Hear about traveling the Dempster Highway as the Amateur Traveler talks to Lisa from TheHotFlashPacker.com about this iconic drive into the Arctic Circle in Canada. 

Hear about travel to Tbilisi and the eastern part of the Republic of Georgia as the Amateur Traveler talks to Tommo & Megsy from FoodFunTravel.com who have settled in Georgia.

After three decades of mystery, the cold case murder of a 17-year-old Ohio teen named Barbara Blatnik has been solved thanks in part to DNA genealogical research. The last time anyone saw Blatnik alive was around midnight on Dec. 19, 1987, when a friend dropped her off in Garfield Heights, Ohio. The following day, Blatnik,…

The post 32 Years After Teen’s Body Found Strangled on Side of Road, Suspect Finally Arrested appeared first on The Western Journal.

At a cost of $7.5 million a patient, they were 16 very expensive field hospitals. Yet, according to NPR, those hospitals are now “stand[ing] down.” You probably remember them from headlines early in the pandemic: makeshift medical centers being assembled at breakneck speed by companies contracted by the Army Corps of Engineers in anticipation of…

The post After Treating Barely Any Patients for a Massive $7.5 Million Each, 16 Emergency COVID Hospitals Are Standing Down appeared first on The Western Journal.

As confetti floated through the air, a baby boy and his family celebrated his final chemotherapy treatment in time to go home before his first birthday. According to KSAZ, young Aaron has been battling a rare form of cancer called acute megakaryoblastic leukemia since he was four months old. Aaron was a patient at Duke…

The post 10-Month-Old Gets Heartwarming Celebration from Hospital Staff After Finishing Chemotherapy appeared first on The Western Journal.

“Outbreaks have sparked riots and propelled public-health innovations, prefigured revolutions and redrawn maps.” – The New Yorker, April 2020 “Nothing will be the same.”  That’s the overwhelming takeaway I’ve heard from dozens of conversations I’ve had with C-suite leaders, physicians, policy experts and media professionals these past few weeks.  When it comes to the business … Continue reading "An Open Letter To American Corporations: It’s Good Business (and Smart Marketing) To Support Quality Journalism"

"We're writing off too many people," Rep. Mick Mulvaney (R-SC) says in "Immigration Battle," a feature film presentation from FRONTLINE and Independent Lens that airs tonight on PBS.

A.C. Thompson and Richard Rowley’s search for answers into the killings of five Vietnamese-American journalists took them from cities like Houston and San Francisco, to the jungles of Southeast Asia, to the corridors of power in Washington.

From 1981 to 1990, five Vietnamese-American journalists were killed in what some suspected was a string of political assassinations. Why did the murders go unsolved?

Just days after the attack in Paris, America’s top intelligence official suggested that recent leaks about classified surveillance programs were partially responsible.

Last year, when we felt interest in artificial intelligence (AI) was approaching a fever pitch, we created a survey to ask about AI adoption. When we analyzed the results, we determined the AI space was in a state of rapid change, so we eagerly commissioned a follow-up survey to help find out where AI stands […]

Rita J. King, co-director and EVP for business development at Science House, recently conducted a series of interviews with business leaders, exploring the challenges and hurdles companies face in evolving business landscapes. In this interview, King chats with Craig Lemasters, CEO of Global Executive Group, about what companies face when navigating the digital transformation. They […]

Rita J. King, co-director and EVP for business development at Science House, recently conducted a series of interviews with business leaders, exploring the challenges and hurdles companies face in evolving business landscapes. In this interview, King chats with Dana Codispoti, head of HR Transformation at AIG, about how to address the human factor in business […]

The Leopards Ate My Face subreddit is dedicated to mocking people who thought the Republican party would hurt their enemies only to be surprised to find that it hurts them, too. Inspired by a tweet by Adrian Bott—'I never thought leopards would eat MY face,' sobs woman who voted for the Leopards Eating People's Faces Party—it has now banned posts about people who claimed Covid-19 was bullshit only to die of Covid-19. There are simply too many, and it's getting depressing.

"We've seen a billion of them in the past two weeks and the vast majority of them don't fit the subreddit," writes moderator u/ROBOT_OF_WORLD. "People dying from their decisions isn't justice, karmic, or funny." Read the rest

It took hundreds of exposures and a complex method of removing occlusions, but this "lucky" shot is the result: a depiction of the hot regions lurking under Jupiter's uppermost clouds.

The picture was captured in infared by the Gemini North Telescope in Hawaii, and is one of the sharpest observations of the planet ever made from the ground. To achieve the resolution, scientists used a technique called "lucky imaging" which scrubs out the blurring effect of looking through Earth's turbulent atmosphere. This method involves acquiring multiple exposures of the target and only keeping those segments of an image where that turbulence is at a minimum.

On his Pluralistic blog, Cory Doctorow writes about a $3 router rebooter. This DIY gadget connects between your home router and its AC outlet. It pings Google periodically and if it doesn't receive a response, it cycles the power on the router to reboot it.

From creator Mike Diamond's website What I Made Today:

How it works In layman's terms, the process is simple. The ESP [ESP8266 01, an  Internet of Things WiFi module board] periodically pings Google through the modem. If it gets a reply, it does nothing; the relay stays closed and the modem stays on.

If the ESP does not get a reply, it will "understand" that the modem is down. When this happens, it turns off the relay, waits 30 seconds, then turns it back on, thus power-cycling the modem.

Who is Patrick Mason? I just ran across a few short horror films he wrote and directed, and they're truly scary. Like edge-of-your-seat gasp-out-loud scary. Not only that, but they're beautifully made with good actors, especially Ayuda (see below). The three videos posted here are the ones I've seen so far, but there are more on his site, which I plan to watch tonight. Can't wait to see where this director takes us next.

Read the rest

An array of scientific evidence suggest that in some cases, the bacteria in your gut–your microbiome–could be tied to neurological and psychological disorders and differences, from anxiety and autism to Parkinson's and schizophrenia. The journal Science published a survey of the field and the Cambridge, Massachusetts start-up Holobiome that hopes to use insight into this "psychobiome" to develop treatments for depression, insomnia, and other conditions with a neurological side to them. From Science:

For example, many people with irritable bowel syndrome are also depressed, people on the autism spectrum tend to have digestive problems, and people with Parkinson’s are prone to constipation.

Researchers have also noticed an increase in depression in people taking antibiotics—but not antiviral or antifungal medications that leave gut bacteria unharmed. Last year, Jeroen Raes, a microbiologist at the Catholic University of Leuven, and colleagues analyzed the health records of two groups—one Belgian, one Dutch—of more then 1000 people participating in surveys of their types of gut bacteria. People with depression had deficits of the same two bacterial species, the authors reported in April 2019 in Nature Microbiology.

Researchers see ways in which gut microbes could influence the brain. Some may secrete messenger molecules that travel though the blood to the brain. Other bacteria may stimulate the vagus nerve, which runs from the base of the brain to the organs in the abdomen. Bacterial molecules might relay signals to the vagus through recently discovered “neuropod” cells that sit in the lining of the gut, sensing its biochemical milieu, including microbial compounds.

RCMP say a 50-year-old man died and a 60-year-old man is in hospital following a crash involving a CP Rail train Friday morning.

The flood stricken Regional Municipality of Wood Buffalo says it is on track to lift its boil water advisory sooner than it was originally projected.

Salomon Rondon says he was on his way to joining Manchester United in January only for Dalian Professional to block the move.

Where is Unemployment Slowing Faster During the...

Peter Kay’s Car Share Synopsis Peter Kay’s Car Share is a situation comedy television series produced by BBC One that premiered in April of 2015. Peter Kay’s Car Share follows the story of John (played by Peter Kay), an assistant manager in a supermarket and his co-worker and promotions rep Kayleigh (played by Sian Gibson). […]

Today, there is a mobile application for every task we do daily. For this reason, the mobile app industry has witnessed enormous growth over the last couple of years, with billions of apps downloaded every year. Businesses of all kinds have certainly benefited from the emergence of mobile applications. One of the apps that’s seen […]

The post Interested in Building a Food Delivery App? appeared first on Dumb Little Man.

In one way or another, social learning has been part of our lives for a long time. We spend a large amount of time at work. During this time, we are bound to learn from our colleagues and get a chance to talk on mutual topics of interest. Moreover, social media has given an outlet […]

The post Social Learning as a Way to Foster Productivity in the Workplace appeared first on Dumb Little Man.

Radoslaw Dobrolecki, US business development director at RTB House, discusses how artificial intelligence can help predict customer behavior at scale.

Pandemic gives TV viewership boost, but will be short-lived   April 28, 2020 (New York, NY) – As stay-at-home orders remain in effect due to COVID-19, TV viewership and time […]

May 6, 2020 (New York, NY) – “Insider Intelligence” is being announced today as the brand name of the newly-formed parent company of eMarketer and Business Insider Intelligence (BII), both […]

This is not where I thought I’d be. If things had gone to plan, I would now be on a bus moving through the Peruvian countryside, smiling at the memory of my meals at Central and Maido, looking forward to sandboarding in Huacachina, seeing Machu Picchu, and exploring the Galapagos a few weeks after that. …

Sheltering in Place in Mexico City Read More »

The post Sheltering in Place in Mexico City appeared first on Adventurous Kate.

With a bright, 8.2-inch HD display and the flexibility to work in almost any vehicle, the Lanmodo Automotive Vast Night Vision System is a near-perfect alternative to factory-installed systems.

The post Brighten Up Your After-Dark Road-Tripping with Lanmodo’s Vast Automotive Night Vision System appeared first on Vagabondish.

By choosing the right brands and most versatile fabrics, you can pack the same men's travel clothes no matter where you're headed.

The post The Men’s Travel Clothes I Pack No Matter Where I’m Headed appeared first on Vagabondish.

MPU 046: Workflows with Merlin Mann II « Mac Power Users

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I have the life that I have because I've made a lot of weird decisions, and they've worked out well.

Not gonna lie to you. I'm a huge nerd. Surprised?

Yep. I can recite big chunks of The Big Lebowski from memory. I can argue for an hour on the merits of Dick York over Dick Sargent. And, I can—and frequently do—catch myself thinking Catwoman, Batgirl, Princess Leia, and Emma Peel should have a light-hearted pillow fight that ends with an hour of genial french-kissing.

Pretty much like you, probably. I dunno, maybe your version includes Kitty Pryde. Po-tay-to/Po-taht-o, right?

Perhaps most saliently, by virtue of having spent a solid 2,399 days as a Fake Productivity Guru, I have been provided with an unquestionably Janusian monkey's paw of a gift; I now know a lot about workflows. Nerdy, nerdy workflows.

I can tell you a few things that almost always work, I can tell you a handful of things that almost never work, and—best or worst of all—I can tell you thousands of things that might work. Sometimes. Maybe. Kinda. For some people. For now.

And, at the risk of gay-marrying my arrogance to my hypocrisy, I can tell you that I also know enough about the unholy diarrhea of potential options for Theoretical Productivity to share two big patterns:

1. Getting your workflow right matters.
2. Getting your workflow right to the exclusion of the actual work is a fool's game.

But. Managing to get the most useful and most elegant and least fiddly mix of 1 and 2 right is super-hard. Especially for nerds. Especially for me.

So, as I type this today, I believe there can be no greater testament to these claims—or, at least, no greater place to test the veracity of these claims for yourself—than in this TWO AND A HALF HOUR-long interview for Mac Power Users.

It is reeeeeeeeally nerdy. Almost intolerably nerdy. Just…overwhelmingly nerdy.

But, man, is it ever really good, and really fat with the most insanely granular details of How I Work.

Lo, even these 928.5 days after officially retiring from productivity pr0n, my desire to not "vend stroke material for your joyless addiction to puns about procrastination and systems for generating more taxonomically satisfying meta-work" is tempered by a (widely under-reported) practical streak.

Yes: I continue to despise empty advice about rearranging deck chairs on The Titanic. But, yes: I do also still very much enjoy talking about how all the tips and tricks can or can't work in the context of work you care about. That matters. It really does.

So. Here goes. A one hundred and forty six minute-long, Joyce-ian amble through the Big Stuff and the Little Stuff. David and Katie were very patient.

How I name text files. Why I break iOS apps. Why I love the letter "x." Why I won't row out to islands any more. How a 115,000 word book manuscript is "like a house full of confederate money." How "The Cloud" broke in New Zealand. How I use MultiMarkdown, Scrivener, TextExpander, OmniFocus, TextMate, Notational Velocity, Dropbox, and an explosive combination of Elements, Notesy, Nebulous, Simplenote, CF Outliner, iThoughts, Instacast, Good Reader, and wow wow wow.

How I try not to fiddle—how I sometimes succeed and often don't. But, how I try.

Anyhow. There you go. A perfectly nerdy bookend to last year's first Magnum Opus MPU interview on these same topics, Mac Power Users Episode 46 is just insanely nerdy. And, what have you.

I hope you like it. I hope it's useful. I hope you don't use it to replace real work.

And, as ever, I really hope Batgirl starts having more sexy pillow fights.

Enjoy. And, God save you.

MPU 046: Workflows with Merlin Mann II « Mac Power Users

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Restaurants have been struggling to stay afloat since the pandemic hit, but there has been a silver lining: relaxed liquor laws mean customers can get their booze delivered along with their meals.

The following article, Donald Trump Jr. Offers To Walk Bride-to-Be Down The Aisle After Liberal Parents Refuse To Attend Her Wedding Because Fiance Is A Conservative, was first published on 100PercentFedUp.com.

TDS or Trump Derangement Syndrome brings out the worst in a lot of people. One young Texan girl’s story of her intolerant parents who refuse to attend her wedding because she’s marrying a conservative, however, is a new low. Lawyer and conservative civil rights activist, Rogan O’Handley tweeted a Tik Tok video of a Texan […]

Continue reading: Donald Trump Jr. Offers To Walk Bride-to-Be Down The Aisle After Liberal Parents Refuse To Attend Her Wedding Because Fiance Is A Conservative ...

The following article, Legal Immigrant in Michigan Sends a Message to MI Gov Whitmer and Media Criticizing Freedom-Loving Protesters, was first published on 100PercentFedUp.com.

The media and even some governors are trying to paint the Americans who are protesting to open businesses up as racists and even Nazis. The Governor of Michigan recently made a derogatory statement about the protesters implying they are racists. Painting a negative picture of the people who want their freedom and businesses demonizes our […]

Continue reading: Legal Immigrant in Michigan Sends a Message to MI Gov Whitmer and Media Criticizing Freedom-Loving Protesters ...

The following article, Video: Salon Owner Shelley Luther Released from Jail After Obama-Loyalist Judge Sentenced Her to 7 Days, was first published on 100PercentFedUp.com.

Salon A La Mode owner Shelley Luther was just released from jail today. The Texas Supreme Court and Texas Governor Greg Abbott both called for her release today (see below). When Luther left jail she was greeted by supporters who yelled “Shelley’s Free!” She thanked all of the new friends she’s made during this difficult […]

Continue reading: Video: Salon Owner Shelley Luther Released from Jail After Obama-Loyalist Judge Sentenced Her to 7 Days ...

The following article, BREAKING: Michigan’s Radical Governor Extends Lockdown AGAIN…Only One Day After Church Leaders and MI Lawmakers File Suit Against Her, was first published on 100PercentFedUp.com.

Michigan was the first state to see protests against draconian lockdown measures by an overreaching governor. On April 15, the Michigan Conservative Coalition organized an in-vehicle protest in Lansing, MI that drew an estimated 15,000 vehicles. Since that time, several protests by Michigan workers who are being devastated by the one-size-fits-all shut down of the […]

Continue reading: BREAKING: Michigan’s Radical Governor Extends Lockdown AGAIN…Only One Day After Church Leaders and MI Lawmakers File Suit Against Her ...

The following article, BREAKING: President Trump’s Fiery Interview On Fox & Friends…”These are dirty politicians and dirty cops…They put our nation in danger with other nations, including Russia” [VIDEO], was first published on 100PercentFedUp.com.

This morning during a nearly one hour interview with Fox & Friends, President Trump addressed the decision by the DOJ to drop the case against the innocent General Michael Flynn. Trump ripped into the “dirty politicians and dirty cops” who went after General Michael Flynn. President Trump called the players involved in the horrible plot […]

Continue reading: BREAKING: President Trump’s Fiery Interview On Fox & Friends…”These are dirty politicians and dirty cops…They put our nation in danger with other nations, including Russia” [VIDEO] ...

The following article, Fed Judge Releases 21-Yr-Old Man To “Clean and Sober House” After Appearing In Court For Sexually Assaulting 12-Yr-Old Girl For One Month While Hiding In Her Bedroom, was first published on 100PercentFedUp.com.

The normalizing of pedophilia is not a far-right conspiracy theory...

Continue reading: Fed Judge Releases 21-Yr-Old Man To “Clean and Sober House” After Appearing In Court For Sexually Assaulting 12-Yr-Old Girl For One Month While Hiding In Her Bedroom ...

The atypical trichromatic cyanobacterial phytochrome NpTP1 from Nostoc punctiforme ATCC 29133 is a linear tetrapyrrole (bilin)-binding photoreceptor protein that possesses tandem-cysteine residues responsible for shifting its light-sensing maximum to the violet spectral region. Using bioinformatics and phylogenetic analyses, here we established that tandem-cysteine cyanobacterial phytochromes (TCCPs) compose a well-supported monophyletic phytochrome lineage distinct from prototypical red/far-red cyanobacterial phytochromes. To investigate the light-sensing diversity of this family, we compared the spectroscopic properties of NpTP1 (here renamed NpTCCP) with those of three phylogenetically diverged TCCPs identified in the draft genomes of Tolypothrix sp. PCC7910, Scytonema sp. PCC10023, and Gloeocapsa sp. PCC7513. Recombinant photosensory core modules of ToTCCP, ScTCCP, and GlTCCP exhibited violet-blue–absorbing dark-states consistent with dual thioether-linked phycocyanobilin (PCB) chromophores. Photoexcitation generated singly-linked photoproduct mixtures with variable ratios of yellow-orange and red-absorbing species. The photoproduct ratio was strongly influenced by pH and by mutagenesis of TCCP- and phytochrome-specific signature residues. Our experiments support the conclusion that both photoproduct species possess protonated 15E bilin chromophores, but differ in the ionization state of the noncanonical “second” cysteine sulfhydryl group. We found that the ionization state of this and other residues influences subsequent conformational change and downstream signal transmission. We also show that tandem-cysteine phytochromes present in eukaryotes possess similar amino acid substitutions within their chromophore-binding pocket, which tune their spectral properties in an analogous fashion. Taken together, our findings provide a roadmap for tailoring the wavelength specificity of plant phytochromes to optimize plant performance in diverse natural and artificial light environments.

Previous studies have shown that sphingosine kinase interacting protein (SKIP) inhibits sphingosine kinase (SK) function in fibroblasts. SK phosphorylates sphingosine producing the potent signaling molecule sphingosine-1-phosphate (S1P). SKIP gene (SPHKAP) expression is silenced by hypermethylation of its promoter in acute myeloid leukemia (AML). However, why SKIP activity is silenced in primary AML cells is unclear. Here, we investigated the consequences of SKIP down-regulation in AML primary cells and the effects of SKIP re-expression in leukemic cell lines. Using targeted ultra-HPLC-tandem MS (UPLC-MS/MS), we measured sphingolipids (including S1P and ceramides) in AML and control cells. Primary AML cells had significantly lower SK activity and intracellular S1P concentrations than control cells, and SKIP-transfected leukemia cell lines exhibited increased SK activity. These findings show that SKIP re-expression enhances SK activity in leukemia cells. Furthermore, other bioactive sphingolipids such as ceramide were also down-regulated in primary AML cells. Of note, SKIP re-expression in leukemia cells increased ceramide levels 2-fold, inactivated the key signaling protein extracellular signal-regulated kinase, and increased apoptosis following serum deprivation or chemotherapy. These results indicate that SKIP down-regulation in AML reduces SK activity and ceramide levels, an effect that ultimately inhibits apoptosis in leukemia cells. The findings of our study contrast with previous results indicating that SKIP inhibits SK function in fibroblasts and therefore challenge the notion that SKIP always inhibits SK activity.

Heterotrimeric G proteins are the core upstream elements that transduce and amplify the cellular signals from G protein–coupled receptors (GPCRs) to intracellular effectors. GPCRs are the largest family of membrane proteins encoded in the human genome and are the targets of about one-third of prescription medicines. However, to date, no single therapeutic agent exerts its effects via perturbing heterotrimeric G protein function, despite a plethora of evidence linking G protein malfunction to human disease. Several recent studies have brought to light that the Gq family–specific inhibitor FR900359 (FR) is unexpectedly efficacious in silencing the signaling of Gq oncoproteins, mutant Gq variants that mostly exist in the active state. These data not only raise the hope that researchers working in drug discovery may be able to potentially strike Gq oncoproteins from the list of undruggable targets, but also raise questions as to how FR achieves its therapeutic effect. Here, we place emphasis on these recent studies and explain why they expand our pharmacological armamentarium for targeting Gq protein oncogenes as well as broaden our mechanistic understanding of Gq protein oncogene function. We also highlight how this novel insight impacts the significance and utility of using G(q) proteins as targets in drug discovery efforts.

The Mycobacterium tuberculosis virulence factor EsxA and its chaperone EsxB are secreted as a heterodimer (EsxA:B) and are crucial for mycobacterial escape from phagosomes and cytosolic translocation. Current findings support the idea that for EsxA to interact with host membranes, EsxA must dissociate from EsxB at low pH. However, the molecular mechanism by which the EsxA:B heterodimer separates is not clear. In the present study, using liposome-leakage and cytotoxicity assays, LC-MS/MS–based proteomics, and CCF-4 FRET analysis, we obtained evidence that the Nα-acetylation of the Thr-2 residue on EsxA, a post-translational modification that is present in mycobacteria but absent in Escherichia coli, is required for the EsxA:B separation. Substitutions at Thr-2 that precluded Nα-acetylation inhibited the heterodimer separation and hence prevented EsxA from interacting with the host membrane, resulting in attenuated mycobacterial cytosolic translocation and virulence. Molecular dynamics simulations revealed that at low pH, the Nα-acetylated Thr-2 makes direct and frequent “bind-and-release” contacts with EsxB, which generates a force that pulls EsxB away from EsxA. In summary, our findings provide evidence that the Nα-acetylation at Thr-2 of EsxA facilitates dissociation of the EsxA:B heterodimer required for EsxA membrane permeabilization and mycobacterial cytosolic translocation and virulence.

Bacterial type VII secretion systems secrete a wide range of extracellular proteins that play important roles in bacterial viability and in interactions of pathogenic mycobacteria with their hosts. Mycobacterial type VII secretion systems consist of five subtypes, ESX-1–5, and have four substrate classes, namely, Esx, PE, PPE, and Esp proteins. At least some of these substrates are secreted as heterodimers. Each ESX system mediates the secretion of a specific set of Esx, PE, and PPE proteins, raising the question of how these substrates are recognized in a system-specific fashion. For the PE/PPE heterodimers, it has been shown that they interact with their cognate EspG chaperone and that this chaperone determines the designated secretion pathway. However, both structural and pulldown analyses have suggested that EspG cannot interact with the Esx proteins. Therefore, the determining factor for system specificity of the Esx proteins remains unknown. Here, we investigated the secretion specificity of the ESX-1 substrate pair EsxB_1/EsxA_1 in Mycobacterium marinum. Although this substrate pair was hardly secreted when homologously expressed, it was secreted when co-expressed together with the PE35/PPE68_1 pair, indicating that this pair could stimulate secretion of the EsxB_1/EsxA_1 pair. Surprisingly, co-expression of EsxB_1/EsxA_1 with a modified PE35/PPE68_1 version that carried the EspG5 chaperone-binding domain, previously shown to redirect this substrate pair to the ESX-5 system, also resulted in redirection and co-secretion of the Esx pair via ESX-5. Our results suggest a secretion model in which PE35/PPE68_1 determines the system-specific secretion of EsxB_1/EsxA_1.

12 February 2020

Invitation Only Research Event