ef

Improving AEDT Modeling for Aircraft Noise Reflection and Diffraction from Terrain and Manmade Structures

Barriers, berms, buildings, and natural terrain may affect the propagation of aircraft noise by shielding or reflecting sound energy. If terrain and manmade structures obstruct the line‐of‐sight between the source and the receiver, then sound energy will be attenuated at the receiver. This attenuation increases with the terrain and structures’ size and proximity to either the source or the receiver. If gaps exist in the terrain or structures, then the potential benefits of acoustical shielding will be su...



  • http://www.trb.org/Resource.ashx?sn=cover_acrp_wod_44

ef

Impacts on Practice: Defining Leadership Roles at the Athens-Ben Epps Airport

TRB's Airport Cooperative Research Program (ACRP) latest Impacts on Practice explores the impact ACRP Research Report 58 : Airport Industry Familiarization and Training for Part-Time Airport Policy Makers has helped airport policy leaders, stakeholders, and policy-related decision makers understand airport administrative and operational requirements in order to assist them in making more informed policy decisions. According to an Airport Authority Board Member and Chair of the Air Service Development Com...



  • http://www.trb.org/Resource.ashx?sn=Coveracrp_iop_058

ef

Star Trek Online: Defense Of Pahvo

Star Trek Online‘s limited-event, Defense of Pahvo, will take place May 7-28 and will be available for captains playing on PC, Xbox...



  • Gaming
  • Defense of Pahvo
  • Star Trek: Online

ef

Climate Resilience and Benefit–Cost Analysis: A Handbook for Airports

TRB’s Airport Cooperative Research Program (ACRP) Research Report 199: Climate Resilience and Benefit–Cost Analysis: A Handbook for Airports provides information on how to apply benefit–cost analysis tools and techniques to improve decision making affecting resilience of airport infrastructure projects in response to potential long-term impacts of climate change and extreme weather events. The handbook is designed to improve the process by which infrastructure investment strategies are evaluated, with an...



  • http://www.trb.org/Resource.ashx?sn=Cover_acrp_rpt_199

ef

Benefit–Cost Analyses Guidebook for Airport Stormwater

Many airports undertake stormwater projects to accommodate facility expansion, address obsolescence, and respond to evolving regulatory requirements. Often, stormwater infrastructure is installed or upgraded on a project-by-project and piecemeal basis, resulting in mismatches of sizes, material types, ages, and conditions. When airports are considering expanding or improving their stormwater facilities, the immediate need for stormwater infrastructure modification may not be clear, and a benefit–cost ana...



  • http://www.trb.org/Resource.ashx?sn=cover_acrp_rpt_208

ef

Airport Energy Efficiency and Cost Reduction

TRB’s Airport Cooperative Research Program (ACRP) Synthesis 21: Airport Energy Efficiency and Cost Reduction explores energy efficiency improvements being implemented at airports across the country that are low cost and short payback.



  • http://www.trb.org/Resource.ashx?sn=acrp_syn_21cover

ef

Recommended Guidelines for the Collection and Use of Geospatially Referenced Data for Airfield Pavement Management

TRB’s Airport Cooperative Research Program (ACRP) Report 39: Recommended Guidelines for the Collection and Use of Geospatially Referenced Data for Airfield Pavement Management offers recommended guidelines for the collection and use of geospatially referenced data for airfield pavement management. The guidelines provide a data schema, data collection methods, data quality requirements, and other relevant information required for developing specifications and standards for integrating geospatial data into...



  • http://www.trb.org/Resource.ashx?sn=coveracrprpt039copy

ef

Airport Greenhouse Gas Reduction Efforts

Airports in the United States are responding to the demand for increased air travel with sustainable development that incorporates more energy-efficient and lower-emission technologies. Funding for greenhouse gas (GHG) emissions-reducing technologies, such as electrification, alternative fuels, and renewable energy, has also become more accessible as technologies are proven to be safe, reliable, and cost-effective. Newer strategies and programs to reduce GHG emissions reach beyond airport operations to i...



  • http://www.trb.org/Resource.ashx?sn=cover_acrp_syn_100

ef

Guidebook on Effective Land Use Compatibility Planning Strategies for General Aviation Airports

Incompatible land uses can threaten the safe utility of airports and expose people living and working nearby to potentially unacceptable levels of noise or safety risk. At the state level, all 50 states have enacted some form of airport zoning legislation since the 1950s. The majority of states (90 percent) have enacted laws mandating or enabling local governments to adopt, administer, and enforce airport zoning regulations. The TRB Airport Cooperative Research Program's ACRP Research Report 206: Guidebo...



  • http://www.trb.org/Resource.ashx?sn=cover_acrp_rpt_206

ef

Židé žijí v Říši středu už od 8. století. Jak se ukrývali za války? Sledujte unikátní pořad na Facebooku Reflexu

Někteří badatelé tvrdí, že dějiny Židů v Číně začínají již v 6. století před naším letopočtem za dynastie Čou, k tomu však nejsou žádné archeologické či jiné materiální důkazy. Všeobecně se tak počítají počátky židovské přítomnosti až od 8. století našeho letopočtu, za vlády dynastie Tang, kdy do Říše středu dorazily první skupinky obchodníků po Hedvábné stezce a usazovali se podél ní. Dnes od 18 hodin můžete na Facebooku Reflexu sledovat premiéru speciálního hudebního pořadu Židé v říši středu. Dějiny izraleského národa a Číny jsou zajímavě propojené.




ef

Online glosář Reflexu o koronaviru: Na venkově končí roušky, hospody někde otvírají dřív

Česko se zastavilo. Vláda kvůli pandemii koronaviru zavedla nouzový stav, který má šířené nemoci zamezit. Jaký je život v nouzovém režimu? Jak se chovají lidé, jak reaguje ekonomika? Hrozí, že vláda současné krize zneužije ke šmírování a omezení práva i po skončení pandemie? V online komentovaném přenosu vážně ale i s nadsázkou odpovidají redaktoři a spolupracovníci Reflexu.




ef

Relief




ef

Hefty Grogol




ef

the Cyprian defence




ef

Beef Medallions




ef

Wherefore?




ef

Reflections




ef

The "Firewalkers" of Karoo: Dinosaurs and Other Animals Left Tracks in a "Land of Fire"

Several groups of reptiles persisted in Jurassic Africa even as volcanism ruined their habitat




ef

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.




ef

Hard News: Has Iran found an effective Covid-19 treatment?

For obvious reasons, there has been a lot of attention paid to work going into developing vaccines that could prevent Covid-19 infection, and drugs that could treat it. In particular, there has been some excitement about new animal trial data for remdesivir, a drug developed by Gilead Sciences. Gilead's share price rose nearly 10% on the day the trial data were announced.
It will be some time yet before the safety and efficacy of remdesvir is established, if ever (it's worth noting that it was tried, unsuccessfully, as a treatment for Ebola). And since I started work on this post…




ef

Sketchy Gets Sketchier: Senator Loeffler Received $9 Million 'Gift' Right Before She Joined The Senate

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.




ef

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.




ef

“‘The days of your life’ refers to in-game time…”

Blacow* speaks of four players: the Wargamer, the Power-Gamer, the Role-Player, and the Story-Teller. The Wargamer, what does he say?...




ef

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.…




ef

O2 be a fly on the wall during BT and Vodafone's video calls: Telefónica's UK biz, Virgin Media officially merge

Multinationals' UK arms pair up to take on Voda and former state-owned telco

Telcos Telefónica and Liberty Global today confirmed plans to join their O2 UK and Virgin Media subsidiaries into one combined entity in a deal analysts branded a "blockbuster merger".…




ef

Go on, hit Reply All. We dare you. We double dare you. Because Office 365 will defeat your server-slamming ways

Even Exchange’s marketing bod reckons tests of new Reply-All-stopper could be a career-defining moment

Microsoft may just have made Reply All storms a thing of the past, by adding a suitable blocker to Exchange in Office 365 environments.…




ef

DEF CON is canceled... No, for real. The in-person event is canceled. We're not joking. It's canceled. We mean it

Virus knocks hackers online: Show will try going virtual amid pandemic

Annual Las Vegas hacker gathering DEF CON has officially called off its physical conference for this year due to the coronavirus pandemic.…




ef

10/02/16 - Before it’s ok




ef

Recognizing energy efficient ceiling fans on the market

Power reliable ceiling followers are a wonderful method to make your home much more inviting, visually pleasing and also, as an added bonus offer, reduced your overall house power air conditioning bill if you currently have a home cooling system.… Continue Reading




ef

Optimism or denial as mental self-defence

---------------------------------------------------[Sat Nov 26 15:25:44 2016]--
From: (S) ease of well-being  (steph)

Subject: Optimism or denial as mental self-defence

A few things recently have given me cause to consider my response to bad things
happening, and my reactions to other people's responses.  First, there's
Trump's election in the US which is undesirable and directly or indirectly
likely to cause some people harm (although I doubt it'll have any effect on me
personally).  I agree that he's not the best or even a good candidate and I
agree that he has incited prejudiced people to show and act on their
prejudices: people are being hurt.  However, I do not like the stream of
articles saying he's a white supremacist or a Nazi or California should secede
or the Electoral College should choose Clinton, or whatever.  Part of this is
doubtless my contrary streak, but part of it is something different.  I observe
that I am semi-consciously adopting a position that `things will turn out all
right' or `it won't be that bad' because countenancing the opposite is not good
for my mental health.

The other thing is some changes in the wider organisation for which I work;
basically there has been a botched reorganisation which has left most people
unhappy and from what I hear from numerous sources with good reason.  This
doesn't currently affect me much and I don't expect it to because of political
realities.  However, even just having the argument with someone closer to the
failing department (and more likely to feel its direct effects) seems to be
followed by my feeling anxious and depressed.  Again, adopting a constructive
positive attitude (which may appear to others pollyannaish, naive, optimistic,
or just in denial) seems to be a defence I've learned here and I suspect it
helps.  But there's more obviously a risk when I'm more involved than I am in
the US case, namely that my optimism will blind me to dangers that will be to
my detriment.

Does my ornery nature come to the rescue, though?  Perhaps because I'm at heart
a bit of a grumpy sod and only respect authorities when I think they deserve it
my tendency to want to probe and prod and query and dig my heels in may
counteract the defensive optimism.  Or alternatively, I'm optimistic in a
different sense: perhaps I just have confidence that I'll win?

LJDW




ef

Striatal Kir2 K+ channel inhibition mediates the antidyskinetic effects of amantadine

Levodopa-induced dyskinesia (LID) poses a significant health care challenge for Parkinson’s disease (PD) patients. Amantadine is currently the only drug proven to alleviate LID. Although its efficacy in treating LID is widely assumed to be mediated by blockade of N-methyl-D-aspartate (NMDA) glutamate receptors, our experiments demonstrate that at therapeutically relevant concentrations, amantadine preferentially blocks inward-rectifying K+ channel type 2 (Kir2) channels in striatal spiny projection neurons (SPNs) — not NMDA receptors. In so doing, amantadine enhances dendritic integration of excitatory synaptic potentials in SPNs and enhances — not antagonizes — the induction of long-term potentiation (LTP) at excitatory, axospinous synapses. Taken together, our studies suggest that the alleviation of LID in PD patients is mediated by diminishing the disparity in the excitability of direct- and indirect-pathway SPNs in the on state, rather than by disrupting LTP induction. This insight points to a pharmacological approach that could be used to effectively ameliorate LID and improve the quality of life for PD patients.




ef

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.




ef

Marked and rapid effects of pharmacological HIF-2α antagonism on hypoxic ventilatory control

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.




ef

Might β3-adrenergic receptor agonists be useful in disorders of glucose homeostasis?

Brown and beige adipose tissues contain thermogenic fat cells that can be activated by β3-adrenergic receptor agonists. In rodents, such drugs both diminish obesity and improve glucose homeostasis. In this issue of the JCI, O’Mara et al. and Finlin and Memetimin et al. report that chronic administration of the approved β3 agonist mirabegron to human subjects was without effect on body weight or fat mass, but improved several measures of glucose homeostasis. Though the mechanisms mediating these metabolic effects are uncertain, the data suggest that β3 agonists could have therapeutic utility in disorders of glucose homeostasis.




ef

Deals: Refurbished 15-Inch MacBook Pro Notebooks on Sale at Woot From $1,580 ($800+ Off)

Woot is ending the week with a refurbished sale on the 15-inch MacBook Pro, available in multiple storage sizes and colors. The sale starts with the 256GB SSD model (16GB RAM, Intel Core i7) for $1,579.99.

Note: MacRumors is an affiliate partner with Woot. When you click a link and make a purchase, we may receive a small payment, which helps us keep the site running.

For more storage, the 512GB SSD model (16GB RAM, Intel Core i9) is on sale for $1,849.99. Woot's refurbished sales are offering more than $800 in savings when compared to the original prices of these notebooks, which began at $2,399.00 when they launched in May 2019.

Similar to previous Woot sales, each MacBook Pro comes with a One Year Limited Woot Warranty. Each device has been refurbished and is ensured to be in full working condition. When shipped, they are packaged in a generic white box.

You can find even more discounts on new MacBooks by visiting our Best Deals guide for MacBook Pro and MacBook Air. In this guide we track the steepest discounts for the newest MacBook models every week, so be sure to bookmark it and check back often if you're shopping for a new Apple notebook.

Related Roundup: Apple Deals

This article, "Deals: Refurbished 15-Inch MacBook Pro Notebooks on Sale at Woot From $1,580 ($800+ Off)" first appeared on MacRumors.com

Discuss this article in our forums




ef

'Effects Achieved as I Had Hoped for This Dosage', by DoctorB (Phenibut)

Erowid Exp98591



  • Erowid : Experience :

ef

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

ef

Summary of Staff Discussion Draft: International Business Tax Reform

Senator Max Baucus, Chairman of the U.S. Senate Committee on Finance, releases a staff discussion draft on international business tax reform. Continue reading



  • Accountants CPA Hartford
  • Articles
  • Chairman Max Baucus U.S. Senate Committee on Finance
  • International Tax Reform
  • international tax system
  • November 19 2013
  • Proposals for tax reform
  • Senator Max Baucus
  • U.S. Senate Committee on Finance

ef

TurboTax accounts hacked, delaying tax refunds, compromising personal information, impairing credit rating

Online criminals have been systematically targeting TurboTax, filing fraudulent tax returns of individuals, and diverting their tax refunds to prepaid debit, cards, stealing their personal information, and using and impairing their credit ratings. Continue reading




ef

TurboTax’s Anti-Fraud Efforts Under Scrutiny

TurboTax’s Anti-Fraud Efforts Under Scrutiny Two former security employees at Intuit — the makers of the popular tax preparation software and service TurboTax – allege that the company has made millions of dollars knowingly processing state and federal tax refunds filed … Continue reading




ef

Intuit’s effort to stop tax fraud under scrutiny – who should be blamed for fraudsters using Turbotax to seal returns

Accountants CPA Hartford Connecticut LLC:  This transcript may contain errors. The Willis Report:  And tonight’s stunning accusation against Intuit, the maker of Turbotax, the popular tax preparation software.  Two whistleblowers claim that Intuit knew that criminals used its tax software … Continue reading




ef

Senator Bernie Sanders before the Senate December 2 2014 presenting an Economic Agenda for America: 12 Steps Forward

THE AMERICAN PEOPLE IN THIS PARTICULAR MOMENT IN OUR HISTORY MUST MAKE A VERY FUNDAMENTAL DECISION, AND THAT DECISION IS DO WE CONTINUE THE STATUS QUO WHICH INCLUDES A 40-YEAR DECLINE OF OUR MIDDLE CLASS AND A HUGE AND GROWING GAP BETWEEN THE VERY, VERY RICH AND EVERYONE ELSE, OR DO WE FIGHT FOR A BOLD AND MEANINGFUL ECONOMIC AGENDA THAT CREATES JOBS, RAISES WAGES, PROTECTS OUR ENVIRONMENT AND PROVIDES HEALTH CARE FOR EVERY AMERICAN Continue reading



  • Accountants CPA Hartford
  • Articles
  • An Economic Agenda for America: 12 Steps Forward
  • Senator Bernie Sanders
  • Senator Bernie Sanders before the Senate December 2 2014 presenting an Economic Agenda for America: 12 Steps Forward
  • transcript
  • video

ef

Is Bernie Sanders out in far-left field or are both political parties out in far-right field

Have you ever observed the mating dance of the birds of paradise? The male moves dramatically, and in response, the female inches away, but ultimately the male conquers the female, and achieves the purpose of this ritualistic, instinctive dance. Well, … Continue reading




ef

Make an Offer that the IRS Can’t Refuse: How to calculate an offer in compromise acceptable to the”Don”

An Offer in Compromise is an agreement between the taxpayer and the government that settles a tax liability for payment of less than the full amount owed. The Internal Revenue Service will generally accept an Offer in Compromise when it … Continue reading



  • Accountants CPA Hartford
  • Articles
  • Cenk Uygur Current TV December 7 2011
  • Collection Information Statement
  • Consigliere of Goombas to the IRS
  • Disposal Income
  • Form 433-A
  • Internal Revenue Service
  • It is what it is
  • Luca Brasi
  • Make an Offer that the IRS Can't Refuse: How to calculate an offer in compromise acceptable to the"Don"
  • Monetary Assets
  • Monthly Income
  • Necessary Living Expenses
  • Non-Monetary Assets
  • offer in compromise
  • Realizable Value
  • Reasonable Collection Potential
  • swim with the fishes
  • The Don has spoken

ef

Ralph Nader: Bernie Sanders’ wonderful effort that he launched is now aborted and is dissipating.

When longtime independent Senator Bernie Sanders lost his bid for the Democratic presidential nomination, he concluded his campaign by endorsing Hillary Clinton instead of a third-party candidate. "This huge, wonderful effort that he launched is now aborted," says our guest, four-time former presidential candidate Ralph Nader. "Sanders hasn’t returned a call from me in 18 years. He is a lone ranger. He doesn’t like to be pushed into more progressive action than he is willing to adhere to. As a result, millions of his voters now are in disarray. They don’t know where to go." Nader has a new book titled "Breaking Through Power: It’s Easier Than We Think." Continue reading




ef

Hillary Clinton and the corporate Democrats lost because Donald Trump ran to their left and outflanked them so don’t blame Jill Stein or sexism or racism. Video and transcript.

There's got to be a reason for the Democrats to suppose to exist. And the reason the Democrats are supposed to exist is to be an opposition party to the Republicans. If you're in bed with the same people, taking money from the same people, you're no longer an opposition party. There's no reason for you to exist. And guess what? Don't be surprised that people don't vote for you. Continue reading




ef

Bob Stefanowski will make Sam Brownback look like a socialist in comparison by eliminating the income tax in Connecticut

NEWS 8 IS YOUR LOCAL ELECTION HEADQUARTERS…. AND TONIGHT…VOODOO ECONOMICS! CHIEF POLITICAL CORRESPONDENT MARK DAVIS TELLING US HOW REPEALING THE STATE INCOME TAX IS THE LATEST HEATED TOPIC BETWEEN THE CANIDATES FOR GOVERNOR.   DEMOCRAT NED LAMONT IS OPENING A … Continue reading




ef

Elizabeth Warren is really just this season’s Hillary Clinton — faithful party robot, stalwart defender of the prerogatives of the establishment.

Tucker Carlson: Elizabeth Warren's enemies on Wall Street and Big Tech are not really her enemies. Elizabeth Warren is really just this season's Hillary Clinton -- faithful party robot, stalwart defender of the prerogatives of the establishment. Continue reading



  • Accountants CPA Hartford
  • Articles
  • Bernie Sanders
  • Charlie Gasparino
  • Chris Sacca
  • Donald Trump
  • Elizabeth Warren is really just this season's Hillary Clinton -- faithful party robot and stalwart defender of the prerogatives of the establishment
  • Emily Tisch Sussman
  • November 11 2019
  • Tucker Carlson
  • Tucker Carlson: Elizabeth Warren's enemies on Wall Street and Big Tech are not really her enemies. Here's why
  • two-cent wealth tax

ef

The Left is trying to end free speech and overturn the First Amendment in addition to the Second Amendment

Tucker: There’s no value more American than free speech Liberals working to crack down on the First Amendment, ban speech they don’t like. GOOD EVENING, AND WELCOME TO “TUCKER CARLSON TONIGHT.” It’s hard to think of an ideal more American … Continue reading




ef

Кавер-версия POST MALONE от ELLEFSON

Группа ELLEFSON, в состав которой входит басист MEGADETH DAVID ELLEFSON, представили собственное прочтение композиции POST MALONE “Over Now”, а с пятнадцатого мая этот трек появится на всех цифровых площадках. Этот трек будет включен в новый альбом, выход которого предварительно намечен на октябрь. #David_Ellefson #DavidEllefson