I was wondering if you might give my little women’s (boomers) some guidance as to a beginning graphic novel for...

A simple and easy dessert that is perfect for individual snacks or can be made as a whole cheesecake.

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Nice way to get to Alpha Centauri though boffin tells us: 'Such a laser system could be used as a weapon'

Coin-sized pieces of graphene can be accelerated by firing low-powered lasers at them in micro-gravity conditions, say scientists. The technology could be a stepping stone to graphene solar sails, which could propel future spacecraft using starlight or a laser array.…

Do you have a fear of standing alone at your company party with nobody to talk to and no way to break the ice? Have no fear, F&J is here! Here’s a quick and dirty arsenal of one-liner jokes that are sure to make you the life of the party. Rest assured that nobody will […]

The post 11 Crappy One-Liners Sure To Leave You A Loser appeared first on Funny & Jokes.

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.

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.

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.

[Image: An example of gravitational lens effects, via Wikipedia.] Over at WIRED, Daniel Oberhaus, author of the recent book Extraterrestrial Languages, takes a look at some proposals from NASA’s Innovative Advanced Concept (NIAC) program. “Among this year’s NIAC grants,” Oberhaus writes, “are proposals to turn a lunar crater into a giant radio dish, to develop … Continue reading "Gravitational Lensing, Interstellar Cinematography, and the Future of Magical Warfare in Space"

IBM Security a annoncé aujourd'hui les résultats de l'IBM X-Force Threat Intelligence Index annuel 2019, qui a révélé que les mesures de sécurité et la prise de conscience accrues poussent les cybercriminels à modifier leurs techniques en quête d'un meilleur retour sur investissement. En conséquence, le rapport détaille deux changements majeurs, à savoir un détournement surprenant des attaques de type ransomware et une diminution du recours aux logiciels malveillants.

Watching the movie Joker, I felt repeatedly that I was watching a film that Greg Heisler could have lit. The use of color was unique, sophisticated and fearless — almost a character unto itself.

In this outstanding 15-minute short produced by Vanity Fair, Joker cinematographer Lawrence Sher dissects his own use of light and color in the movie. Read more »

Hello Everyone!

The pre-order for Starfighter: Chapter 01 has concluded! This means that all comics that are ordered from now on will ship out immediately. My love and undying gratitude to everyone that has ordered so far! You guys are so awesome. Seriously, thank you so much!

If you have any questions about how to order or shipping availability, please email: starfightercomic@gmail.com -HamletMachine

So I got all my wrap-ups written and here’s the short list libraries visited books read places stayed other events (i.e. timeline of big events in 2019) I’m a few days behind last year but more or less on schedule. And like last year, January is a Wikipedia month, staying busy writing articles and making […]