Inslee signs bill allowing WSU med school; funding still in flux – Thu, 02 Apr 2015 PST

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OLYMPIA Gov. Jay Inslee signed a bill Wednesday that allows Washington State University to launch a new medical school inSpokane.

But after he was surrounded by supportive legislators and university leaders for the signing ceremony, Inslee hedged when asked at a news conference how much money the state should spend training doctors during the next twoyears.

Such funding for two state-sponsored medical schools will have to be negotiated between two very different plans in competing House and Senate budgetproposals.

With about 300,000 more people covered by health insurance under the Affordable Care Act and a growing

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Gov. Jay Inslee congratulates WSU President Elson Floyd after signing a bill that gives WSU authority to start its own medical school inSpokane. (Full-size photo)

OLYMPIA Gov. Jay Inslee signed a bill Wednesday that allows Washington State University to launch a new medical school inSpokane.

But after he was surrounded by supportive legislators and university leaders for the signing ceremony, Inslee hedged when asked at a news conference how much money the state should spend training doctors during the next twoyears.

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Inslee signs bill allowing WSU med school; funding still in flux - Thu, 02 Apr 2015 PST

Locking up an oncogenic transcription

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UMMS and UVA scientists develop a new molecule that has potential to extend survival in some leukemia patients

WORCESTER, MA - A novel molecule designed by scientists at the University of Massachusetts Medical School and the University of Virginia inhibits progression of a hard-to-treat form of recurring acute myeloid leukemia (AML) in patient tissue. The small molecule is one of the first designed to specifically target a cancer-causing transcription factor. Previously thought to be an undruggable target, this strategy may be used to design other novel molecules that can specifically inhibit cancer-causing transcription factors. Details of the work were published in Science.

Transcription factors are single- or multi-protein complexes that regulate transcription of DNA into messenger RNA and gene expression by binding to regions on the genome next to a gene. Mutations in transcription factors can result in altered gene expression programs that give way to new, cancer-causing functions. Although these aberrant transcription factors are promising targets for new therapeutics, the complexity of interrupting very specific protein-to-protein interactions has made it difficult to find small molecules or design drugs that treat these cancers.

"When we look at inhibitors, they usually target an enzyme or receptor. There aren't a lot of good examples of transcription factor inhibitors in clinical trials," said Lucio H. Castilla, PhD, associate professor of molecular, cell and cancer biology and co-leader of the study. "Here, we've used our extensive knowledge of a mutant transcription factor found in a subset for acute myeloid leukemia patients to design a molecule that can specifically sequester only the oncogenic mutant. This leaves the normal transcription factor to bind to the DNA and restore gene expression."

Acute myeloid leukemia causes a rapid growth in abnormal white blood cells that accumulate in the bone borrow and interfere with the production of red blood cells. It is the most common form of adult leukemia and survival rates vary depending on specific genetic subsets. Typical treatment involves nonselective chemotherapy, but that can be taxing on some populations, especially the elderly. Therapeutic approaches that target specific genetic anomalies have the potential to be less toxic and yield better results.

AML patients with an inversion on chromosome 16 (known as inv(16) AML) typically respond to initial chemotherapy treatment, but recurrences are likely in a fraction of cases. Leukemia in these patients is caused by a small reversal of the DNA sequence on chromosome 16 that combines a gene which controls production of blood cells and one involved in muscle physiology. When healthy, the core-binding factor-beta (CBFB) protein typically binds with the RUNX protein to form a transcription factor that regulates a number of genes that control production of red and white blood cells. In AML cells with inv(16), the CBFB gene is fused with the smooth muscle myosin heavy chain (SMMHC) gene, and the activity of the CBFB-SMMHC fusion protein causes leukemia.

John H. Bushweller, PhD, a professor of biochemistry at the University of Virginia, screened a library of small molecules and found that the molecule AI-4-57 inhibited the binding of RUNX and CBFB-SMMHC. However, the activity of this molecule was not enough to have a therapeutic effect; by only treating a portion of the AML cells, enough would be left behind for the cancer to return and be resistant to further chemotherapy.

To overcome this problem, Castilla and Bushweller established a collaboration to modify the initial compound to specifically target only the mutant transcription factor (CBFB-SMMHC ) while leaving the normal one (CBFB) being produced by the other copy of chromosome 16 free to do its job of regulating blood cell production.

Taking advantage of the structural differences between the mutant and normal protein, the researchers were able to devise a new compound having the effect they sought. Because normal CBFB is monomeric and CBFB-SMMHC is oligomeric, they developed a bivalent version of the initially screened compound -- AI-4-57. After further refinement, the new drug AI-10-49 prolonged the survival rate of mice with inv(16) AML and was successful in treating in vitro leukemia lines taken from patients.

The polyvalent strategy may serve as a template for new drug discovery efforts focused on selective modulation of aberrant fusion proteins arriving from chromosomal translocation events, wrote Angela N. Koehler, PhD, assistant professor of biological engineering at the Massachusetts Institute of Technology, in a review accompanying the study. This study also serves as a "proof of concept for targeted therapies aimed at dysregulated transcription and should inspire the development of additional directed approaches to control aberrant transcription factor function in cancer and other diseases."

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Locking up an oncogenic transcription

Ex-Abilene ISD dean Michael Trook indicted for having sex with student

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ABILENE, Texas -

A Taylor County grand jury on Thursday indicted Michael Trook former administrator at Holland Medical High School in Abilene ISD for having an improper relationship with a student.

The district attorney's office confirmed Trook was indicted on two counts of improper relationship between a teacher and student. That's a second degree felony.

According to a complaint filed with the DA's office, the charges stem from a sexual relationship Trook allegedly had with a female student in his office at Holland Medical School around December 10th.

Trook, 29, resigned as dean of health sciences at the school that same month.

At the time when Trook resigned and was arrested, then-Abilene ISD Superintendent Heath Burns sent a letter to parents, students and staff at Holland Medical School that said Trook admitted to having engaged in inappropriate, unprofessional and unethical conduct.

Trook was a former associate principal at Abilene High School. He was with the Abilene ISD for three years and at Holland Medical High School between July 2015 and December 2015.

Trooks case ignited a controversy that focused on Abilene ISDs handling of a series of alleged improper employee-student relationships.

Burns resigned suddenly in February as Abilene police continued to investigate the allegations.

Before Burns stepped down as Abilene ISD's superintendent, Abilene Police Chief Stan Standridge had strongly criticized Abilene ISD leaders namely Burns for how the district reported the cases to police. Standridge also questioned Burns cooperation during the investigations.

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Ex-Abilene ISD dean Michael Trook indicted for having sex with student

LIBERTY CITY IN GTA 5! (How To Get To Liberty City in GTA 5 Glitch) – Video

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LIBERTY CITY IN GTA 5! (How To Get To Liberty City in GTA 5 Glitch)
Greatest GTA 5 glitch ever!!! If it doesn #39;t work for you the first time, just keep trying over and over again until your entire day is gone! MidnightMan Apparel http://midnightman.spreadshirt....

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LIBERTY CITY IN GTA 5! (How To Get To Liberty City in GTA 5 Glitch) - Video

Liberty give Laimbeer another shot

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The New York Liberty are such a franchise. But the re-hiring of Bill Laimbeer as coach less than three months after he was fired by the organization is head-scratching even by Liberty standards.

Oh, wait a minute. Not really. This is the Liberty we're talking about.

Let me make haste to say, though, I actually don't think this is a bad decision at all. It's correcting a bad decision, which was firing Laimbeer back in October without a really strong idea of whom the franchise could get to replace him.

From what I gather from sources around the league, Madison Square Garden Company chair James Dolan had some candidates in mind. But they didn't work out. Now with the Knicks being the primo disaster of this NBA season, Dolan probably just wanted to get the Liberty job filled. And ultimately decided to go back to Laimbeer.

Who, apparently, wasn't exactly stunned to get the call to return. Laimbeer was spending the winter fishing and playing golf. And while he wasn't expecting to coach again in the WNBA this summer, he's glad to be doing it.

"My passion is still there for the New York team," Laimbeer said Thursday. "I'd like to accomplish more for this franchise."

The Liberty were 11-23 and then 15-19 in Laimbeer's two seasons, missing the playoffs both years. But Thursday, he repeated something he had also told me back in October when he was let go: That while he didn't always enjoy his first season with the Liberty, this past season he really did like the job and working with the team. (Having a world-class center such as Tina Charles, whom the Liberty got in a trade before the 2014 season, undoubtedly helps in that regard.)

Laimbeer also said something else in October that seems pertinent to the Liberty's reversal in course this week. He talked about the difference in working for the Detroit Shock, where he answered primarily to one person, then-owner Tom Wilson. As compared to working for a public corporation like MSG.

"They've got a lot of moving pieces," Laimbeer said in October about MSG.

Indeed, they do. But from the Liberty's inception in 1997 to 2010, Carol Blazejowski was the team's general manager and front-office point person for the franchise. And while she took her share of barbs (including from me), at least you always knew whose hands were on the Liberty's steering wheel.

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Liberty give Laimbeer another shot

Future uncertain for New York Liberty

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However, in Laimbeer's two seasons in New York, the Liberty did not make the playoffs. And on Tuesday, New York parted ways with Laimbeer and pulled the plug on what New York hoped would be "Trader Bill's" triumphant return to the WNBA. He had led the Detroit Shock to three WNBA titles (2003, '06, '08), then exited the league early in the 2009 season, the Shock's last in Detroit.

Laimbeer spent some time in the shark tank of NBA coaching before returning to the WNBA. It was supposed to be a successful merging: Laimbeer's history of success and edgy personality seemed like it might be the right fit for a Liberty franchise in the doldrums.

But after going 11-23 in 2013 and 15-19 this year, the Liberty didn't renew Laimbeer's contract. Now what?

Well, I asked the Liberty if anyone with the organization could address that very question on Tuesday. Turns out, they couldn't. Or weren't ready to. Or just didn't want to. Whatever, right?

Hey, the Lib fans don't need to hear right away what the game plan is going forward. They should still just be basking in joy about the end of the Liberty's three-year exile to Newark. They got back into refurbished Madison Square Garden this season, so surely they'll be docile and patient waiting however long or short it takes for the Liberty to figure out who takes the reins for 2015 and beyond.

Because if there's one thing New Yorkers are known for, it's patience.

I'm being sarcastic, of course, but in truth, Liberty fans have been much more patient than one might expect. New York's last appearance in the WNBA Finals was in 2002. The closest that the Liberty have come since to returning to the WNBA Finals was in 2008, when they lost the deciding Game 3 of the Eastern Conference finals to Laimbeer's Shock. New York was swept by Atlanta in the 2010 East finals.

Then in the last four years -- the first two under coach John Whisenant -- the Liberty have gone a combined 60-76 and won just one playoff game. In Whisenant (Sacramento, 2005) and Laimbeer, the Liberty have tried coaches who won WNBA titles elsewhere.

So, again ... now what? Might former Liberty player Teresa Weatherspoon be tapped as the team's next coach? Do the Liberty plan on combining the job of coach/GM as they did with Whisenant and Laimbeer? Or return to the formula of having those be separate jobs? That was the case from the franchise's inception in 1997 through the 2010 season when Carol Blazejowski was the GM.

A Liberty spokesman said that no one from the organization was available to comment Tuesday. So all we have is the statement from Knicks' assistant general manager Allan Houston, thanking Laimbeer and saying the organization will "begin our search immediately to secure a general manager and coach to help us move forward and reach our ultimate goal of a WNBA championship."

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Future uncertain for New York Liberty

Sean Gabb: The Cultural Desert of British Libertarianism – A Study in Failure – Video

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Sean Gabb: The Cultural Desert of British Libertarianism - A Study in Failure
A speech given on Tuesday the 17th March 2015 in London to the other Libertarian Alliance. Sean argues that libertarianism has had no impact in Britain since the 1980s because libertarians...

By: seangabb

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Sean Gabb: The Cultural Desert of British Libertarianism - A Study in Failure - Video

Ep. 75: How Does Libertarianism Deal with the Problem of Pollution? (with Matt Zwolinski) – Video

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Ep. 75: How Does Libertarianism Deal with the Problem of Pollution? (with Matt Zwolinski)
Matt Zwolinski joins us to talk about libertarianism and pollution. What does it mean for libertarians to treat pollution as a violation of property rights? Matt Zwolinski joins us this week...

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Ep. 75: How Does Libertarianism Deal with the Problem of Pollution? (with Matt Zwolinski) - Video

Today in Tabs: Facebook Presents Your Year in Tragedy

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Silk Roadthe darknet site that blended techno-libertarianism, unexpected pathos, drugs, and that sweet elixir of larceny Bitcoin into what has already been one of recent historys most entertaining legal proceedingsis not done with us yet! Like all Silk Road related news, the charges against DEA agent Carl Force and former Secret Service agent Shaun Bridges are incredibly implausible and circuitous, but Sarah Jeong does as good a job explaining them as anyone could hope for. Keywords include, but are not limited to: murder for hire (simulated), intimidation (failed), theft (flagrant), and LinkedIn contact request (regrettable). Lauren Smiley has a step by step guide in Matter for Feds interested in catching the Bitcoin-laundering wave, and Kashmir Hill collected 5 of Forces wackiest side-projects for Fusion.

Facebook is in trouble again for algorithmically dredging up painful memories. Who could have predicted this?

In Pacific Standard, Susie Cagle makes a case that the VC funding system does more harm than good. If youre on the fence about that, please do see this Twitter thread where prominent venture capitalist Harry Potter, from the blue-chip Silicon Valley firm of Egg & Rapgenius, "argues with Twitter user "fart" about the definition of electricity."

April Fools is stupid, but its also the day Carnegie Mellons Association for Computational Heresy holds SIGBOVIK, which is one of those nerd events where there are so many layers of in-joke that you cant exactly tell how much (if any) of it is real, or what "real" might mean in this context, but the Proceedings, at least, are very funny. Notably, Tom Murphy made a portmanteau of every English word, which he calls a "portmantout." Just watch the video, its good.

I enjoyed this Colson Whitehead tab about our narcissistic culture because I love reading about myself. You do you, Cols! Alana Massey is right: "Chill" is stupid. The police must be huge Chris Rock fans! Across the land, the question rings out: Can a gay wedding even have pizza? If you dont already know what that post is about, trust me, youll be happier staying that way. And finally: read this boring tab.

Its intern Averys birthday! Today she turns 27! At 27 I was a married home owner and one year away from the birth of my first child, but being a newsletter intern is great too! Happy Birthday Avery!

Today is my twenty-seventh birthday (please, hold your applause). Two decades ago, on this date, I woke up and found a childs snooker table set up for me in our dining room. Not something Id asked for, but still one of the best gifts Ive ever received.

The popularity of snooker is a weird part of British culture. It hardly seems a thrilling spectator sport, but for weeks at a time in the winter you can switch to BBC2 and watch hours of snooker in the eveningtime slot after time slot of the same old static shot. We even had a bizarre snooker-based game show, Big Break, which ran for ten years.

My snooker table got a lot of use at first, but then I returned to the books one could always find me in as a child. I was not destined to be a Ronnie OSullivan, who is profiled in the New Yorker this week. Its a terrific featurea classic story of a shining talent dogged by vice and familial sin.

I remember looking at my snooker table in the garden with the trash, warped and broken-down by rain. Happy birthday.

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Today in Tabs: Facebook Presents Your Year in Tragedy