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.

Lymph node stromal cells (LNSCs) regulate immunity through constructing lymphocyte niches. LNSC-produced laminin α5 (Lama5) regulates CD4+ T cells but the underlying mechanisms of its functions are poorly understood. Here we show that depleting Lama5 in LNSCs resulted in decreased Lama5 protein in the LN cortical ridge (CR) and around high endothelial venules (HEVs). Lama5 depletion affected LN structure with increased HEVs, upregulated chemokines, and cell adhesion molecules, and led to greater numbers of Tregs in the T cell zone. Mouse and human T cell transendothelial migration and T cell entry into LNs were suppressed by Lama5 through the receptors α6 integrin and α-dystroglycan. During immune responses and allograft transplantation, depleting Lama5 promoted antigen-specific CD4+ T cell entry into the CR through HEVs, suppressed T cell activation, and altered T cell differentiation to suppressive regulatory phenotypes. Enhanced allograft acceptance resulted from depleting Lama5 or blockade of T cell Lama5 receptors. Lama5 and Lama4/Lama5 ratios in allografts were associated with the rejection severity. Overall, our results demonstrated that stromal Lama5 regulated immune responses through altering LN structures and T cell behaviors. This study delineated a stromal Lama5–T cell receptor axis that can be targeted for immune tolerance modulation.

Time for a break is here - the new Weekday Escape arrived! This week we get typical escape games only - four rooms with firmly closed door. The first comes Amajeto who locked you in their nice living room and... Tagged as: amajeto, blog, browser, escape, free, gotmail, japanese, pixelkobo, pointandclick, puzzle, rating-g, smartcode, spiceapp, weekday-escape

Hi, it's escaping time! With Amajeto's light and fresh room we move closer to spring and all the cute tiny birds support that feeling. TomoLaSiDo reached us a bit late for Valentine, but never mind it's fun - actually, it's... Tagged as: amajeto, blog, browser, escape, free, japanese, pixelkobo, pointandclick, puzzle, rating-g, rinnogogo, tomolasido, weekday-escape

Another escape Wednesday is here! Very retro Ariyoshi's game is quite short but fun, with refreshing approach to the genre. TomoLaSiDo locked you in their room on the day with special calendar date and you need to gather several outlets... Tagged as: ariyoshi, blog, browser, escape, free, japanese, nicolet, pixelkobo, pointandclick, puzzle, rating-g, tomolasido, weekday-escape

Welcome, this week it's retro time again! Vitamin Hana wants you to escape from an unusual place - from an oceanarium. Then you get locked in Yomino Kagura's prettily decorated room, and then it's time for No1game 's short adventure... Tagged as: blog, browser, escape, escapemen, free, fuwayura, japanese, no1game, pointandclick, puzzle, rating-g, vitaminhana, weekday-escape, yominokagura

Hi! The week is over and the brand new Weekday Escape here! Amajeto helps you to enjoy your stay at home and suggests some activities like looking for lost remote controller in coded drawers and finding ways how to open... Tagged as: amajeto, blog, browser, escape, free, japanese, masa, pixelkobo, pointandclick, puzzle, rating-g, rinnogogo, weekday-escape

Hi, it's time for a break, it's escaping time! Selfdefiant wants you to escape a desert temple which is, very conveniently, placed next to a stream so no worries of dehydration in case you stay here longer than expected. TomoLaSiDo... Tagged as:

Hello - the new WE is here! Wishing you beautiful spring and happy playing during this quarantine time! Amajeto is definitely back and has changed remarkably, the latest game is bigger and feels more like their older escapes. Very nice.... Tagged as: blog, browser, escape, free, gotmail, japanese, nicolet, pointandclick, puzzle, rating-g, selfdefiant, spiceapp, tomolasido, weekday-escape

Hi, it's time to have some fun from the past! This Weekday Escape is retro! Vitamin Hana wants you to escape a room - no surprise - but also to redecorate it. Yomino Kagura isn't so demanding, their escape is... Tagged as: blog, browser, esc-forest, escape, escapemen, free, japanese, no1game, pointandclick, puzzle, rating-g, vitaminhana, weekday-escape, yominokagura

It's Wednesday, it's escape time! Amajeto locked you in their room and wants you to escape, and TomoLaSiDo as well. Puzzles aren't hard so it doesn't take long to leave to enjoy the lovely weather outside. In Spiceapp's escape you... Tagged as: amajeto, blog, browser, escape, free, gotmail, japanese, masa, pointandclick, puzzle, rating-g, spiceapp, tomolasido, weekday-escape

Hi, hope your week is fine so far - now even better with new Weekday Escape! From Amajeto's room you'll escape easily with all the practice you have. Then you get locked in Akatsuki no Yado's one, a bit complicated... Tagged as: akatsukinoyado, amajeto, blog, browser, escape, free, gotmail, japanese, nicolet, pointandclick, puzzle, rating-g, spiceapp, weekday-escape

IBM today announced that IBM Watson Internet of Things (IoT) has been named a Leader in the IDC MarketScape: Worldwide IoT Platforms 2017 Vendor Assessment (Doc # US42033517, July 2017). The report highlights IBM’s Watson IoT Platform on IBM Cloud, which today is being used by thousands of clients and partners across six continents including BMW, KONE, HARMAN and more.

IBM Research scientists have achieved a new world record in tape storage – their fifth since 2006. The new record of 201 Gb/in2 (gigabits per square inch) in areal density was achieved on a prototype sputtered magnetic tape developed by Sony Storage Media Solutions. The scientists presented the achievement today at the 28th Magnetic Recording Conference (TMRC 2017) here.

IBM Security today released a global study examining consumer perspectives around digital identity and authentication, which found that people now prioritize security over convenience when logging into applications and devices. Generational differences also emerged showing that younger adults are putting less care into traditional password hygiene, yet are more likely to use biometrics, multifactor authentication and password managers to improve their personal security.

IBM anunció que fue designada como líder en el prestigiado modelo de evaluación de proveedores “IDC MarketScape: Worldwide Mobile Application Development and Testing Services 2014 Vendor Assessment”.

Papel San Francisco garantiza la continuidad de operaciones aprovechando Servicios de IBM

Daily Photo – Bathhouses in Budapest There are different old Turkish baths all over Budapest. This particular one had about seven different pools, and this was the most ornate. I’m not 100% sure, but I think the roof can partially retract too. I can imagine that a century earlier it would have probably been the […]

Continuing my project to journal all of my travel adventures, we come to an entertaining entry: The Big Island of Hawaii and the Great Luggage Chase of 2013.

The trip was well planned but poorly executed due to weather mishaps. I was supposed to fly DCA-JFK-LAX-KOA but snow dropped visibility to near zero at JFK so my plane was rerouted to Providence, RI after we took off from DCA. After several hours Delta put everyone back on a plane to JFK and rescheduled the connecting flights outbound from there. There was no way I was going to make it out to LAX in time to catch the Delta flight to Hawaii,  but as I was still a shiny Diamond Medallion back then and mattered to the airline, Delta put me on an AA flights to ensure I would get to Hawaii one way or another. The AA flight routed through PDX (Portland) and because of more weather problems our flight into Portland was delayed and I missed my Hawaii flight after all. Now I was stranded in Portland overnight, while my luggage (including my coat) was in LAX (it had remained on my original itinerary). 44 degrees Fahrenheit and I was dressed in anticipation of Hawaii with my sleeveless summer dress and flip-flops. Gah! Are you laughing yet? 

Delta put me up in a hotel for the evening and in the next morning I was back at the airport in my dirty clothes, tired, cranky, and eager to get to Hawaii. Let this vacation start already! I landed on Kona Island (also called Hawaii Island or the Big Island) and was immediately dismayed to find my luggage wasn’t due to arrive until that evening (having missed the evening flight the night before, they put it on the next evening flight available 24 hours later). This was a problem as I was going to be on the road for most of the trip, exploring. I left information with Delta on my whereabouts for that evening and hoped for the best. I hopped into my rental car and headed for Volcano National Park. Along the way, the scenery was gorgeous and for a good portion of the trip my car was the only one on the highways I traveled.

I journeyed to the end of the Chain of Craters Road, which follows along the ocean and dead ends at a lava flow that closed the road beyond.

As I approached Volcano National Park, the sun began to set.

There was a beautiful lava lake in the Halema’uma’u crater (the 2019 eruption of Mt. Kilauea drained it) and I was lucky enough to stand before it that evening and enjoy its stunning ebb and flow. My poor quality cell phone picture cannot capture its essence.

I had an intense dinner at Thai Thai in Volcano. It was the hottest Thai food I have ever had outside of Bankok and it brought on an instant headache and the feeling that my lips were on fire. I recommend the place only if you can stand the heat.

The next morning I was up at 4am with plans to visit the highest point on the island and the summit of the tallest mountain in the world – Mauna Kea. From its base, Mauna Kea is over 10,000 meters tall (Mt. Everest is just 8,850 for comparison). It was a cold journey as my luggage still had not arrived into Hawaii (Delta was frantically searching for my bags and could not locate them in the system at all) and so I had only my summer dress I wore on the flight to Hawaii and the t-shirt/shorts combo I purchased the day before. The view from the top proved more than worth the discomfort of the cold.

As I was descending from the summit, Delta called with some good news. They found my bags at KOA. They said they would hold them for me till later that evening when I arrived for my flight to HNL. And they gave me a $200 delta voucher for my trouble. That made me feel a little bit better, but it reinforced the universal travel truth: checking luggage for a weekend trip is almost always a bad idea.

It was a leisurely drive back to KOA, with more scenic shots along the way.

When I got to KOA airport, Delta had some fun news for me. My bags weren’t at the airport anymore where they were supposed to be. As a “courtesy”, Alaska had picked them up from Delta baggage and sent a courier across the island to the hotel I stayed at the night before (2.5 hours away) to hand deliver them to me. With just a few hours before my departing flight for HNL, I told Delta they needed to get ahold of the driver and advise him to race his ass back to this side of the island to the airport. I was doubtful I would ever see my luggage again, but thirty minutes before takeoff, a very tired and sweaty courier waved at me and handed me my bags. As soon as I got to Waikiki and checked into my hotel, I took a long shower and enjoyed the luxury of putting on clean clothes- a ritual I usually take for granted.

I enjoyed a couple of relaxing days taking in the sun and fruity cocktail drinks on the beaches of Waikiki before heading home to Virginia.  That trip was delayed too, because of storms in Virginia, and I ended up spending the night near LAX and coming home a day later. All in all a good trip, excluding the weather and luggage fiascos. I have since been back to the Hawaiian Islands two or three times (to Oahu and Maui) but the Big Island is definitely the most spectacular of them all.  Go to Oahu for the history and shopping, go to Maui for the food, but go to the Big Island for the rugged scenery that will take your breath away.

Well, April felt simultaneously short and long! I should have just posted these at the beginning of the month, my SIGBOVIK papers from 2020:

Is this the longest chess game? is another needless chess paper, here trying to figure out the longest possible legal game. There are several rules that make sure games can't go on forever, and some surprisingly subtle details/ambiguity to those rules. The whole game is of course included in the paper (17697 moves), but I was far from being the largest waste of space in this year's proceedings, as one provocateur had a paper with 150 pages of citations. Mathieu made a 5-hour video of the chess game I computed for his companion blog post.

What is the best game console? A market-based approach is a silly idea taken too far. It was a year in the making (mostly waiting) and didn't quite turn out the way I was expecting due to world events, but that's part of the "fun" I guess!

Conditional Move For Shell Script Acceleration was another collaboration with Jim (mostly his doing, but I like to lather on an additional patina of absurdity).

This month I have mostly been trying to keep sane and healthy during the shelter-in-place order. It's been harder than usual to find the energy to be creative, but I have had some spurts. I basically only leave the house to run (not going anywhere near other people). But I have been doing that pretty regularly, so between that and the prohibition against going out to bars and ice cream, I'd say I'm currently in the best I have been in ~6 years. Yesterday I claimed some course records for some Strava segments in my neighborhood! I also finished up Doom: Eternal, which was good but you pretty much already know what it's like and I'm playing Animal Crossing and haven't yet gotten sick of that. The timing for the release of that latter game couldn't have been more perfect, huh? Sometimes I need something with a little challenge, so I just started Nuclear Throne. I'm liking it but not sure if I have decided whether it's good enough to invest the time in to win (I almost always play games to the end but these randomized roguelikes demand a certain kind of potentially infinite investment. Like I never did beat the last boss in Wizard of Legend, and even in Dead Cells, which I loved, I had to settle for some modest personal criteria for "winning.") Any other recs? Could use a good Metroidvania perhaps?