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Princess Party




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Tasty Figs




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Specialty Breeds




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safety signs in hell




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The Pointy end




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Gravity loves masonry




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Activity Corner




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Genetics Society of America honors outstanding contributions to genetics with 2020 GSA Awards

The Genetics Society of America (GSA) is pleased to announce the 2020 recipients of its annual awards for distinguished service in the field of genetics. The awardees were nominated and selected by their colleagues and will be recognized with presentations at The Allied Genetics Conference (TAGC), held April 22-26, 2020, in the metro Washington, DC area.




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Smaller Detection Device Effective for Nuclear Treaty Verification, Archaeology Digs

Most nuclear data measurements are performed at accelerators large enough to occupy a geologic formation a kilometer wide. But a portable device that can reveal the composition of materials quickly on-site would greatly benefit cases such as in archaeology and nuclear arms treaty verification. Research published this week in AIP Advances used computational simulations to show that with the right geometric adjustments, it is possible to perform accurate neutron resonance transmission analysis in a device just 5 meters long.




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UTEP Professor Named Fellow of International Society for Optics and Photonics

Raymond C. Rumpf, Ph.D., professor of electrical and computer engineering at The University of Texas at El Paso, was promoted to Fellow of the International Society for Optics and Photonics (SPIE), an educational nonprofit established to advance light-based science, engineering and technology.




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Cambridge Rock Society




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Appeals Court Says Prosecutors Who Issued Fake Subpoenas To Crime Victims Aren't Shielded By Absolute Immunity

For years, the Orleans Parish District Attorney's Office in Louisiana issued fake subpoenas to witnesses and crime victims. Unlike subpoenas used in ongoing prosecutions, these were used during the investigation process to compel targets to talk to law enforcement. They weren't signed by judges or issued by court clerks but they did state in bold letters across the top that "A FINE AND IMPRISONMENT MAY BE OPPOSED FOR FAILURE TO OBEY THIS NOTICE."

Recipients of these bogus subpoenas sued the DA's office. In early 2019, a federal court refused to grant absolute immunity to the DA's office for its use of fake subpoenas to compel cooperation from witnesses. The court pointed out that issuing its own subpoenas containing threats of imprisonment bypassed an entire branch of the government to give the DA's office power it was never supposed to have.

Allegations that the Individual Defendants purported to subpoena witnesses without court approval, therefore, describe more than a mere procedural error or expansion of authority. Rather, they describe the usurpation of the power of another branch of government.

The court stated that extending immunity would be a judicial blessing of this practice, rather than a deterrent against continued abuse by the DA's office.

The DA's office appealed. The Fifth Circuit Appeals Court took the case, but it seemed very unimpressed by the office's assertions. Here's how it responded during oral arguments earlier this year:

“Threat of incarceration with no valid premise?” Judge Jennifer Elrod said at one point during arguments. She later drew laughter from some in the audience when she said, “This argument is fascinating.”

“These are pretty serious assertions of authority they did not have,” said Judge Leslie Southwick, who heard arguments with Elrod and Judge Catharina Haynes.

The Appeals Court has released its ruling [PDF] and it will allow the lawsuit to proceed. The DA's office has now been denied immunity twice. Absolute immunity shields almost every action taken by prosecutors during court proceedings. But these fake subpoenas were sent to witnesses whom prosecutors seemingly had no interest in ever having testify in court. This key difference means prosecutors will have to face the state law claims brought by the plaintiffs.

Based upon the pleadings before us at this time, it could be concluded that Defendants’ creation and use of the fake subpoenas was not “intimately associated with the judicial phase of the criminal process,” but rather fell into the category of “those investigatory functions that do not relate to an advocate’s preparation for the initiation of a prosecution or for judicial proceedings.” See Hoog-Watson v. Guadalupe Cty., 591 F.3d 431, 438 (5th Cir. 2009)

[...]

Defendants were not attempting to control witness testimony during a break in judicial proceedings. Instead, they allegedly used fake subpoenas in an attempt to pressure crime victims and witnesses to meet with them privately at the Office and share information outside of court. Defendants never used the fake subpoenas to compel victims or witnesses to testify at trial. Such allegations are of investigative behavior that was not “intimately associated with the judicial phase of the criminal process.”

Falling further outside the judicial process was the DA's office itself, which apparently felt the judicial system didn't need to be included in its subpoena efforts.

In using the fake subpoenas, Individual Defendants also allegedly intentionally avoided the judicial process that Louisiana law requires for obtaining subpoenas.

The case returns to the lower court where the DA's office will continue to face the state law claims it hoped it would be immune from. The Appeals Court doesn't say the office won't ultimately find some way to re-erect its absolute immunity shield, but at this point, it sees nothing on the record that says prosecutors should be excused from being held responsible for bypassing the judicial system to threaten crime victims and witnesses with jail time.




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Harrisburg University Researchers Claim Their 'Unbiased' Facial Recognition Software Can Identify Potential Criminals

Given all we know about facial recognition tech, it is literally jaw-dropping that anyone could make this claim… especially without being vetted independently.

A group of Harrisburg University professors and a PhD student have developed an automated computer facial recognition software capable of predicting whether someone is likely to be a criminal.

The software is able to predict if someone is a criminal with 80% accuracy and with no racial bias. The prediction is calculated solely based on a picture of their face.

There's a whole lot of "what even the fuck" in CBS 21's reprint of a press release, but let's start with the claim about "no racial bias." That's a lot to swallow when the underlying research hasn't been released yet. Let's see what the National Institute of Standards and Technology has to say on the subject. This is the result of the NIST's examination of 189 facial recognition AI programs -- all far more established than whatever it is Harrisburg researchers have cooked up.

Asian and African American people were up to 100 times more likely to be misidentified than white men, depending on the particular algorithm and type of search. Native Americans had the highest false-positive rate of all ethnicities, according to the study, which found that systems varied widely in their accuracy.

The faces of African American women were falsely identified more often in the kinds of searches used by police investigators where an image is compared to thousands or millions of others in hopes of identifying a suspect.

Why is this acceptable? The report inadvertently supplies the answer:

Middle-aged white men generally benefited from the highest accuracy rates.

Yep. And guess who's making laws or running police departments or marketing AI to cops or telling people on Twitter not to break the law or etc. etc. etc.

To craft a terrible pun, the researchers' claim of "no racial bias" is absurd on its face. Per se stupid af to use legal terminology.

Moving on from that, there's the 80% accuracy, which is apparently good enough since it will only threaten the life and liberty of 20% of the people it's inflicted on. I guess if it's the FBI's gold standard, it's good enough for everyone.

Maybe this is just bad reporting. Maybe something got copy-pasted wrong from the spammed press release. Let's go to the source… one that somehow still doesn't include a link to any underlying research documents.

What does any of this mean? Are we ready to embrace a bit of pre-crime eugenics? Or is this just the most hamfisted phrasing Harrisburg researchers could come up with?

A group of Harrisburg University professors and a Ph.D. student have developed automated computer facial recognition software capable of predicting whether someone is likely going to be a criminal.

The most charitable interpretation of this statement is that the wrong-20%-of-the-time AI is going to be applied to the super-sketchy "predictive policing" field. Predictive policing -- a theory that says it's ok to treat people like criminals if they live and work in an area where criminals live -- is its own biased mess, relying on garbage data generated by biased policing to turn racist policing into an AI-blessed "work smarter not harder" LEO equivalent.

The question about "likely" is answered in the next paragraph, somewhat assuring readers the AI won't be applied to ultrasound images.

With 80 percent accuracy and with no racial bias, the software can predict if someone is a criminal based solely on a picture of their face. The software is intended to help law enforcement prevent crime.

There's a big difference between "going to be" and "is," and researchers using actual science should know better than to use both phrases to describe their AI efforts. One means scanning someone's face to determine whether they might eventually engage in criminal acts. The other means matching faces to images of known criminals. They are far from interchangeable terms.

If you think the above quotes are, at best, disjointed, brace yourself for this jargon-fest which clarifies nothing and suggests the AI itself wrote the pullquote:

“We already know machine learning techniques can outperform humans on a variety of tasks related to facial recognition and emotion detection,” Sadeghian said. “This research indicates just how powerful these tools are by showing they can extract minute features in an image that are highly predictive of criminality.”

"Minute features in an image that are highly predictive of criminality." And what, pray tell, are those "minute features?" Skin tone? "I AM A CRIMINAL IN THE MAKING" forehead tattoos? Bullshit on top of bullshit? Come on. This is word salad, but a salad pretending to be a law enforcement tool with actual utility. Nothing about this suggests Harrisburg has come up with anything better than the shitty "tools" already being inflicted on us by law enforcement's early adopters.

I wish we could dig deeper into this but we'll all have to wait until this excitable group of clueless researchers decide to publish their findings. According to this site, the research is being sealed inside a "research book," which means it will take a lot of money to actually prove this isn't any better than anything that's been offered before. This could be the next Clearview, but we won't know if it is until the research is published. If we're lucky, it will be before Harrisburg patents this awful product and starts selling it to all and sundry. Don't hold your breath.




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Anti-Trump Ad Demonstrates Both The Streisand Effect & Masnick's Impossibility Theorem

Well, this one hits the sweet spot of topics I keep trying to demonstrate: both a Streisand Effect and Masnick's Impossibility Theorem. As you may have heard, a group of Republican political consultants and strategists, who very much dislike Donald Trump, put together an effort called The Lincoln Project, which is a PAC to campaign against Trump and Trumpian politics. They recently released an anti-Trump campaign ad about his terrible handling of the COVID-19 pandemic, called Mourning in America, which is a reference to Ronald Reagan's famous Morning in America campaign ad for the 1984 Presidential election. The new ad is, well, pretty powerful:

And while it's unlikely to convince Trump fans deep into their delusions, it certainly got under the President's skin. He went on one of his famous late night Twitter temper tantrums about the ad, and later lashed out at the Lincoln Project when talking to reporters. He was super, super mad.

And what did that do? Well, first it got the ad a ton of views. Earlier this week, one of the Lincoln Project's founders, Rick Wilson, noted that the ad had already received 15 million views across various platforms in the day or so since the ad had been released. Also, it resulted in the Lincoln Project getting a giant boost in funding:

The Lincoln Project, which is run by Republican operatives who oppose President Donald Trump, raised $1 million after the president ripped the group on Twitter this week – marking it the super PAC’s biggest day of fundraising yet.

Reed Galen, a member of the Lincoln Project’s advisory committee, told CNBC that the total came after the president’s Tuesday morning Twitter tirade in reaction to an ad titled “Mourning in America,” which unloads on Trump’s response to the coronavirus pandemic. It recently aired on Fox News, which Trump often watches and praises. Galen said it was the Lincoln Project’s best single-day fundraising haul

Not only that, but it has opened up more opportunity for the Lincoln Project team to get their word out. With so much interest in the ad, it opened up opportunities for the project members to get their message in various mainstream media sources. Reed Galen wrote a piece for NBC:

What we accomplished this week was not something to be celebrated. No commercial should have the power to derail the leader of the free world.

And another Lincoln Project founder, George Conway (who, of course, is the husband of Trump senior advisor Kellyanne Conway), wrote something similar for the Washington Post:

It may strike you as deranged that a sitting president facing a pandemic has busied himself attacking journalists, political opponents, television news hosts and late-night comedians — even deriding a former president who merely boasted that “the ‘Ratings’ of my News Conferences etc.” were driving “the Lamestream Media . . . CRAZY,” and floated bogus miracle cures, including suggesting that scientists consider injecting humans with household disinfectants such as Clorox.

If so, you’re not alone. Tens of thousands of mental-health professionals, testing the bounds of professional ethics, have warned for years about Trump’s unfitness for office.

Some people listened; many, including myself, did not, until it was too late.

That's the kind of media exposure you can't buy, but which you get when you have a President who appears wholly unfamiliar with the Streisand Effect.

And that then takes us to the Impossibility Theorem, regarding the impossibility of doing content moderation at scale well. After Trump's ongoing tirade, Facebook slapped a "Partly False" warning label on the video when posted on Facebook. While the whole situation is ridiculous, it's at least mildly amusing, considering how frequently clueless Trumpkins insist that Facebook censors "conservative" (by which they mean Trumpian) viewpoints. Also, somewhat ironic in all of this: the only reason that Facebook now places such fact check labels on things is because anti-Trump people yelled at how Facebook needed to do more fact checking of political content on its site. So, now you get this.

Part of the issue is that Politifact judged one line in the ad as "false." That line was that Trump "bailed out Wall St. but not Main St." Politifact says that since the CARES Act Paycheck Protection Program has given potentially forgivable loans to some small businesses, and because the bill was done by Congress, not the President, that line is "false." And yet, because angry (usually anti-Trump) people demanded that Facebook do more useless fact checking, the end result is that the video now gets a "false" label.

Of course, this shows both the impossibility of doing content moderation well and the silliness of betting big on fact checking with a full "true or false" claim. One could argue that that line has misleading elements, but is true in most cases. Tons of small businesses are shuttering. Many businesses have been unable to get PPP loans, and under the current terms of the loans, they're useless for many (especially if they have no work for people to do, since the loans have to be mostly used on payroll over the next couple months). But does that make the entire ad "false"? Of course not.

And Rick Wilson is super mad about this. He's right to be mad about Politifact's designation, though it's really a condemnation of the religious focus on "true or false" in fact checking, rather than in focusing on what is misleading or not:

But the ad doesn’t actually claim that small businesses received zero help. Rather, it makes the point that Main Street America is still seriously struggling as the economic fallout from the coronavirus pandemic continues.

But Wilson is also mad at Facebook:

Speaking exclusively to Mediaite, Wilson called the decision “the typical fuckery we’ve come to expect from both the Trump camp and their tame Facebook allies.”

“Facebook is perfectly content to allow content from QAnon lunatics, anti-vaxxers, alt-righters, and every form of Trump/Russian — but I repeat myself — disinformation,” he pointed out. “This is a sign of just how powerfully ‘Mourning In America’ shook Donald Trump and his allies. Their attempt to censor our ad isn’t a setback for us; it’s a declaration of an information war we will win.”

Separately, the Lincoln Project also sent out an email to supporters, again blaming Facebook:

... it's no secret that Facebook has stood by and done little to nothing as lie after lie — from the Liar-In-Chief himself — runs wild on their platform.

(Oh, and let's also not forget the conspiracy theories, foreign disinformation campaigns and negligence that got Mark Zuckerberg questioned by the United States Congress.)

But, this? This is an entirely different and dangerous kind of collusion.

And what is Facebook's excuse for playing favorites with its recently-transferred former employees in the Trump campaign?

They say a "fact-checker" labeled our claim that "Donald Trump helped bailout Wall Street, not Main Street" was untrue.

....Really?

The email goes on to justify the "main street" line with a bunch of links, and then again argues that Facebook is "censoring the truth" to help Trump:

Is that "Partly False?" Of course not.

We told the truth about Donald Trump...

He lost his damn mind over it on Twitter...

Attacked us in front of Air Force One...

Then sent his spin machine to discredit us...

And now his allies at Facebook are doing his damage control by censoring the truth he doesn't like.

I get the frustration -- and I find it at least a bit ironic that the whole "fact checking" system was a response to anti-Trump folks mad at Facebook for allowing pro-Trump nonsense to spread -- but this is just another example of the Impossibility Theorem. There is no "good" solution here. We live in a time where everyone's trying to discredit everyone they disagree with, and many of these things depend on your perspective or your interpretation of a broad statement, like whether or not Trump is helping "main street."

We can agree that it's silly that Facebook has put this label on the video, but also recognize that it's not "Trump's allies at Facebook" working to "censor the truth he doesn't like." That's just absurd (especially given the reason the fact checking set up was put together in the first place).

But, hey, outrage and claims of censorship feed into the narrative (and feed into the Streisand Effect), so perhaps it all is just designed to work together.




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Identifying Unintended Harms of Cybersecurity Countermeasures

In this paper (winner of the eCrime 2019 Best Paper award), we consider the types of things that can go wrong when you intend to make things better and more secure. Consider this scenario. You are browsing through Internet and see a news headline on one of the presidential candidates. You are unsure if the … Continue reading Identifying Unintended Harms of Cybersecurity Countermeasures




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Twitter sticks a beak in, Clippy-style: Are you sure you want to set your account alight with that flame?

No, you still can't edit tweets

Although editing published tweets still remains strictly verboten on Twitter, the microblogging anger echo chamber intends to prompt English-speaking iPhone-wielding users to double-check content before posting a reply that they might regret.…




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American tech goliaths decide innovation is the answer to Chinese 5G dominance, not bans, national security theater

Microsoft, Cisco, Google etc gang up to form Open RAN Policy Coalition

Some of America’s super-corps have remembered how the US became the dominant global technology force it is, and have vowed to use innovation over threats to counter Chinese dominance in 5G markets.…




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Senior MP tells UK Defence Committee on 5G security: Russia could become China's cyber-attack dog

One has the vulns, the other has the brass neck to pull off heists. Right?

Russia might begin carrying out cyber attacks against Britain's 5G networks "at the behest of China", the chairman of a Parliamentary Select Committee has ventured.…




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As coronavirus catches tech CEOs with their pants down, IBM's Ginni Rometty warns of IT's new role post-pandemic

Middle management is about to learn just how necessary they are

Last night, one of the most senior figures in the IT industry from one of the biggest companies gave the strongest indication that when COVID-19 lockdowns gradually begin to lift, people will not return to the jobs they once had. That means both tech jobs, and how technology supports other business roles.…




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Bored at home? Cisco has just the thing: A shed-load of security fixes to install, from a Kerberos bypass to crashes

Switchzilla issues a whopping 30+ patches in time for the long UK weekend

Cisco has emitted a fresh round of software updates to address nearly three dozen security holes in its products.…




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Equinix says Zoom bought plenty more stuff in Q1. Which is just what Oracle said, too

Despite you know what, little evidence of a rush to new racks

Equinix has posted its Q1 FY2020 results for the period ending March 31st, along with some interesting insights into how the COVID-19 pandemic has impacted data centre consumption.…




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India’s Jio Platforms scores third US cash injection in three weeks - this time $1.5bn from Vista Equity Partners

It's like three buses showing up at once carrying $8bn

India’s largest mobile carrier, Jio, has just scored a third new investor in three weeks!…




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If you miss the happier times of the 2000s, just look up today's SCADA gear which still has Stuxnet-style holes

Schneider Electric patches vulns after Trustwave raises alarm

Two Schneider Electric SCADA products had vulnerabilities similar to the ones exploited in the Iran-bothering Stuxnet worm, an infosec outfit has claimed.…




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10/04/15 - A plague that swept through the city




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MediaTek Dimensity 1000 Plus: флагманский процессор с поддержкой 5G для двух SIM и дисплеев с частотой до 144 Гц

Компания MediaTek анонсировала свой новый флагманский процессор, который должен составить конкуренцию чипам Qualcomm.




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LG готовит еще один смартфон со стилусом — Stylo 6

Судя по рендерам, новая модель будет значительно отличаться от прошлогоднего Stylo 5.




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Utility Battery Projects Driven By Price Drops

For large electric power storage projects the cost of batteries has plummeted. 2008, when battery prices were 10 times higher than they are today. This advance is timely as photovoltaic electric power prices have dropped so far that in SoCal PV is causing a growing drop in mid-day demand and therefore a much bigger spike in evening demand. Therefore there's a growing need for a cheaper way to store power generated in mid day and deliver it in the evening. You can see how much solar power output surges each day in California by clicking on some of the Daily Renewables Watch links at the Cal ISO site (the organization that manages California's electric grid). The growing supply of wind...




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Those Dirty Pirates

A pirate is starting his first day aboard his new ship and the captain is giving him the tour. ”There’s the plank for trouble makers, there’s the deck that needs swabbing everyday and there’s the barrel for all you sexual needs.” ”Whatcha mean? my sexual needs?” ”Well, you stick your willy in the hole and […]

The post Those Dirty Pirates appeared first on Funny & Jokes.




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Myeloid-specific Asxl2 deletion limits diet-induced obesity by regulating energy expenditure

We previously established that global deletion of the enhancer of trithorax and polycomb (ETP) gene, Asxl2, prevents weight gain. Because proinflammatory macrophages recruited to adipose tissue are central to the metabolic complications of obesity, we explored the role of ASXL2 in myeloid lineage cells. Unexpectedly, mice without Asxl2 only in myeloid cells (Asxl2ΔLysM) were completely resistant to diet-induced weight gain and metabolically normal despite increased food intake, comparable activity, and equivalent fecal fat. Asxl2ΔLysM mice resisted HFD-induced adipose tissue macrophage infiltration and inflammatory cytokine gene expression. Energy expenditure and brown adipose tissue metabolism in Asxl2ΔLysM mice were protected from the suppressive effects of HFD, a phenomenon associated with relatively increased catecholamines likely due to their suppressed degradation by macrophages. White adipose tissue of HFD-fed Asxl2ΔLysM mice also exhibited none of the pathological remodeling extant in their control counterparts. Suppression of macrophage Asxl2 expression, via nanoparticle-based siRNA delivery, prevented HFD-induced obesity. Thus, ASXL2 controlled the response of macrophages to dietary factors to regulate metabolic homeostasis, suggesting modulation of the cells’ inflammatory phenotype may impact obesity and its complications.




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Hepatic CEACAM1 expression indicates donor liver quality and prevents early transplantation injury

Although CEACAM1 (CC1) glycoprotein resides at the interface of immune liver injury and metabolic homeostasis, its role in orthotopic liver transplantation (OLT) remains elusive. We aimed to determine whether/how CEACAM1 signaling may affect hepatic ischemia-reperfusion injury (IRI) and OLT outcomes. In the mouse, donor liver CC1 null mutation augmented IRI-OLT (CC1-KO→WT) by enhancing ROS expression and HMGB1 translocation during cold storage, data supported by in vitro studies where hepatic flush from CC1-deficient livers enhanced macrophage activation in bone marrow–derived macrophage cultures. Although hepatic CC1 deficiency augmented cold stress–triggered ASK1/p-p38 upregulation, adjunctive ASK1 inhibition alleviated IRI and improved OLT survival by suppressing p-p38 upregulation, ROS induction, and HMGB1 translocation (CC1-KO→WT), whereas ASK1 silencing (siRNA) promoted cytoprotection in cold-stressed and damage-prone CC1-deficient hepatocyte cultures. Consistent with mouse data, CEACAM1 expression in 60 human donor liver biopsies correlated negatively with activation of the ASK1/p-p38 axis, whereas low CC1 levels associated with increased ROS and HMGB1 translocation, enhanced innate and adaptive immune responses, and inferior early OLT function. Notably, reduced donor liver CEACAM1 expression was identified as one of the independent predictors for early allograft dysfunction (EAD) in human OLT patients. Thus, as a checkpoint regulator of IR stress and sterile inflammation, CEACAM1 may be considered as a denominator of donor hepatic tissue quality, and a target for therapeutic modulation in OLT recipients.




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Epigenetic driver mutations in ARID1A shape cancer immune phenotype and immunotherapy

Whether mutations in cancer driver genes directly affect cancer immune phenotype and T cell immunity remains a standing question. ARID1A is a core member of the polymorphic BRG/BRM-associated factor chromatin remodeling complex. ARID1A mutations occur in human cancers and drive cancer development. Here, we studied the molecular, cellular, and clinical impact of ARID1A aberrations on cancer immunity. We demonstrated that ARID1A aberrations resulted in limited chromatin accessibility to IFN-responsive genes, impaired IFN gene expression, anemic T cell tumor infiltration, poor tumor immunity, and shortened host survival in many human cancer histologies and in murine cancer models. Impaired IFN signaling was associated with poor immunotherapy response. Mechanistically, ARID1A interacted with EZH2 via its carboxyl terminal and antagonized EZH2-mediated IFN responsiveness. Thus, the interaction between ARID1A and EZH2 defines cancer IFN responsiveness and immune evasion. Our work indicates that cancer epigenetic driver mutations can shape cancer immune phenotype and immunotherapy.




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Specificity of bispecific T cell receptors and antibodies targeting peptide-HLA

Tumor-associated peptide–human leukocyte antigen complexes (pHLAs) represent the largest pool of cell surface–expressed cancer-specific epitopes, making them attractive targets for cancer therapies. Soluble bispecific molecules that incorporate an anti-CD3 effector function are being developed to redirect T cells against these targets using 2 different approaches. The first achieves pHLA recognition via affinity-enhanced versions of natural TCRs (e.g., immune-mobilizing monoclonal T cell receptors against cancer [ImmTAC] molecules), whereas the second harnesses an antibody-based format (TCR-mimic antibodies). For both classes of reagent, target specificity is vital, considering the vast universe of potential pHLA molecules that can be presented on healthy cells. Here, we made use of structural, biochemical, and computational approaches to investigate the molecular rules underpinning the reactivity patterns of pHLA-targeting bispecifics. We demonstrate that affinity-enhanced TCRs engage pHLA using a comparatively broad and balanced energetic footprint, with interactions distributed over several HLA and peptide side chains. As ImmTAC molecules, these TCRs also retained a greater degree of pHLA selectivity, with less off-target activity in cellular assays. Conversely, TCR-mimic antibodies tended to exhibit binding modes focused more toward hot spots on the HLA surface and exhibited a greater degree of crossreactivity. Our findings extend our understanding of the basic principles that underpin pHLA selectivity and exemplify a number of molecular approaches that can be used to probe the specificity of pHLA-targeting molecules, aiding the development of future reagents.




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The lymph node stromal laminin α5 shapes alloimmunity

Lymph node stromal cells (LNSCs) regulate immunity through constructing lymphocyte niches. LNSC-produced laminin α5 (Lama5) regulates CD4+ T cells but the underlying mechanisms of its functions are poorly understood. Here we show that depleting Lama5 in LNSCs resulted in decreased Lama5 protein in the LN cortical ridge (CR) and around high endothelial venules (HEVs). Lama5 depletion affected LN structure with increased HEVs, upregulated chemokines, and cell adhesion molecules, and led to greater numbers of Tregs in the T cell zone. Mouse and human T cell transendothelial migration and T cell entry into LNs were suppressed by Lama5 through the receptors α6 integrin and α-dystroglycan. During immune responses and allograft transplantation, depleting Lama5 promoted antigen-specific CD4+ T cell entry into the CR through HEVs, suppressed T cell activation, and altered T cell differentiation to suppressive regulatory phenotypes. Enhanced allograft acceptance resulted from depleting Lama5 or blockade of T cell Lama5 receptors. Lama5 and Lama4/Lama5 ratios in allografts were associated with the rejection severity. Overall, our results demonstrated that stromal Lama5 regulated immune responses through altering LN structures and T cell behaviors. This study delineated a stromal Lama5–T cell receptor axis that can be targeted for immune tolerance modulation.




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Pathogenesis of peritumoral hyperexcitability in an immunocompetent CRISPR-based glioblastoma model

Seizures often herald the clinical appearance of gliomas or appear at later stages. Dissecting their precise evolution and cellular pathogenesis in brain malignancies could inform the development of staged therapies for these highly pharmaco-resistant epilepsies. Studies in immunodeficient xenograft models have identified local interneuron loss and excess glial glutamate release as chief contributors to network disinhibition, but how hyperexcitability in the peritumoral microenvironment evolves in an immunocompetent brain is unclear. We generated gliomas in WT mice via in utero deletion of key tumor suppressor genes and serially monitored cortical epileptogenesis during tumor infiltration with in vivo electrophysiology and GCAMP7 calcium imaging, revealing a reproducible progression from hyperexcitability to convulsive seizures. Long before seizures, coincident with loss of inhibitory cells and their protective scaffolding, gain of glial glutamate antiporter xCT expression, and reactive astrocytosis, we detected local Iba1+ microglial inflammation that intensified and later extended far beyond tumor boundaries. Hitherto unrecognized episodes of cortical spreading depolarization that arose frequently from the peritumoral region may provide a mechanism for transient neurological deficits. Early blockade of glial xCT activity inhibited later seizures, and genomic reduction of host brain excitability by deleting MapT suppressed molecular markers of epileptogenesis and seizures. Our studies confirmed xenograft tumor–driven pathobiology and revealed early and late components of tumor-related epileptogenesis in a genetically tractable, immunocompetent mouse model of glioma, allowing the complex dissection of tumor versus host pathogenic seizure mechanisms.




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Donor glucose-6-phosphate dehydrogenase deficiency decreases blood quality for transfusion

BACKGROUND Glucose-6-phosphate dehydrogenase (G6PD) deficiency decreases the ability of red blood cells (RBCs) to withstand oxidative stress. Refrigerated storage of RBCs induces oxidative stress. We hypothesized that G6PD-deficient donor RBCs would have inferior storage quality for transfusion as compared with G6PD-normal RBCs.METHODS Male volunteers were screened for G6PD deficiency; 27 control and 10 G6PD-deficient volunteers each donated 1 RBC unit. After 42 days of refrigerated storage, autologous 51-chromium 24-hour posttransfusion RBC recovery (PTR) studies were performed. Metabolomics analyses of these RBC units were also performed.RESULTS The mean 24-hour PTR for G6PD-deficient subjects was 78.5% ± 8.4% (mean ± SD), which was significantly lower than that for G6PD-normal RBCs (85.3% ± 3.2%; P = 0.0009). None of the G6PD-normal volunteers (0/27) and 3 G6PD-deficient volunteers (3/10) had PTR results below 75%, a key FDA acceptability criterion for stored donor RBCs. As expected, fresh G6PD-deficient RBCs demonstrated defects in the oxidative phase of the pentose phosphate pathway. During refrigerated storage, G6PD-deficient RBCs demonstrated increased glycolysis, impaired glutathione homeostasis, and increased purine oxidation, as compared with G6PD-normal RBCs. In addition, there were significant correlations between PTR and specific metabolites in these pathways.CONCLUSION Based on current FDA criteria, RBCs from G6PD-deficient donors would not meet the requirements for storage quality. Metabolomics assessment identified markers of PTR and G6PD deficiency (e.g., pyruvate/lactate ratios), along with potential compensatory pathways that could be leveraged to ameliorate the metabolic needs of G6PD-deficient RBCs.TRIAL REGISTRATION ClinicalTrials.gov NCT04081272.FUNDING The Harold Amos Medical Faculty Development Program, Robert Wood Johnson Foundation grant 71590, the National Blood Foundation, NIH grant UL1 TR000040, the Webb-Waring Early Career Award 2017 by the Boettcher Foundation, and National Heart, Lung, and Blood Institute grants R01HL14644 and R01HL148151.




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Chronic mirabegron treatment increases human brown fat, HDL cholesterol, and insulin sensitivity

BACKGROUND Mirabegron is a β3-adrenergic receptor (β3-AR) agonist approved only for the treatment of overactive bladder. Encouraging preclinical results suggest that β3-AR agonists could also improve obesity-related metabolic disease by increasing brown adipose tissue (BAT) thermogenesis, white adipose tissue (WAT) lipolysis, and insulin sensitivity.METHODS We treated 14 healthy women of diverse ethnicities (27.5 ± 1.1 years of age, BMI of 25.4 ± 1.2 kg/m2) with 100 mg mirabegron (Myrbetriq extended-release tablet, Astellas Pharma) for 4 weeks in an open-label study. The primary endpoint was the change in BAT metabolic activity as measured by [18F]-2-fluoro-d-2-deoxy-d-glucose (18F-FDG) PET/CT. Secondary endpoints included resting energy expenditure (REE), plasma metabolites, and glucose and insulin metabolism as assessed by a frequently sampled intravenous glucose tolerance test.RESULTS Chronic mirabegron therapy increased BAT metabolic activity. Whole-body REE was higher, without changes in body weight or composition. Additionally, there were elevations in plasma levels of the beneficial lipoprotein biomarkers HDL and ApoA1, as well as total bile acids. Adiponectin, a WAT-derived hormone that has antidiabetic and antiinflammatory capabilities, increased with acute treatment and was 35% higher upon completion of the study. Finally, an intravenous glucose tolerance test revealed higher insulin sensitivity, glucose effectiveness, and insulin secretion.CONCLUSION These findings indicate that human BAT metabolic activity can be increased after chronic pharmacological stimulation with mirabegron and support the investigation of β3-AR agonists as a treatment for metabolic disease.TRIAL REGISTRATION Clinicaltrials.gov NCT03049462.FUNDING This work was supported by grants from the Intramural Research Program of the NIDDK, NIH (DK075112, DK075116, DK071013, and DK071014).





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Apple Stores in Germany to Begin Reopening May 11 With Enhanced Health and Safety Measures

Apple today announced that it will begin reopening its retail stores in Germany on May 11, nearly two months after they were closed due to the global health crisis.


In a statement shared with German website Macerkopf, Apple said the stores will initially be focusing on Genius Bar service and support. Enhanced health and safety measures will be implemented, such as body temperature checks prior to entry, limits on how many customers can be in the store at once, social distancing, and reduced hours of operation.

Apple operates 15 retail stores in Germany and will be posting specific hours of operation for each location on its website.

Apple closed all of its retail stores outside of the Greater China region in mid-March. The company has since started to reopen some locations, including in South Korea, Austria, and Australia. All locations in the United States remain closed.

Related Roundup: Apple Stores

This article, "Apple Stores in Germany to Begin Reopening May 11 With Enhanced Health and Safety Measures" first appeared on MacRumors.com

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Digging up Positivity - Furry charity and good news - February 2020 (Transcript)

Video from Thabo Meerkat, transcribed

Welcome to another edition of Digging Up Positivity! This episode is dedicated to the many volunteers that make all those amazing conventions and charities possible. But besides them, we are covering some animation news and other (maybe otter?) tidbits!

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Digging up Positivity - Furry charity and good news - April 2020

Video from Thabo Meerkat, transcribed

Hey there, and welcome to the April 2020 edition of Digging Up Positivity from a rapidly changing world. But even in these weird times, there are still a lot of positive things to be found!

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6 SaferParty Results (Switzerland)

6 SaferParty Results (Switzerland)



  • Erowid : DrugsData :

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'Empathy', by motty (MDMA)

Erowid Exp102582



  • Erowid : Experience :

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Cenk Uygur says President Obama will definitely cut the entitlements of Social Security, Medicare, and Medicaid

On the Young Turks, Cenk Uygur quotes passages from Bob Woodward's book, "The Price of Politics", quoting statements made by President Obama proving that he intends to cut entitlements like social security, medicare, and medicaid. Continue reading



  • Accountants CPA Hartford
  • Articles
  • Blue dog Democrats are conservative
  • Blue dog Democrats are not progressive
  • Bob Woodward book The Price of Politics
  • Cenk Uygur
  • Cenk Uygur says President Obama will definitely cut the entitlements of Social Security Medicare and Medicaid
  • Obama said he would cut social security and Medicare and Medicaid
  • Obama says he will bring Democrats along to cut entitlements
  • President Obama is a blue dog Democrat
  • President Obama to cut entitlements
  • The Young Turks

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Bernie Sanders can win even though the Democratic Party is run by the Corporate Democrats and they have already anointed Hillary Clinton as their candidate for President

Even though Corporate America has anointed Hillary Clinton as its next President, Senator Bernie Sanders' populist message is already in a week's time raising individual contributions totaling millions of dollars from hundreds of thousands of people! Continue reading



  • Accountants CPA Hartford
  • Articles
  • bankers
  • Bernie Sanders can win - deal with it
  • Bernie Sanders can win even though the Democratic Party is run by the Corporate Democrats and they have already anointed Hillary Clinton as their candidate for President
  • Can Bernie Sanders Beat Hillary Clinton
  • DCCC
  • Democratic Party split
  • Ed Schultz
  • Farron Cousins
  • Hillary Clinton
  • Keystone XL Pipeline
  • Mike Papntonio
  • populist
  • progressives vs corporate democrats
  • Ring of Fire Radio
  • The Democratic Party is run by the Corporate Democrats and they have already anointed Hillary Clinton
  • The Democratic Party is run by the Corporate Democrats and they have already anointed Hillary Clinton as their candidate for President but Senator Bernie Sanders can win
  • The Democratic Party is run by the Corporate Democrats and they have anointed Hillary Clinton as their candidate for President
  • the Ed Show
  • Tom Hartmann
  • TPP
  • TransCanada
  • transcript
  • video
  • Wall Street

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Berlin Connecticut needs candidates from a third political party to stop the strict partisan voting on the Town Council

Berlin needs an independent candidate on its Town Council to counter and prevent the dominance of a major political party from unilaterally imposing its agenda and will on the citizens of Berlin. Our Town Council has been voting along strict party lines on key issues even though members pledged to reach across the aisle. It has dismissed or circumvented the results of referendums, reducing them to mere dog-and-pony shows. Berlin has more unaffiliated voters than those of the two major parties. Let's petition, nominate, and place on the ballot an independent candidate to represent these citizens and prevent the control of our Town by the dominant party on the Town Council. If interested, please contact us: berlinctpropertyownersassn@gmail.com. Continue reading




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Is the DNC Afraid of Democracy? Clinton WH Counselor Says Party a “Dead Carcass” for Stifling Debate

"This is supposed to be a political party. In a healthy society, there would be a democratic process in the Democratic Party, by which elected people would be overseeing these issues by making sure there wasn’t just nepotism and insider dealing," Curry says. "That the political party itself — which is supposed to be the progressive party — has become mortgaged to a small group of Washington insiders, who raise money from large corporate PACs, [and] has become just a dead carcass of what it once was, is the most important piece of information that this contretemps over the data files has emphasized. It’s time for progressives in this country to stand up and demand a genuinely democratic process." Continue reading




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Green Party’s Jill Stein — What We Fear from Donald Trump We Have Already Seen from Hillary Clinton

Green Party's Jill Stein says that what we Fear from Donald Trump is what we have already seen from Hillary Clinton. Continue reading




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Julian Assange says that we must have political accountability–a general deterrence set to stop political organizations behaving in a corrupt manner.

we know how politics works in the United States. Whoever—whatever political party gets into government is going to merge with the bureaucracy pretty damn fast. It will be in a position where it has some levers in its hand. And so, as a result, corporate lobbyists will move in to help control those levers. So it doesn’t make much difference in the end. What does make a difference is political accountability, a general deterrence set to stop political organizations behaving in a corrupt manner. Continue reading




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Bernie Sanders was never a real candidate but was merely this election’s sheepdog for Hillary Clinton to herd progressives back into the corral of the Democratic Party.

Bernie Sanders and Jane Sanders are mere actors serving as pressure valves which release from time to time all excess heat emanating from failed policies, scandals, and the worsening economic conditions, so that a catastrophic systems’ collapse can be prevented. They are sheepdogs for Hillary Clinton, preventing progressives from supporting a third party progressive candidate and to herd them back into the corral of the Democratic Party. Continue reading




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Chris Hedges and Jill Stein and Ralph Nader are the real revolutionaries while Bernie Sanders and Robert Reich and Hillary Clinton are part of the devil’s Democratic Party

"Well, reducing the election to personalities is kind of infantile at this point. The fact is, we live in a system that Sheldon Wolin calls inverted totalitarianism. It’s a system where corporate power has seized all of the levers of control. There is no way to vote against the interests of Goldman Sachs or ExxonMobil or Raytheon." Continue reading