No, you still can't edit tweets

Although editing published tweets still remains strictly verboten on Twitter, the microblogging anger echo chamber intends to prompt English-speaking iPhone-wielding users to double-check content before posting a reply that they might regret.…

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.…

Doesn't play well on iPhones, but bureaucrats rushed it out rather than wait months for perfection. Meanwhile serious bug reports have emerged

Australia’s “COVIDSafe” contact-tracing app was rushed to market in the knowledge it would perform poorly on some devices and without agreements in place to let actual contact-tracers use the data it collects. As a result, no collected data has been used in at least 10 days since its launch.…

Lee Jae-yong ends dynastic control and will even let staff join a union

Samsung's heir has said that he will not pass down management of the South Korean conglomerate to his children, ending three generations dynastic rule.…

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.…

Secarma may be next for Inflexion buyout

Cloud hosting biz UKFast's founders, Laurence and Gail Jones, have "exited the business" as a private equity firm ups its stake – all as UKFast itself starts eyeing up Jones-owned infosec biz Secarma.…

John Cena!* Online resources only for free and end users due to the 'unprecedented period'

Video conferencing darling of the hour, Zoom, has tightened up support rules in order to "better serve" users.…

High-frequency audio could be used to stealthily track netizens

Technical folks looking to improve web privacy haven't been able to decide whether sound beyond the range of human hearing poses enough of a privacy risk to merit restriction.…

There's revenue to be had with being a participant in the payments web, and the Apple experience to measure up against

Samsung has announced it will launch a debit card.…

iGiant not only screwed up the wiring, it knew it was shipping dodgy gear, it is claimed

Apple is potentially facing a class-action lawsuit over the failure of displays on its MacBook Pro line.…

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.…

Zero-click remote-code exec hole found by Googler, updates emitted

Samsung has patched a serious security hole in its smartphones that can be exploited by maliciously crafted text messages to hijack devices.…

-Album Details- Title: The Legend of Zelda: Link’s Awakening Original Soundtrack Publisher: Nippon Columbia Catalog Number: COCX-41117~20 Release Date: March 18th, 2020 Ripped by: Razakin -Info- Soundtracks to the new Switch and the way better Game Boy versions of Link’s Awakening. Enjoy. Purchase Link(s) CDJapan

-Album Details- Title: Chocobo’s Mystery Dungeon EVERY BUDDY! Original Soundtrack Publisher: Square Enix Music Catalog Number: SQEX-10710 Release Date: April 24th, 2019 Ripped by: Razakin -Info- Khew!  Some classic FF tracks arranged again for a Chocobo-game, the 2019 remaster of Final Fantasy Fables: Chocobo’s Dungeon. Enjoy. Purchase Link(s) CDJapan

A review by raiden_is_dj (2). Real fun in this game

Недавно мы писали, что Google, вслед за Apple, собирается выпустить свою собственную дебетовую карту. Сейчас о таких планах объявила компания Samsung.

Смартфон появился на сайте Google Play Console, благодаря чему стали известны его некоторые характеристики и дизайн.

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 →

I realize that sounds kinda nuts — why are we asking PARENTS to show us their KIDS being independent? Who, after all, is better at making videos? Mom or little Ava (who’s 5)? But legally we can’t ask anyone under 13 to do anything. So go document your children doing something new on their own, […]

This flow chart, created by University of Virginia Psychology Professors Jim Coan and Daniel Willingham, is just plain terrific. “Could a child do this alone?” asks the chart. Then let ’em! “Could a child do this with some instruction?” Then let ’em. Etc. etc. Check it out — print it out! — by clicking here. […]

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...

It's hard to keep up with the Zoomers!

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В 1943 году цензуру нацистской диктатуры прорвала радиостанция «Свободная Германия». Пока в Берлине уверяли, что русские на месте убивают каждого немца, немецкие антифашисты передавали из подмосковного Красногорска весточки от солдат, попавших в плен под Сталинградом и в других частях Восточного фронта.

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.

Chronic pancreatitis (CP) is considered an irreversible fibroinflammatory pancreatic disease. Despite numerous animal model studies, questions remain about local immune characteristics in human CP. We profiled pancreatic immune cell characteristics in control organ donors and CP patients including those with hereditary and idiopathic CP undergoing total pancreatectomy with islet autotransplantation. Flow cytometric analysis revealed a significant increase in the frequency of CD68+ macrophages in idiopathic CP. In contrast, hereditary CP samples showed a significant increase in CD3+ T cell frequency, which prompted us to investigate the T cell receptor β (TCRβ) repertoire in the CP and control groups. TCRβ sequencing revealed a significant increase in TCRβ repertoire diversity and reduced clonality in both CP groups versus controls. Interestingly, we observed differences in Vβ-Jβ gene family usage between hereditary and idiopathic CP and a positive correlation of TCRβ rearrangements with disease severity scores. Immunophenotyping analyses in hereditary and idiopathic CP pancreases indicate differences in innate and adaptive immune responses, which highlights differences in immunopathogenic mechanisms of disease among subtypes of CP. TCR repertoire analysis further suggests a role for specific T cell responses in hereditary versus idiopathic CP pathogenesis, providing insights into immune responses associated with human CP.

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 The anti–programmed cell death 1 (anti–PD-1) antibody pembrolizumab is clinically active against non–small cell lung cancer (NSCLC). In addition to T cells, human natural killer (NK) cells, reported to have the potential to prolong the survival of patients with advanced NSCLC, also express PD-1. This study aimed to investigate the safety and efficacy of pembrolizumab plus allogeneic NK cells in patients with previously treated advanced NSCLC.METHODS In total, 109 enrolled patients with a programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of 1% or higher were randomly allocated to group A (n = 55 patients given pembrolizumab plus NK cells) or group B (n = 54 patients given pembrolizumab alone). The patients received i.v. pembrolizumab (10 mg/kg) once every 3 weeks and continued treatment until the occurrence of tumor progression or unacceptable toxicity. The patients in group A continuously received 2 cycles of NK cell therapy as 1 course of treatment.RESULTS In our study, patients in group A had longer survival than did patients in group B (median overall survival [OS]: 15.5 months vs. 13.3 months; median progression-free survival [PFS]: 6.5 months vs. 4.3 months; P < 0.05). In group A patients with a TPS of 50% or higher, the median OS and PFS was significantly longer. Moreover, the patients in group A treated with multiple courses of NK cell infusion had better OS (18.5 months) than did those who received a single course of NK cell infusion (13.5 months).CONCLUSIONS Pembrolizumab plus NK cell therapy yielded improved survival benefits in patients with previously treated PD-L1+ advanced NSCLC.TRIAL REGISTRATION ClinicalTrials.gov NCT02843204.FUNDING This work was supported by grants from the National Natural Science Foundation of China (NSFC) – Guangdong Joint Foundation of China (no. U1601225); the NSFC (no. 81671965); the Guangdong Provincial Key Laboratory Construction Project of China (no. 2017B030314034); and the Key Scientific and Technological Program of Guangzhou City (no. 201607020016).

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).