The National Cooperative Highway Research Program's NCHRP Web-Only Document 272: Existing and Emerging Highway Infrastructure Preservation, Maintenance, and Renewal Definitions, Practices, and Scenarios provides appendices to NCHRP Report 750, Volume 7: Preservation, Maintenance, andRenewal of Highway Infrastructure .

Федеральные власти по-прежнему отказываются считать похищения людей на Кавказе военными преступлениями, позволяя виновным избегать наказания

A new study indicates that, contrary to what has been previously argued, galaxies like our own may be the most likely place to find intelligent life

The post Galaxies Like the Milky Way are the Best for Life appeared first on Universe Today.

Tiny meteorites that fell to Earth 2.7 billion years ago suggest that the atmosphere at that time was high in carbon dioxide, which agrees with current understanding of how our planet's atmospheric gases changed over time.

Pixie, you came to us beaten, starved, scared and lonely. No one wanted to take on a rescue Staffordshire Bull Terrier, but we did as company for our

Для того, чтобы узнать дату, необходимо решить несложную задачу.

Компания Xiaomi осенью прошлого года выпустила смартфон Mi Note 10, но обновление Android 10 добралось до аппарата только сейчас.

Компания Xiaomi, неожиданно для всех, объявила дату анонса очередного смартфона из линейки Redmi K30.

Мы уже не раз писали о том, что компания Xiaomi готовит к выходу бюджетный смартфон Redmi 9. Сейчас в сети появилась очередная утечка, намекающая на его скорый анонс.

Экспедиционная группа из Китая поднялась на гору Эверест и решила там же протестировать в экстремальных условиях камеры смартфонов.

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 […]

Hearing loss caused by the death of sensory hair cells of the inner ear is an unfortunate side effect for many patients treated with aminoglycoside antibiotics or platinum-containing chemotherapy agents. In animal models, induction of heat shock confers substantial otoprotection against aminoglycoside- and cisplatin-induced hair cell death. In this issue of the JCI, Breglio et al. demonstrate that inner ear tissue released exosomes carrying heat shock protein 70 (HSP70) in response to heat stress. HSP70 acted by a paracrine mechanism that engaged the Toll-like receptor 4 (TLR4) on hair cells to protect them from death. Exosomes and the HSP70/TLR4 pathway could thus provide treatment targets for the protection of hair cells from chemically induced death or from other insults, such as noise.

Curing HIV infection will require the elimination of a reservoir of infected CD4+ T cells that persists despite HIV-specific cytotoxic T cell (CTL) responses. Although viral latency is a critical factor in this persistence, recent evidence also suggests a role for intrinsic resistance of reservoir-harboring cells to CTL killing. This resistance may have contributed to negative outcomes of clinical trials, where pharmacologic latency reversal has thus far failed to drive reductions in HIV reservoirs. Through transcriptional profiling, we herein identified overexpression of the prosurvival factor B cell lymphoma 2 (BCL-2) as a distinguishing feature of CD4+ T cells that survived CTL killing. We show that the inducible HIV reservoir was disproportionately present in BCL-2hi subsets in ex vivo CD4+ T cells. Treatment with the BCL-2 antagonist ABT-199 was not sufficient to drive reductions in ex vivo viral reservoirs when tested either alone or with a latency-reversing agent (LRA). However, the triple combination of strong LRAs, HIV-specific T cells, and a BCL-2 antagonist uniquely enabled the depletion of ex vivo viral reservoirs. Our results provide rationale for novel therapeutic approaches targeting HIV cure and, more generally, suggest consideration of BCL-2 antagonism as a means of enhancing CTL immunotherapy in other settings, such as cancer.

Systemic sclerosis (SSc) is an autoimmune fibrotic disease whose pathogenesis is poorly understood and lacks effective therapies. We undertook quantitative analyses of T cell infiltrates in the skin of 35 untreated patients with early diffuse SSc and here show that CD4+ cytotoxic T cells and CD8+ T cells contribute prominently to these infiltrates. We also observed an accumulation of apoptotic cells in SSc tissues, suggesting that recurring cell death may contribute to tissue damage and remodeling in this fibrotic disease. HLA-DR–expressing endothelial cells were frequent targets of apoptosis in SSc, consistent with the prominent vasculopathy seen in patients with this disease. A circulating effector population of cytotoxic CD4+ T cells, which exhibited signatures of enhanced metabolic activity, was clonally expanded in patients with systemic sclerosis. These data suggest that cytotoxic T cells may induce the apoptotic death of endothelial and other cells in systemic sclerosis. Cell loss driven by immune cells may be followed by overly exuberant tissue repair processes that lead to fibrosis and tissue dysfunction.

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.

Эксперты из DxOMark протестировали камеры новых смартфонов iPhone 11 Pro и 11 Pro Max, и в результате испытаний новинки от компании Apple оказались недостаточно хороши, чтобы возглавить рейтинг. В общ...

There's got to be a reason for the Democrats to suppose to exist. And the reason the Democrats are supposed to exist is to be an opposition party to the Republicans. If you're in bed with the same people, taking money from the same people, you're no longer an opposition party. There's no reason for you to exist. And guess what? Don't be surprised that people don't vote for you. Continue reading →

With only 37 days until Britain leaves the EU, its biggest foreign and trade policy shift in more than 40 years, divisions over Brexit are redrawing the political landscape.

European Union leaders have offered Britain a Brexit extension until May 22.

I'm getting so very tired of safety/accident researchers claiming that root cause analysis is an invalid, blame-focused practice that ignores systems and complexity. Most root cause investigators that I know are pretty well oriented towards process, organization, and system issues as the fundamental sources underlying problems and accidents... and even some of our simplest analysis […]

My previous post about root causes in complex systems, in retrospect, looks a little bit like a rant. That doesn't bother me too much, really... but I wish I had included the following info: it is one way to go about resolving the mess that complex systems can make of your root cause analysis. Basically, when […]

IBM anunció hoy que un 40% de los principales bancos e instituciones financieras en el país cuentan con protección de fraudes en línea que se sustentan en la solución Trusteer de IBM, con la cual la seguridad de los clientes está respaldada al realizar transacciones electrónicas.

IBM suma esfuerzos con Movimiento STEM, una asociación civil sin fines de lucro que busca involucrar a diferentes actores sociales para impulsar la educación en México en Ciencia, Tecnología, Ingeniería y Matemáticas, con enfoque de género.

IBM ha revelado IBM 5 en 5: las 5 innovaciones científicas y tecnológicas que en los próximos 5 años tendrán un gran impacto en la manera que funciona el mundo. Todas ellas suponen una importante evolución en computación como nunca antes se había visto.

Este año IBM cumple 90 años de ser un jugador clave en el progreso de México, impulsando a diferentes generaciones a través de la transformación de industrias y profesiones, e impactando el panorama económico, académico y social del país gracias a la estrecha colaboración con todos los actores de la sociedad.

IBM es y ha sido un jugador clave en el progreso de México, liderando en el transcurso de 90 años a diferentes generaciones a través de la transformación de industrias y profesiones, e impactando el panorama económico, académico y social del país gracias a la estrecha colaboración con todos los actores de la sociedad.

Como parte de las celebraciones del 90 aniversario de IBM en México, la empresa realizó por primera vez en el país, los días 7 y 8 de octubre en el Campus Tecnológico de IBM en Guadalajara, el festival de hackeo para desarrolladores cognitivos: HackaPalooza.

IBM anuncia el lanzamiento de IBM Cloud Private, una plataforma de software creada para los clientes que requieren la flexibilidad y capacidad de una nube pública en un ambiente privado. IBM Cloud Private transforma los sistemas de TI (Tecnologías de la Información) en un ambiente de nube flexible para crear un puente hasta las nubes públicas y acelerar el desarrollo de aplicativos.

IBM reveló un nuevo estudio acerca de la manera en que los profesionales de marketing y ventas están adoptando soluciones cognitivas o de Inteligencia Artificial (IA). A pesar de que el 64% de los Directores de Marketing -CMOs por sus siglas en inglés- y líderes de ventas encuestados cree que sus industrias estarán listas para adoptar ese tipo de tecnologías en los próximos tres años, sólo 24% de los encuestados cree que tiene una estrategia establecida para hacerlo en la actualidad.

La compañía energética BP anunció el lanzamiento de su aplicación móvil BPme, desarrollada con capacidades de inteligencia artificial (IA) de IBM Watson, buscando mejorar constantemente la experiencia de los usuarios de las estaciones de servicio de BP en México.

IBM y Crown Holdings, Inc., proveedor global líder en productos de empaques metálicos, anunciaron hoy la firma de un contrato de varios años que incluye servicios de TI y servicios administrados corriendo en la robusta plataforma de cómputo en la nube de clase empresarial de IBM.

IBM realizó por 5ª ocasión en México la edición del concurso de emprendedores: IBM SmartCamp, organizado por el IBM Global Entrepreneur Program. El evento tuvo lugar en las instalaciones del espacio de co-working, CoWdf, de la Ciudad de México, resultando ganadora del primer lugar la startup Apli.jobs, en tanto que el segundo lugar fue otorgado a la startup Bayonet.io.

Con la finalidad de apoyar el desarrollo de proyectos de alto impacto en la Ciudad de México, la Asociación Mexiana de Ayuda a Niños con Cáncer (AMANC), Fondo Unido México, Fundación Carlos Slim, el Patronato del Museo Nacional de Antropología e IBM, ponen en marcha el día de hoy el programa de consultoría Corporate Service Corps (CSC), en su edición Ciudad de México.

La Universidad Anáhuac México e IBM México celebraron hoy la firma de la Cátedra Corporativa en beneficio de la comunidad universitaria. El acuerdo fue signado por el Dr. Cipriano Sánchez, LC, Rector de la Universidad Anáhuac México y Antonio Martins, Presidente y Gerente General de IBM México.

IBM México anunció hoy el nombramiento de Eduardo Gutiérrez como Presidente y Gerente General de la compañía en el país. El directivo mexicano sucederá a Antonio Martins, quien ha sido nombrado Presidente de IBM Brasil.

Universidad del Valle de México firma convenio de colaboración con IBM México

La UNAM Firma Convenio de Colaboración con IBM México

Less than half of global CEOs believe their enterprises are adequately prepared to handle a highly volatile, increasingly complex business environment, according to a major new survey by IBM of more than 1,500 Chief Executive Officers from 60 countries and 33 industries worldwide, including 22 respondents from New Zealand – the largest number of respondents in eight years of research.

You do something long enough, you'll eventually learn the little things you can do to help interesting stuff happen. One thing I have learned is this phrase:

"I'm a photographer. What can I do to help you?"

Just something as simple as that opens up all kinds of doors and possibilities. This week, it's how I ended up shooting Mexican sodas on a table-top studio in my basement.
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Let's take a moment to talk about the series Exit: The Game, which debuted in the United States in 2016.

Designed by Inka and Marcus Brand and published by Thames and Kosmos, the games are advertised as an Escape Room in a box. In an escape room, you and a group a friends are placed into a room (you may literally be locked in, depending on the fire code of the city where you book the room). Then,  a timer is set, a story is told to you to provide context and atmosphere for your puzzling adventure, and you attempt to solve a series of puzzles, the answers to which will eventually lead you to a key or combination to escape the room - hopefully before time runs out. These rooms typically book for $30+ per person, so the promise of replicating the escape room experience out of a tiny little box for a fraction of the cost is very appealing.

But does Exit: The Game live up to its promise? It does. It absolutely does, with one caveat - some of the games have you puzzling to solve a mystery within the time limit, but you aren't trying to escape anything.

Earlier titles in the series are fairly straightforward. A paper booklet of puzzles; a set each of riddle cards (pair with the booklet to solve the puzzles), answer cards (used to validate puzzle solutions and lead you to new riddle cards),  and help cards (hints for solving the puzzles); a decoder wheel (used to input codes derived from the puzzles); a simple rulebook; and various accessories (usually constructed of cardboard or paper) provide the core of the game experience. Players need to come equipped with scissors (destruction of components is required in nearly every game), pens/pencils, rulers, and a sharp wit to finish the game and calculate their score (measured in stars). The puzzle mechanisms vary, but they will be at least somewhat familiar to players who have done escape rooms or puzzle hunts before.  Depending on the title chosen, the puzzles also vary in difficulty. There is a difficulty rating printed on each box. We found that on average, we finish every Exit title in about 75 minutes; what varies for us across difficulty ratings is how many hint cards we lean on to solve the puzzles.

As the series has progressed in maturity, Inka and Marcus have been able to deliver titles with creative new puzzle mechanisms, changes in solving methodology (such as varying whether the puzzles in the paper booklet must be completed in sequential order or not), and meta puzzles. Meta puzzles are those which you cannot solve without getting a piece of the solution from some or all of the other puzzles included. For example, a puzzle that has you solve for a sentence comprised of words derived from other puzzle solutions is a meta puzzle. A good example of a title from the Exit: The Game series with a meta puzzle is Exit: The Game  - Dead Man on the Orient Express. It includes a meta puzzle that requires players to pay close attention to the passengers, their possessions, and locations throughout the game in order to solve it successfully. That game also introduced envelopes to open as the game progressed and it’s one of the titles that doesn’t see players escaping anything; instead they are trying to issue a code at the end to transmit the identity of a killer to authorities.

By the time the series release of Exit: The Game – The Catacombs of Horror  came around, I really thought the Brands couldn’t have any new tricks up their sleeve. I was wrong. With Catacombs of Horror, they have introduced the two part adventure, giving players a longer puzzling experience in one box. You can play straight through the entire game (allot yourself at least 2 hours) or play the first half and come back to the second half another time. There are also some fantastic new twists on the puzzling mechanisms (a candle is included and must be lit to solve one of the puzzles, for example), and the components got an upgrade (I’m holding onto the adorable little skulls indefinitely). Alongside the puzzle elements, the theming in the series has gotten better and better as new titles are released. Catacombs of Horror provides a well written narrative, albeit very very dark. As we solve puzzles, we find ourselves chasing down what happened to a friend of ours who disappeared into the Catacombs of Paris. It seems he may have met a dark end after having crossed paths with some demonic forces. This title is definitely not for the kiddos, which might be its only drawback. We have clever tweens who enjoy puzzle games, and this isn’t something we can share with them.

There have been at least three more titles released in the Exit: The Game series since Catacombs of Horror  was published in 2018 and more are on the way for 2020. If you’ve previously purchased any of the series, I’d strongly recommend adding Catacombs of Horror  to your must-play list. If this is the first you’ve heard of the series, do yourself a favor, and start with one of the easier titles, such as Exit: The Game – The Sunken Treasure. Then if you have a good time, move onto Exit: The Game – The Pharoh’s Tomb, before sinking your teeth into the most difficult titles like Exit: The Game  - Dead Man on the Orient Express or this one (Exit: The Game – The Catacombs of Horror ).

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Publisher: Thames and Kosmos
Players: 1-4 (we always play with 2)
Actual Playing Time (vs the guideline on the box): About 2 and a half hours
Game type: puzzle, cooperative
Rating:

Jenni’s rating scale:
OUI: I would play this game again; this game is ok. I probably would not buy this game myself but I would play it with those who own it and if someone gave it to me I would keep it.
OUI OUI: I would play this game again; this game is good. I would buy this game.
OUI OUI OUI: I LOVE THIS GAME. I MUST HAVE THIS GAME.
NON: I would not play this game again. I would return this game or give it away if it was given to me.