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My grad schools days are long behind me, and as time goes on, my memories of the pain and suffering become more of a blur. But, there was one day that I will never forget.  Not only did I lose an entire days work, but I was lucky to avoid serious injury. It was the day I made the biggest mistake I ever made in the lab.My graduate school was in a southern area of the country where obnoxio; (read more)

Source: Suzy - Discipline: Misc

What expression does — did — your mom use all the time? What skill did you learn from her?  What does (or did) she encourage you to do? These are great questions for any mom and child, whether the kid is 5 or 50. And if you click here, you can print out a very […]

1.8 million people in the United States drive heavy trucks for a living and are at risk of losing their jobs when trucks become autonomous. That number is from the BLS category heavy and tractor-trailer trucking with 1.8 million employees. A separate category Delivery Truck Drivers and Driver/Sales Workers has 1.3 million workers. The heavy duty truckers are more at risk than the local delivery drivers because it is easier to automate long haul driving on interstates than to automate driving on more complex (cross traffic, pedestrians, parked cars, etc) local roads. Plus, delivery drivers have to run up to houses and businesses to make most deliveries. Building robots to do that work will take longer. Railroad operation is easier...

Uber also made a deal with Volvo to cooperate on self-driving cars. Self-driving cars are an existential threat to Uber if Uber doesn't develop them first. Suppose Ford makes self-driving cars viable a few years before does and rolls them out in many cities. Uber gets wiped out by Ford's ability to charge less for a ride. Uber's big competitive advantage from a large set of recruited drivers could vanish as fast as sufficiently safe autonomous vehicles can get manufactured. Sufficiently safe: that's the challenge. But autonomous vehicle makers who limit themselves to some urban markets can lower the bar for their initial roll-out by just excluding any streets and corners that are too tricky to handle. They'll lose some...

The Miami Beach danger zone for mosquitoes carrying Zika virus is expanding. This isn't just about microcephaly in developing fetuses. Since Zika attacks neural progenitor cells it might cause lasting damage in adults too. A case of acute sensory polyneuropathy in an adult caused symptoms that lasted for months. It is suspected that Zika causes inflammation of sensory nerves and possibly an auto-immune response. So Zika is bad. What should we do about it? Wipe out the mosquitoes that carry it. Totally drive them to extinction. These mosquitoes are invasive in the Western Hemisphere. If a mosquito causes major health problems for the human species we should just wipe it out. Wiping out a mosquito species could be done with...

In a nutshell: editing offspring DNA at the embryo stage will eventually offer so many advantages that lots of people will cave in on some advantage. Don't want to make your kid smarter? Make him or her better looking? Don't want that? How about a throwing arm competitive in major league baseball? Opposed to that? How about avoiding passing along your terrible allergies, need for braces, terrible eyesight, tendency to get depressed or perhaps anxiety attacks or eating disorders? Lots of ways to be persuaded to step over the line once the tech becomes safe. If asked whether one would genetically engineer one's offspring today many people would answer "No" to the hypothetical question. But today choosing genes for your...

Elon Musk thinks a universal basic income is inevitable. Musk doesn't see plausible alternatives. I hope not. So here's the optimistic scenario: On the one hand, manual and low skilled work will mostly get automated out of existence. So one could imagine why demand for people at lower skill levels and lower levels of cognitive ability could just evaporate. On the other hand, automation will cut costs and boost the wealth of those still employed. Even if the pay of manual laborers is low the goods a manual laborer will need to survive should become very cheap. So any upper class people who can find a use for them might pay them enough to survive. But I see a stronger...

The National Highway Traffic Safety Administration (NHTSA) finds Tesla's Autopilot cuts crashes by 40%. How cool is that? Autonomous vehicles are going to cause a huge decline in accidents and deaths. Even short of autonomous vehicles, when you get your next car try to get one that supports automatic braking on imminent collision detection. You could get a large fraction of the collision avoidance benefit at a much lower cost today. Check out Insurance Institute for Highway Safety ratings of collision avoidance systems in current cars. Watch a Tesla react to a crash in front of it: Watch a Tesla avoid hitting a reckless driver: A recent analysis finds that autonomous vehicles will allow 2 million disabled people to get...

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...

Daron Acemoglu of MIT and Pascual Restrepo of Boston University find that robots really do decrease human employment. As robots and other computer-assisted technologies take over tasks previously performed by labor, there is increasing concern about the future of jobs and wages. We analyze the effect of the increase in industrial robot usage between 1990 and 2007 on US local labor markets. Using a model in which robots compete against human labor in the production of different tasks, we show that robots may reduce employment and wages, and that the local labor market effects of robots can be estimated by regressing the change in employment and wages on the exposure to robots in each local labor market—defined from the national...

We all have a rope to pull!

Contes de fées aux enfants - Dodo le mouton et le landau mystérieux.

Contes de fées aux enfants - Bonne route, les amis !.

Date: May 8, 2020

Location: South Korea

Tags: Parents' Day, carnations, flowers, stop-motion, Animation

The post The Angler’s Code: What are the Best Practices for a Better Fishing Future? appeared first on Ocean Blue Fishing Adventures.

The post Fishing in 2030 | 7 Future Megatrends | How will it affect us as anglers? appeared first on Ocean Blue Fishing Adventures.

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.

Alterations in calcium signaling in pancreatic acinar cells can result in pancreatitis. Although pressure changes in the pancreas can elevate cytosolic calcium (Ca2+) levels, it is not known how transient pressure-activated elevations in calcium can cause prolonged calcium changes and consequent pancreatitis. In this issue of the JCI, Swain et al. describe roles for the mechanically activated plasma membrane calcium channels Piezo1 and transient receptor potential vanilloid subfamily 4 (TRPV4) in acinar cells. The authors used genetic deletion models and cell culture systems to investigate calcium signaling. Notably, activation of the Piezo1-dependent TRPV4 pathway was independent of the cholecystokinin (CCK) stimulation pathway. These results elegantly resolve an apparent discrepancy in calcium signaling and the pathogenesis of pancreatitis in pancreatic acinar cells.

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.

Familial dysautonomia (FD) is the most prevalent form of hereditary sensory and autonomic neuropathy (HSAN). In FD, a germline mutation in the Elp1 gene leads to Elp1 protein decrease that causes sympathetic neuron death and sympathetic nervous system dysfunction (dysautonomia). Elp1 is best known as a scaffolding protein within the nuclear hetero-hexameric transcriptional Elongator protein complex, but how it functions in sympathetic neuron survival is very poorly understood. Here, we identified a cytoplasmic function for Elp1 in sympathetic neurons that was essential for retrograde nerve growth factor (NGF) signaling and neuron target tissue innervation and survival. Elp1 was found to bind to internalized TrkA receptors in an NGF-dependent manner, where it was essential for maintaining TrkA receptor phosphorylation (activation) by regulating PTPN6 (Shp1) phosphatase activity within the signaling complex. In the absence of Elp1, Shp1 was hyperactivated, leading to premature TrkA receptor dephosphorylation, which resulted in retrograde signaling failure and neuron death. Inhibiting Shp1 phosphatase activity in the absence of Elp1 rescued NGF-dependent retrograde signaling, and in an animal model of FD it rescued abnormal sympathetic target tissue innervation. These results suggest that regulation of retrograde NGF signaling in sympathetic neurons by Elp1 may explain sympathetic neuron loss and physiologic dysautonomia in patients with FD.

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.

The physical integrity of endothelial cells (ECs) lining the blood vessels regulates the inflammatory response. Both innate immunity and inflammatory disorders hinge on the EC-neutrophil interaction. Neutrophil binding, rolling, and migrating along and between ECs is associated with vascular permeability. In this issue of the JCI, Owen-Woods et al. tracked neutrophils in vivo in venules of mouse striated muscle and revealed how endothelial permeability can affect neutrophil trafficking. Strikingly, many neutrophils that migrated between EC junctions were able to rejoin the blood circulation. Further, the chemokine and neutrophil chemoattractant, CXCL1, drove this reverse transendothelial migration (rTEM). This paradigm-shifting study provides a mechanism for distal organ damage as well as an explanation for sepsis-associated acute respiratory distress syndrome.

Increased microvascular permeability to plasma proteins and neutrophil emigration are hallmarks of innate immunity and key features of numerous inflammatory disorders. Although neutrophils can promote microvascular leakage, the impact of vascular permeability on neutrophil trafficking is unknown. Here, through the application of confocal intravital microscopy, we report that vascular permeability–enhancing stimuli caused a significant frequency of neutrophil reverse transendothelial cell migration (rTEM). Furthermore, mice with a selective defect in microvascular permeability enhancement (VEC-Y685F-ki) showed reduced incidence of neutrophil rTEM. Mechanistically, elevated vascular leakage promoted movement of interstitial chemokines into the bloodstream, a response that supported abluminal-to-luminal neutrophil TEM. Through development of an in vivo cell labeling method we provide direct evidence for the systemic dissemination of rTEM neutrophils, and showed them to exhibit an activated phenotype and be capable of trafficking to the lungs where their presence was aligned with regions of vascular injury. Collectively, we demonstrate that increased microvascular leakage reverses the localization of directional cues across venular walls, thus causing neutrophils engaged in diapedesis to reenter the systemic circulation. This cascade of events offers a mechanism to explain how local tissue inflammation and vascular permeability can induce downstream pathological effects in remote organs, most notably in the lungs.

Being back in a cold and rainy climate reminds me of Tokyo. No, seriously. Washington has four seasons, just like Tokyo did, and just like Hawaii didn’t. I suppose that’s what has been making me feel really nostalgic these days. I’m in a place with the weather of Japan, but way less awesome. I have seriously owned around seventeen kajillion books about Japan in my lifetime, and I’ve given away, donated, or sold back almost the same amount. Some of them I bought, some of them were given to me, and I even found one or two. But the thing is that I have moved so many times that the only ones I’ve kept are those that I absolutely, positively, do not want to live without. (Well, maybe I could live without them, but then would I really be living?) Anyays! Right now, I only own three books in English about Japan, and these are them, and here is why I really like them:   1. The Otaku Encyclopedia: An Insider’s Guide to the Subculture of Cool Japan Disclaimer: A friend of mine wrote this, but that’s not why I’m recommending it.  Pat has written a bunch of books and papers, and they’re all great, but this is the one that I wish that every single otaku in the world could have. What is it? It’s seriously a dictionary, but not the kind of dictionary that we used when I was a little kid to look up stuff for our school essays. I never had a dictionary like this. You probably know what Hatsune Miku is, but do you know what a Heta-uma is? How about a kuchi-paku? Guess where you can find all of that information that you didn’t know that you needed to have? In this freaking book. I know a fair amount about Otaku culture. I lived and breathed it in Japan for almost a whole decade. But I didn’t know half of the stuff that Patrick wrote about in his book, and that’s why you need it. Plus, it’s got a lot of color, a cute mascot, and some really cool exclusive interviews. You can even learn about Tenimyu!   2. Tokyo on Foot So. I saw this book in the book store in Japan, even though it’s written in English. Maybe that’s because although there is a story in it, it’s mostly drawings and you don’t need to be able to read to get the gist of it. It was written/drawn by an artist that came to stay in Tokyo while his girlfriend was there for an internship. He spent almost every day of his six months there wandering the city with colored pencils and a pad of paper and drawing what he saw. Not only are his drawings aces, I absolutely love his little comments about places and people and things. Right after I bought this book (years ago), I was so enamored that I tried emulating his style with less than stellar results. Me and colored pencils don’t mix, which kind of makes this book even more cool (somehow)! Part of the reason that I really enjoyed this book was because it made me nostalgic for my own first days in Tokyo. I remembered thinking a lot of the same things. I just wish that I’d been good with colored pencils (and had enough confidence to write a book). You can read about my first year here on my blog, though! Honestly, I don’t think that this book is as much a must-have for otaku as the other two, but if art and impressions of Japan is your thing, I think you will love it as much as I do. I seriously only brought two English-language books back with me when I moved out of Japan, and this was one. The other was an ancient copy of The Mysterious Island that my father got when he was a kid and passed on to me.   3. Tokyo Geek’s Guide Aaaaalright. I was really, really skeptical about this one. I’ve seen a hundred other “guides to Tokyo” for otaku, but I didn’t keep any of them. This one, though? I am not only keeping it forever, I am going to give a copy to any of my friends traveling to Japan on their own to go otaku-shopping. Holy cow, I wish this book had existed when I first moved to Japan, because it covers things that it took me years of living there to find on my own! It’s a bona-fide travel guide, minus all of the generic stuff that you can find in a normal travel guide. It doesn’t focus on hotels or nice restaurants. Instead, it lists maid cafes, anime shops, and AWESOME stuff like Swallowtail (don’t know what that is? You need to get this book and find out because it is awesome!). The book is split into districts of Tokyo, and lists otaku-related info about each area along with detailed maps and how to get to all of these places. It’s kind of big and heavy for a travel guide, but it’s seriously the only one that I’m interested in having with me next time that I travel to Tokyo. There are places in it that I haven’t even been to. Oh, and bonus? There is a whole section in the latter part of the book talking about Geeky festivals like Comicket and JUMP Festa. I REALLY, REALLY WISH THAT THIS HAD BEEN AROUND WHEN I MOVED TO JAPAN. It’s 14 years too late for that, but not too late for my next trip, and not too late for yours! It’s also in full color. If you’re reading this, I think that you will probably want this book. GO BUY IT.   This has absolutely NOT been a paid advertisement. I am just a geeky girl honestly recommending things that she likes to you that she thinks you need. :3 See you again soon la la la!

This isn’t in the photos, but it’s foggy and cold this morning in western Washington. It’s the weirdest summer I’ve ever experienced — foggy, frigid mornings, cool days, and then freezing nights! It’s not very pleasant for a desert creature like myself, but it’s quite nice to sit inside and write in my blog a least. I have to say, it sure is weird, though. It’s August and I wear a sweater or sweatshirt most of the time and then I’m still cold! ^^; There are a few sunny days here and there, though. I get out on those days, into the wilderness and bright blue beyond. Sometimes, I just drive and drive in my still-unnamed yellow bug, and other times I find something that not a lot of people know about. This is about one of them. ^^ I love to wander, to find all of the nooks and crannies of wherever I happen to be. Tourist sites? Well, they’re usually cool and I want to see them, but it’s the little, hidden things off the beaten trail that really get my soul revving. So, Johns River (no apostrophe, it was named back when apostrophes weren’t used on maps) was one of those things. I found out about it by googling and googling, thinking that someone, somewhere, must have written about something other than the two really traveled trails in Grays Harbor. I mean, this area is the gateway to the wild peninsula of Washington, where according to Stephanie Meyer and Patricia Briggs, vampires and werewolves run wild. I also loooooooove mountain meadows. Johns river is not in the mountains, so I suppose that it mostly qualifies as grassland surrounded by trees? It’s just a little concrete path, and it’s not even a mile (0.6 miles one way) long, but with the river on one side and a huge expanse of pasture to the other side, it took my breath away.   Just look at this. Elk supposedly graze around here a lot, and I didn’t see any since I went during midday, but I bet it’s really a sight at sunset. It’s not far, so I will definitely have to come back. Can’t you just imagine little river sprites lounging on the bank, cleaning themselves? And little fairies flitting through the air? I bet this is a really magical place at sunset.   The little shack in the distance is off the trail. It’s supposedly for hunters (YUCK) and photographers. It would make a wonderful place to watch the sprites from. This shack is at the very end of the trail, and the same thing. It’s boring inside. I didn’t see any geldings, but I saw a few mosquitoes and a spider. If you’re lucky enough to have a horse that loves to take you along on its adventures, you can continue. I was wearing shorts, so I didn’t go, because ticks! But I will come back. Yes, I will come back. :3 Road to nowhere. Ignore the buildings. They’re only there for magical curse removal. Here’s a panorama of wildness. I’m feeling really magical today, can’t you tell? I think it’s because I have Daniel Waples playing in the background, and it’s all foggy outside. That reminds me that I want a handpan so badly. I need to find a handpan that I can afford soooooo badly, because I think it’s a music that speaks to my inner essence. Does anyone know what these gorgeous purple flowers are? They’re not lavender. The River People watch over this creek. Be careful to please them. It’s me. Sometimes I wear bright colors, sometimes I wear pastels. I don’t think that a magical being has to stick to  neutrals. (That hand thing is a shaka, a very cool gesture that I learned during my time in Hawaii that means “hang loose.” I like to think that it also means that you should be yourself and follow your instincts.) I think that I’ll go research handpans again. I should write down how much they cost so that I can be sure to stock my Airstream with one when I get it. ???? Here’s to the future! Excelsior! (Is that a good “to infinity, and beyond!!” kind of quote? If not, what should I use instead? I feel like “banzai!” is overused) Oh, and I’ve been arting on my Tumblr lately. I’ve been writing a serial ficiton that is mysterious connected to my soon-to-come comic, Denkiki on my other tumblr. Go check them out!  I’m going to start using my mailing list soon, too, to keep people updated, so stay tuned and I’ll post the link soon! Or make it a popup, I’m not sure. But I want to offer something cool for when people sign up. ???? Chaoness!

It’s release day for my new MM romance! My last release was Christmas 2018, so I’m very excited to finally have a new book for you. When I was in Australia earlier this year, I got hooked on Bondi Rescue, and this (completely fictional!) romance between a trainee and an older, very closeted lifeguard was born. […]

Apple in mid-April reopened Apple Garosugil, its lone store in South Korea, located in the Seoul's Gangnam District.


Apple's South Korea reopening has served as a test ground for further store reopenings, and Apple created an instructional video on reopening practices that's now being shared with other retail employees around the world as they prepare to reopen stores. We're not able to share the video, but it provides a good overview of the measures Apple is putting in place to safely operate retail locations.

Retail employees are following a strict set of guidelines that very heavily emphasize social distancing of two meters (or six feet in the United States). Apple is taking the following measures:

• Prior to when work starts, all employees undergo a health screening complete with a temperature check, with the results logged in a daily spreadsheet.


• Daily briefings are done in the mornings in the Forum area at Apple Stores, with employees making sure to sit at least two meters apart.


• Prior to being allowed in the store, customers are also given a temperature check.


• All ‌Apple Stores‌ are providing hand sanitizer, which customers are encouraged to use.


• Stores are limiting the number of people inside, forming lines with customers waiting at least two meters apart.


• Products purchased by customers or returned after repair are delivered from the back in a relay system, being handed off from employee to employee to allow each person to stay in a separated zone without back and forth.


• Product specialists and Genius Bar staff are positioning themselves across tables away from customers in order to maintain distance.


• In the forum area, employees sit one cube away from customers they're interacting with.


• Employees are encouraged to communicate with one another through the Talk app to cut down on unnecessary movement within the store.


• Half of the workstations in the back are empty, with employees working at alternating workstations to keep more distance between them.


• Tables have been rearranged to put products on corners to prevent customers from being near one another.


• Products on tables have been reduced.


• Communal tables and couches have been removed from employee break rooms and have been replaced with individual chairs evenly spaced about the room.


• Operating hours are reduced.


• Employees are all wearing face masks.

After opening its South Korea store on April 16, Apple has reopened its sole store in Vienna, Austria, and 21 stores located in Australia. Stores in Germany will begin reopening on May 11, and all of the newly opened locations are following many of the same guidelines listed above to keep both customers and employees safe.

There's no word yet on when Apple retail stores in the United States will start to reopen, but Apple CEO Tim Cook last week said that stores in North America will begin reopening starting in the month of May.

Apple plans to evaluate data and make reopening decisions on a city by city, county by county basis, following local guidelines and recommendations before opening up a store.
This article, "Apple Preparing Retail Employees to Return to Work With Tips From South Korea Reopening" first appeared on MacRumors.com

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