Dan Cohen AUTHOR The Defense Department would be prohibited from holding a round of base closures, under the portion of the fiscal 2016 defense authorization bill marked up Tuesday by the Senate Armed Services’ Readiness Subcommittee. “At a time when the department cannot afford to fully fund … readiness requirements, I do not support giving the department the authority to pursue a BRAC round,” said Subcommittee Chair Kelly Ayotte (R-N.H.), reported CQ Roll Call.The panel’s rejection of the Obama administration’s request to hold a BRAC round in 2017 was not a surprise as Ayotte has made her opposition clear in recent years. She pointed to the potential for a new round to incur significant upfront costs, as the last one did, in explaining her stance at a hearing of the subcommittee in March.The text of the legislation is not expected to be available until the full committee completes its markup. Its deliberations begin this morning and are expected to run until Thursday night or beyond.The measure also contains language to reform DOD’s weapons acquisition process. Ayotte said the proposals are similar to those in the House bill but did not discuss its specific provisions, according to the story.“In this era of growing threats and shrinking defense budgets, the old methods of acquisition and … acquisition overruns are no longer sufficient,” Ayotte said.
See the best Marvel Avengers cosplay from San Diego Comic-Con 2019 AVENGERS ASSEMBLE! Bring home Marvel Studios’ @Avengers: Endgame on Digital July 30 and Blu-ray August 13: https://t.co/6wVet96bw0 pic.twitter.com/luboLlLCvL— Marvel Studios (@MarvelStudios) June 26, 2019 Share your voice Comments Now playing: Watch this: 30 Photos TVs Blu-ray Players Media Streamers TV and Movies Avengers: Endgame could have been very different Amazon Fire TV Note that CNET may get a share of revenue from the sale of merchandise featured on this page. Getting a disc or digital version with the directors’ commentary and deleted scenes will shed some new light on the movie, even for hardcore Marvel fans. See Avengers: Endgame (plus bonus features) at AmazonAlso notable for the home release is that Endgame is one of the first movies to support Dolby Vision and Dolby Atmos on the Movies Anywhere service — at least when viewed on 4K-capable Apple TV, Fire TV, Chromecast and Android TV hardware on compatible 4K TVs. Those premium HDR video and surround audio features will also be retroactively added to some previous 4K Movies Anywhere releases throughout the summer and fall. See Avengers: Endgame in 4K HDR at Movies AnywhereBefore you plunk down more cash to see it again, however, keep in mind it’s also slated to hit the Disney Plus streaming service on Dec. 11. That online channel arrives in November and will cost $7 per month. Avengers: Endgame takes disc form today. Marvel Studios The humble Blu-ray disc hasn’t been Thanos’d yet. Avengers: Endgame, the biggest movie in the world, hit stores today on Blu-ray, UHD 4K and DVD, joined by a handful of older Marvel films.Avengers: Endgame is now available at most outlets for $22.99 (1080p), $29.99 (UHD 4K Blu-ray). Best Buy has an exclusive SteelBook version for $34.99 — basically, a fancy case — while Target has a version with an exclusive book — Avengers Initiative: The First 10 Years — for the same price.The release of Endgame is accompanied by five other remastered Marvel titles on UHD 4K Blu-ray — Iron Man, Iron Man 2, Iron Man 3, Thor, and Thor: The Dark World — with more expected soon.See Avengers: Endgame SteelBook Edition at Best BuyThe $20 digital version of Endgame was released earlier this month on sites such as Amazon, iTunes and Vudu. In July, Endgame surpassed Avatar as the highest-grossing movie of all time, thanks in part to a theatrical re-release in recent weeks that included a post-credits scene and Stan Lee tribute. Marvel Thor Amazon Iron Man 3 News • Apple Music is now available on Amazon Fire TV Review • Amazon Fire TV: Affordable Alexa-infused 4K streaming Tags 2:00
D.C. Council member Vincent OrangeD.C. Council member Vincent Orange (D-At-Large) held a hearing recently on a bill he introduced that would help returning citizens learn skills to start and operate businesses.The hearing for the bill, which would create a $10 million operating fund, was held on Jan. 28. Called “The District of Columbia Incarceration to Incorporation Entreprenuership Program Act of 2015,” Orange’s bill calls for the Department of Employment Services and the Department of Small and Local Business Development to set up the program.The legislation calls for the University of the District of Columbia and its community college to offer courses to returning citizens on business subjects and GED attainment, and provide scholarships and grants to help pay for the classes. Orange said keeping returning citizens positively engaged is the way to avoid criminal activity.“Statistics have shown that within three years of coming home from prison, returning citizens will be re-arrested,” Orange said. “Stable employment is the key to keeping people out of prison and owning a business can be a part of that.”There are an estimated 60,000 District residents with criminal records. Studies and testimonies from returning citizens reveal that even though the city has tolerant laws and public policy towards them, it is difficult for returning citizens to find employment. Skeptical employers have cited possible criminal activity and not wanting to deal with stigmatized employees as reasons for not hiring returning citizens.Orange said returning citizens with stable jobs have a recidivism rate of only 7 percent as opposed to 51.8 percent according to U.S. Bureau of Justice statistics. The council member said that Oklahoma and Pennsylvania have programs similar to one he is proposing and they are considered national models of success.Orange’s legislation has the support of D.C. Council member Yvette Alexander (D-Ward 7). D.C. Council member Charles Allen (D-Ward 6) likes the idea but is worried about program implementation. “The incarcerated population is the hardest to reach,” Allen said. “I don’t think DOES serves returning citizens well and I want to make sure that DOES works for everyone. There is no shortage of really good intentions in this city and I hope that it reaches individuals who can be set up for success.”A number of witnesses testified on Orange’s bill. No one voiced opposition to Orange’s concept but some had concerns about implementation and focus. “The bill could be improved by emphasizing cooperative businesses and should provide co-op specific business training,” said Eugene Puryear, director of field operations for the advocacy organization Justice First. Puryear wants Orange’s bill to include provisions to appoint a returning citizen on a panel that would oversee the program, to require a review by the council after its fifth year, and provide “a hard cap [on funding the program] on the initial appropriation [to] encourage program effectiveness and community input.”Debra Rowe, the executive director of Returning Citizens United, testified in support of Orange’s bill, but said more support is needed for those participating in the program. “To start a business in the District of Columbia, you have to pay a lot of fees,” Rowe said. “The people that the legislation is designed to help generally cannot pay the fees to the city agencies that are needed to get their businesses going.”Rowe doesn’t want the program Orange proposes to become “another certification for returning citizens.”“We have every certification that you can think of but we can’t get the jobs,” she said. “I also think that businesses that are run by returning citizens that are successful certified business enterprises should mentor those who want to go into business.”
Back in 2006, researchers in Japan were able to effectively generate stem cells from skin cells without the need for oocytes (eggs) or other embryonic cells. By expressing the four transcription factors, Oct4, Sox2, KLF4 and c-Myc, they could generate cells that, at least in theory, could turn into any other kind of cell. Unfortunately, not only the overall yield of viable stem cells was low, the “rejuvenated” cells that were able to be extracted were generally unsuitable for subsequent patient treatment. The problem is that even when transplanting stem cells obtained from a person’s own skin, immune rejection or tumor formation still occurred. This disharmony results from the fact that the immune system, while trained over a lifetime, can be confused by the “dissonance” in expression of youthful protein isoforms, particularly when encountered astride those of more adult cells. By inducing the expression of all four transformation factors at different times, the Chinese researchers eventually hit upon the optimal sequence. In a nutshell, introducing a combination of Oct4 and Klf4 first, followed later by c-Myc, and then finally Sox2, the maximal yield could be obtained. They were surprised to find that this sequential protocol activated an epithelial-to-mesenchymal (EMT) transition, which was then followed by a delayed reverse (MET) transition. It had been known for some time that in mouse fibroblasts, reprogramming to the pluripotent stem cell state begins by going through a MET conversion. Therefore finding upregulation of the proteins SLUG and N-cadherin, factors generally associated with an EMT, was not anticipated.In embryogenesis, cells interconvert between epithelial and mesenchymal phenotypes as they lay out the basic body plan. In the epithelial state, cells possess inherent polarity and show preferential adhesion, while in the mesenchymal state, these properties are lost as cells becomes migratory and invasive. This game of run-the bases is recapitulated as more option-constrained cells later rough out the critical form of each organ. Each time cells alights in either camp, they express part of an overlapping subset of various state indicators, but their genetic arrangements are never quite the same. The authors looked at a few additional factors that might help explain the appearance of a brief mesenchymal state in the sequential procedure. By applying TGF-beta to the simultaneous factor expression protocol early on, they were able to mimic the appearance of the mesenchymal state. This was found to be accompanied by an enhancement in the reprogramming yield, but the effect disappeared when the TGF-beta was applied using a 12-day treatment protocol.TGF-beta is a whole new can of worms since it is expressed by many cells and does many things, even opposite things in different cells. It is traditionally termed a cytokine, although the distinction between that and a hormone is becoming increasingly blurred. Generally hormones are active at nanomolar concentrations in the blood and vary by less than an order of magnitude. Cytokines by contrast often circulate at less than picomolar concentration and ramp up 1000-fold when called upon during injury or infection.Capturing the essential behavior of the thousands of downstream regulators or even just four transcription factors, is just not realistic with a flowchart or state diagram. Beyond a certain level of complexity, if the transition probabilities are too low, or the branch points and exceptions too numerous, new constraints are needed before any sensible algorithmic description might be attempted. In the absence of any such obvious constraints, the authors hypothesized that while multiple pathways exist for conversion between epithelial-mesenchymal states, some are shorter or easier to access than others. They believe that their sequential recipe tips the balance towards a brief mesenchymal state which ultimately leads to a better stem cell yield. Citation: Optimal stem cell reprogramming through sequential protocols (2013, May 28) retrieved 18 August 2019 from https://phys.org/news/2013-05-optimal-stem-cell-reprogramming-sequential.html (Phys.org) —Gaining control of the ability of mature tissues to generate stem cells is the central medical challenge of our day. From taming cancer, to providing compatible cell banks for replacement organs, knowledge of how cells interconvert between stable points on the complex cellulo-genetic landscape will deliver to the doctor the same mastery the programmer now holds over bits. While researchers often speak of “reprogramming” cells, most recipes today consist only of a crude and partial ingredient list, with little consideration of sequence, quantity or prior state. We recently took stock of the latest in stem cell technology and reviewed the four major factors used to revert adult cells back into omnipotent progenitors. We also just reported on further attempts to rigorously define appropriate level of factors to supply. Researchers from China have now reported that stem cell generation can be regulated by the precise temporal expression of these factors. Publishing in the journal Nature Cell Biology, they show that the efficiency and yield of stem cells can be optimized by controlling the sequencing of the transforming factors, and furthermore provide a theoretical exploration of the possible mechanisms going on behind the scenes. Stem Cell Induction. Credit: stemcellschool.org More information: Sequential introduction of reprogramming factors reveals a time-sensitive requirement for individual factors and a sequential EMT–MET mechanism for optimal reprogramming, Nature Cell Biology (2013) doi:10.1038/ncb2765AbstractPresent practices for reprogramming somatic cells to induced pluripotent stem cells involve simultaneous introduction of reprogramming factors. Here we report that a sequential introduction protocol (Oct4–Klf4 first, then c-Myc and finally Sox2) outperforms the simultaneous one. Surprisingly, the sequential protocol activates an early epithelial-to-mesenchymal transition (EMT) as indicated by the upregulation of Slug and N-cadherin followed by a delayed mesenchymal-to-epithelial transition (MET). An early EMT induced by 1.5-day TGF-β treatment enhances reprogramming with the simultaneous protocol, whereas 12-day treatment blocks reprogramming. Consistent results were obtained when the TGF-β antagonist Repsox was applied in the sequential protocol. These results reveal a time-sensitive role of individual factors for optimal reprogramming and a sequential EMT–MET mechanism at the start of reprogramming. Our studies provide a rationale for further optimizing reprogramming, and introduce the concept of a sequential EMT–MET mechanism for cell fate decision that should be investigated further in other systems, both in vitro and in vivo. This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only. Protein central to cancer stem cell formation provides new potential target © 2013 Phys.org Journal information: Nature Cell Biology Explore further