Tumor radiation therapy creates therapeutic vaccine responses to the colorectal cancer antigen GUCY2C.

PURPOSE: Radiation therapy (RT) is thought to produce clinical responses in cancer patients, not only through direct toxicity to cancer cells and supporting tumor stroma cells, but also through activation of immunologic effectors. More recently, RT has potentiated the local and systemic effects of cancer immunotherapy (IT). However, combination regimens that maximize immunologic and clinical efficacy remain undefined. METHODS AND MATERIALS: We evaluated the impact of local RT on adenoviral-mediated vaccination against the colorectal cancer antigen GUCY2C (Ad5-GUCY2C) in a murine subcutaneous tumor model using mouse CT26 colon cancer cells (CT26-GUCY2C). Immune responses were assessed by ELISpot, and clinical responses were assessed by tumor size and incidence. RESULTS: The specific sequence of tumor-directed RT preceding Ad5-GUCY2C IT transformed inactive therapeutic Ad5-GUCY2C vaccination into a curative vaccine. GUCY2C-specific T cell responses were amplified (P CONCLUSIONS: Optimal sequencing of RT and IT amplifies antigen-specific local and systemic immune responses, revealing novel acute and long-term therapeutic antitumor protection. These observations underscore the importance of modality sequence optimization before the initiation of clinical trials of RT and IT to maximize immune and antitumor responses

Wellness and Multiple Sclerosis: The National MS Society Establishes a Wellness Research Working Group and Research Priorities

Background: People with multiple sclerosis (MS) have identified “wellness” and associated behaviors as a high priority based on “social media listening” undertaken by the National MS Society (i.e. the Society). Objective: The Society recently convened a group that consisted of researchers with experience in MS and wellness-related research, Society staff members, and an individual with MS for developing recommendations regarding a wellness research agenda. Method: The members of the group engaged in focal reviews and discussions involving the state of science within three approaches for promoting wellness in MS, namely diet, exercise, and emotional wellness. Results: That process informed a group-mediated activity for developing and prioritizing research goals for wellness in MS. This served as a background for articulating the mission and objectives of the Society’s Wellness Research Working Group. Conclusion: The primary mission of the Wellness Research Working Group is the provision of scientific evidence supporting the application of lifestyle, behavioral, and psychosocial approaches for promoting optimal health of mind, body, and spirit (i.e. wellness) in people with MS as well as managing the disease and its consequences

Quantitative Global Heat Transfer in a Mach-6 Quiet Tunnel

This project developed quantitative methods for obtaining heat transfer from temperature sensitive paint (TSP) measurements in the Mach-6 quiet tunnel at Purdue, which is a Ludwieg tube with a downstream valve, moderately-short flow duration and low levels of heat transfer. Previous difficulties with inferring heat transfer from TSP in the Mach-6 quiet tunnel were traced to (1) the large transient heat transfer that occurs during the unusually long tunnel startup and shutdown, (2) the non-uniform thickness of the insulating coating, (3) inconsistencies and imperfections in the painting process and (4) the low levels of heat transfer observed on slender models at typical stagnation temperatures near 430K. Repeated measurements were conducted on 7 degree-half-angle sharp circular cones at zero angle of attack in order to evaluate the techniques, isolate the problems and identify solutions. An attempt at developing a two-color TSP method is also summarized

Characterization of traverse slippage experienced by Spirit rover on Husband Hill at Gusev crater

Spirit rover experienced significant slips traversing Husband Hill. This paper analyzes the slippage Spirit experienced from Sol 154 to Sol 737. Slippage with respect to terrain type and slope is computed using data downlinked from the rover, rover position, and orientation estimations from visual odometry (VO) and photogrammetry based bundle adjustment (BA) method. Accumulated slippage reached a maximum of 83.86 m on Sol 648. However, as Spirit descended into the Inner Basin, the direction of slippage reversed, and accumulated slippage approached zero by the end of the entire traverse. Eight local regions with significant slips and nineteen traverse segments have been analyzed. Slippage was found to be highly correlated to slope direction and magnitude; the reverse of slope directions in the ascending and descending portions of the traverse proves to be the main contributor to the observed cancellation of slippage. While the horizontal component of the slippage almost canceled out, the difference in elevation continually accumulated, mainly during the ascent. In general, long traverse segments created more slips than short ones. This is reflected in both the accumulated and individual slippages. In considering the four major Mars terrain types, Spirit performed best on bedrock, managing to drive on slopes close to 30°. Fine-grain surfaces were the most challenging; though progress was made on slopes up to 15°, slippages of over 100% (more slippage than distance traveled) occurred for short segments. The results of this work can be incorporate into a traverse planning framework in which rover slippage is minimized. Results can be employed in landed planetary missions for precision navigation to avoid potentially dangerous regions by considering expected slippage

Rheumatic heart disease in pregnancy: strategies and lessons learnt implementing a population-based study in Australia

Background The global burden of rheumatic heart disease (RHD) is two-to-four times higher in women, with a heightened risk in pregnancy. In Australia, RHD is found predominantly among Aboriginal and Torres Strait Islander peoples. Methods This paper reviews processes developed to identify pregnant Australian women with RHD during a 2-year population-based study using the Australasian Maternity Outcomes Surveillance System (AMOSS). It evaluates strategies developed to enhance reporting and discusses implications for patient care and public health. Results AMOSS maternity coordinators across 262 Australian sites reported cases. An extended network across cardiac, Aboriginal and primary healthcare strengthened surveillance and awareness. The network notified 495 potential cases, of which 192 were confirmed. Seventy-eight per cent were Aboriginal and/or Torres Strait Islander women, with a prevalence of 22 per 1000 in the Northern Territory. Discussion Effective surveillance was challenged by a lack of diagnostic certainty, incompatible health information systems and varying clinical awareness among health professionals. Optimal outcomes for pregnant women with RHD demand timely diagnosis and access to collaborative care. Conclusion The strategies employed by this study highlight gaps in reporting processes and the opportunity pregnancy provides for diagnosis and re/engagement with health services to support better continuity of care and promote improved outcomes.The authors gratefully acknowledge aid from the Australian National Health and Medical Research Council (NHMRC) project grant #1024206 and NHMRC Postgraduate Scholarship #11332944; University of Technology Sydney Chancellor’s Research Scholarship; and END RHD Centre of Research Excellence, Telethon Kids Institute, University of Western Australia

Exoplanet Atmosphere Measurements from Transmission Spectroscopy and other Planet-Star Combined Light Observations

It is possible to learn a great deal about exoplanet atmospheres even when we cannot spatially resolve the planets from their host stars. In this chapter, we overview the basic techniques used to characterize transiting exoplanets - transmission spectroscopy, emission and reflection spectroscopy, and full-orbit phase curve observations. We discuss practical considerations, including current and future observing facilities and best practices for measuring precise spectra. We also highlight major observational results on the chemistry, climate, and cloud properties of exoplanets.Comment: Accepted review chapter; Handbook of Exoplanets, eds. Hans J. Deeg and Juan Antonio Belmonte (Springer-Verlag). 22 pages, 6 figure

Methodological implementation of mixed linear models in multi-locus genome-wide association studies

The mixed linear model has been widely used in genome-wide association studies (GWAS), but its application to multi-locus GWAS analysis has not been explored and assessed. Here, we implemented a fast multi-locus random-SNP-effect EMMA (FASTmrEMMA) model for GWAS. The model is built on random single nucleotide polymorphism (SNP) effects and a new algorithm. This algorithm whitens the covariance matrix of the polygenic matrix K and environmental noise, and specifies the number of nonzero eigenvalues as one. The model first chooses all putative quantitative trait nucleotides (QTNs) with ≤ 0.005 P-values and then includes them in a multi-locus model for true QTN detection. Owing to the multi-locus feature, the Bonferroni correction is replaced by a less stringent selection criterion. Results from analyses of both simulated and real data showed that FASTmrEMMA is more powerful in QTN detection and model fit, has less bias in QTN effect estimation and requires a less running time than existing single- and multi-locus methods, such as empirical Bayes, settlement of mixed linear model under progressively exclusive relationship (SUPER), efficient mixed model association (EMMA), compressed MLM (CMLM) and enriched CMLM (ECMLM). FASTmrEMMA provides an alternative for multi-locus GWAS

Divergence of Arctic shrub growth associated with sea ice decline

Arctic sea ice extent (SIE) is declining at an accelerating rate with a wide range of ecological consequences. However, determining sea ice effects on tundra vegetation remains a challenge. In this study, we examined the universality or lack thereof in tundra shrub growth responses to changes in SIE and summer climate across the Pan-Arctic, taking advantage of 23 tundra shrub-ring chronologies from 19 widely distributed sites (56°N to 83°N). We show a clear divergence in shrub growth responses to SIE that began in the mid-1990s, with 39% of the chronologies showing declines and 57% showing increases in radial growth (decreasers and increasers, respectively). Structural equation models revealed that declining SIE was associated with rising air temperature and precipitation for increasers and with increasingly dry conditions for decreasers. Decreasers tended to be from areas of the Arctic with lower summer precipitation and their growth decline was related to decreases in the standardized precipitation evapotranspiration index. Our findings suggest that moisture limitation, associated with declining SIE, might inhibit the positive effects of warming on shrub growth over a considerable part of the terrestrial Arctic, thereby complicating predictions of vegetation change and future tundra productivity

Genetic risk for autism spectrum disorders and neuropsychiatric variation in the general population

Almost all genetic risk factors for autism spectrum disorders (ASDs) can be found in the general population, but the effects of that risk are unclear in people not ascertained for neuropsychiatric symptoms. Using several large ASD consortia and population based resources, we find genetic links between ASDs and typical variation in social behavior and adaptive functioning. This finding is evidenced through both inherited and de novo variation, indicating that multiple types of genetic risk for ASDs influence a continuum of behavioral and developmental traits, the severe tail of which can result in an ASD or other neuropsychiatric disorder diagnosis. A continuum model should inform the design and interpretation of studies of neuropsychiatric disease biology