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In the raucous debate over the cuts in federal spending, also known as the sequester, which began taking effect Friday, a lot of numbers are being tossed around -- $85 billion, $42 billion, $1.2 trillion. And lots of adjectives, too -- "massive," "deep," "severe," "arbitrary" and more.
You'd think that numbers would be more precise than adjectives, but there's no agreement on the correct number to describe the size of the spending cuts required by the 2011 Budget Control Act.
CNBC's John Harwood joins Lester Holt for more on the sequester.
The Congressional Budget Office explained last week that while the often-used figure of $85 billion "represents the reduction in budgetary resources available to government agencies this year" – the cash that would be on hand for agencies to spend -- in fact "not all of that money would have been spent in this fiscal year."
Why is that?
Federal departments and agencies would have used some of that $85 billion to "enter into contracts to buy goods or services to be provided and paid for next year or in subsequent years," the CBO said.
For instance, if the Navy is buying some submarines or if the Missile Defense Agency is buying new satellites, it may take them a few years to spend the money to do so.
Thus, since not all of the $85 billion would have been spent anyway in the current fiscal year, the CBO said that in fact $42 billion will be the actual size of the cut in outlays in the fiscal year which ends on Sept. 30.
And how large is $42 billion when compared to the total amount of federal outlays?
The federal government's outlays this fiscal year will total $3.55 trillion, according to the CBO's latest estimate. Do the arithmetic and you'll see that $42 billion is 1.16 percent of what the federal government would have spent this year if there had there been no sequester.
A 1.16 percent cut does not seem "massive."
But the cuts do not apply equally across the board to every single category of federal spending – even though the term "across the board" is often used to describe the cuts.
In reality, the Budget Control Act was designed to shield much federal spending from the spending cuts.
Pablo Martinez Monsivais / AP
The White House is seen through a chain-link fence where the inaugural reviewing stand once stood, Monday, March 4, 2013, in Washington, as the tear down on Pennsylvania Avenue from the inaugural neared completion.
What's exempt is most mandatory spending -- the spending that goes to Medicare and Social Security for the old and the disabled, Medicaid and SNAP payments ("food stamps") for the poor, payments to low-income people in the form of tax credits, interest payments on the debt, federal employee retirement benefits, and other categories.
(The sequester does cut Medicare's payments to hospitals, physicians, and the administrators of certain Medicare services by two percent.)
Since mandatory spending, which accounts for two-thirds of all federal spending, is mostly off limits, the spending cuts are highly concentrated on the remaining third of the budget, what's called "discretionary spending" – the kind of spending that Congress would normally decide each year in its appropriations bills, sometimes increasing the amount spent on some items and perhaps lowering the amounts spent on others.
An example of discretionary spending: the money that goes to the National Science Foundation, which has an annual budget of about $7 billion and funds research in everything from the stickiness of spider webs to the demise of coral reefs in the Florida Keys.
In percentage terms, the CBO said, the amount available to spend for defense (other than for military personnel) will be cut by about 8 percent and the amount available for nondefense discretionary items will be cut by about 6 percent.
The Obama administration's Office of Management and Budget has a higher estimate: a reduction in available money of 13 percent for defense programs and 9 percent for nondefense programs for the remaining seven months of this fiscal year.
Defense spending accounted last year for about 18 percent of all federal spending. Under the sequester, defense spending will bear a disproportionately large share of the cuts. And since the law gave President Obama the discretion to exempt military service members' pay from the cuts (and he did so) the defense cuts will fall heavily on daily operations and maintenance, activities such as training missions for Navy aviators.
Finally, what about that other number that Obama used in his State of the Union address: "about a trillion dollars' worth of budget cuts"?
Obama was referring to the full 10-year budget forecasting period and assuming that the Budget Control Act will remain in effect for the entire period.
If the automatic spending cut provisions were to remain in effect, they would reduce deficits by at least $1.2 trillion over the 10-year period from 2012 to 2021, the CBO has estimated. Total federal outlays over the next ten years will amount to $45 trillion.
This story was originally published on Mon Mar 4, 2013 10:37 AM EST


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Olympus E-P1 Hands-On Video Preview
By David Rasnake and Allison Johnson
I don't put much stock in concepts. I've been following the camera industry long enough to know that what a manufacturer shows off under glass at a trade show is, more likely than not, going to live and die right there – under glass, at trade shows. A handful of notable exceptions aside, under-glass concepts – in photography, as elsewhere – rarely flow down the production pipeline to actual products with actual specs without significant functional and stylistic revisions.
Olympus's Micro Four Thirds concept
Which is why I did my best not to get sucked into the vaporware vortex swirling around Olympus's Micro Four Thirds concept launch back at Photokina last September. What Olympus showed us was a beautiful, elegant mock-up of a rangefinder-inspired camera – with no publicly aired development timeline and lots of caginess about how closely any future production version would hew to the concept's pocketable form factor and classic styling.
If I sound a little jaded on this topic, it's only because we've heard these kinds of promises before: Panasonic built similar buzz around the G1, its Micro Four Thirds platform, and while the G1 is an excellent camera in its own right, the general feeling around here has always been that it never fully took advantage of the form-factor and functional opportunities afforded by Micro Four Thirds.
But Olympus's announcement today of the production-ready version of its Micro Four Thirds concept – known officially as the E-P1, and at least semi-officially as the "Digital Pen" – looks to change all of this. For the E-P1, Olympus went back to the drawing board, or at least, back to the filing cabinet. Vintage camera nuts will immediately recognize the aesthetic influence of Olympus's classic Pen F – a half-frame 35mm camera from the middle of the last century, and one of the manufacturer's early attempts at miniaturization – in the converging body lines of the E-P1's top panel.
The original Pen series's use of a half-frame format (in which each shot is exposed on half of a standard 35mm frame) provides an interesting parallel for the Micro Four Thirds equipped E-P1. The new Pen's 12 megapixel Four Thirds sensor – the same sensor used in Olympus's current DSLRs – is smaller than the APS-C imagers found in many consumer SLRs these days, but also significantly larger than the largest typical point-and-shoot sensors.
Combine that with some impressive early buzz in noise reduction fine tuning and the ability to shoot at full res up to ISO 6400 and you have all of the makings of an interesting small camera indeed: powerful enough to take "serious" photos, flexible enough (with its interchangeable lenses) to handle a range of shooting situations, and small and accessible enough to not intimidate newbies. All in all, it sounds a lot – on the surface, at least – like the Micro Four Thirds camera we've been waiting for since the technology was first unveiled last summer.
Hands on with the E-P1
Olympus was kind enough to provide us with a pre-production of the E-P1, and while we weren't able to share results from field testing or studio shooting at this point, we were able to spend some time shooting with the E-P1 and checking out its array of features. If you want to cut to the chase, we've summarized our findings in a short hands-on preview video.
Like Panasonic's related offering, the E-P1's Micro Four Thirds technology mandates a full-time live view shooting experience. With this in mind, Olympus has carefully adapted its traditional DSLR interface to better suit a shooting environment in which shot composition is taking place solely on the LCD. Those familiar with Olympus's E-series DSLRs will find the menus and status screens largely unchanged, but a nicely laid out sidebar menu provides access to commonly adjusted parameters while leaving space shot composition – similar to the arrangement used in many point-and-shoot cameras these days.
A unique two-axis control arrangement allows shooters to navigate the sidebar – and the rest of the E-P1's menus – using the scroll wheel to move vertically within screens, and a new second scrolling control (the silver column on the camera's back panel) to move horizontally. If it sounds complex, rest assured that in use we found the arrangement intuitive, and quicker to use on the fly than your typical four-way controller (though the E-P1 comes equipped with one of those too).
As a design exercise, the E-P1 closely follows the look and feel of the rangefinder-inspired mock ups that we saw previously. A unique fold-down zoom lens provides a dense and heavy (for its size) if very compact package that rivals a larger fixed lens, small-sensor camera in form factor.
Retro touches – including a recessed mode dial, chrome finish, and a rubberized grip panel – are done tastefully in this case, and the build quality of our pre-production sample was top notch. Likewise, we found the E-P1's display to be an excellent performer in a range of shooting situations, providing a solid foundation for the rest of this full-time live view camera's performance.
More to come…
At this point, that's about as much as we can offer about the E-P1's performance. It's certainly an impressive camera in hand, and as our video preview shows, it impressed us with its straightforward operation and retro-chic appeal during our time with an early sample. Olympus is hosting a press event a little later today to officially unveil the new model, and we'll have even more in-depth reporting on what's undoubtedly one of the most important developments in the camera market – including, we hope, some sample images from a full production E-P1 – before the end of the day. Stay tuned…

subset: commoncrawl


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Stock Swindle
New Internationalist 358 July 2003
Corporate crime / MARKET MANIPULATION
In the bad old days of rugged, unrestrained capitalism, Wall Street was virtually synonymous with lawful thievery. Stock trading was the province of cold-blooded insiders. Wall Street was a place where shrewd operators fleeced the unwary piker by spreading false information, issuing paper in non-existent companies or borrowing against assets they did not own. After the stock-market crash of 1929, Congress established the Securities and Exchange Commission (SEC) to impose some order. Financial reforms of the 1930s required companies to file audited financial reports, outlawed 'insider trading' and forced banks to spin off their stock-brokerage operations.
This made Wall Street a somewhat safer place to do business. But periodic price-rigging and insider-trading scandals led small investors to shun stocks. By the 1970s, only about one American family in ten owned any stock at all.
Then came the 401(k) retirement accounts. Introduced in the mid-1980s, 401(k)s allow US workers to turn a portion of their earnings, tax free, over to their employers, who invests the money in company stock, mutual funds and other financial vehicles. With traditional employer-sponsored retirement plans on the decline, 401(k)s have proved a nifty device for shifting the financial risks of retirement from corporations to individual workers. They have also tossed the life savings of half the US population into the lion's den of Wall Street.
As retirement savings flooded into the market, media commentators heralded a new era of 'populist' finance where worker-shareholders, armed with internet research and common sense, were supposed to be able to outwit market pros and make a bundle. Investment clubs sprang up in small towns throughout the nation and high schools added investment games to their civics curriculum.
When the stock bubble deflated in 2000, though, it turned out that Wall Street had once again taken the investing public for a ride. As Americans poured money into stocks, insiders shoveled it out, scrambling to sell their own shares before the unprecedented scale of the swindle became evident and crashed the market.
Some firms, like Enron, adopted byzantine financing schemes that shifted costs and debts into purportedly independent 'partnerships', while moving revenues and assets from the partnerships to Enron. Some, like WorldCom, engaged in plain vanilla accounting fraud, booking routine costs as capital expenditures (which need not be deducted from revenues in full) to inflate earnings. Others, like Tyco, puffed up earnings by buying up hundreds of smaller firms. In fact, the schemes and scams were myriad. Firms established to sell electricity or broadband capacity conspired in fictitious trading with one another. Both parties booked revenue from the trades. Others entered into contracts expected to generate modest earnings over a number of years, yet booked the entire projected revenue stream for the current year.
CEOs made ambitious earnings forecasts, manipulated accounts to exceed the forecasts then triumphantly announced bested expectations. Share prices shot up and executives exercised their options.
An investigation by the Wall Street Journal and Thompson Financial analysts estimated that top telecommunications executives captured a staggering $14.2 billion in gains from stock sales between 1997 and 2002. 'All told, it is one of the greatest transfers of wealth from investors – big and small – in American history,' Journal reporter Dennis Berman wrote. 'Telecom executives… made hundreds of millions of dollars, while many investors took huge, unprecedented losses.' The industry is now reeling, 60 firms are bankrupt and 500,000 jobs lost.
Fortune Magazine analyzed 1,035 companies whose stock dropped at least 75 per cent between 2000 and 2002. They discovered that 'executives and directors of the 1,035 companies took out… roughly $66 billion.' Telecommunications giant Global Crossing imploded amid accusations of accounting irregularities. Global Crossing's stock, which had traded at nearly $100 per share, became virtually worthless, but not before CEO Gary Winnick, exercised stock options and walked away with $734 million. Qwest Communications director Phil Anschutz sold stock worth $1.6 billion in the two years before the firm stumbled under a crushing debt load. The stock subsequently lost 96 per cent of its value.
Executives in the energy and telecom sectors were not the only ones to rake in impressive gains. Dennis Kozlowski, CEO of the manufacturer Tyco International, received an annual salary and other compensation valued at $30 million, reaped $258 million selling Tyco stock and captured another $150 million in forgiven loans. Kozlowski defended this windfall with the claim that his leadership had 'created $37 billion in shareholder wealth.' By the time Kozlowski quit Tyco under indictment for sales-tax fraud in 2002, some $80 billion of Tyco's value had evaporated.
Media exposés uncovered dozens of deals that yielded extraordinary gains not only for executives, but for political cronies as well. Terry McAuliffe, chair of the Democratic National Committee, parlayed a $100,000 investment in Global Crossing into $18 million a few years later – a mind-boggling 17,900 per cent rate of return. Vice President Dick Cheney earned $36 million in 2000 from the sale of stock in Halliburton Corporation. During Cheney's stint as chief executive, Halliburton 'altered its accounting policies so it could report as revenue more than $100 million in disputed costs on big construction projects', according to an investigation by the SEC.
Economic historian Robert Brenner estimates that executives and their boards also kept share prices aloft by devoting hundreds of billions in corporate profits and in borrowed funds to repurchasing their own outstanding stock. Between 1995 and 2000, over $1 trillion in corporate wealth was devoted to buying up the shares that were given out as executive stock options.
As conditions deteriorated in the high-tech sector presumably-independent financial analysts at top investment firms like Morgan Stanley, Salomon Smith Barney and Merrill Lynch issued strong 'buy' recommendations to gullible investors. Any rational analysis would suggest that the bull market was over and prices had peaked. Serious allegations of accounting irregularities were already starting to emerge, yet fewer than one percent of analyst reports recommended unloading stock.
Wall Street insiders attributed this bullishness to optimism about new technologies. But investigations by New York Attorney General Eliot Spitzer found internal emails in which Merrill and Salomon employees privately dismissed the stocks they were touting to the public as 'crap' or 'junk.'
Salomon Smith Barney analyst Jack Grubman actively plugged Global Crossing and WorldCom shares until just a month before the telecom behemoths filed for Chapter 11 bankruptcy. Grubman earned $20 million in 2001 for steering telecom corporate finance accounts to Salomon. He resigned in August 2002 with $32 million severance. Merrill technology analyst Henry Blodget earned his keep not by providing sound analysis to the firm's brokerage clients, but by courting business from the companies he analyzed. For 'generating $115 million in revenue from 52 deals… Blodget's compensation quadrupled – from $3 million to $12 million – in 1999 and 2000,' according to Business Week.
Major investment firms routinely 'wooed analysts with multimillion-dollar contracts based on their ability to generate investment banking fees' from the very firms they were supposed to analyze, says the Wall Street Journal. Enron alone paid $323 million in banking fees to Wall Street and was touted as a great buy all over the street.
In the aftermath of the scandal, US politicians promised to prosecute wrong-doing and restore 'investor confidence'. But few of the recent scams violated any laws. Financial markets are and probably always will be the province of insiders. Concepts like earnings, revenues and even costs are highly elastic. They are easily 'massaged' through creative accounting practices. Sound information about corporate finances is the province of senior executives and the lawyers, consultants and auditors in whom they confide, and the investment bankers who advise them and the politicians who court them. Insiders have every incentive and plenty of opportunity to skate along on legal thin ice. They are confident that not they, but the mobs following behind, will go under.
Writing in the New York Times Magazine, financial journalist Michael Lewis held the investing public to blame for its own greed. How else to explain, Lewis asks, people's credulity as stocks doubled, tripled, quintupled in value? What else accounts for the stratospheric prices reached by dot.com start-ups without earnings or even sales? Sure, Wall Street analysts and television pundits plugged stocks shamelessly, but Americans were primed to buy.
But Lewis misses an important point. This is not just a cautionary tale of ruthless cons and greedy marks. Millions of small-scale savers who bought high were ushered to the table courtesy of their employers and a woefully inadequate public pension system.
Consider Enron. Elevators in Enron's Houston headquarters sported TV sets tuned to CNBC, constantly tracking the firm's stock price and acclaiming stocks generally. These daily market updates made employees – 60 per cent of whose retirement accounts were held in company stock – feel quite wealthy. But Enron workers were not free to sell this stock. For a full month before the bankruptcy filing the company executives who managed the plan froze employee accounts. Meanwhile Enron executives and board members dumped their own personal stock and options, netting $1.2 billion cash – almost exactly the amount employees lost.
Could the workers have been smarter, more savvy, have diversified their portfolios more diligently? No doubt. Caveat emptor has always been the soundest financial advice for small-scale investors. But it is not a principle on which a civilized country builds a national retirement system.
© Copyright 2003 New Internationalist
Publications Ltd. All rights reserved.
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the July 2003 issue
of New Internationalist.
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I doubt anyone reading Hot Air will mind this, but it looks like the UN won't get a chance to dictate terms of the Second Amendment any time soon. Yesterday evening, talks on an international arms-trade treaty collapsed when the US and a few other nations demanded an extension of time before committing to a position. The rest of the participants suspended the entire effort — and activists pointed their fingers at Barack Obama:
The United Nations indefinitely suspended action on an international arms trade treaty Friday after the United States and several other countries asked for more time.
The decision sparked angry reactions from human rights groups often allied with the Obama administration, who believed a treaty to regulate the export of deadly weapons to rogue regimes was within reach. The UN had spent the entire month of July hammering out a deal, and Friday was the deadline for an agreement on a treaty that has met with the staunch opposition of the National Rifle Association and bipartisan concerns in the Senate.
"This was stunning cowardice by the Obama administration, which at the last minute did an about-face and scuttled progress toward a global arms treaty, just as it reached the finish line," said Suzanne Nossel, the executive director of Amnesty International USA. "It's a staggering abdication of leadership by the world's largest exporter of conventional weapons to pull the plug on the talks just as they were nearing an historic breakthrough that would have required all nations to deny arms export licenses where there was an overriding risk that the weapons would be used to facilitate serious crimes against humanity."
And Scott Stedjan, Oxfam America's senior policy advisor, called the failure "a tremendous loss for thousands of innocent civilians around the globe who die each year from armed violence fueled by the unregulated transfer of arms."
It wasn't just a few activist groups that vented their frustrations, either. A statement put forward by the UK, France, Germany, and 87 other nations complained that the draft treaty was all but ready to be adopted. Without naming Obama, the nations pointed out their own "compromises" and had "overwhelming support of the international community" before the US demanded more time to consider it.
Frankly, Obama didn't have much choice. A majority of 51 Senators had already signed a letter promising to vote against ratification if the treaty covered "small arms" and/or "light weapons," which the draft treaty does — in fact, it explicitly includes "small arms and light weapons" in Article 2, Section A1h. Obama could have signed this draft a hundred times, and it still would have had no chance of passing in its current form. Had the UN struck that provision, this treaty might have won the required 67 votes for approval in the Senate, and it still would have been a big step forward in arms control … at least on paper.
The problems with this treaty mirror those of the Nuclear Non-Proliferation treaty: it sets up a UN agency that has no teeth, where enforcement ends up being a game between the West on one side and Russia and China on the other. Meanwhile, North Korea has already gone nuclear, and Iran isn't too far away, while Russia and China protect their client states and the West vainly tries to enforce the agreement. This would have put the US in the same position, only this treaty would have the force of law inside the US, which would mean we would bind ourselves to its terms while the rest of the world's kleptocrats and tyrants would ignore it.
For now, though, it's a moot point. Obama will end up taking the blame for this "failure," which might seem unfair — but Obama chose to participate in this folly in 2009 after the US had previously refused, so he only has himself to blame for the impossible position in which he now finds himself. That's called smart power, apparently.


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We are looking forward to your arrival at Maryville College.
Our faculty and staff are here to help you get the most from your academic experience. Many of our faculty and staff are international or have lived and/or traveled overseas. This section of our website will answer many of your questions about arrival on campus and getting settled in the community.
The Center for International Education is located at International House, and provides services and programs for the international students, faculty and staff at Maryville and their families. Our international student services include: an International Student Orientation program, International & Exchange
Student Advising, information on cultural adjustment, airport pick-up service, a variety of social, cultural & educational programs throughout the year, tax workshop/information and compliance, referrals to other campus services to assist with issues related to health, housing, language and student development, immigration advising and visa compliance and registration, language testing and placement, Social Security information, on-campus/off-campus work, host family program, International House – a gathering space for international students and internationally-minded students, faculty and staff, & the Global Citizenship Organization (GCO).


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Anyway, I also remember the teacher who ran the weight room after school. He was way into aerobics. I had to pay a price to lift weights whenever he was around – I had to run on the treadmill (or sometimes the stair master) for fifteen minutes.
That sucked. I was there for the bench and the squat cage. That's what I wanted to do. That was what I found rewarding. That was where I knew what I was doing and learned to wear mesh shorts, not Umbros, to the weight room.
I am no longer remotely fit – don't let the skating helmet fool you. I need a summer in the woods with Adam Burk and a bear threatening to eat me if I don't do at least PS, like, 20X.
However, I still have a treadmill. I use it occasionally, and it still sucks.
And the treadmill makes me think that school – the way it is – sucks, too.
School is our curriculum treadmill. No matter what our kids want to learn, at school, we put them on the treadmill. No matter what our kids find rewarding, we put them on the treadmill. No matter what our kids know how to do, we put them on treadmill, and we set it to the pace of the school year.
We can say what we want about differentiation, but as it stands the school day is the school day, a class period is a class period, a marking period is a marking period, and a grade level is a grade level. Kids are not allowed to touch those pacing controls, no matter how variable their skills or interests.
Those barely ready to walk are made to run and told to get up when they fall down and get hurt.
Those ready to run do what we expect and we remain uncritical of them, ourselves, and what else we could be doing.
Those ready to run faster speed up and slow down and try to change their stride to play around on the track, but they have no where to go and no guarantee that any or all of their teachers will adjust the controls for them.
No kid gets a break. No kid gets to try a different piece of equipment. No kid gets out of the gym on our watch. No exercise done outside the gym counts.
We insist, and kids learn, that the treadmill is what's good for them – that being on the treadmill is learning. We try to convince ourselves and our students that the treadmill is what causes learning – that the machine is in charge of their time with us – that its internal systems is responsible for the exercises we do. Those who fall are made to feel crummy for it. Those who are praised try not to cringe (mind like a tree trunk!). Those who are left alone finish their time and leave.
Moreover, we're setting our clients' goals without consulting them.
It's Spring in North America. Throw a wrench in the curriculum treadmill. Throw away the little tab thing that lets it start. Kick off the gym shoes and get outside the gym. Let learning run free.
My strength coach embarrassed me sometimes, but he helped me accomplish my goals in the gym so that I could accomplish my goals outside it in playing ball and standing up to the bullies on my team.
The weight room advisor just made sure that I did what he wanted – that I ran – before I did what I wanted.
They both lasted a long time in the same school system. That's the way it goes; teachers have competing values.
And here I am, wrapping up my tenth year. It's no longer a question for me of who I want to be.
It's a question of who I am willing to be.
I'm still tweaking those treadmill controls, but I'm also looking out the gym door. My students and I have some ideas to talk over with management despite all those funny looks from the other trainers, those captains, and the treadmill in the other room.


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Programme Description
A Masters – your passport to the business world.
The Access Masters Tour will introduce you to a wide range of Masters programs and will connect you to representatives from some of the world's best business schools. By registering, you will gain access to the full program of the event.
Open Fair
The Open Fair gives prospective students the chance to meet school representatives at their stands without any prior appointment, but after registration for the event. Masters programs presented during this part of the event cover a wide range of fields including Engineering, Finance, and Accounting, Humanities, Information Technology, International Relations, Law and Legal Studies, Management, Marketing, Mathematics, Medicine and Nursing, Science, Social Sciences.
One-to-One and Duo Meetings
The One-to-One and Duo meetings are dedicated to candidates specifically interested in business programs in Management, Marketing, and Finance. Prospective students who register for the event will be scheduled for 20-minute meetings with admissions directors and school representatives. The meeting slots are carefully assigned by the Access Masters team prior to the event so that candidates get to meet the business schools that match their interests and requirements.
Additional benefits
- Get advice and support for your Master's preparation
- Obtain GMAT, GRE, TOEFL, IELTS, and scholarship information
- Take part in the draw to win a free campus visit
Register online free of charge prior to the event in order to be able to meet with universities' and business school representatives.
- Date of the event – Sunday, February 18, 2018
- Venue – To be announced
- The timing of the event:
- 11:00 AM – 5:40 PM: Conferences, Open Fair, One-to-One and Duo Meetings.
- Incentives – win a free GMAT course by Jamboree
- Schools –Syracuse University, Hult Business School, University of Nottingham Business School, University of San Francisco School of Management
About the School
The 2018 Access Masters Spring Tour begins on 24 January with an event in Brussels, offering Masters aspirants the opportunity to meet the best schools One-on-One. Between January and April 2018, the ... Read More


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Tokyo 2011 Observations
 Jul 14, 2011
I've spoken at InfoTrends' On Demand Japan conference for many years now. My annual visit to Tokyo is a high point of the year because it gives me a chance to visit face-to-face with our Japanese clients and to catch up with InfoTrends employees here. Since I was here last July, of course, Japan has suffered a tremendous natural disaster followed by a nuclear plant accident with long-lasting implications. It's only been four months since the earthquake and as I arrived I wondered what changes I would see in Tokyo since my last visit.
Here are a few observations:


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As a rule, I avoid malls and busy stores and I aim toward buying, making, and giving handmade goods as there are some amazing artisans out there who infuse quality handiwork with unique design and receiving these treasures just makes a person feel extra special, rather than just feeling like a check box on a list.
So avoid cookiecutter gifts this year… Well, unless they are actual cookie cutters (I just scored a gnome shaped one! I'm going to make gingerbread gnomes this year with Alex!)… And you can find plenty of handmade, unique cookie cutters that blow the socks off the typical shapes.


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March 9, 2011
Brian France
KERRY THARP: Good afternoon, everyone. We appreciate you joining our special NASCAR teleconference today, featuring NASCAR chief executive officer and chairman Brian France.
Brian, at this time I'm turn the floor over to you for some opening comments.
BRIAN FRANCE: Thanks, Kerry. Good afternoon, everyone. We're just having on our off week here a little bit of a discussion about the start of the year, some of the things that are going on, some progress reports in a few areas. I'm going to reserve most of the time to take as many questions as we can.
But obviously in general with a very dynamic Daytona 500, having a really young star born, having the iconic 21 Wood Brothers team in Victory Lane, with 74 lead changes, very interesting way the competition played out during the Daytona 500. We started there and then on to Phoenix, getting Jeff Gordon back in Victory Lane, record lead changes again there, attendance up across the board.
Obviously, the competition has never been better. That's been brewing in terms of going in the right direction for a number of months, dating back well into last year where, as you know, we made a number of changes in the new car, which is not a new car anymore, but to get the car racing as good as we possibly can.
There's still some challenges for us and for many, many sports, many companies with still an uncertain outlook for the economy. As we said all along, we're not economists, we're not building around a doom-and-gloom, robust economy, we're doing what we think we need to do in general terms.
Obviously fuel prices are never helpful to our fans or anybody who needs to drive to an event, or anywhere. So those things are always out there.
The last thing that I would mention above competition that I think is important, we said during the last couple years that when the economy does what it does, you have some challenges, that's the time to look around and look deep at some of the areas for the future that you think you might be able to improve on.
Those reviews range, as you know, from the communications review, which brought us our IMC structure, Brett Jewkes, a number of new hires that are coming, has obviously been completed and we're implementing that on behalf of the industry and ourselves.
Then everything that would range from digital media, how effective are we in that new medium, range from the fans' experience at track, away from the track, trying to really get connected to our future in some meaningful ways.
Those reviews - I've sat through them all - are going very well. They're going to give us good ways to make sure this sport keeps on getting bigger, better and grows in the future.
With that I'll turn it over to questions.
KERRY THARP: Thank you, Brian. We'll open it up now to questions for Brian France.
Q. Brian, I wanted to ask you in regards to the TV ratings, different people said different things about them, I know there were challenges last year from going against the Winter Olympics, the Daytona pothole, the Vegas race. I wanted to ask you, shouldn't the ratings have been up this much anyway based off of not having that competition? People in the industry talk about the long-term broader picture. While the numbers are up from last year, they're down from 2009. How do you view that?
BRIAN FRANCE: I've always sed ratings are a function of many things: the competition, how you're viewed at the time by the fan base in a given moment, how the actual race is playing out. There's all kinds of things that go into it.
No one around here is celebrating. We're obviously pleased we're up dramatically in our ratings. But we know that is an ebb-and-flow thing. We're focused on a lot of things that will give us growth down the road. We're going to work on those, not get too excited or too down.
I look at the interest level of the sport, and that's growing after having peaked and maybe dropped back a little bit for some reasons a couple years ago. The general interest level is going up and that's what we're going to be working on, is creating new fans.
Q. You have the races where you grow ratings and attendance, then you have the off week. Can you detail the reasons why you have this off week so early in the season? Are you going to change that for next year?
BRIAN FRANCE: Well, it's historically how many events in the calendar we want to run, regardless when they ran. Historically it has been around this time where we do have an off weekend.
Arguably you would like to have that come down eight or ten races later. But that's just how the schedule and the climate issues that we face with certain markets and everything else has played out.
The reason for changing it is mostly driven that the other sports calendars are going to change on us - not just the NFL, but maybe some other things. So we're trying to get into the right date.
It also does accomplish, when we change next year, moving back the 500 a week, we'll eliminate the early schedule gap here. That will probably be a good thing.
Q. Brian, a lot of feedback that we in the media get from fans is about the post-race show or the lack of a post-race show. There seems to be a sense of frustration that fans invest so many hours into an event, then they get under 10 minutes of reaction after from the drivers that they've been watching. Is that something that NASCAR is hearing from your fan council? Do you have any input with FOX to try to solve this dilemma fans are faced with?
BRIAN FRANCE: We do have a fair amount of programming that happens with the SPEED Channel throughout the post race, even into the evening typically.
But, yeah, I think generally speaking we would agree, that it would be nicer to have a longer post-race. But if you think about it, most sports don't have a particularly long post end of a game, whatever else. The networks don't stick around for an additional half hour. It's not something FOX should be thinking about because, after all, that's just not the norm with network or even cable television.
Once the game is over, there's typically a short post-race. You hope the rest of it, social media, NASCAR online, places to digest good post-race information is where they go.
Q. Several of the manufacturers have talked about the next generation of car being redesigned for 2013. Can you bring us up to speed on how that project is coming along?
BRIAN FRANCE: Going well. Obviously lots of dialogue with the car manufacturers. We're addressing those needs, which is the need to keep the competition and safety and all that stuff where it is today, which is at a very high level. At the same time, evolving the car to give them even more identity with their manufacture make.
There's a way to do both. It kind of coincides with some of their new model launches and some things. So we're working pretty closely, as you can imagine.
It's going well. That's the beauty of the R&D center today. We can do multiple tasking with big, big initiatives, and do them hopefully all fairly well.
Q. What do you see as the biggest impact on television ratings? Sponsorship revenues you and the tracks can earn or now are they becoming more critical on the rights fees as you start negotiating in the next couple years?
BRIAN FRANCE: We spend a lot of time looking at obviously traditional broadcast television. Our cable partners are critically important. We spent a lot of time recently looking at the other media, which is social and digital media, where that's all going, where people are getting information, content and everything else.
We have a plan. We have a robust plan in the long run. We'll try to capture both. But one of the ratings impact is people are getting their news, updates, their fix, if you will, in lots of different ways today. We're going to want to, as a sport, make sure that we're taking advantage of all of them.
Q. Brian, can you address the ethanol situation and what challenges have you faced with the implementation to the new fuel in the three top series?
BRIAN FRANCE: Well, the fact that we haven't had a discussion is evidentiary proof of how well it's working. We couldn't be happier with it. From the early testing, we got good performance numbers. The teams certainly think it's working well. It obviously takes us another step. Especially now that you see energy prices going where they're going, it takes us a way down the road with a real biofuel that we're using in the car. They've just been a really good partner so far and it's going well.
Q. Will the elimination of the open week early continue after next season? Will the Daytona 500 still be moved up in years past this? Can you tell me the thought process why there always seems to be an open week early.
BRIAN FRANCE: As I said, it comes from the fact that we want to have 36 events, plus the All-Star Race, all that stuff. It's just a logistical matter where you can place events, February, March, in some parts of the country. There was an open weekend even though it might not be ideal. We're going to move that. It's going to fix that, although it wasn't the main driving reason.
In my view, all things being equal, we'd probably like to be racing this weekend. But I don't believe that to be a significant challenge for us because we happen to have an open week. We have a long season, we're going to have some open weeks.
In the long run, with the 500 moving, it will by definition take care of that. Our schedules are year-to-year, but you typically can see we have a lot of continuity.
Q. I asked you earlier in the year of the potential of an NFL lockout. How do you think NASCAR is now positioned should that happen? Why do you think we're seeing the growth in the younger demos so soon?
BRIAN FRANCE: First of all, my hope is that they will figure that out. I am not close to that any more than anyone else is. We're wishing that all of the leagues do well. That is just the reality of how we look at that. We don't pay any attention to where they are, where they're not. It's obviously out of our control.
The younger demo is the bigger question. That's good. I think having a young winner, and Jeff Gordon runs up our young fan base, and then Junior, arguably he's competitive more than he was a year ago. Probably a lot of reasons. I think the kind of racing we had, just to get off to kind of a good start.
But the young demo is something we're going to keep working at. It goes to candidly reaching new young fans. This is not a one-dimensional effort here just to get people to tune in on television. It's to get young fans really interested for the long run in every aspect of enjoying NASCAR the way we want them to enjoy NASCAR.
Q. I'm intrigued by the schedule-making process. This year you added testing to Daytona. You can actually point to that as a catalyst for a big Speedweeks to where we are now. What is the process that you go through as you look at the 2012 schedule right now?
BRIAN FRANCE: Well, you look at historical dates obviously. We have been a sport that's tried to build continuity around that. A lot of other motorsports, that's not necessarily so important. With us, it is. Then you look at the broader sports calendar, the notable big events that we're always looking at: the Masters, obviously the Super Bowl, other major events throughout the year that you want to make sure that you're putting your events in the right place as to get everybody the most room to be successful that you can.
It's all those factors. And the last point would be we have some limits as to moving dates around beyond even the continuity of events, which we've changed when we've had to. There are seasonality issues. You can't run a race in Phoenix, Arizona, in July. You're not running Cincinnati in February. On and on it goes. There's a lot of things that have to go into making up the ideal schedule.
Q. We know you've been a big supporter of the diversity program. Where does that stand now? Has it taken a little longer to get minority drivers into the top three series?
BRIAN FRANCE: I really didn't have a timeline. After all, there are limited seats available in the first place. But I will say that when we've had to change the program to maximize it, we've ended up partnering up with Revolution Racing, which has given some of these talented, diverse drivers a better opportunity to show their skills. It's not just giving them the opportunity, it's giving them the right opportunity.
I will tell you Darrell Wallace is a young African American driver that's winning. He's doing that now. We're going to have a breakthrough in that area. It's going to be on my watch, and I'll be very proud of that when that occurs.
Q. A couple of the drivers after recent races have expressed a level of concern about the level of rough driving going on out there these days, especially at places that don't normally feature that. Do you share their concern or do you think it's normal racing?
BRIAN FRANCE: No, I don't share that concern at all. They're the best guys in the world. We've said, You have to mix it up, this is a contact sport. We feel really good about that.
It's made the racing better. They've got to figure that out. They're doing that largely. I would say, too, with the wild card situation, where the last two spots are going to be decided by wins, if you don't happen to have the perfect top-10 performance in the first 26 events, I think you saw the disappointment with Tony not winning when he thought he should have won last weekend, he now counts that because he doesn't start fast. He may need that.
I think you're going to see an escalation of that. That's what great competition is. I'm actually happy to hear people complaining about that. It means it's working.
Q. Daytona obviously saw kind of a different style of racing than in the past. What did you think of that? Do you like that better or worse than the 30-car packs that we'd seen before?
BRIAN FRANCE: To tell you the truth, we were curious, too. It was a phenomenon. We'd never seen anything like that. We were curious going into Sunday. I remember talking to Mike in the tower. We didn't know how that was going to play out.
But 74 lead changes, dramatic racing all the way through, although it looked a little bit different, the competition level went up. We look at a lot of things to come to that, but we like it. It's different. But, generally speaking, if competition goes up, the races are exciting, we're going to like it.
Q. What do you think was the single most important factor in getting the buzz and the ratings up? Was it Trevor winning? Was it Jeff Gordon, Danica?
BRIAN FRANCE: You know, I don't know. We can't monitor things and measure things that closely. We went out in a strong way, as you know, in 2010 down to the last laps. We hadn't had that in a few years. You want to go out strong. It's really important to have a good playoff, a good finale. You see where that's helped the Super Bowls of late, which have been very competitive. So have some other series, other sports. You want to go out on a real high. We have a very short window to launch. If you're going out a little bit down, a little harder to ramp up.
So it's probably all those things.
Q. Are there any things that are worth pointing out innovative that NASCAR is going to do like what they're doing this weekend in the 1:00 special that will showcase on an off weekend a culmination of tape that hadn't been seen before? Are there other things like that coming up?
BRIAN FRANCE: You know, the programming schedule, it's pretty set. There will be a couple special shows that you'll see. One will be on the ethanol and the biofuel transformation we're working on. By and large, we'll zero in on the events. FOX, they're off to a very fast start. We'll be working with Turner for the mid-summer package, and ultimately ESPN and ABC as we conclude to make sure that they're getting everything they need from us and we're getting everything we need from them.
Q. Regarding the schedule, do you see any changes?
BRIAN FRANCE: Do we see any major changes in the schedule? We don't release that for another month or so. We did have a fair amount of changes last year and even some in the last couple years.
So by definition I don't think you're going to see a lot of changes. We'll see how some of the new dates, their new time on the calendar works out. But I don't think there will be as much as there was, say, in 2010.
We don't want there to be. We prefer to have a good continuity. That's our preference.
Q. What do you think of Danica's run last week, historically what that did, the highest finish by a female in any NASCAR national series?
BRIAN FRANCE: I think that elevated her. There was some discussion, did she have the right stuff to compete in the Nationwide Series. You know, I think she dispelled a lot of that. There's always circumstances in the start of a new career. But sometimes things are out of your control, people can crash in front of you, a hundred other things.
I think she elevated herself quite nicely. That's nice to see. She's a very competitive person. She's always said she's here to compete, not just happy to be here. That fits my criteria.
KERRY THARP: Brian, thank you very much. We appreciate everyone's participation today on the teleconference. We'll see you at the racetrack real soon.
BRIAN FRANCE: Thank you all.
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2015 Group 2 Project
Extracellular Matrix 2015 Projects: Group 1 | Group 2 | Group 3 | Group 4 | Group 5 | Group 6 | Group 7
Projects are now locked for final Assessment.
- 1 Integrins
- 1.1 History
- 1.2 Structure
- 1.3 Function
- 1.4 The Role of Integrins in Disease
- 1.5 Glossary
- 1.6 References
Integrins are a group of transmembrane cell adhesion proteins which anchor the cell to the extracellular matrix (ECM) by its cytoskeleton. Integrins not only anchor the cell, they are also involved in cell to cell adhesion[1]. However, integrins are not just adhesion proteins, as they can also induce intracellular signalling pathways in the extracellular matrix, which makes them play an important role in development, immune response, leukocyte trafficking and haemostasis.
The integrin family is one of the most highly studied cell adhesion receptor within the cell.[2] The family comprises of different combinations of an alpha and a beta subunit joined together. In total there are 18 alpha and 8 beta subunits which can give rise to 24 different integrin receptors. This difference in structure causes integrins to have different properties and distribution throughout the cell, as well as interactions with different components of the extracellular matrix.[3] However, for an integrin to function, they must be activated by binding a ligand to its receptor. This page focuses mainly on the structure and function of integrins but also its history and its role in disease.
|Online Editor (2019)
|Please note inaccuracies have been identified in this student prepared background history section. The bullet point information shown below should now be correct:
Integrins were discovered by Richard O Hynes in 1985. He spent many years researching trying to find a protein based on the idea that there must be a transmembrane connections between the extracellular matrix and the cytoskeleton. The major breakthrough was made by Greve and Gottlieb in 1982.[4] They found that JG22 and CSAT, which are two monoclonal antibodies (an antibody produced by a single clone of cells)[6] prevented the adhesion of myoblasts to synthetically made matrix coated surfaces. This means that these antibodies are binding to their specific antigen within the cell which prevents adhesion. They came to the conclusion that the JG22 and CSAT antigens must be the proteins causing the adhesion of myoblasts to the matrix, which was supported by the immunofluorescence pictures produced in the Clayton Bucks and Rick Horwitz lab. These images showed that these antigens lined up with a variety of cytoskeleton proteins such as fibronectin and actin. From this, Hynes worked with these proteins and was eventually able to prove that they were the transmembrane protein which binded the extracellular matrix to the cytoskeleton of cells.[7] At the same time, Erkki Ruoslahti also made steps towards the discovery of integrins. He found that the RGD sequence (Arg-Gly-Asp) in fibronectin served as the main receptor which caused cell adhesion. Many of the different types of integrins which have been discovered are now known to recognise this sequence in their adhesion ligand while other types bind to related sequences.[8]
Future Research
The discovery of integrins sparked interest in research across various fields such as immunology.{{#pmid:15533754|PMID15533754} There have been thousands of research projects on this protein since its discovery and now it is one of the best understood cell adhesion protein. However, there are still many mysteries to this cell adhesion protein which scientists are trying to unravel.
The main focus for integrin research seems to be heading towards finding its role in cancer. Recently, Lee published an article on insulin-like growth factor binding protein-3 which found that it might be a good cancer therapeutic agent by blocking adhesive activity of integrins in a tumour cell.[9] This provides a path for future research and the hope that cancer might one day be curable. Other paths in the future research of integrins investigate the role of integrins in the progression and prevention of diseases, such as the prevention of angiogenesis, or growing of new blood vessels, and perhaps even the role of integrins in the progression of viral diseases and infections.
There are still many potential fields, most prominently in the understanding of the role of integrins in many diseases, and therefore it will be paramount to understand these roles, which may provide a stepping stone for therapies to improve and prevent the progression of deadly diseases.
Interest in Integrins
Graph 1: This graph depicts the number of articles about integrins found on the pubmed database by searching 'integrin' since when they were discovered to present year.
According to Graph 1, interest in researching integrins increased drastically in the following years after their discovery. The number of articles published about integrins increased every year until 2005 where it decreased slightly. The highest interest in researching integrins was in 2012 where 3701 articles were published on the pubmed database while the lowest was in 1985. It was expected to be the lowest in 1985 as Richard O Hynes had only just discovered them.
Integrins are cell adhesion molecules that are present on all cells in organic beings[1]. They are essential for cell-cell and cell-matrix interactions (extracellular matrix) as they are involved in mechanotransduction and in actin cytoskeleton organization. Due to the fact that they provide linkage between intracellular and extracellular components, they are implicated in almost all kinds of bodily functions ranging from tissue repair to pathogenesis of disease. Understanding the structure of integrins is thus, essential for the understanding of how integrins interact in the body.
General structure
Integrins are heterodimers formed by the noncovalent bonding of two transmembrane glycoproteins[10]; an alpha and beta subunit. As they are transmembrane proteins, they consist of both a relatively large extracellular component and a short cytoplasmic component. The extracellular component of the alpha subunit contains approximately 1000 amino acids, while the extracellular component of the beta subunit contains around 700 amino acids. Some of the alpha subunits contain an I-domain which is vital because it is the binding site for ligands [11]. These ligand proteins activate and determine the way integrins interact with the actin cytoskeleton and initiate the transduction of intracellular signals. The beta subunit also possess an I like domain which functions similarly to the alpha subunit, however, it only plays an important role when the alpha subunit does not contain an I domain. The I domains affinity for a ligand is dependant on the concentration of metal ions such as magnesium. This is because they contain a 'metal ion dependent adhesive site' (MIDAS). This site allows for the binding of metal cations, which is essential for ligand binding and thus, integrin activation. In regards to the Figure 2 on the right, when cations flood to the MIDAS, they form a 'clustering' complex which can be seen in the 3rd state (iii.). This 'clustered' state represents the most active state of integrins, and is what allows integrin to interact with the actin cytoskeleton and/or transduce signals through the plasma membrane [11]
File:Integrin structure simplified.jpg
Figure 4: A simplified image of Integrin subunit structure (Z3415735 Integrin structure simplified.jpg Figure deleted due to copyright violation.)
Integrins are considered trans-membrane proteins. As such, they are produced within the intracellular endoplasmic reticulum and Golgi apparatus components and must embed themselves into the plasma membrane. The protein is assisted through the ER membrane with the help of a trans-location channel. Once the channel closes, the protein is embedded in the ER membrane. Vesicles then break off the ER membrane, containing the trans-membrane protein, and travel to the plasma membrane where they embed into the membrane. This is regulated by normal protein synthesis functions such as STOP sequences and START sequences. The video below helps to visually explain the process of trans-membrane protein synthesis [12].
<mediaplayer width='500' height='300'>https://www.youtube.com/watch?v=SKMIzmAe0do</mediaplayer>[13]
Functional structure
Integrins are able to mediate communcations between intracellular and extracellular components due to the fact that they span the plasma membrane. Their complex extracellular components are important for binding to ligands[1]. Ligand binding is essential for Integrins because this allows them to interact with the extracellular matrix for function. Similarily, their intracellular components are important for binding to the cytoskeleton and cytoplasmic elements of the cell. Specifically, they bind to talins and kindlins, which help in mechanotransduction and also assist in preparing integrins for ligand binding in their extracellular component. These details are explained more deeply within Function.
RGD Sequence
The RGD (Arg-Gly-Asp) sequence is an important structural component in fibronectin proteins as it is the main recognition motif for the integrin family. The RGD sequence is also the receptor of cell adhesion molecules in general. This means that many of the different types of integrins recognise and interact with this specific sequence which results in the cytoskeleton being anchored down to the ECM. The different types of integrins which bind to this sequence can be clearly seen in the table below. [14]
Table 1: This table demonstrates how the RGD sequence interacts with many different types of integrins compared to other sequences
Mammals possess 18 α subunits and 8 β subunits that can combine to form up to 24 different types of receptors - this range of receptor types is essential for the specificity that integrins need for cellular functions[1]. This range of different configurations can be seen on the table to the right (Table 1).
General Function
Integrin proteins are present at high concentrations in both active and inactive forms on the cell membrane and largely serve two main cellular functions.[7] Primarily, observations revealed a key association between these specific proteins and their "integral" relationship with the extracellular matrix (ECM) and the actin cytoskeleton, suggesting a structural role of the proteins within the cell. Further investigations revealed that integrins reinforce overall cellular stability by acting as the chief adhesion receptor for ECM proteins.[15] However, subsequent research has also revealed a secondary function as being responsible for significant signal transduction pathways that heavily rely on integrin proteins for facilitating cell signaling pathways both within and between cells[16]. Overall, integrin functionality is mediated through "inside-out" signalling in which various intracellular binding results in conformational changes to other domains of the integrin that affect their affinity to extracellular ligands and their interactions with the ECM.[17]
Interaction with the Extracellular Matrix
The video below breifly shows how integrins interact with the ECM. It depicts how integrins can be in an active or inactive form depending if an ligand is bound which then allows the integrins to anchor the cytoskeleton to the ECM.
Movie Reference[18]
Integrin Trafficking
Integrin proteins are constantly being trafficked in and around the cell via clathrin dependent or clathrin independent carrier proteins, and these follow either a long-loop pathway or a short-loop pathway of transport (Figure 5.). These trafficked proteins then undergo a sorting process to determine which proteins are destined for degradation and which are able to be recycled. Integrin recycling provides the cell with a replenished supply of integrins ready to engage in new adhesions with the extracellular matrix. Research suggests that this dynamic recycling mechanism allows for 2-D and 3-D cell migration when paired with proper cell signaling from the extracellular matrix ligands[16].
Fibronectin is an ECM glycoprotein that functions as an adhesion molecule and actively binds to integrin proteins, particularly α5β1 integrins[19]. Fibronectin-integrin interactions do not exist in a static concentration, but rather exist in a dynamic relationship based on the result of regulated cellular pathways initiated by numerous tensile factors related to the cytoskeleton, focal adhesions and the structural stability of the cell[20].
The extracellular matrix is maintained and regulated by the remodeling and recycling of a number of proteins including collagen I, the major protein component of the extracellular matrix.In humans, there are four integrins that are known as distinct collagen receptors, α1β1, α2β1, α10β1 and α11β1[21].Research shows that β1 integrins play a key role in the regulation of the endocytosis of ECM collagen.[22]
Laminins are a group of ECM proteins largely associated with basement membrane assembly[23] and are known to interact with 10 integrin isoforms, with α3β1, α6β1, α7β1, and α6β4 being most common, in addition to other associated adhesion receptor proteins[24]. These integrin-laminin interactions help to initiate and regulate the signal transduction pathways associated with the ECM and the cytoskeleton[23]. Integrins, along with dystroglycan, facilitate this mediation of signal transduction by acting as signal receptors and relaying activating signals to other associated receptor components of the pathway[23].
Actin Cytoskeleton Association
An integrin protein exists in either an active or an inactive state, which correspond to associated levels of affinity for various extracellular ligands, such as fibronectin. An integrin will experience a conformational change from an inactivated state to an activated state when talin, a cytoskeletal protein, binds to the tail of a β integrin.Once ligands have engaged with their associated integrins the cytoplasmic domain of the β1 integrin recruits several proteins, including integrin-linked kinases[23], to bind the integrin tail and this binding complex then associates with actin filaments from the cytoskeleton[19]. Once the activated integrin is bound internally to the cytoskeleton, nearby integrins will then migrate and cluster together to form focal adhesions on the surface of the cell membrane. These focal adhesions act as major anchoring points for the cell[20].
The Role of Integrins in Disease
There has been no conclusive data in recent and previous research in regards to the role of integrins directly causing disease in individuals, however there has been much interest in the field of cancer. In the last decade, and more so in the last few years, there has been a lot of interest revolving around the role of integrins in the metastatic characteristic of a range of cancers. It can be seen that integrins themselves can be overexpressed, or can interact with other cell adhesion molecules to mark the behavioural change of cancer cells.
Recent Research: Cancer Metastases
Integrins are a significant molecule that allows for the communication between the extracellular matrix and tumour cells. Cells change in response to changes in extracellular matrix, where integrins are the mediators for signalling between the internal and external environment of the cell.
Initiation of Metastasis and Interaction with Extracellular Matrix Components
From the results of many studies, it is now suggested that integrins are responsible for initiating metastases, and also driving tumour cells to become independent of the extracellular matrix. In particular, as mentioned in the review, tumour initiating cells, or TICs, have been studied and it has been discovered that they express particular integrins, depending on the type of cancer. This ultimately leads the cancer to developing drug resistance and the ability to metastasise.[25] Subsequently, specific integrins on the surface of cancers cells can identify them as TICs, and these features potentially allow doctors to label integrins with their expressed behavioural characteristic in cancer cells. Tumour cells can interact with platelets via platelet integrin αIIbβ3, allowing TICs to travel in the bloodstream and attach onto the endothelium. Following attachment and tumour cell arrest, platelet integrin αIIbβ3 in melanoma cancers
and the tumour cell integrin αvβ3 then interacts with fibrinogen and other extracellular matrix components to metastasise into the tissue. In the review[26], it is mentioned that β1 integrins are another notable group of integrins that contribute to the metastases of cancers. The complexity in interactions between the integrins of tumour cells and the environment beyond the extracellular matrix allows its to metastasise.
Another factor to consider is the relationship between the cell-cell adhesion molecules and also the cell-extracellular matrix molecules, namely the integrins, in the process of tumour cells gaining the ability to metastasise. As mentioned in the review, e-cadherin is a major molecule involved in the association, maintenance and disassociation of adherens junctions by binding to both the actin cytoskeleton via the beta catenin molecules and corresponding e-cadherin molecules on surrounding cells[27]. Both the e-cadherin and the integrin molecules bind to the actin cytoskeleton via mediating molecules, and crosstalk between the two are most likely caused by conformational changes in the actomyosin wrapping the actin filaments[28]. When analysing the proteins involved in both e-cadherin and integrin functionality, it can be see that the proto-oncogene Src and FAK play a role in regulating adherens junctions and also the cell's connection with the extracellular matrix. In tumour cells, especially when integrins are activated, it is observed that mutated Src phosphorylates the components of adherens junctions[29], and FAK phosphorylates beta-catenin[30], both of these processes contributing to the breakdown of cell-cell junctions. Mutated Src can also affect the expression of beta catenin on the cell membrane by stopping the endocytosis that allows for beta-catenin to be on the extracellular side of the cell membrane, which affects the actomyosin expression and thus integrin function. This process usually contributes to the metastatic characteristic of tumours.
Stiffening of the Extracellular Matrix
Not only is there the interaction between the overexpression of particular integrins on the cellular membrane and the environment that is the extracellullar matrix, the stiffening of the extracellular matrix around a tumour promotes metastases. It has been shown that some genes have an effect on the extracellular matrix stiffening, in particular MiRNAs which are microRNAs[31]. They play a big role in the regulation of tumour suppressor genes and oncogenes, which induce changes in the extracellular matrix, however what the MiRNAs cause can also depend on mechanic stress. These changes to the extracellular matrix have the potential to increase the expression of some integrins on tumour cells, promoting metastases. It has been suggested that the tumour stroma stiffening is due to some expressions of MiRNA causing fibroblasts to turn into cancer associated fibroblasts (CAFs) which lay down collagen, the key scaffolding protein of the extracellular matrix[32]. However, the mechanism which causes the conversion of CAFs is not yet well understood. The upregulation and downregulation of specific MiRNAs in different cancers are able to influence the plasticity of fibroblasts to allow the scaffolding of the stroma.
It is key to understand the method by which cancers gain the ability to metastasise through the stiffening of the extracellular matrix around them. It is known that the stiffness caused by the laying down of collagen causes integrin mechanotransduction, where the integrins translate the forces from the extracellular matrix to regulate cellular changes[33]. The stiffness promotes the creation of more focal adhesions caused by the activity of focal adhesion kinase (FAK), and the subsequent increased number of integrins causes the change in localisation of different integrins on the tumour cell surface[34]. These changes in integrin expression increases the mobility of the tumour cells,
and consequently its ability to metastasise. The increase in integrins also increases the integrin mechanotransduction, which induces the MiRNA MiR-8a to affect the amount of HOXA9, a protein which functions as a developmental patterning protein[31]. Phosphatase and tensin homologue (PTEN) transcription is dependent on the amount of HOXA9 in a cell[35], and subsequent decrease in HOXA9 inhibits PTEN transcription. Therefore, PTEN, as an inhibitor of the phosphoinositide-3 kinase (PI3K) pathway, is unable to fulfil its role of regulating the PI3K pathway. It can be observed that the stiffening of the extracellular matrix allows for the overactivation of the PI3K pathway, which mediates cellular functions that allow for cancer metastases, growth, angiogenesis and many other key processes for the initiation and development of cancers[36].
Integrins are a diverse transmembrane molecule that serve a role in many different processes that transduce the changes in the extracellular matrix to affect the behaviour of a cell, and this is best illustrated in the roles that integrins have in the metastases of cancer cells. There is more that can be explored in the field, especially regarding the interaction between cancer cell integrins and the integrins of platelets that allow them to survive and metastasise through haematogenous means, and this is the direction that current labs can consider to gain a better understanding of the role of integrins in cancer.
|across a cell membrane
|cancer associated fibroblasts with the stroma that develops the tumour's microenvironment in such a way that it encourages growth, angiogenesis and metastases
|tumour suppressor gene that codes for an enzyme that dephosphorylates PI3K, thus inhibiting the PI3K/AKT pathway that promotes cell proliferation, growth and survival
|microRNA, a small non-coding RNA molecule that is involved in gene silencing and regulation
|the conversion of mechanical stress into electrochemical activity
- ↑ 1.0 1.1 1.2 1.3 Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. Integrins. Available from: http://www.ncbi.nlm.nih.gov/books/NBK26867/
- ↑ Struzak-Wysokińska M, Wysokińska-Miszczuk J & Kamińska K. (1988). [Central teeth]. Czas Stomatol , 41, 103-8. PMID: 3248401
- ↑ Castillo-Ferrando JR, Pérez-Ojeda E, Rueda T & Serrano JS. (1986). Effect of peripheral benzodiazepine receptor agonist (RO 5-4864) on inotropism in isolated rat atria. Arch Farmacol Toxicol , 12, 125-8. PMID: 3039929
- ↑ 4.0 4.1 Greve JM & Gottlieb DI. (1982). Monoclonal antibodies which alter the morphology of cultured chick myogenic cells. J. Cell. Biochem. , 18, 221-9. PMID: 7068780
- ↑ Horwitz AR. (2012). The origins of the molecular era of adhesion research. Nat. Rev. Mol. Cell Biol. , 13, 805-11. PMID: 23151664
- ↑ http://www.medicinenet.com/script/main/art.asp?articlekey=4425
- ↑ 7.0 7.1 Hynes RO. (2004). The emergence of integrins: a personal and historical perspective. Matrix Biol. , 23, 333-40. PMID: 15533754
- ↑ Ruoslahti E. (1996). RGD and other recognition sequences for integrins. Annu. Rev. Cell Dev. Biol. , 12, 697-715. PMID: 8970741
- ↑ Lee HJ, Lee JS, Hwang SJ & Lee HY. (2015). Insulin-like growth factor binding protein-3 inhibits cell adhesion via suppression of integrin β4 expression. Oncotarget , 6, 15150-63. PMID: 25945837
- ↑ You TJ, Maxwell DS, Kogan TP, et al. A 3D structure model of integrin alpha 4 beta 1 complex: I. Construction of a homology model of beta 1 and ligand binding analysis. Biophysical Journal. 2002;82(1 Pt 1):447-457.
- ↑ 11.0 11.1 Danen EHJ. Integrins: An Overview of Structural and Functional Aspects. In: Madame Curie Bioscience Database [Internet]. Austin (TX): Landes Bioscience; 2000-. Available from: http://www.ncbi.nlm.nih.gov/books/NBK6259/
- ↑ Lodish H, Berk A, Zipursky SL, et al. Molecular Cell Biology. 4th edition. New York: W. H. Freeman; 2000. Section 17.5, Insertion of Membrane Proteins into the ER Membrane. Available from: http://www.ncbi.nlm.nih.gov/books/NBK21731/
- ↑ William Orfanos, 9/11/2014, Synthesis of Secreted Membrane bound Proteins, https://www.youtube.com/watch?v=SKMIzmAe0do
- ↑ Edward F. Plow, Thomas A. Haas, Li Zhang, Joseph Loftus, Jeffery W. Smith, Ligand Binding to Integrins, Journal of Biological Chemistry.
- ↑ Tal R & Havivi E. (1970). Lipids in vitamin A deficient chicken cartilage and new bone. Int Z Vitaminforsch , 40, 3-8. PMID: 4314628
- ↑ 16.0 16.1 De Franceschi N, Hamidi H, Alanko J, Sahgal P & Ivaska J. (2015). Integrin traffic - the update. J. Cell. Sci. , 128, 839-52. PMID: 25663697
- ↑ Israeli-Rosenberg S, Manso AM, Okada H & Ross RS. (2014). Integrins and integrin-associated proteins in the cardiac myocyte. Circ. Res. , 114, 572-586. PMID: 24481847
- ↑ Kosi Gramatikoff [Kosigrim], 3/11/2008, Integrin Binding Collagen, https://www.youtube.com/watch?v=8BMFqRmbbes
- ↑ 19.0 19.1 Saito K, Fukumoto E, Yamada A, Yuasa K, Yoshizaki K, Iwamoto T, Saito M, Nakamura T & Fukumoto S. (2015). Interaction between fibronectin and β1 integrin is essential for tooth development. PLoS ONE , 10, e0121667. PMID: 25830530
- ↑ 20.0 20.1 <pubmed>22899715</pubmed>
- ↑ Schmalbach TK & Borch RF. (1989). Myeloprotective effect of diethyldithiocarbamate treatment following 1,3-bis(2-chloroethyl)-1-nitrosourea, adriamycin, or mitomycin C in mice. Cancer Res. , 49, 2574-7. PMID: 2540902
- ↑ Shi F, Harman J, Fujiwara K & Sottile J. (2010). Collagen I matrix turnover is regulated by fibronectin polymerization. Am. J. Physiol., Cell Physiol. , 298, C1265-75. PMID: 20107040
- ↑ 23.0 23.1 23.2 23.3 Yurchenco PD & Patton BL. (2009). Developmental and pathogenic mechanisms of basement membrane assembly. Curr. Pharm. Des. , 15, 1277-94. PMID: 19355968
- ↑ Ishikawa T, Wondimu Z, Oikawa Y, Gentilcore G, Kiessling R, Egyhazi Brage S, Hansson J & Patarroyo M. (2014). Laminins 411 and 421 differentially promote tumor cell migration via α6β1 integrin and MCAM (CD146). Matrix Biol. , 38, 69-83. PMID: 24951930
- ↑ Seguin L, Desgrosellier JS, Weis SM & Cheresh DA. (2015). Integrins and cancer: regulators of cancer stemness, metastasis, and drug resistance. Trends Cell Biol. , 25, 234-40. PMID: 25572304
- ↑ Bendas G & Borsig L. (2012). Cancer cell adhesion and metastasis: selectins, integrins, and the inhibitory potential of heparins. Int J Cell Biol , 2012, 676731. PMID: 22505933
- ↑ Canel M, Serrels A, Frame MC & Brunton VG. (2013). E-cadherin-integrin crosstalk in cancer invasion and metastasis. J. Cell. Sci. , 126, 393-401. PMID: 23525005
- ↑ de Rooij J, Kerstens A, Danuser G, Schwartz MA & Waterman-Storer CM. (2005). Integrin-dependent actomyosin contraction regulates epithelial cell scattering. J. Cell Biol. , 171, 153-64. PMID: 16216928
- ↑ Behrens J, Vakaet L, Friis R, Winterhager E, Van Roy F, Mareel MM & Birchmeier W. (1993). Loss of epithelial differentiation and gain of invasiveness correlates with tyrosine phosphorylation of the E-cadherin/beta-catenin complex in cells transformed with a temperature-sensitive v-SRC gene. J. Cell Biol. , 120, 757-66. PMID: 8425900
- ↑ Koenig A, Mueller C, Hasel C, Adler G & Menke A. (2006). Collagen type I induces disruption of E-cadherin-mediated cell-cell contacts and promotes proliferation of pancreatic carcinoma cells. Cancer Res. , 66, 4662-71. PMID: 16651417
- ↑ 31.0 31.1 Rutnam ZJ, Wight TN & Yang BB. (2013). miRNAs regulate expression and function of extracellular matrix molecules. Matrix Biol. , 32, 74-85. PMID: 23159731
- ↑ Mitra AK, Zillhardt M, Hua Y, Tiwari P, Murmann AE, Peter ME & Lengyel E. (2012). MicroRNAs reprogram normal fibroblasts into cancer-associated fibroblasts in ovarian cancer. Cancer Discov , 2, 1100-8. PMID: 23171795
- ↑ Ross TD, Coon BG, Yun S, Baeyens N, Tanaka K, Ouyang M & Schwartz MA. (2013). Integrins in mechanotransduction. Curr. Opin. Cell Biol. , 25, 613-8. PMID: 23797029
- ↑ Mitra SK & Schlaepfer DD. (2006). Integrin-regulated FAK-Src signaling in normal and cancer cells. Curr. Opin. Cell Biol. , 18, 516-23. PMID: 16919435
- ↑ Sze KM, Wong KL, Chu GK, Lee JM, Yau TO & Ng IO. (2011). Loss of phosphatase and tensin homolog enhances cell invasion and migration through AKT/Sp-1 transcription factor/matrix metalloproteinase 2 activation in hepatocellular carcinoma and has clinicopathologic significance. Hepatology , 53, 1558-69. PMID: 21520171
- ↑ Gonzalez-Angulo AM, Ferrer-Lozano J, Stemke-Hale K, Sahin A, Liu S, Barrera JA, Burgues O, Lluch AM, Chen H, Hortobagyi GN, Mills GB & Meric-Bernstam F. (2011). PI3K pathway mutations and PTEN levels in primary and metastatic breast cancer. Mol. Cancer Ther. , 10, 1093-101. PMID: 21490305


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The group has taken the decision to postpone the Festival Weekend this year with a view to returning in May 2021
Display a Heart to show your support!
Newmilns Regeneration Association were pleased to support Newmilns Gala Day with our float!
Our Celebrity Chef for the 2019 Food Festival has been confirmed as Tony Singh, MBE!
Loudoun Valley Trust Announce 2019 Calendar!
Lord-Lieutenant presents The Queen's Award for Voluntary Service
The Association Attends Garden Party Hosted By The Queen
Buckingham Palace Honours Voluntary Activities of Ayrshire Group
Ongoing Makeover For Former Post Office
Streets Are Shining In Our Town
Newmilns Festival Weekend Gets New Website
Placemaking Plan Is Delivered To Cabinet At East Ayrshire Council
Food Festival Welcomes A Masterchef!
Former Post Office Face-lift Continues
Newmilns Regeneration Association Secures Festival Funding
2017 Round up of Newmilns Regeneration Association's Events & Accounts.
We are extremely excited to announce our main prizes for the raffle at this years Newmilns Food Festival, generously donated by J H DONALD!
Newmilns Easter Egg Hunt - Sunday 9th April, Lanfine Estate - in conjunction with Darvel Improvement Group - free to attend event.
Today saw the official handover of keys from the last Postmaster, David Gulline, to Loudoun Valley Trust, who have agreed to lease the Post Office to Newmilns Regeneration Association
Public Meeting - Sunday 24th April 2pm-4pm in the Morton Hall - give us your ideas, opinions and feedback on the Action Plan for Newmilns
Announcing the first Newmilns Food Festival! Saturday 17th September 2016, 11.00am - 5.00pm at Jamieson Park, Newmilns.
Organised by the Newmilns Regeneration Association and supported by local businesses, the Community Food Fund and Awards for All, this FREE to attend Food Festival will showcase the best of local food and drink.
Annual General Meeting Tuesday 8th September at 7pm
The NRA are holding a "Coffee, Cake and Reminisicing Morning" on Saturday 16th May in the Church Hall 10am - 12 noon
The new NRA Notice Board has now been erected in Newmilns
Meeting to be held in the Morton Hall on Thursday 30th April 2pm-6pm for all Newmilns Groups and Businesses
Darvel Music Festival 2015 runs from 1st May to 10th July in Darvel Town Hall
Just in time for the Newmilns Gala, we're very proud to launch our Love Newmilns range of products.
NRA's Love Newmilns Facebook page has had overwhelming support from across the planet!
A team of our NRA members headed off to the capital to present a petition from the town.
Loudoun Church Holiday Club 11-15 August 2014
The Newmilns Gala Day will be held on Saturday 9th August 2014
Newmilns launch new action plan and is one of six areas to benefit from funding from Ayrshire programme which aims to transform 21 local communities.
The group has taken the decision to postpone the Festival Weekend this year with a view to returning in May 2021


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When some strange thing happens once, it's probably a God thing. When the same strange thing happens twice, it's probably a God thing - and He's trying to get your attention.
Last Monday afternoon, much to the chagrin of my sweat glands, I hooked up my dog Maggie for her constitutional around the neighborhood. Given that the average heat index was around 106 or so during the afternoon last week, this walk was not exactly the most pleasant of experiences for either of us (although she can claim to at least have gotten SOME relief out of it). But, dutiful father that I am, I knew she needed to go out, despite the fact I also knew I was going to kill a 64 ounce bottle of Gatorade the second we got home.
As part of her approved poop route, we had to walk past the new athletic building for the university being constructed on the other side of our neighborhood. Now, again, keep in mind: the heat index is in the lower 100's. The temperature itself is cracking 100. Warnings have been issued for people to limit their time outside for fear of dehydration or heat stroke. And what did we have to walk past? About a dozen or so men, building a brick wall around this complex, which takes up the greater part of the block it is located on.
Yeah. Carrying and laying bricks. In the heat. Having to stand outside while the mortar dries so as to be able to lay the next level. In the heat. Standing in what is in essence still a construction site, complete with tilled earth, no trees, and no shade whatsoever. In. The. Heat.
Because neither of us felt like walking at our typical brisk pace, we were able to actually overhear some of the conversation taking place with the men. Not that we were intentionally eavesdropping, but their voices were somewhat loud. Boisterous. And what we heard...well, there are things one stereotypically expects to hear from construction workers. Factor in that they were having to work under conditions unfit for most people, and you can imagine what was being said.
Actually...you can't. Because I couldn't believe it myself.
As a group, they were discussing church. They church service they had attended mostly together, from what I could gather. And they were peppering their talk with shouts of "Glory!" or "Amen!" Even the ones who weren't at the service were piping in - positively! - on what the discussion was about. Being thankful. Being grateful. In spite of one's circumstances. Thanking God always. Seriously. Now, not only were they discussing faith, but they we doing it in public. Discussing what had been said at church. The day after the services. Under such adverse conditions that would have most people either not speaking at all (so as to just get through the day and make it to the end of it) or if they were speaking, probably not in the most positive or upbeat of tones.
Most of the time, I wonder if what I say even manages to make it as a topic of conversation out of the doors of the church, let alone to the car ride home. For it to be talked about the day after? Yeah. Impossible to comprehend.
The sad stereotype is the when we as Christians leave church on Sunday to go to a restaurant, our witness is dulled by the customer service we demand and the crappy tip we leave. If we talk about what was said or done at church, it is almost always a critique - can you believe what someone wore; I can't believe how bad the worship was; I think I've heard the pastor give that sermon before; why is it always about tithing, anyway; and so on. And if we are that bad the day - heck, within the HOUR - that we leave church, how much progressively worse, gripe-laden, or un-Christ-like do we become...until we show up for our small group or mid-week church gathering?
For these guys to have been talking about church the day after in and of itself was mind boggling enough. For them to have been using the sermon - and the words of Christ - as a positive application for their life given the conditions they had to endure? I was humbled. Massively humbled.
Not because I wanted to have that kind of a church experience, but because I want to have that kind of a heart.
The fact that earlier today, with a temperature of 104 and a heat index of 109, I walked Maggie past this same group of men, doing the same work, under the same conditions, carrying on a strikingly similar conversation - this time, about being strong and courageous - it was just...a God thing. A strange, beautiful, smile-because-you-just-have-to God thing.
I think tomorrow Maggie and I may carry Gatorade on our walk. About a dozen bottles of it.


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Richard Querna "likes to film the ones with talent." But what does he mean by talent? "When [Mankato policeman Dale Stoltman] asked if Querna likes to film the ones that are good looking, the man "acknowledged that might be true." Ah.
Querna was caught red (yet, thankfully empty) handed at a game this week when a parent noticed that he was filming the same girl and continually zoomed in on her.
The parent alerted the basketball player's father, and the two men confronted Querna, who "got real nervous and tried to leave," according to the police report. Querna wound up in a meeting with school athletic director Ken Essay and gave him permission to review the footage on the camcorder. Essay found a video of Querna sitting in an office chair masturbating while yelling out girls' names.
In the video, Querna could be seen "grabbing" his nipple with one hand, while "stroking" his penis with the other. Querna narrated the act in the scene, saying he had "four separate camcorders recording his activity," according to the police report.
He was also yelling out "individual girl(s) names" and "appeared to be watching a video of something, possibly basketball as it sounded like cheering in the background."
What. A. Mess. Compounding things, Querna appears to be the world's worst liar. Initially he tells police that he just decided to pop in to the girls high school basketball game—with his video camera—after running some errands in the neighborhood. He then confessed he had come from another girl's game in a nearby town. Or, try this slip of the tongue, in further conversations with the police "Querna said he 'does a lot of recording' and 'especially likes attending and recording girl's basketball games.' He 'corrected himself' to say he likes recording 'all sporting events.'"
Police were unable to determine that a crime was committed so he was not arrested and was able to return to his New Richland home, about 45 minutes away. Unless it was too late, in which case he probably could have crashed on the bed in the back of his van that he travels in "to 'save on hotels.'"
h/t Gregory
Richard Querna banned from high school games after admitting he masturbates to homemade video of girls playing basketball [City Pages]


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Look at this long line of people in Australia.
They're queued up to gaze in wonder at the 500-year-old mummified right forearm of some Catholic saint. I've got a few things I'd want to ask them.
"What the hell is wrong with you people?"
"Do you really think fragments of corpses have magic powers?"
"Are you aware that many people find Catholics extremely creepy? Do you have any hypotheses about why that would be so?"
"Is it true that later tonight you'll be burrowing in the local cemetery to feast on the decaying flesh of the dead?"


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I just installed the new 476th Range Targets pack in to Open Alpha. All of the DMPI targets make my screen black. All containers and other objects show up great. Is this an issue in 18.104.22.168442.
I just installed the new 476th Range Targets pack in to Open Alpha. All of the DMPI targets make my screen black. All containers and other objects show up great. Is this an issue in 126.96.36.199442.
We didn't see this during testing in 2.0.4.x. Do you have a screenshot of the issue?
The first is of the view of the Target. All black. You also can see the image label. And thanks for your work on these targets. It makes NTTR that much more enjoyable.
I have a version that has building e,o,u and dpi 04,06,22,01,14 that works great.
Not sure what the issue might be, honestly. You experience this issue on ALL the "DMPI" targets? If not all of them are affected, it would be helpful to know which ones are causing the issue, and which aren't.
Does your hardware meet the minimum specs for DCS? If yes, can you verify that your DCS installation and graphics drivers are both up to date? DCS 2.0 Open Alpha should be at version 22.214.171.124428. If that doesn't fix the issue, please let me know your hardware specs.
Also, try downloading our NTTR mission here: http://www.476vfightergroup.com/down...do=file&id=403 and see if the issue persists.
There wa a switch in renderer logic between 2.0.3.x and 2.0.4.x
Which version of range objects are you using? Which object is the one in question?
Da FAC?
First thing that comes to mind is that the installation of the mod isn't complete.
Could you verify that you have the edm (en lod) files for the dmpi targets in the "shapes" folder of the mod? Looks to me like they are missing.
For the example of the screenshots above, you are using 62-11 DMPI 01. Have a look in the shapes folder of you see the files "NTTR Target 62-11 DMPI 01.edm" and "NTTR Target 62-11 DMPI 01.lod"
Providing CAS when you're all out of HUA!
My computer is up to date. Sabertooth z77/ I5-3570k Hd7970 Windows 7. All emd and lods are in the shape folder for the DMPI targets. All DMPI dont show up. I even tryed then in model viewer. Im not running 2.0.4 because I cant. 2.0.4 freezes on me. So if all of the testing is in 2.0.4 i might be out of luck.
Hey Chardly,
I'm sorry to say that I don't know what might be causing your issue. It appears to be something local to your machine though, and the fact that 2.0.4 won't run on your machine indicates the possibility that something larger is going on.
Have you tried posting about the DCS crash issue on the ED forum? I'd probably focus on finding out why 2.0.4 isn't working first, because I think that might be the heart of the issue.
Thanks Noodle. I have posted my problem along with others ( a small few) with a response this is a hard problem to find. Im not a computer guy so getting help would be nice but doesnt all ways happen.


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Dublin hospital expanding emergency department | Community Spirit
Title (Max 100 Characters)
Four rural hospitals across the state in the past two years have shut their doors.
But Monday, Fairview Park Hospital in Dublin announced a $4 million expansion of its emergency department.
"Our waiting times have started growing because we don't have the capacity," said the hospital's CEO, Don Avery.
But the expansion will change that, increasing the 12-patient bed unit to 22, Avery said.
"More spaces we have for patients and that's more people we have to hire to cover those," he said.
It could provide a dozen jobs or more between doctors, nurses and practitioners.
"The emergency department, the hospital, isn't just a day job," Avery said. "That's a 24-hour, 7 day a week commitment. So that's even more jobs than you might expect to see."
He also says the renovated department will have a new pediatric unit and a behavioral health unit.
State representative Bubber Epps says those additions are welcome news in the midst of a rural health care crisis.
"Rural Georgia is just facing a monumental task in providing health care services of the people on an affordability and an ability to pay basis. This hospital sees that," Epps said.
Avery says the expansion is fueled by community need... as those in Dublin and surrounding counties choose Fairview.
The next closest hospital is in Macon, about an hour away.
"Historically, people have left rural communities to get health care in larger towns and that's not happening as much," Avery said. "This hospital has been successful because more and more people are using the services that we provide."
He says the number of patients visiting Fairview's emergency department has jumped from 28,000 in 2009 to 38,000 today.
Construction starts in July and will last about a year.
Avery says the current emergency department will continue to accommodate patients.
Follow 13WMAZ's Anita Oh on Twitter @anita_oh and on Facebook at Anita Oh WMAZ.