Australia bit barn outfit NEXTDC adds classic film reference to usual mix of resilience, connectivity and security

Australian serial entrepreneur Bevan Slattery has revealed that he told the architects of a data centre he funded to make it resemble the sets used in classic submarine flick The Hunt for Red October.…

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

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

Enterprise demand set to soften, offset tier-two cloud, telco sales

Global server shipments reached an industry record-breaking 3.3 million units in the first quarter of 2020, marking a 30 per cent year-on-year growth, Omdia analysts estimated this week.…

Cracks the 150,000-employee mark as revenue falls just short of $10bn

Indian services giant HCL Technologies has wound up its 19/20 financial year by reporting 15 percent annual growth but a flat Q4.…

At last, we can write headlines with all the letters intact

For a company defined by design and attention to detail, the Butterfly keyboard was a tremendous humiliation for Apple. Conceived in 2015, it replaced the previous scissor-switch mechanism for one with a smaller profile, allowing Cupertino to continue shrinking already-svelte laptops.…

NoSQL, no problem for Facebook-originating RocksDB

MongoDB and fellow database biz Rockset have integrated products in a bid to make it easier to work with the NoSQL database through standard relational database query language SQL.…

'B' is for basic controls that up and disappeared

A study of the UK online advertising market, conducted by global accounting firm PwC, has found that publishers get just half of what advertisers spend, with the other half siphoned off by ad-supply chain intermediaries.…

Advertise your open positions here for free, no catch, and find opportunities within

Job Alert This week we've got job openings from all over the globe to tempt you, your friends or your past colleagues back into work, or indeed into new ventures.…

Things will change forever, nods ex-Facebooker Alex Stamos

Video conferencing software biz Zoom has bought Keybase in a surprise move just weeks after hiring Facebook's one-time CSO.…

Tune in online this month to find out how to protect your business from data extortionists

Webcast It's been "the year of ransomware" for about the past three years. And while you may be tired of hearing about the trend and just getting used to the reality, you may also like to remember: instances of attacks are climbing – quickly – and we’re now reaching a level where more than half of ransomware schemes result in a business paying out.…

'Extra time for you to test,' you lucky, lucky developers

Google has applied the brakes to Android 11, pushing things out by a month as it grapples with a world that is much changed since planning for the release began.…

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

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

Hayabusa 2 expected to return with out-of-this-world material in December

Video Close-up footage of asteroid Ryugu, taken by the Hayabusa 2 spacecraft as it touched down to retrieve a sample, reveals the near-Earth object’s surface may have been torched by the Sun as its orbit changed over time.…

Индийский инсайдер Судханшу Амбхоре (Sudhanshu Ambhore)‏ продолжает публиковать подробности о новом смартфоне Realme X3 SuperZoom.

Компания Meizu провела в Китае мероприятие, на котором анонсировала свою новую флагманскую линейку смартфонов — Meizu 17.

Mold is a fungus with the Ability to flourish in just about any circumstance. While found almost everywhere in nature, mold can cause serious problems when found in residential areas and must be quarantined and removed as soon as possible.… Continue Reading →

Every house resident understands how quickly she or he can build up a lot of unwanted junk, broken items as well as simply simple rubbish. For those who often tend to hoard, or delay disposal of garbage, this buildup can… Continue Reading →

OED Word of the Day: simony, n. The buying or selling of ecclesiastical or spiritual benefits; esp. the sale or purchase of preferment or office in the church

“Even after weeks of staying home, my kids are just not interested in all the stuff we have. Let’s be honest. If a toy isn’t getting any action amid this distraction-free, stuck-at-home living, chances are it’s never getting touched again.” Liz Russell figures out what really engages and changes kids during the quarantine, and will […]

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 […]

At least for some kids, yes, being flung from the stress of a super-structured, super-supervised existence is having a calming, life-expanding effect. I discuss this amazing phenom in this Big Think article, including six short essays by kids themselves, and also in this interview with Bored Panda,  the  pop culture site, where I note that […]

These “cards” are really an excuse for kids to interview their moms and shower them with the ultimate gifts: attention to mom’s quirky uniqueness, gratitude, and offers of help! Here you go — click here! (Mother’s Day is SUNDAY!)

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...

Spiegel has a piece Inside the Desperate Battle against Sports Doping. Lots of athletes get away with it. Pretty unfair for the ones who do not cheat. I've made this argument many times: anti-doping efforts are a losing cause. Doping techniques will become harder to detect. They will also become more powerful. But there is hope of a sort on the horizon: In 10 years time we have orders of magnitude more understanding of how genetic variants cause differences in human performance. This is inevitable due to the plunging costs of DNA sequencing. As a result it will become possible to measure a person's genetic potential to perform in various sports. Test the genetic potential. Then report for each athlete...

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

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A man walks in a bar with his pet monkey. He sits down and orders a drink, meanwhile the monkey is running around all over the place and jumps up on a pool table. He grabs the 8 ball, shoves it into his mouth and swallows it hole. “Holy crap!” says the bartender, completely livid. […]

The post The Not So Stupid Monkey appeared first on Funny & Jokes.

Date: April 30, 2020

As COVID-19 continues to impact communities around the world, people and families everywhere are spending more time at home. In light of this, we’re launching a throwback Doodle series looking back at some of our popular interactive Google Doodle games!

Stay and play at home with today’s featured throwback: 

Our 2016 Doodle game celebrating Clara Rockmore!
 

Help stop the spread of COVID-19 by following these steps.
 

Learn more here about the latest ways we’re responding, and how our products can help people stay connected during this time.

Location: Global

Tags:

Date: May 3, 2020

Location: Hungary, Lithuania, Portugal, Romania, Spain

Tags:

Date: May 10, 2020

All that glitters is not gold, but sometimes it comes in handy.

Whether they're near or far, make Mom a little piece of art from your heart in today’s interactive, digital card-maker Doodle.

Learn more about the inspiration that led to the creation of this Doodle on our official Google Blog.

Happy Mother’s Day!

Cut out some time to send a mom some love today! Search for ”GoogleDoodles” in Gboard, GIF Keyboard by Tenor, or the GIF search in your favorite social apps.

Below, the Doodlers behind today’s Doodle share their own MOM-umental creations:
 

Anthony Irwin, UX Designer

Collin Irwin, Engineer

Grace Chen, Marketing

Perla Campos, Marketing

Tom Tabanao, Engineer

More behind-the-scenes of the making of today’s Doodle:
 

It begins! Special thanks to the Takara and McGupta Families for materials.

Early Bead Tests

Angle Reference for the Doodle G

Turtle In-Progress

Glitter Star Animation Frames

❤️ MOTHER’S DAY 2020 TEAM ❤️

Lead Artist | Alyssa Winans

Engineering | Brian Murray, Collin Irwin, Tom Tabanao, Jacob Howcroft, Nicole Patten, Yumi Kim

Producer | Gregory Capuano, Colin Duffy

UX Design | Anthony Irwin, Diana Tran

Sound Design | Jacob Howcroft

Marketing | Perla Campos, Grace Chen

Business Affairs Lead & Partnerships | Madeline Belliveau

Doodle Team Lead | Jessica Yu, Brian Kaas

Location: Global

Tags: Interactive, National Holiday, greeting card, turtles, macaroni, buttons, sequins, hearts, dragonflies, giraffes, seashells, stars, glitter

Organ shortage continues to limit the lives of patients who require liver transplantation. While extending criteria for liver organs provides a needed resource, tissue damage from prolonged ischemic injury can result in early allograft dysfunction and consequent rejection. In this issue of the JCI, Nakamura et al. used a mouse transplantation model with prolonged ex vivo cold storage to explore liver graft protection. The authors found that liver grafts with absent carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) exhibited increased ischemia-reperfusion injury inflammation and decreased function in wild-type recipients. The authors went on to correlate CEACAM1 levels with postreperfusion damage in human liver transplant recipients. Notably, this study identified a potential biomarker for liver transplant donor graft quality.

Hepatocellular carcinoma (HCC) is clearly age-related and represents one of the deadliest cancer types worldwide. As a result of globally increasing risk factors including metabolic disorders, the incidence rates of HCC are still rising. However, the molecular hallmarks of HCC remain poorly understood. Neuropeptide Y (NPY) and NPY receptors represent a highly conserved, stress-activated system involved in diverse cancer-related hallmarks including aging and metabolic alterations, but its impact on liver cancer had been unclear. Here, we observed increased expression of NPY5 receptor (Y5R) in HCC, which correlated with tumor growth and survival. Furthermore, we found that its ligand NPY was secreted by peritumorous hepatocytes. Hepatocyte-derived NPY promoted HCC progression by Y5R activation. TGF-β1 was identified as a regulator of NPY in hepatocytes and induced Y5R in invasive cancer cells. Moreover, NPY conversion by dipeptidylpeptidase 4 (DPP4) augmented Y5R activation and function in liver cancer. The TGF-β/NPY/Y5R axis and DPP4 represent attractive therapeutic targets for controlling liver cancer progression.

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.

An in-depth understanding of immune escape mechanisms in cancer is likely to lead to innovative advances in immunotherapeutic strategies. However, much remains unknown regarding these mechanisms and how they impact immunotherapy resistance. Using several preclinical tumor models as well as clinical specimens, we identified a mechanism whereby CD8+ T cell activation in response to programmed cell death 1 (PD-1) blockade induced a programmed death ligand 1/NOD-, LRR-, and pyrin domain–containing protein 3 (PD-L1/NLRP3) inflammasome signaling cascade that ultimately led to the recruitment of granulocytic myeloid-derived suppressor cells (PMN-MDSCs) into tumor tissues, thereby dampening the resulting antitumor immune response. The genetic and pharmacologic inhibition of NLRP3 suppressed PMN-MDSC tumor infiltration and significantly augmented the efficacy of anti–PD-1 antibody immunotherapy. This pathway therefore represents a tumor-intrinsic mechanism of adaptive resistance to anti–PD-1 checkpoint inhibitor immunotherapy and is a promising target for future translational research.

BACKGROUND Since December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, and is now becoming a global threat. We aimed to delineate and compare the immunological features of severe and moderate COVID-19.METHODS In this retrospective study, the clinical and immunological characteristics of 21 patients (17 male and 4 female) with COVID-19 were analyzed. These patients were classified as severe (11 cases) and moderate (10 cases) according to the guidelines released by the National Health Commission of China.RESULTS The median age of severe and moderate cases was 61.0 and 52.0 years, respectively. Common clinical manifestations included fever, cough, and fatigue. Compared with moderate cases, severe cases more frequently had dyspnea, lymphopenia, and hypoalbuminemia, with higher levels of alanine aminotransferase, lactate dehydrogenase, C-reactive protein, ferritin, and D-dimer as well as markedly higher levels of IL-2R, IL-6, IL-10, and TNF-α. Absolute numbers of T lymphocytes, CD4+ T cells, and CD8+ T cells decreased in nearly all the patients, and were markedly lower in severe cases (294.0, 177.5, and 89.0 × 106/L, respectively) than moderate cases (640.5, 381.5, and 254.0 × 106/L, respectively). The expression of IFN-γ by CD4+ T cells tended to be lower in severe cases (14.1%) than in moderate cases (22.8%).CONCLUSION The SARS-CoV-2 infection may affect primarily T lymphocytes, particularly CD4+ and CD8+ T cells, resulting in a decrease in numbers as well as IFN-γ production by CD4+ T cells. These potential immunological markers may be of importance because of their correlation with disease severity in COVID-19.TRIAL REGISTRATION This is a retrospective observational study without a trial registration number.FUNDING This work is funded by grants from Tongji Hospital for the Pilot Scheme Project, and partly supported by the Chinese National Thirteenth Five Years Project in Science and Technology for Infectious Disease (2017ZX10202201).

BACKGROUND Preclinical experiments have shown that donor blood cells, modified in vitro by an alkylating agent (modified immune cells [MICs]), induced long-term specific immunosuppression against the allogeneic donor.METHODS In this phase I trial, patients received either 1.5 × 106 MICs per kg BW on day –2 (n = 3, group A), or 1.5 × 108 MICs per kg BW on day –2 (n = 3, group B) or day –7 (n = 4, group C) before living donor kidney transplantation in addition to post-transplantation immunosuppression. The primary outcome measure was the frequency of adverse events (AEs) until day 30 (study phase) with follow-up out to day 360.RESULTS MIC infusions were extremely well tolerated. During the study phase, 10 treated patients experienced a total of 69 AEs that were unlikely to be related or not related to MIC infusion. No donor-specific human leukocyte antigen Abs or rejection episodes were noted, even though the patients received up to 1.3 × 1010 donor mononuclear cells before transplantation. Group C patients with low immunosuppression during follow-up showed no in vitro reactivity against stimulatory donor blood cells on day 360, whereas reactivity against third-party cells was still preserved. Frequencies of CD19+CD24hiCD38hi transitional B lymphocytes (Bregs) increased from a median of 6% before MIC infusion to 20% on day 180, which was 19- and 68-fold higher, respectively, than in 2 independent cohorts of transplanted controls. The majority of Bregs produced the immunosuppressive cytokine IL-10. MIC-treated patients showed the Immune Tolerance Network operational tolerance signature.CONCLUSION MIC administration was safe and could be a future tool for the targeted induction of tolerogenic Bregs.TRIAL REGISTRATION EudraCT number: 2014-002086-30; ClinicalTrials.gov identifier: NCT02560220FUNDING Federal Ministry for Economic Affairs and Technology, Berlin, Germany, and TolerogenixX GmbH, Heidelberg, Germany.

Regenerative pain medicine, which seeks to harness the body’s own reparative capacity, is rapidly emerging as a field within pain medicine and orthopedics. It is increasingly appreciated that common analgesic mechanisms for these treatments depend on neuroimmune modulation. In this Review, we discuss recent progress in mechanistic understanding of nociceptive sensitization in chronic pain with a focus on neuroimmune modulation. We also examine the spectrum of regenerative outcomes, including preclinical and clinical outcomes. We further distinguish the analgesic mechanisms of regenerative therapies from those of cellular replacement, creating a conceptual and mechanistic framework to evaluate future research on regenerative medicine.