did Chicago's 2016 Olympic bid no good with his 11th hour fly-by and soporific speech in the final presentation to International Olympic Committee voters 14 months ago in Copenhagen.
Yes, the gripes of some IOC members about being held on buses because of security involved for the president's late arrival were childish. But the planning for his brief visit made Obama the only head of state whose presence caused significant inconvenience. After he committed to the trip, he should have done what his peers have in recent IOC host elections: stay long enough to do personal lobbying for votes.
You can say all you want about how ridiculous it is for presidents and prime ministers to fawn over the self-appointed grandees who vote for Olympic and World Cup hosts -- and every word would be justified. But if you are in this game, you have to live with its absurd rules and understand the silly presumptions of the culture that surrounds it.
2. The IOC all but said it is too hot for an Olympics in the Qatari summer when it announced in 2008 that the Summer Games must take place in a period from July 15 - Aug. 31, the dates favored by global broadcasters. In its bid for the 2016 Olympics, Doha, Qatar had proposed dates of Oct. 14-30 because of the extreme heat in the desert summer.
That gave the IOC a reason not to include Doha among the four finalists for 2016, even though its bid got a higher technical score in the IOC's preliminary evaluation of the bidders (tied for third with Chicago) than eventual winner Rio, which was fifth.
So how can the World Cup go to Qatar in June and July?
The Qataris have promised a cooling system in all the stadiums, training areas and fan sites to keep the temperature at 78 degrees. As my colleague Alan Abrahamson noted after getting an on-site preview, the system works.
And why wouldn't that work for an Olympics?
So many Olympic events, especially endurance events like the marathon and cycling road races, take place outside stadiums, and cooling those vast areas might require putting a dome over a large chunk of the small country (don't count out such an idea; Qatar has the money and the will to do it.)
Maybe some of those events could be run at night, when the intense desert sun would not be a factor. I don't think the Qataris, with their enormous natural gas reserves, would have trouble fueling a lighting system.
Yes, there have been other very hot Olympics. The first day in Atlanta (1996) was unbearable. It was well over 100 degrees on the floor of the Barcelona (1992) Olympic Stadium during several days of the track competition. Athens (2004) temperatures frequently hit the mid-90s in the afternoon, but the dry nights were beautiful. And Beijing (2008) mixed heat, oppressive humidity and pollution.
There is another issue that should be a more significant impediment to an Olympics in Qatar.
Beginning in 1984, the country has sent an aggregate 98 athletes in 10 sports to the past seven Summer Olympics.
Not one was female.
And changing a culture may be harder than coping with a climate.
3. Qatar's soccer team finds itself in a similar position to that of the United States when it was awarded the 1994 World Cup in 1988.
At that point, the U.S. men had not qualified for a World Cup since 1950. And the team would need a dramatic victory in the final qualifying match against tiny Trinidad & Tobago to make the 1990 World Cup.
Qatar has tried unsuccessfully to qualify for every World Cup since 1978. The Qataris made it to the final round of Asian qualifying for 2010, finishing a distant fourth in a five-team group, after being eliminated in the first round of qualifying for 2006.
4. Who knows how much final presentations count in these host city votes?
But I do know Qatar's was brilliant in showing off the modernity and global connection of a country many still see as an isolated, sandy empire.
Its Emir and bid committee president, Sheikh Mohammed bin Hamad al-Thani, spoke beautiful English and French. (He also has a Facebook page). It brought out Bora Milutinovic, the citizen of the world who has coached five countries' teams (including the U.S.) in the World Cup, to tell the audience in Spanish why the compact Qatar plan would increase the level of play by decreasing the amount of travel. Its bid CEO also spoke English and Spanish.
(By comparison, the U.S. bid team spoke only English.)
It brought out an Iraqi to tell what the World Cup would mean to the entire Middle East, a region which has never hosted a World Cup or an Olympics.
And its final speaker was a woman, Sheikha Moza bint Nasser, chair of her country's foundation for education, science and development, who pulled no punches in opening her presentation by asking simply, 'When?' as the word appeared in capital letters on a large video screen behind her.
A few minutes later, hectoring FIFA voters the way Brazilian President Lula had done to IOC voters last October about bringing the first Olympics to South America, she repeated the question, then answered it by saying, 'The time has come. The time is now.'
The voters agreed.
-- Philip Hersh

subset: commoncrawl


text:
Grapenuts Pie Crust
Submitted by: Susan
Here's a recipe I've used for pie crust. I have to warn you, though, that it will never fool anyone into thinking it's "real" pie crust. It's fairly simple:
2 cups grapenuts cereal
1/2 cup apple juice concentrate
Crush the cereal in a food processor. Put it in a bowl and mix in the apple juice concentrate. Press the mixture into the bottom and onto the sides of a pie pan. Bake at 350 for 10 minutes if you plan to use a no-bake filling, OR just fill and bake according to pie recipe instructions.
I've heard of people using flour tortillas as pie crusts (just line a pie pan with them) but I've never tried that. Also, you can line a pie pan with several sheets of phyllo dough. I've done that before, and it's pretty good. Finally, you can always just leave off the crust–radical, I know, but really cuts the calories! 🙂


text:
Latest links for easy consumption over the May long weekends – I missed out on March so have dropped some of the less interesting ones to keep the list short.
Organisational Behaviour
Programmers, Teach Non-Geeks The True Cost of Interruptions – a simple way to show to your boss how drive-by-management kills programmer productivity. Also work reading Maker's Schedule, Manager's Schedule which highlights the differences. If this is still a problem then this notice might be your only solution…
The Death Of Expertise – The Dunning-Kruger effect is often strong in semi-technical managers especially in industries where confidence plays a large part in success such as finance. This article discusses some of the problems related to treating all opinions as equal and ignoring experts.
Save Your Software from the Start: Overcoming Skewed Thinking in the Project Planning Stage – Very simply, why we always underestimate the true complexity and cost of a project plus some tools to help overcome these psychological effects.
Why Good Managers Are So Rare - Gallup finds that companies fail to choose the candidate with the right talent for the job 82% of the time. Managers account for at least 70% of variance in employee engagement scores across business units.
I Give Up: Extroverted Barbarians at the Gates – Anyone remember the "perpendicular transparent red lines" video doing the rounds? This is an on-the-nail deconstruction of what is happening and why it happens. If you are an introvert then this other post might feel very familiar to you.
Coconut Headphones: Why Agile Has Failed – A rant about how modern agile methodologies seem to only consist of management practises. Take note of the end points to being successful.
The death of agile? – Additional comment on the above.
Writing User Stories for Back-end Systems – The real functionality a user sees in a business intelligence project is quite small and can easily be described in a few words. This makes breaking up user stories into sprint sized chunks hard. This article gives some great advice that can be translated to BI projects.
Design Your Agile Project, Part 1 – So how do you pick the right kind of agile project? When should you use Kanban and when should you use Scrum? How is the business side of equation handled? Also Part 2, Part 3, and Part 4.
Large Agile Framework Appropriate for Big, Lumbering Enterprises – A perfect solution to doing agile in finance organisations (wink). Love the concept of 'Pair Managing'.
Metrics that matter with evidence-based management – Its long but Martin does a great job looking at lots of the metrics in use today, why their use is limited and a far better approach to designing metrics that really help.
Is ETL Development doomed? – "Long term, the demand for ETL skills will decline". The demand will mutate into one for more abstract ETL capabilities.
Intro to Unit Testing 9: Tips and Tricks – A handy list of tips that can make maintaining unit test code a little easier.
FsCheck + XUnit = The Bomb – Even if you write code in C# it may be wise to think about writing unit tests in F# since the code is more concise, easier to read and with FxCheck can find things you might not.
Data Visualization
5 Tips to Good Vizzin' – Should be required reading for anyone who is thinking about creating dashboards in Tableau.
A Natural Approach to Analytics – This explains why using tools such as Tableau for largely static dashboards is a waste of time. Users need to interact with the data in a way they cannot do when relegated to dashboard consumers.
Big Data/Hadoop
Modern Financial Services Architectures Built with Hadoop – Hortonworks looks at big data in financial services.
Beyond hadoop: fast queries from big data – I think Hadoop might be catching up here but it is still a bit of an elephant compared to SQL Server/Oracle etc when it comes to raw query performance.
Don't understand Big Data? Blame your genes! – 5 common errors for dealing with big data.
The Parable of Google Flu: Traps in Big Data Analysis – Big data answers are not always correct. This paper looks at some of the pitfalls.
No, Hadoop Isn't Going To Replace Your Data Warehouse – More thoughts on modern data architectures and hybrid transactional/analytical processing.
Discuss this on Twitter or LinkedIn


text:
Like a starting pistol, the buzzer sounded at 10 a.m. and nine robed justices entered the chamber. Chief Justice John Roberts immediately called on his colleagues to announce the court's decisions. Several hundred people listened in silence with bated breath.
Though June 24 marked my first visit to the Supreme Court, I'm passingly familiar with the institution. As a high school teacher, I explain the court's function every year. Students learn that the top body of the judicial branch interprets the Constitution and strives to provide "equal justice under law." Personally, though, I've wondered whether the justices fully live up to these principles.
Some appear to be politicians in robes, voting more for their political interests than objectively on the law. The court's 2000 order to stop Florida's vote count and assure George W. Bush the presidency and the Citizens United case which unleashed unlimited corporate campaign spending are examples. Justices seem to respect states' rights, voter preferences, long-established laws and precedents when they suit them and ignore them otherwise. "Don't they just do whatever they want?" a student once asked me. I found it hard to disagree.
So I was eager to get a closer look at the court when an opportunity arose through Street Law, a nonprofit group that provides instruction about our legal system. During a week-long class, this outstanding program put our group of teachers face-to-face with an array of experts from attorneys to court clerks, providing insight into many aspects of the court's function. "Watch the justices' reaction during dissents," one speaker advised us.
That proved good advice during the hearing we attended, in which the court announced greater scrutiny of affirmative action in college admissions. Justice Ruth Ginsburg disagreed with the conservative majority, and as she explained why, her colleagues exhibited behavior that a teacher might describe as adolescent. Justice Samuel Alito shook his head and rolled his eyes. Justice Clarence Thomas chewed gum, closed his eyes, put his hand to his face and exchanged whispers with Justice Antonin Scalia, who stared at the ceiling and rocked in his chair.
Clearly these justices with lifetime tenure, who are both more powerful and further beyond reproach than perhaps anyone else in the nation, do not enjoy criticism. Their main decision on the following day reinforced my impression of them as political agents.
By a 5-4 vote, the court's Republican appointees struck down the heart of the 1965 Voting Rights Act. Under the VRA, the Justice Department prevented election fraud by monitoring states and counties which repeatedly undermined voting rights. The Fifteenth Amendment to the Constitution appears to clearly permit this and Congress voted overwhelmingly to renew the act in 2006, though the law later became a target of GOP activists.
But on the last day of its session, the court took two big steps towards vindicating itself in my eyes. The justices struck down the Defense of Marriage Act, which prohibited married same-sex couples from receiving federal recognition or benefits. Providing the critical fifth vote was Justice Anthony Kennedy, who broke with typical Republican sentiments by finding that DOMA violated the constitutional promise of due process.
Similarly, Justice Roberts and Justice Scalia broke with their opposition to same sex marriage (which they expressed in dissents on the DOMA ruling) to dismiss an appeal seeking to reinstate Prop. 8, California's gay marriage ban. This upheld Judge Vaughn Walker's 2010 district court ruling that Prop. 8 violated the equal protection clause of the Fourteenth Amendment. As their decision resulted in same-sex marriages resuming in California, I credit the senior justices for voting against their apparent political desires.
Ecstasy swept the courthouse steps after the justices announced these decisions. The plaintiffs, their attorneys and hundreds of supporters celebrated with hugs, cheers, beaming smiles and tears of joy. The scene powerfully demonstrated the Supreme Court's power to right our nation's wrongs.
"Today is a great day for American children and families," said plaintiff Kristin Perry.
"Thank you to the Constitution and thank you to the justices today who served in this court," said plaintiff Sandy Stier.
"Thank you! Thank you!" chanted the crowd, followed by "USA! USA!"
Before the Street Law class ended, one more memorable event occurred. Our group attended a reception at the high court hosted by Justice Ginsburg. She spoke movingly about progress on women's rights during her lifetime and shared some thoughts about serving on the court. "This is the hardest and the best job I've ever had," she said. Yet despite the disagreements between the justices, they get along and work together well, said Ginsburg, calling her institution "the finest high court in the world."
Leaving Washington with a wealth of new information plus a few great personal memories to share in class, I decided to take her word for it.
— Matt Johanson is a freelance writer and a high school social studies teacher. His writing can be found at www.mattjohanson.com.


text:
(CNN) -- In a blistering speech before the United Nations General Assembly, Iranian President Mahmoud Ahmadinejad blamed "a few bullying powers" for creating the world's problems and said the "American empire in the world is reaching the end of its road."
And while he insisted Iran's nuclear activities are peaceful, Ahmadinejad blamed the same powers for seeking to hinder it "by exerting political and economic pressures on Iran, and threatening and pressuring" the International Atomic Energy Agency.
Those powers, meanwhile, are building or maintaining nuclear stockpiles themselves, unchecked by anyone, he said.
As Ahmadinejad spoke, the only person at the United States table was a note-taker; no U.S. diplomat was present. When President Bush spoke earlier Tuesday, however, Ahmadinejad was in the room.
"As long as the aggressors, because of their financial, political and propaganda powers, not only escape punishment, but even claim righteousness, and as long as wars are started and nations are enslaved in order to win votes in elections, not only will the problems of the global community remain unsolved, but they will be increasingly exacerbated," the Iranian leader said.
He accused the United States of oppressing Iraqis with six years of occupation, saying Americans were "still seeking to solidify their position in the political geography of the region and to dominate oil resources." Watch Ahmadinejad say the "American empire" is nearing "the end of its road" »
Meanwhile, he said, Palestinians have undergone "60 years of carnage and invasion ... at the hands of some criminal and occupying Zionists." Watch Ahmadinejad blast U.S., Israel, "bullying powers" »
He said Zionists in Israel "have forged a regime through collecting people from various parts of the world and bringing them to other people's land, by displacing, detaining and killing the true owners of that land."
The Security Council, he said, "cannot do anything, and sometimes under pressure from a few bullying powers, even paves the way for supporting these Zionist murders."
He stopped short of calling for Israel to be politically wiped off the map as he has in the past. He called for "a free referendum in Palestine for determining and establishing the type of state in the entire Palestinian lands."
Ahmadinejad pointed to what he said are signs of hope, saying an increasing number of nations are turning their backs on "the bullying powers" and seeking to establish new relations.
"Today the Zionist regime is on a definite slope to collapse," he said.
The Anti-Defamation League released a statement saying the Iranian leader showed he "is deeply infected with anti-Semitism" and displayed "the true threat the Iranian regime poses to Israel, the United States and the West."
Hours before Ahmadinejad's speech, Bush told the General Assembly that Iran was among the nations that "continue to sponsor terror."
"Yet their numbers are growing fewer, and they're growing more isolated from the world," Bush said.
Bush also said U.N. members needed to enforce sanctions against Iran for failing to suspend its nuclear program, which the United States and other Western nations believe is intended to develop nuclear weapons.
Before Ahmadinejad spoke to the U.N., he told CNN's Larry King that he is willing to meet with presidential candidates Sens. John McCain and Barack Obama -- even in front of the media -- to discuss world issues and debate.
But he has no preference between the two, he said in the interview that aired Tuesday night on "Larry King Live." Watch Ahmadinejad discuss the role of the next U.S. president »
"We believe that these are issues relating to the domestic affairs of the United States," Ahmadinejad told Larry King of the presidential race, according to a transcript of the interview.
"And decisions pertaining to that must be made by the American people. And it's not important to us either," Ahmadinejad said. "What matters essentially is that the president that is chosen by the American people should adopt a path and a policy approach and for us to observe the policy approach.
"This is the campaign period, anyone can say anything. So we disregard that. What matters is that once someone is in office, we have to watch and see if that person will bring about some changes in policy or continue the same old path."
Ahmadinejad was in New York City for the United Nations General Assembly meeting, which began Tuesday.
"I have said that, in fact, on this very trip, currently in New York, that I am ready to speak with the presidential candidates before the press," he told Larry King. "I believe that we've really done whatever we could do in this respect." Watch Ahmadinejad say he'd debate U.S. presidential candidates »
Asked whether he fears a U.S. attack, Ahmadinejad told King that attacking Iran would be the "worst thing the U.S. government can do ... I think that in the United States, there are enough reasonable people, smart people, who would not allow the U.S. government to make such a big mistake."
Withdrawal of U.S. troops from Iraq, meanwhile, would be "the best scenario," Ahmadinejad said. "But I think that it needs a timetable ... the presence of the United States there has not reduced tension and it has not limited terrorism either. In fact, it has increased terrorism."
On hostility between the United States and Iran, Ahmadinejad told King: "The hostility has not been from our end. Up to this day, we have always been interested in having friendly relations."
Iran, he said later, "throughout history ... has demonstrated that it is a nation that is for peace and friendly with others."
And he insisted Iran's nuclear program is for peaceful purposes, despite Western nations' concern to the contrary.
"Their concerns about us are not new," he told King of the West. "They've always been concerned. They were the ones who inspired Saddam [Hussein] to attack Iran and get us involved in an eight-year war. The terrorist groups that killed our president, our prime minister, our officials, are now freely asked to live in the Western countries."
The nuclear issue, he said, has been politicized and is not a legal struggle at all, noting the International Atomic Energy Agency, the U.N.'s nuclear watchdog group, has "not detected any noncompliance or deviation" on the part of Tehran. Watch Ahmadinejad talk about nuclear weapons »
Ahmadinejad spoke extensively of Iran's support for Palestinians. The Iranian leader previously has made statements suggesting that Israel be politically "wiped off the map," though he insists that can be accomplished without violence. He has questioned the existence of the Holocaust, the genocidal Nazi campaign against European Jews, and warned Europeans that they may pay a heavy price for its support of Israel.
He insisted, however, that he and his country wish no harm to Jews.
"We have no problems with Jewish people," he said. "There are many Jews who live in Iran today ... but please pay attention to the fact that the Zionists are not Jews. They have no religion ... they just have -- wear masks of religiosity. How can you possibly be religious and occupy the land of other people?" Watch Ahmadinejad say he has no problems with Jews
On the Holocaust, he said an impartial group should research whether it happened as has been claimed.
"There is a claim that the extent of the calamity was what it was," Ahmadinejad said. "There are people who agree with it. There are people who disagree."
Ahmadinejad has also caused controversy by previously suggesting there were no homosexuals in Iran. Regarding that statement, he told King: "I said it is not the way it is here. In Iran this is considered a very -- obviously, most people dislike it. And we have, actually, a law regarding it and the law is enforced."
However, he said, "we do pay attention that in Iran nobody interferes in the private lives of individuals. We have nothing to do with the private realm of people. This is at the -- non-private, public morality. In their own house, nobody ever interferes."
All About Mahmoud Ahmadinejad • Iran • United Nations


text:
Common Lisp the Language, 2nd Edition
A readtable is a data structure that maps characters into syntax types for the Lisp expression parser. In particular, a readtable indicates for each character with syntax macro character what its macro definition is. This is a mechanism by which the user may reprogram the parser to a limited but useful extent. See section 22.1.5.


text:
FT: Hull City 1-1 Stoke City
The Tigers had James Chester sent off after only 14 minutes but appeared on course to claim an unlikely win after Nikica Jelavic's instinctive finish gave them the lead shortly before half-time.
Indeed, for much of the 76 minutes they played with a man disadvantage they were the better side, outpassing, outchasing and outworking a Potters team that lacked direction.
Hide AdAdvertisement
Hide AdBut they rescued a result, and a first point of the season, when Phil Bardsley's angled shot ricocheted off the inside of the post, against goalkeeper Allan McGregor and was nudged over the line by the waiting Shawcross.
Hull were left to fume with the goal coming from a Stoke throw-in which should have gone the home side's way.
A point was arguably more than Mark Hughes' side deserved for such a listless showing but Hull must surely have feared worse when they were asked to play the majority of the game at a numerical disadvantage.
Hull were eager to assert themselves in the opening minutes, looking to get on the front foot and attempting to target Bardsley at right-back.
Hide AdAdvertisement
Hide AdAndrew Robertson was the chosen outlet and he began to find his range with a couple of teasing crosses from the left.
Yet despite Hull's positive start, exemplified by the busy Stephen Quinn, Stoke were threatening on the break.
Their first warning came after only three minutes when Peter Odemwingie played in Mame Diouf.
He shook off Chester to leave himself clean through but was judged to have fouled the defender in the process.
Hide AdAdvertisement
Hide AdChester was not so lucky next time, when Livermore's underhit back pass invited Glenn Whelan to charge at goal.
All the momentum lay with the Irishman, who was left in a heap by an outstretched leg that had denied a clear scoring chance.
Referee Jonathan Moss did not hesitate to produce the red card, leaving the hosts with a mountain to climb.
The tactical reshuffle was relatively simple, Ahmed Elmohamady and Robertson swapping wing-back to full-back and Tom Ince dropping deeper into midfield.
Hide AdAdvertisement
Hide AdIt was a system Stoke struggled to pick holes in despite their advantage.
Their were half-chances - an Odemwingie dribble into the area, Erik Pieters' wayward drive - but the hosts were holding up well.
Hughes responded by sending on summer signing Bojan Krkic four minutes before half-time, with Whelan sacrificed, but he was unimpressive in Hull's opener just seconds later.
Lacking the bite that Whelan would have offered, he allowed Tom Huddlestone to breeze past him before unleashing a low shot that Asmir Begovic could only palm back out.
Hide AdAdvertisement
Hide AdJelavic anticipated well, beat Marc Wilson to the ball and hooked home from a tight angle.
It was the least Hull's battling response deserved and it was the hosts who ended the half pressing for a second as Stoke lost all semblance of calm.
Hughes' half-time words seemed to have some effect, with his side much improved after the break.
McGregor was called on twice in as many minutes, saving low from Shawcross following a free-kick routine then diving in front of Diouf to smother a cross.
Hide AdAdvertisement
Hide AdThe respective managers quickly re-drew the battle lines, Hughes sending Peter Crouch on as a second striker and Steve Bruce replacing Ince with another defender in Liam Rosenior.
Stoke had their best chance yet when Bojan's deft pass played in Crouch after 64 minutes but a clumsy touch allowed McShane to make a covering challenge.
The ball looped invitingly for Diouf but his cushioned header landed a yard wide.
Stoke's final substitute, Charlie Adam, was into the game immediately, firing a 25-yarder that McGregor flicked over the crossbar.
Hide AdAdvertisement
Hide AdThe game was gradually building towards Stoke's response but Hull did not seem liable to crack.
It took a wrongly-awarded throw-in and an unusal bounce of the ball to breach them, Bardsley hitting Bojan's cross into the ground and watching it rear up and bounce off the frame of the goal.
McGregor, briefly disorientated, allowed it to come back off him instead of gathering it and Shawcross did just enough - his effort confirmed by goal-line technology.
There would no winner but Hull, ever game for the fight, ended the game bravely seeking one.


text:
How to tune into BloggerCon. I'm linking to the MP3s as they become available (about 20 minutes after each session, thanks to CNET). Kevin Marks' video webcast feed. The song: The Hokey Pokey. Another famous Marc Canter sleeping photo. Movie of the room during Phil Torrone's session. Dan Farber is blogging the conference. Phil's photos for the Tools discussion. We're live at CNET, we got the tunes playing, people are starting to arrive, life is good. Just got a report that the webcast has been tested and works. SF weather: "Highs in the 60s to lower 70s." Cooool! I switched to Colloquy, which is a much nicer IRC client. Chris Pirillo: Users vs Developers. Scott Karp: Digg vs the NY Times. Mike Arrington: "No one crafts a sentence like you, Steve." Two years ago today: "This time the pros beat the crap out of the blogs in a story about blogs. Something to think about. This time they fact-checked your ass. " New header graphic, the Rockies west of Denver shot on a flight from New York to San Francisco. Whether you're remote or local, you can participate in BloggerCon in many ways. 1. Tune into the IRC at irc.freenode.net/bloggercon. 2. Or the webcast. (Murphy-willing.) 3. Doc Searls is the technographer. If you're in the conference room, you'll see his outline projected on either side of the room. If you're coming in over IRC and/or the webcast, you can view the outlines in a web browser through the table of contents. They are also available in OPML, so they are viewable in any environment that works with OPML. One interesting idea to try out is to follow a discussion using the Instant Outliner in the OPML Editor. 4. Listen to some funky music and get yo rear end in motion! 5. Listen to the MP3s as they become available. 6. Kevin Marks's video webcast feed. Jake is producing the BloggerCon webcast. Rex Hammock, Terry Heaton, Paolo Valdemarin With Robert Cox in the background. Post partum before startup coffee notes It's 4:20AM, I'm awake, drinking coffee, and running over in my head, one more time, the checklist of things we still have to do, which of course are largely the things we won't do. And then there are the things we didn't do at previous BloggerCons that I must remember to do at this one. And the things I'm worrying about, because I know theny went wrong before and I'm wondering what will go wrong this time. 1. What if no one shows up? 2. What if the air conditioning doesn't work? 3. We didn't get signage, will people think that's tacky? 4. What if no one shows up? 5. What if the wrong people show up and the wrong people don't show up? 6. What if we can't think of a song? 7. And on and on over and over. Face it, I'm a worrier. Someone who doesn't worry can't ship software. But that isn't why I feel unsettled. I actually know why. There's a little bit of a story to it. About two weeks before BloggerCon I, in September 2003, I returned a call from to brother, he was boarding a plane in Chicago (I think) and he said I'll call you back when I get to my seat. That's when I knew something bad had happened. In the two minutes my mind raced. Was it my mother, my father, was someone sick, had someone died? It turned out it was my uncle. He was young, just 58, and had died suddeny in Jamaica. I decided not to go to Jamaica to participate in the settling of his affairs, I stayed in Cambridge to make sure BloggerCon came off. It was one of the most hyper-real couple of weeks, every minute of it in shock, depressed, but also participating in what would turn out to be a great event. Now I don't remember the unsettled feeling, trying to sleep at night in the last days before the first conference, or should I say I don't usually remember; but last night at the party, someone unexpected was there, Mark Stahlman, who I had last seen in Negril with my uncle, and he had stories to tell, and didn't know that Ken had died. It stirred up everything, and that's why this morning, there are unresolved feelings to feel, and it's totally appropriate to process them in the hours before the fourth BloggerCon. |
Comment on today's |
© Copyright 1997-2006 Dave Winer. Previous/Next |


text:
Yitzchak Spiegel |
His path of life was not paved with roses, but its entire path was a line of simplicity in approach to life, cordiality in his relationship to all people, and the internal essence of someone who knows what suffering is. These traits stood with him to overcome all struggles of life. In every situation, he had a smile on his face, beaming from him whenever one would meet him. He was a man of a simple path, honest, doing good, and with a pure heart. Wherever he went and whatever he did, he was straight with himself and with the faith that dwelt in his midst. His simplicity drew its source from the deep spiritual foundations of the Jewish town of Rozniatow in the Diaspora; from the sublime character traits of the family with many children who already spread out to different lands and places during their youth in order to find sustenance for their souls.
He was full of energy, blessed with strength, quiet in his demeanor, and everyone who met him on his path of life became a friend. His thirst for knowledge knew no bounds. He excelled in his great patience and his rational sense of judgement. People placed their faith in him and trusted him.
When he arrived in the Land as the pioneer of his family, his first actions and purpose for his efforts was to bring over his family to the Land despite the conditions of those times to the shore of promises, to this poor and meager land regarding which he knew the conditions of those years very well.
The man did not rest until he was able to say to himself that he did whatever was possible within human power, and even more so. Upon this altar he offered up the greatest sacrifice that a person could offer, his personal life, for he did not establish a family but rather dedicated his entire holy effort to other members of his family.
Only later did he build up his own family with Freda, may she live long. Then, he continued his effort at nurturing family relations with those near and distant with greater energy, forging links with acquaintances, friends, and workmates, in both joy and sorrow. They all regarded him as a faithful friend.
His heart stopped on the 14th of Av, 5731 (1971).
He was an interesting and complex personality. He was an only son to his parents, and was nurtured by the judge Reb Yehuda Hirsch Koren. He spoke calmly and politely. It was indeed a pleasure to sit in his home and listen to his conversation, that was always spiced with words of the sages. His jokes that he told had a special charm. His statements of opinion were measured, weighed, and calm, without fire. He and his father worshipped in the Beis Midrash, but when he studied in the kloiz he would also remain there for prayer. His service and dedication made him appreciated by everyone.
There was a period when his wife's family took him to Germany, but his longing for the town and its people gave him no rest. He returned to Rozniatow and dedicated himself to his desires, to swim in the sea of Talmud. Once again he sat in the kloiz and occupied himself with Torah. His Torah was his faith.
He made aliya in 1934. Despite his depressed economic situation, he was always content with his lot. He did not change his customs. He performed all types of difficult labor, and he dedicated every free hour to the study of Torah.
When his brothers-in-law Yisrael Horowitz of blessed memory and, may he live Tzvi Fesberg built the theater in Petach Tikva, he was hired by them as a cashier. As always, he excelled in his honesty, uprightness and modestly. He was generally appreciated, and everyone treated him with honor and respect.
When he died in Petach Tivka in 5632 (1972) thousands accompanied him on his final journey.
He was born in the village of Knizisk near Rozniatow. He was the grandson of Tzvi Yaakov Stern and Reb Mordechai Stern. He was the son of the sister of Reb Yosef Shimon Stern. He studied Gemara with Reb Yitzchak Branik. At the age of 16, he worked for Leizer Yitzchak Leib.
He left home and traveled to Vienna prior to the First World War. There he completed studies as an accountant, and later worked in one of the banks. He was diligent in studying Torah in the evenings.
He was a faithful friend to his Torah and his people. He absorbed rooted and traditional Jewish culture.
During one of the memorial gatherings for the martyrs of our city, he lectured about the Jews of our city from the previous generation, about the great and important ones of that time.
At one memorial gathering, he guided the gathering and spoke about a memorial book for the martyrs of our city, and even promised to take part in the writing of the book. He poured out his bitter heart with pain and anguish over what the Nazi enemy did to us. He expressed his great joy that he merited to see Jerusalem built up. He requested that Yad Vashem demand that the enemies Kruger and Muller be tried.
He was a member of the committee for the publication of this book. He was greatly anguished that he could not write his memoirs on account of his illness.
He passed away before his time. He was an illustrious man, a man of truth, graced with Torah and wisdom.
May his memory be a blessing!
(He was born in the city of Kalusz in 1875 and died in Jerusalem in 5700 / 1940.) He was accepted as a shochet in the community of Rozniatow in 1903. He was graced with many talents. He was a veteran Torah reader, a prayer leader for the High Holidays, with a pleasant voice and a pleasant demeanor. He endeared himself to the community, which eased his absorption into his community.
The community of Strettiner Hassidim, who were a small minority in Rozniatow in comparison to the Hassidim of Dolina (Zidichow) but strong in their faith to the Strettin dynasty, found him to be man of like mind, which greatly eased his integration into society. He was numbered among the chief scholars of the Chevra Shas. He gave a class to the Or Hachayim circle of young married men on Sabbath eves. He was the rabbi of a number of youths, friends of his sons, who studied Talmud every morning before the Morning Service.
He raised his family throughout a number of years. He was blessed with a family of ten sons and daughters. The needs of his household and yoke of debts that were related to building his house brought the family to economic straits. This was the reason that they left Rozniatow and moved to Germany in 1912, where they lived until the entire family made aliya to the Land of Israel in 1931-1933.
This organization would arrange an annual completion of the Talmud ceremony with festivities, joy and large crowds. This was an important event among the scholars of the city. That night, they would divide up once again the tractates among the members for the next year. This took place each year.
Even though our community is small, the angel of death has already succeeded in snatching from us the best of our sons through the manner that is unique to them: war and accidents.
Uncaptioned. Apparently Eliahu Hausler |
He was the son of Leah and Baruch, the only child to his parents. He was born in Germany on June 5, 1930. From his youth, he was educated in a school under the supervision of Dr. Rothschild, and was a good student. However, the Second World War interrupted his studies. When he was eight years old, the Nazis broke into the school where he studied, and snatched him and his friends. That year, he arrived in the Land with his parents, and they settled in Petach Tikva. There, he studied in the PIKA School. He quickly mastered the Hebrew language and excelled in his studies. He also excelled in sports. He worked in a garage after he finished his studies, for he was attracted to mechanics. He was a member of the Haganah from the age of 14. He participated in the defense of the Shefiim Kibbutz which was attacked by the British.
He enlisted in the army when the War of Independence broke out. He was only 17 and a half years old. He fulfilled his duty as a guard of the people, and from there he was sent to a sniper's course. He excelled at that course, and was transferred to an active unit where he served as a sniper. He was very successful at sniping, and was the assistant and right hand man of the captains. He participated in the battles of Tantura and Kakon, and endeared himself to his comrades as a friend and a fighter. He participated in the conquest of Migdal Tzedek, and he fell when he was defending it against a fierce attack.
On July 12, 1948, Eliahu was shielding the machine gunners of his division with his targeted sniping, as he was leaning against a rock. A bullet shot him in the heart, and his friends found him dead while he was still leaning against the rock.
The next day, he was laid to eternal rest in the cemetery of Petach Tikva.
The son of Yosef and Chana. He fell while standing guard in the south of the country during the War of Independence in 1948.
The son of Yisrael and Chana. He was born on July 24, 1922 in Hamburg, Germany. He fought in the British army against the Nazi enemy and fell in a sea battle near Malta. His boat sunk in the sea. 138 Jewish soldiers died along with him.
The son of Yisrael and Rivka. He was born in 1928 in Germany, the son of a religious family. He was the only son in a family with three sisters. He joined the machteret (underground army) of the Irgun Tzvai Leumi and was very active in it. His parents wished to send him to relatives in America to remove him from the constant danger that threatened him both externally and internally. However, he conducted his life in accordance with his response: We have been drafted for all of life. Only death frees us from duty. When the disturbances broke out again, he was among the first who went to the Old City and organized its defense. This was a small group of youths who stood their stand.
On January 20, 1948, he went to Bikur Cholim with two friends to transmit a message by telephone. Along the way, they were snatched by members of a gang who were accompanied by a British policeman who had given his weapons to one of the Arabs. He shot the three of them. Yoel remained there injured for approximately three quarters of an hour, as the Arabs tortured him. When the members of the Irgun Tzvai Leumi broke through to the place, they found him dying.
His last words were: Tell them that they beat us I feel that this is my end, but it was worthwhile.
The son of Yaakov and Miriam. The grandson of Reb Lipa Tanne of Rozniatow as well as of Yosef Sternberg who served in the court of the Admor of Chortkow of blessed memory.
He was born on the 11th of Tishrei, 5707 (October 6, 1946). He studied in the Bilu School. After he concluded his studies in the Bar-Ilan School, he studied diligently in City High School A. His desire was to merge Torah and work. He worked in the security unit in the mornings, and he dedicated his evenings to studies. On the eve of his draft in February 1965, he managed to write several matriculation exams, at which he was highly successful. He intended to complete the rest of them during his army service. He was a youth of many interests, and was involved in various hobbies (chess, stamp and coin collecting, and autograph collecting). He was interested in sports, and participated in races, among other things. He loved to read books, and delved into them until his final day.
His boundless love for his family, his dedication and faithfulness to them, and his concern for every one of them, exudes from his letters to them while in the army.
He was prepared to help his fellow, and therefore, he was loved by all of his acquaintances. His modesty and righteousness were among his traits that endeared him to everyone.
He was able to delay his enlistment until his older brother finished his service. However, he refused to do so. He enlisted in the Israel Defense Forces when the time came. He was placed in a battle unit, and he said: It is a great honor to serve in such a unit.
He did not even manage to serve for a half a year, for on the 13th of Av 5625 (August 11, 1965), he fell. He was brought to eternal rest in the army cemetery in Kiryat Shaul. May his soul be bound in the bonds of eternal life.
He was born on January 7, 1918 in Hamborn, Germany. He served as a guard. He fell on his guard on the 7th of Nissan 1939, as he accompanied a postal bus in Haifa. His parents, Moshe and Sara (nee Adler) Dingut died in Haifa.
Perpetuated by his uncle Binyamin Adler and his sisters Tova and Ruth
Uncaptioned1 |
He was born on September 1, 1898 in Perehinsko, Poland. He lived in Germany from 1926, and was a merchant of furniture and confectionery. He made aliya to the Land with his family in 1938, at the beginning of the Second World War. In the Land, he volunteered to serve as a guard in the Israel Police force during the time of the British Mandate. He particpiated along with his son and many others in the defense of Kibbutz Shefiim, at the time that the British were searching for arms. He earned his livelihood from managing a restaurant, until the time that tragedy struck, when his only son fell during the War of Independence in 1948 during the conquest of Migdal Tzedek. The tragedy crushed him deeply, and he was not able to continue managing the restaurant. He accepted a job in the office of commerce and manufacturing. He was a member of the Committee of Bereaved Families in Petach Tikva from the day of its founding.
He bore the pain of the memory of his son for 20 years, and on the eve of Yom Haatzmaut (Israel Independence Day), 4th of Iyar 1968, during the memorial at the monument of Migdal Tzedek, he fell to the ground as he was walking up to lay a wreath for the fallen. Immediately upon his arrival home after the memorial service, he did not even have a chance to say a word, and he died. He suffered a heart attack.
May his memory be a blessing.
JewishGen, Inc. makes no representations regarding the accuracy of
the translation. The reader may wish to refer to the original material
for verification.
JewishGen is not responsible for inaccuracies or omissions in the original work and cannot rewrite or edit the text to correct inaccuracies and/or omissions.
Our mission is to produce a translation of the original work and we cannot verify the accuracy of statements or alter facts cited.
Rozhnyatov, Ukraine Yizkor Book Project JewishGen Home Page
Copyright © 1999-2024 by JewishGen, Inc.
Updated 2 Oct 2006 by LA


text:
Search History
Uh oh.
Sony SupportSpeakers
To get instruction manuals, help guides, or download PDF documents, please select your model in the list below, or type the model name in the search box.
Support Community
A place where you can find solutions and ask questions
Contact support
Contact our Support team
Warranty Information
Find information on Tourist Limited Warranty
Service Centres
List of Sony offices in Asia Pacific region that provide after-sales service activities
Support by Sony (Mobile App)
Never miss an update again! Find information and receive instant notifications about your product
Professional product support and services
Find support information for Broadcast & Professional products
Please accept Youtube cookies to watch this video
Access your cookie preferences below and make sure to switch on the Youtube cookie under the 'Functional' section.


text:
Just wanted to pass on our appreciation for always being there for us! This past Saturday (when it was crazy hot) out chillers went down briefly – but when our weekend staff called it in, your response was crazy quick. I know it was appreciated by all here at the library.
Thanks again, Zac
Zac T. Laugheed
Building Manager & Reference Assistant
Oregon State University Valley Library


text:
Introduction: Mary Harrell-Sesniak is a genealogist, author and editor with a strong technology background. In this guest blog post, Mary looks through newspaper articles to find stories about the oldest people to have ever lived—and issues a challenge to readers to find even greater claims of longevity in the newspapers.
With the Baby Boomers aging and advances in medicine, longevity is a hot topic in the news these days. There's a lot of talk about how long people lived in the past—and speculation about how long people will live in the near future.
Newspapers are a great resource to research how long our ancestors lived—and a good way to keep up with current health, medicine and aging issues going forward. According to knowledgeable sources, the oldest verified person to have ever lived attained the astonishing age of 122 years, 164 days!
Her name was Jeanne Calment (1875-1997), a resident of France. According to this 1997 Georgia newspaper article, she was interred in Trinquetaille Cemetery in Arles, France.
Several groups track longevity, including Wikipedia on this Oldest People webpage. Guinness World Records tracks the oldest person by specific activities. Some oldest-person GWR listings include the oldest person to have a total hip replacement, the oldest person to obtain a pilot's license, and the oldest person to sail around the world.
Those Guinness senior citizen records are all interesting, but it is more intriguing to focus on overall longevity.
Jeanne Calment, who received her certificate from Guinness Records in 1988 at the age of 113, passed away on 4 August 1997. This 1988 South Dakota newspaper article shows her in her ripe old age holding a large certificate noting her birth on 21 February 1875.
After her in the rankings of greatest longevity are three other centenarian women: Sarah Knauss (119 years), Lucy Hannah (117 years) and Marie-Louise Meilleur (117 years), although some verification of their ages is disputed.
Another entry in the greatest-longevity rankings whose age is disputed is Carrie White, who was supposedly 116 when she died in 1991. She was said to have been born in 1874, a time "when Ulysses S. Grant was president and Gen. George Armstrong Custer was still two years away from his last stand" according to this 1991 newspaper article from Illinois.
In 1998, when Sarah Knauss was informed of her honor as the oldest person alive, she reacted with a simple "So what?" according to this 1998 Illinois newspaper story found in the online archives.
Genealogical Challenge: Find the Oldest People to Ever Live
But who's really counting when you are a centenarian of distinction?
We are, that's who! So readers, we challenge you to verify the life of a centenarian older than any of the women mentioned above—or, alternatively, find the oldest claimed age at death. You'll find an outrageous assortment of longevity claims reported in GenealogyBank's historical newspaper archives, though certainly none as old as the Bible figure Methuselah—who reportedly attained an age of 969 years!
By browsing this collage of obituaries, you can review a succession of extraordinary longevity claims.
It's as if each newspaper wanted the bragging rights for the oldest centenarian. Did Andy Roark and Cato Pidgeon really attain the age of 130 years? Was it possible for Nancy Lawton to reach 140, and who was R. Sarman, reported to have lived to 160?
- Andy Roark: 130 years
- Cato Pidgeon: 130 years
- John Hannah: 136 years
- Nancy Lawton: 140 years
- Antionio Infante: 150 years
- Mary Tecuyas: 150 years
- R. Sarman: 160 years
I tried to verify these age claims, but was not successful. See if you can verify any of these ages—or, if not, see what other incredible age claims you can find in the newspapers.
Follow these guidelines and let us know what you find in the comments on our FaceBook or Blog page. There are two ways to participate in this longevity challenge.
Part 1: Verify a previously unknown oldest person
Submit evidence to prove and verify a centenarian's age older than Jeanne Calment.
Show supporting documentation, supported by generally accepted genealogical records (GAGR).
These may include civil and church registration, census, family records, and other documentation to show longevity. Tombstone photos alone do not suffice as evidence, as errors in birth years are often caused by confusion between persons of the same name.
Part 2: Find the oldest person as reported in an obituary
Even if you can't verify the longevity, let's see who can find the oldest reported person in an obituary or other newspaper article. No evidence is required—just an obituary or newspaper article from GenealogyBank, printed around the time of death. Recollections or reprints from long afterwards do not count.
Let's see who can come up with the most convincing proof of extreme longevity—and who can come up with the most incredible and unbelievable claim of extreme old age!
Good luck! We look forward to your responses.
"In this world nothing can be said to be certain, except death and taxes."
—The Works of Benjamin Franklin (1817)


text:
Polycom VVX 401 12 Line VoIP Phone w/power supply
The Polycom VVX 401 replaces the Polycom VVX 400 and comes with these enhancements:
- Enhanced processing power
- Improved memory
- Additional USB port
The Polycom VVX 401 is a 12 line HD Voice business media phone with a 3.5" color LCD display and dual 10/100 RJ45 ports. Designed with office staff and knowledge workers in mind the VVX 401 has an easy thanks to the color display and easy integration with third-party UC and productivity applications.
Polycom VVX 401 12 Line VoIP Phone Overview
The Polycom VVX 401 is an expandable color business media phone that delivers crystal clear communications enhanced collaboration and personal productivity.
With the VVX 401 Polycom phone you can bring a high-quality, cost-effective desktop telephony solution to front line staff handling moderate volume of calls through advanced UC telephony features. The intuitive color user interface of the VVX 401 makes navigation easy and requires minimal training. Unsurpassed voice quality and clarity The VVX 401 delivers breakthrough Polycom HD Voice quality for life-like conversations, while minimizing fatigue making calls more efficient and productive.
The VVX 401 you can improve personal productivity by complementing workplace applications on the computer. Users can view and manage their Microsoft Exchange Calendars, receive meeting reminders and alerts, access the corporate directory and Instant Messaging/presence status right on their phone display, even while waiting for their PC to boot. They can also extend their PC's desktop to include this Polycom VVX phone's screen for mouse/keyboard navigation and interaction.
The Polycom VVX 401 phone is easy to deploy and simple to manage. Using an enterprise-grade, web-based, configuration method allows administrators to easily provision and maintain even a small number of phones throughout the entire organization.
This multimedia VoIP phone provides personalized information at a glance, through built-in web applications and custom backgrounds. The VVX 401 phone also comes ready for future expansion modules as your users' need and business grows.
Polycom VVX 401 Features and Functions:
- 12 Line appearances
- Polycom HD Voice
- 3.5" (320x240) Backlit Color LCD
- Dual 10/100 RJ45 Ports
- RJ9 headset port
- Built-in auto sensing IEEE 802.3 af Power over Ethernet
- 48V DC power supply included


text:
During the expansion of fat mass in obesity, vascularization of adipose tissue is insufficient to maintain tissue normoxia. Local hypoxia develops and may result in altered adipokine expression, proinflammatory macrophage recruitment, and insulin resistance. We investigated whether an increase in adipose tissue angiogenesis could protect against obesity-induced hypoxia and, consequently, insulin resistance. Transgenic mice overexpressing vascular endothelial growth factor (VEGF) in brown adipose tissue (BAT) and white adipose tissue (WAT) were generated. Vessel formation, metabolism, and inflammation were studied in VEGF transgenic mice and wild-type littermates fed chow or a high-fat diet. Overexpression of VEGF resulted in increased blood vessel number and size in both WAT and BAT and protection against high-fat diet–induced hypoxia and obesity, with no differences in food intake. This was associated with increased thermogenesis and energy expenditure. Moreover, whole-body insulin sensitivity and glucose tolerance were improved. Transgenic mice presented increased macrophage infiltration, with a higher number of M2 anti-inflammatory and fewer M1 proinflammatory macrophages than wild-type littermates, thus maintaining an anti-inflammatory milieu that could avoid insulin resistance. These studies suggest that overexpression of VEGF in adipose tissue is a potential therapeutic strategy for the prevention of obesity and insulin resistance.
Obesity, an epidemic disease whose prevalence is increasing at an alarming rate, is a major risk factor for serious chronic diseases, including insulin resistance, type 2 diabetes, and cardiovascular disease (1,2). However, the mechanisms through which obesity leads to these metabolic complications are not fully understood. Adipose tissue mass increases during obesity, and to provide sufficient oxygen and nutrients to all cells, angiogenesis has to support adipose tissue growth (3). Several studies postulate that during obesity, this enlargement of the vascular network is not sufficient to supply enough oxygen to all adipocytes and local hypoxia occurs (4–7). It has been hypothesized that this insufficient adipose tissue blood flow may trigger insulin resistance via effects on inflammation, adipokine expression, and/or adipocyte differentiation (8–10).
Adipose tissue macrophages (ATMs) play an important role in the establishment of the chronic inflammatory state associated with obesity and its metabolic dysfunctions (11,12). Lumeng et al. (13) demonstrated in recent studies that ATMs from lean mice are M2 or "alternatively activated" macrophages, whereas ATMs from obese mice are predominantly M1 or "classically activated" macrophages. Whereas M2 macrophages present anti-inflammatory properties and are associated with angiogenesis and wound repair, M1 macrophages are associated with inflammation. The cross-talk among proinflammatory macrophages, adipocytes, and endothelial cells during obesity may aggravate the inflammatory state, resulting in increased secretion of proinflammatory molecules, including acute-phase reactants, procoagulant factors, cytokines, and chemokines (8,14,15). These factors can cause local and/or systemic insulin resistance in a paracrine, autocrine, and/or endocrine fashion.
We therefore hypothesized that an increase in adipose tissue angiogenesis may protect from obesity-induced hypoxia, and consequently, from inflammation and insulin resistance in this tissue. Vascular endothelial growth factor (VEGF) is a key factor involved in adipose tissue angiogenesis (16–18); however, its role and expression levels during obesity remain unclear (6,7,19). Thus, to determine the effects of an increase in VEGF levels in adipose tissue, transgenic mice overexpressing VEGF in WAT and BAT were obtained. Our results indicate that VEGF overexpression led to increases in vascularization and in the amount of M2 anti-inflammatory macrophages, which protected transgenic mice not only against high-fat diet (HFD)–induced obesity but also insulin resistance.
Transgenic mice expressing the aP2/Vegf chimeric gene were obtained by microinjection of oocytes from C57Bl6/SJL mice. Mice were kept in a pathogen-free facility (Servei d'Estabulació de Ratolins-Centre de Biotecnologia Animal i Teràpia Gènica) and maintained under a 12-h light–dark cycle at 22°C. Mice were fed ad libitum for 15 weeks with a chow diet (2018S Harlan Teklad, Madison, WI) or an HFD (TD88137 Harlan Teklad). When stated, mice were fasted for 16 h.
An indirect open circuit calorimeter (Oxylet, Panlab, Cornellà, Spain) was used to monitor oxygen consumption, carbon dioxide production, and locomotor activity in eight metabolic chambers simultaneously. Mice were individualized and acclimated to the metabolic chambers for 24 h, and data were collected every 15 min for 3 min in each cage. Data were taken from the light and dark cycle. The LE5007 system (Panlab) was used to measure blood pressure, and animals were kept in a restrainer and heated using the Heater Scanner LE 5650/6 (Panlab). Animals were anesthetized and killed, and tissues of interest were excised and kept at −80°C or preserved with formalin until analysis. Animal care and experimental procedures were approved by the Ethics Committee in Animal and Human Experimentation of the Universitat Autònoma de Barcelona.
Gene expression analysis.
For quantitative real-time PCR analysis, total RNA was extracted from different tissues using TriPure isolation reagent (Roche, Mannheim, Germany) for nonfat tissues and QIAZOL (Qiagen, Hilden, Germany) for fat tissues, and Rneasy Mini Kit (Qiagen). Total RNA (1μg) was retrotranscribed using the SuperScript VILO cDNA Synthesis Kit (Invitrogen, Carlsbad, CA). Real-time PCR was performed in a SmartCycler II (Cepheid, Sunnyvale, CA) using EXPRESS 2× qPCR SuperMix (Invitrogen). Oligonucleotide sequences were: Vegfa164–FW: 5′-AGACAGAACAAAGCCAGAAATC-AC-3′, RV: 5′-CACGTCTGCGGATCTTGGAC-3′; Pecam-1–FW: 5′-CTGGTG-CTCTATGCAAGCCTC-3′, RV: 5′-CGGTGCTGAGACCTGCTTT-3′; Kdr–FW: 5′-AGCTTGGCTCACAGGCAACAT-3′, RV: 5′-TGGCCCGCTTAACGGTCCG-TA-3′; Srebf1–FW: 5′-GGAGCCATGGATTGCACATT-3′, RV: 5′-GCTTCCAGA-GAGGAGGCCAG-3′; Fasn–FW: 5′-GCTGCGGAAACTTCAGGAAAT-3′, RV: 5′-AGAGACGTGTCACTCCTGGAC-3′; Il10–FW: 5′-CTATGCTGCCTGCTCT-TACTG-3′, RV: 5′-AACCCAAGTAACCCTTAAAGTC-3′; Arg1–FW: 5′-GGAATC-TGCATGGGCAACCTGTGT-3′, RV: 5′-AGGGTCTACGTCTCGCAAGCCA-3′; Hif1a–FW: 5′-GACTAGACAAAGTTCACCTGAGA-3′, RV: 5′-CGCTATCCA-CATCAAAGCAA-3′; Cxcl12–FW: 5′-TGCATCAGTGACGGTAAACCA-3′, RV: 5′-TTCTTCAGCCGTGCAACAATC-3′; Lep–FW: 5′-GAGACCCCTGTGTCGGT-TC-3′, RV: 5′-CTGCGTGTGTGAAATGTCATTG-3′; Adipoq–FW: 5′-TGTTCCT-CTTAATCCTGCCCA-3′, RV: 5′-CCAACCTGCACAAGTTCCCTT-3′; and 36B4–FW: 5′-TCCCACCTTGTCTCCAGTCT-3′, RV: 5′-ACTGGTCTAGGACCCGA-GAAG-3′.
Western blot analysis.
Tissues were homogenized in protein lysis buffer as previously described (20). Primary antibodies were anti-VEGF (Abcam ab46154, Cambridge, U.K.); anti–hypoxia-inducible factor (HIF)-1α (Abcam ab1); anti-uncoupling protein (UCP)1 (Abcam ab10983); anti-peroxisome proliferator–activated receptor γ coactivator (PGC)-1α (Chemicon AB3242, Millipore, Billerica, MA); anti-Akt (Cell Signaling 9272, Danvers, MA) and anti–phospho-Akt (Ser473) (Cell Signaling 9271).
Immunohistochemical and morphometric analysis.
Tissues were fixed for 24 h in formalin, embedded in paraffin, and sectioned. For immunohistochemical detection, sections were deparaffinized and incubated overnight at 4°C with antibody against Mac-2 (Cederlane CL8942AP, Ontario, Canada) or against VEGF (Abcam ab46154), washed with PBS three times for 5 min for each wash, incubated with the corresponding secondary antibodies, and revealed with ABC Complex (Vector Laboratories Ltd., Peterborough, U.K.). Sections were counterstained in Mayer's hematoxylin.
Measurement of the adipocyte area.
A morphometric study of adipocytes size was performed in WAT sections stained with hematoxylin-eosin. Adipocytes area was determined as previously described (21). Four animals per group were used and at least 250 adipocytes per animal were analyzed.
Transmission electron microscopy analysis.
WAT and BAT samples were processed as described elsewhere (22).
Fluorescein angiography.
Mice were injected with 10 mL/kg fluorescein isothiocyanate–conjugated dextran solution (50 mg/mL; Sigma-Aldrich, St. Louis, MO). After 10 min, animals were killed and tissues were dissected and placed in formalin. Samples were incubated with rhodamine-phalloidin, placed on glass slides covered with mounting media for fluorescence (Vectashield, Peterborough, U.K.), and analyzed on a laser-scanning confocal microscope (Leica Mycrosystems, Wetzlar, Germany) at original magnification ×400. Each image represents an overlay of 20 images (WAT) or 30 images (BAT) separated by 1 μm. For morphometric analysis, the vessel area of 10 consecutive images was measured.
Hypoxyprobe staining.
Hypoxyprobe staining was performed using the Hypoxyprobe-1 Kit (Hypoxyprobe Inc., Burlington, MA). Pimonidazole (60 mg/kg) was injected into mice via a tail vein 30 min before sampling. Samples were removed, fixed, and processed according to the manufacturer's instructions.
Glucose and insulin-tolerance tests.
Glucose and insulin-tolerance tests were performed as previously described (20). Briefly, mice were given an intraperitoneal injection of glucose or insulin, and the glucose concentration was determined in blood samples at indicated time points.
Insulin signaling.
To study insulin signaling, overnight fasted animals were anesthetized and quadriceps and a piece of epididymal adipose tissue were excised and frozen into liquid nitrogen. Immediately, mice were intraperitoneally injected with insulin (0.15 units/g body weight). Ten minutes later, other tissues were excised and frozen. Protein extracts of different samples were obtained for Western blot analysis.
Enzyme, metabolite, and hormone assays.
Tissue triglyceride content was determined by extracting total lipids from liver, quadriceps, kidney, and heart samples with chloroform-methanol (2:1 vol/vol), as described by Carr et al. (23). Triglycerides, total cholesterol, and HDL cholesterol were quantified spectrophotometrically using an enzymatic assay kit (Horiba-ABX, Montpellier, France). Serum free fatty acids (FFAs) were measured by the acyl-CoA synthase and acyl-CoA oxidase methods (Wako Chemicals GmbH, Neuss, Germany). Serum glycerol concentration was determined enzymatically (Randox Laboratory, Crumlin, U.K.). All biochemical parameters were determined using a Pentra 400 Analyzer (Horiba-ABX). Glucose was determined using a Glucometer Elite analyzer (Bayer, Leverkusen, Germany), and insulin levels were measured using the Rat Insulin ELISA Kit (Crystal Chemical, Chicago, IL). Leptin concentration was determined using the Mouse Leptin ELISA Kit (Crystal Chemical). VEGF protein levels were measured using the Mouse VEGF ELISA Kit (Calbiochem, Darmstadt, Germany). Serum monocyte chemoattractant protein (MCP)-1 levels were determined using the Mouse MCP-1 ELISA Kit (eBioscience, San Diego, CA), and serum adiponectin levels were measured by mouse/rat RIA Kit (Millipore, Billerica, MA). MCP-1, interferon (IFN)-γ, interleukin (IL)-6, and tumor necrosis factor (TNF)-α WAT protein levels were measured by Luminex xMAP using Millipore reagents and instructions.
Isolation of the WAT stroma vascular fraction.
WAT was excised and put in a tube containing PBS/BSA 0.5% solution (2 mL) at 37°C. The tissue was minced and digested at 37°C for 30 min by the addition of 1 mg/mL collagenase P from Clostridium histolyticum (Roche). The supernatant was filtered through a 30-μm pore filter (Partec CellTrics, Görlitz, Deutschland) to obtain a single cell suspension, and the filtrate was recollected in Falcon tubes. After the addition of PBS/BSA 0.5%, the filtrate was spun. Supernatant was eliminated, and the pellet was resuspended in RBC lysis buffer (eBioscience) and incubated for 5 min to break the erythrocytes. After addition of PBS/BSA 0.5% and a spin, the pellet was resuspended in 500 μL PBS/BSA 0.5%.
Flow cytometry.
The stroma vascular fraction was incubated with specific antibodies: phycoerythrin (PE) anti-mouse cluster of differentiation (CD)11b (BD Pharmigen 557397, Franklin Lakes, NJ), PE/Cy7 anti-mouse CD11b (Biolegend 101216, San Diego, CA), PE anti-mouse CD11c (BD Pharmigen 557401), fluorescein isothiocyanate anti-mouse F4/80 (Biolegend 123107), AlexaFluor 488 anti-mouse CD301 (AdB Serotec MCA2391A488T, Düsseldorf, Germany), and PE/Cy5 anti-mouse major histocompatibility complex (MHC) II (Biolegend 107611). Flow cytometric analysis was performed on a FC500 MPL (Beckman Coulter) equipped with an argon ion laser (488 nm, 20-mW output) and a red helium-neon laser (633 nm, 20-mW output). Data were analyzed using FCS3 Express software (De Novo Software, Los Angeles, CA).
Isolation and culture of bone marrow–derived macrophages (BMDMs).
BMDMs were prepared from the femur and tibia of mice. Cells were cultured with complete RPMI supplemented with macrophage colony-stimulating factor (Gibco, Invitrogen) for 7 days (24) and then treated with 100 ng/mL recombinant mVEGF (Cell Signaling) for 24 h before collection of the cells.
Statistical analysis.
All values are expressed as the mean ± SEM. Differences between groups were compared by Student t test. Statistical significance was considered if P < 0.05.
Adipose-specific overexpression of VEGF leads to increased vessel density.
Two transgenic mouse lines (L1 and L2) expressing VEGF under the control of the adipose-specific aP2 promoter were obtained. L1 showed a slight increase in VEGF expression levels (data not shown), whereas L2 showed a high increase and this line was further studied. After Northern blot analysis, a marked increase in total Vegf mRNA levels was detected in WAT and BAT but not in skeletal muscle or liver from transgenic animals (Fig. 1A). Moreover, Vegf164 mRNA levels were highly increased in different WAT depots (epididymal, retroperitoneal, and subcutaneous) and in interscapular BAT of transgenic mice (Fig. 1B). This increase was parallel to an increase in VEGF protein levels detected by immunohistochemistry or by Western blot (Fig. 1C and D). However, no differences in VEGF serum levels were detected between groups, probably due to the retention of VEGF by the extracellular matrix (Fig. 1E).
Because VEGF is a potent activator of angiogenesis, the effects of VEGF overexpression on vascularization were analyzed. Macroscopic observation showed that WAT and BAT were reddish (Fig. 1F), suggesting increased blood flow in the adipose tissue of transgenic mice. After tail-vein dextran-conjugated fluorescein injection and phalloidin staining, WAT and BAT angiographies showed an increase in functional blood vessels in the transgenic mice (Fig. 1G). The vessel/adipocyte area in wild-type compared with transgenic mice related to adipocyte area was increased in epididymal (0.27 ± 0.08 and 1.16 ± 0.17%, n = 4; P ≤ 0.01), retroperitoneal (0.24 ± 0.06 and 0.59 ± 0.10%, n = 4; P ≤ 0.05), and subcutaneous (0.23 ± 0.05 and 0.47 ± 0.05%, n = 4; P ≤ 0.05) fat depots. Moreover, the specificity of the increase in vessel density in epididymal, retroperitoneal, subcutaneous WAT and interscapular BAT was corroborated by Pecam-1 and Kdr expression levels (Supplementary Fig. 1A and B).
Transmission electron microscopy showed that capillaries from transgenic WAT and BAT were highly dilated (Fig. 1H), suggesting increased blood flow and oxygen supply to surrounding cells. Some edema was observed, suggesting an effect of VEGF on vessel permeability, although no fenestrations and a similar number of vesicles were observed in BAT capillaries of transgenic mice (Supplementary Fig. 1C and D). Metabolic parameters were determined in 6- and 12-month-old mice, and no differences between wild-type and transgenic mice were observed (Supplementary Table 1).
Lower adiposity in aP2VEGF transgenic mice fed an HFD.
To examine whether an increase in adipose tissue angiogenesis could protect against obesity-induced hypoxia and, consequently, avoid inflammation and insulin resistance, transgenic mice were studied under HFD conditions. After 15 weeks of the HFD, weight gain increased by 30% in wild-type mice but only by 10% in aP2VEGF transgenic mice (Fig. 2A), although food intake was similar between the groups (Fig. 2B). In parallel to weight gain, the WAT weight and the adipocyte mean size increases were greater in wild-type mice than in transgenic mice (Fig. 2C and D). The frequency distribution of the area of white adipocytes was also different between groups. Wild-type mice fed an HFD presented fewer small adipocytes and an increase in the number of large adipocytes (Fig. 2E). In contrast, transgenic mice fed an HFD only presented an increased number of intermediate-sized adipocytes (Fig. 2E). Therefore, the HFD-induced hypertrophy of adipocytes observed in wild-type mice was attenuated in transgenic mice overexpressing VEGF. In addition, local hypoxia in WAT was only detected in control mice fed an HFD, suggesting that transgenic mice did not develop hypoxia (Fig. 2F). Accordingly, the HFD increased mRNA and protein levels of the hypoxia-inducible transcription factor (Hif1a) in wild-type mice but not in transgenic mice (Fig. 2G and H). Thus, VEGF overexpression in adipose tissue protected transgenic mice from diet-induced obesity and local hypoxia.
Transgenic mice showed increased thermogenesis activity.
Histologic analysis of BAT in mice fed the chow diet showed that the morphology of this tissue was altered in transgenic mice, probably due to the presence of high vascularization (Fig. 3A). In addition, the interscapular BAT weight was almost twofold higher in transgenic mice than in wild-type animals (Fig. 3B). In contrast, when fed an HFD, BAT weight increased only in wild-type animals (Fig. 3B), probably due to less lipid deposition in transgenic mice. Total UCP1 (Fig. 3C) and PGC-1α (Fig. 3D) protein levels increased significantly in BAT of transgenic mice fed an HFD compared with wild-type mice. Accordingly, the energy expenditure of HFD-fed transgenic mice during the dark cycle (activity phase) was higher than that of wild-type mice (Fig. 3E), without changes in spontaneous locomotor activity (Fig. 3F). Body temperature was also more elevated in transgenic mice fed a chow diet compared with wild-type mice (Fig. 3G). However, body temperature increased to the same extent in wild-type and transgenic mice fed an HFD (Fig. 3G). Altogether, these data suggest that transgenic mice have increased thermogenic activity.
Less fat accumulation in nonadipose tissues of transgenic mice.
Liver histologic sections showed no morphologic alterations in transgenic mice fed a chow diet. When fed an HFD, wild-type mice showed increased lipid accumulation in hepatocytes compared with transgenic mice (Fig. 4A and B). Similarly, sterol regulatory element-binding protein-1c (Srebf1) and fatty acid synthase (Fasn) expression were both increased in wild-type animals fed an HFD but not in transgenic mice fed an HFD (Fig. 4C and D). No differences in triglyceride content in skeletal muscle, heart, and kidney were detected between groups fed a chow diet. On an HFD, triglyceride content in skeletal muscle increased to a greater extent in wild-type animals than in transgenic mice but remained unchanged in heart and kidney (Fig. 4E–G).
Lipid profile after an HFD.
Wild-type animals fed an HFD presented increased serum FFA and glycerol, whereas transgenic mice had a similar increase in FFA but not in glycerol levels (Fig. 5A and B). This suggested differences in FFA re-esterification between wild-type and transgenic mice. Similarly, transgenic mice fed an HFD presented lower triglyceride levels than wild-type mice (Fig. 5C). Transgenic mice also showed a lower HFD-induced increase in total and HDL cholesterol levels than wild-type mice (Fig. 5D and E). The origin of these alterations is not known. No changes in blood pressure were observed in transgenic mice (Fig. 5F).
aP2VEGF transgenic mice are protected against diet-induced glucose intolerance and insulin resistance.
Wild-type and transgenic animals fed a chow diet were normoglycemic, normoinsulinemic, and presented similar insulin sensitivity and glucose tolerance (Fig. 6). However, glucose and insulin levels significantly increased in wild-type mice fed an HFD but remained lower in transgenic mice (Fig. 6Aand B). An intraperitoneal insulin-tolerance test showed that insulin response was blunted in HFD-fed wild-type mice, whereas glucose levels were reduced by 40% in transgenic mice, indicating that they remained insulin-sensitive (Fig. 6C). In addition, wild-type mice fed an HFD presented impaired glucose tolerance whereas transgenic mice showed preserved glucose response (Fig. 6D). Accordingly, in adipose tissue and skeletal muscle, insulin-stimulated phosphorylation of Akt on Ser473 remained unaltered by the HFD in transgenic mice, whereas the insulin response was blunted in wild-type mice (Fig. 6E). Therefore, these results indicated that transgenic mice fed an HFD remained glucose-tolerant and insulin-sensitive.
VEGF overexpression increases M2 anti-inflammatory macrophages and reduces M1 proinflammatory macrophages in adipose tissue.
In addition to inducing angiogenesis, VEGF is involved in macrophage recruitment (25). In wild-type mice, cells positive for the macrophage marker MAC-2 were only detected in BAT and WAT under HFD conditions (Fig. 7A). In contrast, transgenic mice fed an HFD or chow presented MAC-2–positive cells in both WAT and BAT (Fig. 7A). The population of the infiltrate was further analyzed by flow cytometry analysis. Accordingly, the percentage of CD11b+F480+ cells was lower in wild-type mice fed chow than in all the other groups (Fig. 7B). The percentage of MHCII+CD11b+ and MHCII+CD11c+ double-positive cells was increased in HFD-fed wild-type mice but not in transgenic mice (Fig. 7C and D), indicating that the HFD induced a higher capacity for antigen presentation in macrophages and dendritic cells of wild-type mice. Moreover, transgenic mice fed both chow and the HFD presented lower M1 proinflammatory macrophages (decreased CD11chigh F4/80+ cells; Fig. 7E) and an increase in M2 anti-inflammatory macrophages (increased MGL1+CD11b+ cells; Fig. 7F).
The enrichment of M2 vs M1 macrophages in the WAT of transgenic mice could influence the profile of proinflammatory cytokines production. Indeed, levels of leptin and MCP-1 were dramatically increased in wild-type mice fed an HFD but were only slightly increased in transgenic mice (Fig. 8A–D). Similarly, the WAT of wild-type but not transgenic mice presented increased IFN-γ protein levels under the HFD (Fig. 8E). In addition, transgenic mice had lower IL-6 and TNF-α WAT protein levels (Fig. 8F and G). In contrast, levels of the anti-inflammatory adipokine, adiponectin, remained unchanged in all groups (Fig. 8H and I).
To examine whether VEGF could switch macrophages to the M2 phenotype, BMDMs were treated with VEGF; however, this treatment did not lead to an increase in M2 markers such as Arg1 or Il10 (Fig. 8J and K). Because VEGF receptor 2 (VEGFR2) (Kdr) together with the chemokine stromal cell-derived factor (SDF)-1 (Cxcl12) are involved in VEGF-induced macrophage mobilization and retention in adipose tissue (26), expression of Kdr in macrophages and Cxcl12 in adipose tissue was examined. In transgenic mice, Kdr and Cxcl12 expression were both increased compared with wild-type mice (Fig. 8L and M). These results suggest that VEGF may attract M2 macrophages in adipose tissue through macrophage-VEGFR2 and SDF1.
Studies have reported that angiogenesis fails to maintain normoxia in adipose depots and that local hypoxia occurs in obesity (4,5). Thus, it has been hypothesized that this reduction in adipose tissue blood flow may trigger insulin resistance. To examine whether an increase in adipose tissue angiogenesis could protect against insulin resistance, transgenic mice overexpressing VEGF in adipose tissue were generated. Although adipose tissue angiogenesis can be promoted by several factors, such as leptin, HIF-1α, or VEGF, overexpression of leptin in adipose tissue failed to induce angiogenesis (27), and transgenic mice with dominant, active HIF-1α presented fibrosis but not vessel growth (28). Our study showed that overexpression of VEGF164 was able to induce vessel formation in both WAT and BAT. Moreover, fluorescein angiographies and electron microscopy studies both showed that these blood vessels were functional and more dilated. In accordance with our results, other studies in which VEGF164 was expressed demonstrated the ability of this isoform to induce the development of new vessels (29). Furthermore, we did not observe an increase in vessel density in nonadipose tissues of the transgenic mice. Indeed, to enhance angiogenesis, the correct relationship between VEGF gradient and concentration is determinant (30), and in our transgenic mice, this may only be present in the site of production.
To our knowledge, this is the first time that the effects of increased angiogenesis on adipose tissue growth and insulin resistance have been studied. However, because it is well established that the expansion of adipose tissue is supported by angiogenesis (31), several studies have developed antiangiogenesis approaches to achieve a therapeutic intervention of obesity. Administration of angiogenic inhibitors to obese mice has resulted in decreased adipose tissue mass and concomitant weight loss (17,32,33). Although the inhibition of angiogenesis seems to prevent the expansion of adipose tissue mass, our results demonstrate that an increase in vessel density does not result in an increase in the mass of WAT.
Noticeably, the protection against HFD-induced obesity of transgenic mice could be explained by the enhanced energy expenditure and the increase in total protein levels of key genes involved in thermogenesis and mitochondrial biogenesis in BAT, such as UCP1 and PGC-1α (34). In accordance with our studies, transgenic mice overexpressing UCP1 in adipose tissue are protected against HFD-induced obesity (35). Moreover, the greater BAT vessel density of transgenic mice may be comparable to that observed during cold exposure. Indeed, cold exposure enhances BAT angiogenesis in a hypoxia-independent but VEGF-dependent process (36), and increased BAT vessel density enables higher rate of blood perfusion to supply oxygen and FFAs and to facilitate heat dissipation, all of them necessary for UCP1-induced thermogenesis. Taken together, our data suggest that increased vascularization in the BAT of transgenic mice increases BAT size and enhances UCP1 expression and thermogenesis. Thus, phenotypic changes in the body weight of aP2VEGF transgenic mice may be attributed to the increased energy expenditure and thermogenic activity of BAT. Furthermore, recent studies suggest that BAT is more abundant in adult humans than previously recognized (37–40). As a consequence, strategies aimed at stimulating the generation and/or activation of BAT, such as enhancing BAT angiogenesis, might lead to new approaches to counteract obesity.
Transgenic mice were protected not only against HFD-induced obesity but also systemic insulin resistance. Glucose tolerance and insulin sensitivity were both improved in transgenic mice. The absence of insulin resistance in these mice may be linked not only to a lack of fat accumulation but also to decreased infiltration of proinflammatory macrophages. It is well accepted that adipose tissue contains BMDMs and that the content of these macrophages correlates with the degree of obesity and insulin resistance (12,41). Strikingly, despite being neither obese nor insulin resistant, transgenic mice presented significant macrophage infiltration when fed not only an HFD but also the chow diet. However, flow cytometry analysis indicated lower M1 proinflammatory and increased M2 anti-inflammatory macrophages in the adipose tissue of aP2VEGF transgenic mice.
Our current understanding of how adipose tissue macrophages promote obesity-associated insulin resistance is based on the model proposed by Lumeng et al. (13), in which the recruitment of M1 macrophages promotes the change of the anti-inflammatory milieu maintained by M2 macrophages toward an inflammatory state. Therefore, the decrease in M1 proinflammatory and increased presence of M2 anti-inflammatory macrophages in adipose tissue of our mice may be protecting them from insulin resistance. In line with our studies, the ablation of CD11c+ cells in mice leads to a marked reduction in proinflammatory cytokines and an improvement of insulin sensitivity (42). Furthermore, selective inactivation of peroxisome proliferator–activated receptor (PPAR)-γ in macrophages results in an impairment of M2 macrophages maturation, leading to insulin resistance and glucose intolerance (43). The amount of dendritic cells and macrophages positive for MHCII was also reduced. MHCII is often linked with increased inflammatory response. Indeed, MHCII knockout mice exhibit reduced secretion of proinflammatory cytokines in macrophages (44). In accordance with the reduced infiltration by M1 macrophages, the expression of adipose tissue proinflammatory cytokines, such as leptin, IFN-γ, MCP-1, IL-6, and TNF-α, was reduced in HFD-fed transgenic mice compared with wild-type mice. This decrease may, in turn, have led to lower grade of adipose tissue M1 macrophage infiltration. Therefore, the reduction of M1 adipose tissue macrophages and the lower proinflammatory cytokine secretion in our mice may protect them from the development of insulin resistance.
We demonstrate that VEGF enhances the presence of M2 anti-inflammatory macrophages in the adipose tissue of these mice. However, whether VEGF acts as a specific chemotactic for M2 macrophages in adipose tissue or promotes macrophage polarization switch toward an M2 phenotype remains unclear. The inability of VEGF to increase the expression of M2 markers in BMDMs suggests that VEGF alone is not able to induce the switch toward the M2 phenotype. Recent studies have demonstrated that another cytokine, adiponectin, is able to promote macrophage polarization toward an M2 phenotype (45,46). However, adiponectin levels remained unchanged in our model, thus excluding a role of this adipokine in the transgenic phenotype. This suggests that VEGF is probably attracting M2 macrophages to adipose tissue. Consistent with this, VEGF plays a major role in wound repair and angiogenesis, processes likely involving mobilization of M2 macrophages (47,48). In addition, VEGF enhances angiogenesis in adipose tissue by inducing macrophage recruitment and retention through its receptor VEGFR2 (Kdr) (26). The chemokine SDF-1 (Cxcl12) is critical in this process (26). Moreover, SDF-1 is upregulated by VEGF (49). In agreement with this, expression of macrophage Kdr and adipose tissue Cxcl12 were both increased in aP2VEGF mice, suggesting that the increase in M2 macrophages is due to the chemotactic activity of VEGF. Altogether, these results suggest that VEGF may attract M2 macrophages to adipose tissue through VEGFR2 and SDF1.
In summary, we show that overexpression of VEGF displays beneficial effects. In BAT, our results highlight the crucial role of vascularization in promoting its size and thermogenesis as a means to counteract the development of HFD-induced obesity. In WAT, the increase of angiogenesis promoted by VEGF overexpression did not lead to an increase in adipose tissue mass. Moreover, adipose tissue from animals overexpressing VEGF presented increased recruitment of M2 anti-inflammatory macrophages, thus maintaining an anti-inflammatory milieu and avoiding insulin resistance. Therefore, targeting VEGF expression in adipose tissue may offer the opportunity for a novel therapeutic approach to prevent or even treat the progression of obesity-related insulin resistance.
This work was supported by grants from the Ministerio de Ciencia e Innovación, Plan Nacional I+D+I (SAF2008-00962) and Generalitat de Catalunya (2009 SGR-224), Spain, and the European Community's FP6 EUGENE2 (LSHM-CT-2004-512013) and EUMODIC (LSHG-CT-2006-037188). L.V. received postdoctoral fellowship Juan de la Cierva (Ministerio de Ciencia e Innovacion).
No potential conflicts of interest relevant to this article were reported.
I.E. and S.F. conceived the experiments, researched data, contributed to discussion, and wrote the manuscript. T.F. researched data and contributed to discussion. L.V., S.T., S.M., C.R., D.R., A.P., E.R., and J.R. researched data. F.B. conceived the experiments, contributed to discussion, and wrote the manuscript. F.B. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
The authors thank Drs. Malcolm Watford (Rutgers University) and Virginia Haurigot (Universitat Autònoma de Barcelona) for helpful discussion and Marta Moya (Universitat Autònoma de Barcelona) and Mireia Zaguirre (Universitat Autònoma de Barcelona) for technical assistance.


text:
The Rock Cycle Influences Climate
The Rock Cycle Influences Climate (and Other Global Changes) Over a Long Timescales!
Plate tectonics: Plate tectonics is responsible for the positions of continents which can have a large effect on regional and global climates.
- When all continents come together to forms supercontinents, the amount of coastal area is decreased and the amount of dry continental interiors is increased.
- If continents are moved to high latitudes, more ice sheets form and sea level falls.
- Growth of mountain ranges affects atmospheric circulation patterns and the number of alpine glaciers.
- Change in the rate of tectonic activity causes changes in the amount of volcanism. More volcanism means more sulfuric acid/ash blocking solar radiation
- Increased sea floor spreading causes sea level rise since newly formed ocean crust will "float" higher on the mantle decreasing the volume of ocean basins.
Rate of limestone production: Marine limestone sequesters carbon, decreasing the amount in seawater, and ultimately decreasing the amount of the greenhouse gas carbon dioxide in the atmosphere.
Rate of fossil fuel production: Fossil fuels sequester carbon deep underground (until they are extracted and burned, releasing carbon dioxide into the atmosphere).
Evolution of new species: Organisms affect the composition of the atmosphere, so new species can have a new effect on the amount of greenhouse gases. For instance, about 3.5 billion years ago stromatolites (blue-green algae) oxygenated the atmosphere through photosynthesis, and extensive swamps during the Pennsylvanian period trapped carbon.