She appeared on ‘Meet the Press’ Sunday.

Scores of women and Black-owned businesses were shut out.

May 8 would have been his 26th birthday.

She battled depression after the birth of her third child.

Also, Malcolm-Jamal Warner speaks on Ebony Cosby cover.

The pop icon says she’s “very lucky.”

The Elle UK cover girl hints at her future plans.

You'll want to look very, very closely.

Don't get it twisted.

When you first started looking at our program, you may have asked yourself why we are called the Fisher College of Business. Then you probably shrugged and forgot all about it. Well, I’m here to answer that burning question for you. Like many business schools, we are named after a benefactor who contributed a significant … Continue reading "Why is it called “Fisher” College of Business?"

One of the most fascinating things about planet Earth is the way that life shapes the Earth and the Earth shapes life. We only have to look back to the Great Oxygenation Event (GOE) of 2.4 billion years ago to see how lifeforms have shaped the Earth. In that event, phytoplanktons called cyanobacteria pumped the …

Continue reading "New Data Show How Phytoplankton Pumps Carbon Out of the Atmosphere at an Enormous Scale"

The post New Data Show How Phytoplankton Pumps Carbon Out of the Atmosphere at an Enormous Scale appeared first on Universe Today.

Množství politiků po celém světě v posledních dnech trápí zásadní otázka. Jak zabránit druhé vlně koronaviru bez škrcení ekonomiky? Možnou cestu ukázalo hlavní město Litvy. Majitelé menších podniků zde museli stejně jako na jiných místech v Evropě dočasně pozastavit svou živnost. Vedení Vilniusu ve snaze zabránit jejich krachu v rámci uvolňovaní restriktivních opatření rozhodlo o umožnění bezplatného využití veřejných prostor.

Giant-scale physics experiments are increasingly reliant on big data and complex algorithms fed into powerful computers, and managing this multiplying mass of data presents its own unique challenges. To better prepare for this data deluge posed by next-generation upgrades and new experiments, physicists are turning to the fledgling field of quantum computing.

The PHP development team announces the immediate availability of PHP 7.2.30. This is a security release.All PHP 7.2 users are encouraged to upgrade to this version.For source downloads of PHP 7.2.30 please visit our downloads page, Windows source and binaries can be found on windows.php.net/download/. The list of changes is recorded in the ChangeLog.

Kelly Loeffler is, by far, the wealthiest elected official in Congress, with an estimated net worth of half a billion dollars (the second wealthiest is Montana Rep. Greg Gianforte (famous for his body slamming a journalist for asking him a question and then lying to the police about it)). Loeffler may be used to getting away with tearing up the red tape in her previous life, but in Congress, that often looks pretty corrupt. In just the last few months since she was appointed, there were concerns about her stock sales and stock purchases, which seemed oddly matched to information she was getting during briefings regarding the impact of COVID-19. She has since agreed to convert all her stock holdings to managed funds outside of her control (something every elected official should do, frankly).

Now, the NY Times is noting another form of what we've referred to as "soft corruption" -- moves that might technically be legal, but which sure look sketchy as hell to any regular non-multimillionaire elected official. In this case, Senator Loeffler received what was, in effect, a gift worth $9 million from her former employer, Intercontinental Exchange (the company that runs the NY Stock Exchange, and where her husband is the CEO).

The key issue was that since she was leaving the job to go join the Senate, she had a bunch of unvested stock. For normal people, if you leave a job before your stock vests, too bad. That's the deal. The vesting period is there for a reason. But for powerful, rich people, apparently the rules change. Intercontinental Exchange changed the rules to grant her the compensation that she wasn't supposed to get, because why not?

Ms. Loeffler, who was appointed to the Senate in December and is now in a competitive race to hold her seat, appears to have received stock and other awards worth more than $9 million from the company, Intercontinental Exchange, according to a review of securities filings by The New York Times, Ms. Loeffler’s financial disclosure form and interviews with compensation and accounting experts. That was on top of her 2019 salary and bonus of about $3.5 million.

The additional compensation came in the form of shares, stock options and other instruments that Ms. Loeffler had previously been granted but was poised to forfeit by leaving the company. Intercontinental Exchange altered the terms of the awards, allowing her to keep them. The largest component — which the company had previously valued at about $7.8 million — was a stake in an Intercontinental Exchange subsidiary that Ms. Loeffler had been running.

The entitlement factor oozes out of the statement put out from her office in response to this:

“Kelly left millions in equity compensation behind to serve in public office to protect freedom, conservative values and economic opportunity for all Georgians,” said Stephen Lawson, a spokesman for Ms. Loeffler. “The obsession of the liberal media and career politicians with her success shows their bias against private sector opportunity in favor of big government.”

No, Stephen, that's not the issue. The issue is that normal people who haven't vested yet, don't get to have the board change the vesting rules as you're leaving to go legislate in order to give you a $9 million windfall you didn't earn because it hadn't vested. If it had just been a question of compensation, no one would be complaining. If she had played by the rules that everyone else played by, lived up to her end of the contract and vested the equity, then no big deal. The problem is the last minute changing of the rules to get her a pretty massive payout (perhaps not by her standards, but by anyone else's).

Indeed, the details show that this wasn't just a timing thing, like a standard vesting deal, but that Loeffler was supposed to reach certain milestones to be able to get the equity. She didn't, but she still gets it. That's the part that has people concerned.

In February 2019, Intercontinental Exchange gave Ms. Loeffler a stake in a limited liability company that owned a stake in Bakkt, according to a March 2019 securities filing. The company at the time estimated the award was worth $15.6 million. But Ms. Loeffler would be able to cash in on the award only under certain circumstances, including if Bakkt’s value soared or if it became a publicly traded company.

When Ms. Loeffler stepped down from the company less than 10 months later, she was poised to forfeit much of that Bakkt stake. But Intercontinental Exchange sped up the vesting process so that she got half of it immediately.

The company, of course, puts a nice spin on it, saying "We admire Kelly’s decision to serve her country in the U.S. Senate and did not want to discourage that willingness to serve,” but what else are they going to say anyway?

Still waiting for that supposed swamp draining we keep hearing about.

Decades-old theory may require a rethink thanks to Japanese probe

The Moon is believed to have formed from the leftovers of a proto-Earth smashing into a Mars-sized Theia nearly 4.5 billion years ago.…

Drive more reaction when you fabricate your image story at the purpose of decision. A point of decision is where a possibility or purchaser will make a move activity to move to the subsequent stage in the purchasing procedure. Research,… Continue Reading →

The post What’s Cooking: Why Bleeding your Fish is Important? appeared first on Ocean Blue Fishing Adventures.

The post Unpacking After a Fishing Trip: Why is it so Important? appeared first on Ocean Blue Fishing Adventures.

BACKGROUND Neurofibroma/schwannoma hybrid nerve sheath tumors (N/S HNSTs) are neoplasms associated with larger nerves that occur sporadically and in the context of schwannomatosis or neurofibromatosis type 2 or 1. Clinical management of N/S HNSTs is challenging, especially for large tumors, and established systemic treatments are lacking.METHODS We used next-generation sequencing and array-based DNA methylation profiling to determine the clinically actionable genomic and epigenomic landscapes of N/S HNSTs.RESULTS Whole-exome sequencing within a precision oncology program identified an activating mutation (p.Asp769Tyr) in the catalytic domain of the ERBB2 receptor tyrosine kinase in a patient with schwannomatosis-associated N/S HNST, and targeted treatment with the small-molecule ERBB inhibitor lapatinib led to prolonged clinical benefit and a lasting radiographic and metabolic response. Analysis of a multicenter validation cohort revealed recurrent ERBB2 mutations (p.Leu755Ser, p.Asp769Tyr, p.Val777Leu) in N/S HNSTs occurring in patients who met diagnostic criteria for sporadic schwannomatosis (3 of 7 patients), but not in N/S HNSTs arising in the context of neurofibromatosis (6 patients) or outside a tumor syndrome (1 patient), and showed that ERBB2-mutant N/S HNSTs cluster in a distinct subgroup of peripheral nerve sheath tumors based on genome-wide DNA methylation patterns.CONCLUSION These findings uncover a key biological feature of N/S HNSTs that may have important diagnostic and therapeutic implications.FUNDING This work was supported by grant H021 from DKFZ-HIPO, the University Cancer Center Frankfurt, and the Frankfurt Research Funding Clinician Scientist Program.

Facioscapulohumeral muscular dystrophy (FSHD) results from expression of the full-length double homeobox 4 (DUX4-FL) retrogene in skeletal muscle. However, even in cases of severe FSHD the presence of DUX4 is barely detectable. In this issue of the JCI, Bosnakovski et al. used an inducible, muscle-specific human DUX4 to reproduce the low-level, sporadic DUX4 expression of human FSHD muscle as well the myopathology seen in human FSHD disease. Notably, dysregulated fibroadipogenic progenitors accumulated in affected muscles, thus providing a mechanism for the replacement of muscle by fibrosis and fat.

Lamin A is a component of the inner nuclear membrane that, together with epigenetic factors, organizes the genome in higher order structures required for transcriptional control. Mutations in the lamin A/C gene cause several diseases belonging to the class of laminopathies, including muscular dystrophies. Nevertheless, molecular mechanisms involved in the pathogenesis of lamin A–dependent dystrophies are still largely unknown. The polycomb group (PcG) of proteins are epigenetic repressors and lamin A interactors, primarily involved in the maintenance of cell identity. Using a murine model of Emery-Dreifuss muscular dystrophy (EDMD), we show here that lamin A loss deregulated PcG positioning in muscle satellite stem cells, leading to derepression of non–muscle-specific genes and p16INK4a, a senescence driver encoded in the Cdkn2a locus. This aberrant transcriptional program caused impairment in self-renewal, loss of cell identity, and premature exhaustion of the quiescent satellite cell pool. Genetic ablation of the Cdkn2a locus restored muscle stem cell properties in lamin A/C–null dystrophic mice. Our findings establish a direct link between lamin A and PcG epigenetic silencing and indicate that lamin A–dependent muscular dystrophy can be ascribed to intrinsic epigenetic dysfunctions of muscle stem cells.

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.

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.

Hypoxia-inducible factor (HIF) is strikingly upregulated in many types of cancer, and there is great interest in applying inhibitors of HIF as anticancer therapeutics. The most advanced of these are small molecules that target the HIF-2 isoform through binding the PAS-B domain of HIF-2α. These molecules are undergoing clinical trials with promising results in renal and other cancers where HIF-2 is considered to be driving growth. Nevertheless, a central question remains as to whether such inhibitors affect physiological responses to hypoxia at relevant doses. Here, we show that pharmacological HIF-2α inhibition with PT2385, at doses similar to those reported to inhibit tumor growth, rapidly impaired ventilatory responses to hypoxia, abrogating both ventilatory acclimatization and carotid body cell proliferative responses to sustained hypoxia. Mice carrying a HIF-2α PAS-B S305M mutation that disrupts PT2385 binding, but not dimerization with HIF-1β, did not respond to PT2385, indicating that these effects are on-target. Furthermore, the finding of a hypomorphic ventilatory phenotype in untreated HIF-2α S305M mutant mice suggests a function for the HIF-2α PAS-B domain beyond heterodimerization with HIF-1β. Although PT2385 was well tolerated, the findings indicate the need for caution in patients who are dependent on hypoxic ventilatory drive.

If you were to Google the definition of a comedian you would see it defined by Dictionary.com as an entertainer whose act is designed to make an audience laugh. Likewise the New York Times has a comedy critic, Jason Zinoman, who defines comedy in a moment of reflecting on his own career of analyzing them.

This often dictates the form of my column, since while the goal of comedy is to make you laugh, what’s fascinating about the art form — especially these days, when it’s so fragmented and aesthetically diverse — is that there are many ways artists accomplish that goal.

However, if you were to ask one furry who considers himself one, 2 Gryphon, you’d find an entirely different etymology of the word, and what the job of a comic is.

It's the JOB of the comic to bring forth uncomfortable things and question them in a way that makes people think about them.Since that has become "wrong", expect that the Western world will not be laughing as much. https://t.co/EIExUX5W2h— 2, The Ranting Gryphon (@2_gryphon) June 9, 2019

It is this quote that we are going to be over-analysing today. I have broken this down into three main points as to why this definition of the job of a comedian is not only a fundamental misunderstanding of the role, but also a resignation of the foundational principles of comedy.

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