RAS-mediated tumor stress adaptation and the targeting opportunities it presents

Cellular stress is known to function in synergistic cooperation with oncogenic mutations during tumorigenesis to drive cancer progression. Oncogenic RAS is a strong inducer of a variety of pro-tumorigenic cellular stresses, and also enhances the ability of cells to tolerate these stresses through multiple mechanisms. Many of these oncogenic, RAS-driven, stress-adaptive mechanisms have also been implicated in tolerance and resistance to chemotherapy and to therapies that target the RAS pathway. Understanding how oncogenic RAS shapes cellular stress adaptation and how this functions in drug resistance is of vital importance for identifying new therapeutic targets and therapeutic combinations to treat RAS-driven cancers

A Panchromatic View OF NGC 602: Time-Resolved Star Formation with the Hubble and Spitzer Space Telescopes

We present the photometric catalogs for the star-forming cluster NGC 602 in the wing of the Small Magellanic Cloud covering a range of wavelengths from optical HST/ACS (F555W, F814W) and SMARTS/ANDICAM (V, I) to infrared (Spitzer/IRAC 3.6, 4.5, 5.8, and 8 micron and MIPS 24 micron). Combining this with IRSF (InfraRed Survey Facility) near-infrared photometry (J, H, Ks), we compare the young main sequence (MS) and pre-main sequence (PMS) populations prominent in the optical with the current young stellar object (YSO) populations revealed by the infrared (IR). We analyze the MS and PMS population with isochrones in color-magnitude diagrams to derive ages and masses. The optical data reveal ~565 PMS candidates, low mass Stage III YSOs. We characterize ~40 YSOs by fitting their spectral energy distributions (SEDs) to a grid of models (Robitaille et al. 2007) to derive luminosities, masses and evolutionary phase (Stage I-III). The higher resolution HST images reveal that ~70% of the YSO candidates are either multiples or protoclusters. For YSOs and PMS sources found in common, we find a consistency in the masses derived. We use the YSO mass function to derive a present-day star-formation rate of ~0.2-1.0 Msun/yr/kpc^2, similar to the rate derived from the optical star formation history suggesting a constant star formation rate for this region. We demonstrate a progression of star formation from the optical star cluster center to the edge of the star forming dust cloud. We derive lifetimes of a few 10^5 years for the YSO Stages I and II.Comment: 55 pages, 18 Figures; High resolution images available form author Accepted to Ap

Experiences and perceptions about cause and prevention of cardiovascular disease among people with cardiometabolic conditions: findings of in-depth interviews from a peri-urban Nepalese community

Background: Nepal currently faces an increasing burden of cardiovascular disease (CVD). Earlier studies on health literacy and the behavior dimension of cardiovascular health reported a substantial gap between knowledge and practice. Objective: This qualitative study aimed to deepen understanding of the community perspective on cardiovascular health from the patients’ viewpoint. Design: We conducted in-depth interviews (IDIs) with 13 individuals with confirmed heart disease, hypertension, or diabetes mellitus. All participants provided verbal consent. We used an IDI guide to ask respondents about their perception and experiences with CVD, particularly regarding causation and preventability. We manually applied qualitative content analysis to evaluate the data and grouped similar content into categories and subcategories. Results: Respondents perceived dietary factors, particularly consumption of salty, fatty, and oily food, as the main determinants of CVD. Similarly, our respondents unanimously linked smoking, alcohol intake, and high blood pressure with cardiac ailments but reported mixed opinion regarding the causal role of body weight and physical inactivity. Although depressed and stressed at the time of diagnosis, respondents learned to handle their situation better over time. Despite good family support for health care, the financial burden of disease was a major issue. All respondents understood the importance of lifestyle modification and relied upon health professionals for information and motivation. Respondents remarked that community awareness of CVD was inadequate and that medical doctors or trained local people should help increase awareness. Conclusions: This study provided insight into the perceptions of patients regarding CVD. Respondents embraced the importance of lifestyle modification only after receiving their diagnosis. Although better health care is important in terms of aiding patients to better understand and cope with their disease, interventions should be tailored to improve the community's cardiovascular health literacy and preventive practices

Origins Space Telescope: trades and decisions leading to the baseline mission concept

International audienceThe Origins Space Telescope will trace the history of our origins from the time dust and heavy elements permanently altered the cosmic landscape to present-day life. How did galaxies evolve from the earliest galactic systems to those found in the universe today? How do habitable planets form? How common are life-bearing worlds? We describe how Origins was designed to answer these alluring questions. We discuss the key decisions taken by the Origins mission concept study team, the rationale for those choices, and how they led through an exploratory design process to the Origins baseline mission concept. To understand the concept solution space, we studied two distinct mission concepts and descoped the second concept, aiming to maximize science per dollar and hit a self-imposed cost target. We report on the study approach and describe the concept evolution. The resulting baseline design includes a 5.9-m diameter telescope cryocooled to 4.5 K and equipped with three scientific instruments. The chosen architecture is similar to that of the Spitzer Space Telescope and requires very few deployments after launch. The cryo-thermal system design leverages James Webb Space Telescope technology and experience