Contextual Analysis of Large-Scale Biomedical Associations for the Elucidation and Prioritization of Genes and their Roles in Complex Disease

Vast amounts of biomedical associations are easily accessible in public resources, spanning gene-disease associations, tissue-specific gene expression, gene function and pathway annotations, and many other data types. Despite this mass of data, information most relevant to the study of a particular disease remains loosely coupled and difficult to incorporate into ongoing research. Current public databases are difficult to navigate and do not interoperate well due to the plethora of interfaces and varying biomedical concept identifiers used. Because no coherent display of data within a specific problem domain is available, finding the latent relationships associated with a disease of interest is impractical. This research describes a method for extracting the contextual relationships embedded within associations relevant to a disease of interest. After applying the method to a small test data set, a large-scale integrated association network is constructed for application of a network propagation technique that helps uncover more distant latent relationships. Together these methods are adept at uncovering highly relevant relationships without any a priori knowledge of the disease of interest. The combined contextual search and relevance methods power a tool which makes pertinent biomedical associations easier to find, easier to assimilate into ongoing work, and more prominent than currently available databases. Increasing the accessibility of current information is an important component to understanding high-throughput experimental results and surviving the data deluge

A Chandra Study: Are Dwarf Carbon Stars Spun Up and Rejuvenated by Mass Transfer?

Carbon stars (with C/O> 1) were long assumed to all be giants, because only AGB stars dredge up significant carbon into their atmospheres. The case is nearly iron-clad now that the formerly mysterious dwarf carbon (dC) stars are actually far more common than C giants, and have accreted carbon-rich material from a former AGB companion, yielding a white dwarf and a dC star that has gained both significant mass and angular momentum. Some such dC systems have undergone a planetary nebula phase, and some may evolve to become CH, CEMP, or Ba giants. Recent studies indicate that most dCs are likely from older, metal-poor kinematic populations. Given the well-known anti-correlation of age and activity, dCs would not be expected to show significant X-ray emission related to coronal activity. However, accretion spin-up might be expected to rejuvenate magnetic dynamos in these post mass-transfer binary systems. We describe our Chandra pilot study of six dCs selected from the SDSS for Halpha emission and/or a hot white dwarf companion, to test whether their X-ray emission strength and spectral properties are consistent with a rejuvenated dynamo. We detect all 6 dCs in the sample, which have X-ray luminosities ranging from logLx= 28.5 - 29.7, preliminary evidence that dCs may be active at a level consistent with stars that have short rotation periods of several days or less. More definitive results require a sample of typical dCs with deeper X-ray observations to better constrain their plasma temperatures.Comment: 13 pages, 5 figures. Revised and resubmitted June 20, accepted June 21, 2019 to Ap

The Effects of a Pre-Workout Energy Drink on Measures of Physical Performance

The purpose of this study was to investigate the effects of a pre-workout commercial energy drink on parameters of exercise performance, including anaerobic power, muscular endurance, speed, and reaction time. This study used a randomized, double blind, placebo controlled, parallel design. Participants visited the laboratory on two different occasions. On the first visit, participants were assessed for anaerobic power (via a vertical jump test), muscular endurance, reaction time, reactive sprint test, and aerobic power (via a 1.5 mile run). On the second visit, participants were randomly assigned to ingest four ounces of the energy drink beverage or a similar-tasting placebo beverage 30-minutes prior to engaging in these same physical performance tests. The energy drink treatment had no effect on anaerobic power (vertical jump), reaction time, reactive sprint test, or aerobic power. For the push-up to fatigue test, a significant difference (p = 0.014) was observed with the energy drink treatment enhancing performance by 12% as compared to the placebo treatment (improvement of ~ 4%). For the sit-up to fatigue test, a non-significant difference (p = 0.075) was observed with the energy drink treatment resulting in an enhancement of performance by ~13% as compared to no improvement for the placebo treatment. In light of these findings, individuals whose upper-body muscular endurance performance is part of their physical fitness assessment program may benefit from pre-workout energy drink consumption. In contrast, individuals needing to demonstrate anaerobic/aerobic power, or reactive abilities should not expect an improvement in performance from pre-workout energy drink consumption

A systematic comparison of genome-scale clustering algorithms

Background: A wealth of clustering algorithms has been applied to gene co-expression experiments. These algorithms cover a broad range of approaches, from conventional techniques such as k-means and hierarchical clustering, to graphical approaches such as k-clique communities, weighted gene co-expression networks (WGCNA) and paraclique. Comparison of these methods to evaluate their relative effectiveness provides guidance to algorithm selection, development and implementation. Most prior work on comparative clustering evaluation has focused on parametric methods. Graph theoretical methods are recent additions to the tool set for the global analysis and decomposition of microarray co-expression matrices that have not generally been included in earlier methodological comparisons. In the present study, a variety of parametric and graph theoretical clustering algorithms are compared using well-characterized transcriptomic data at a genome scale from Saccharomyces cerevisiae. Methods: For each clustering method under study, a variety of parameters were tested. Jaccard similarity was used to measure each clusters agreement with every GO and KEGG annotation set, and the highest Jaccard score was assigned to the cluster. Clusters were grouped into small, medium, and large bins, and the Jaccard score of the top five scoring clusters in each bin were averaged and reported as the best average top 5 (BAT5) score for the particular method. Results: Clusters produced by each method were evaluated based upon the positive match to known pathways. This produces a readily interpretable ranking of the relative effectiveness of clustering on the genes. Methods were also tested to determine whether they were able to identify clusters consistent with those identified by other clustering methods. Conclusions: Validation of clusters against known gene classifications demonstrate that for this data, graph-based techniques outperform conventional clustering approaches, suggesting that further development and application of combinatorial strategies is warranted

A nonclassical non-Vα14Jα18 CD1d-restricted (type II) NKT cell is sufficient for down-regulation of tumor immunosurveillance

The importance of immunoregulatory T cells has become increasingly apparent. Both CD4+CD25+ T cells and CD1d-restricted NKT cells have been reported to down-regulate tumor immunity in mouse tumor models. However, the relative roles of both T cell populations have rarely been clearly distinguished in the same tumor models. In addition, CD1d-restricted NKT cells have been reported to play a critical role not only in the down-regulation of tumor immunity but also in the promotion of the immunity. However, the explanation for these apparently opposite roles in different tumor models remains unclear. We show that in four mouse tumor models in which CD1d-restricted NKT cells play a role in suppression of tumor immunity, depletion of CD4+CD25+ T cells did not induce enhancement of immunosurveillance. Surprisingly, among the two subpopulations of CD1d-restricted NKT cells, Vα14Jα18+ (type I) and Vα14Jα18− (type II) NKT cells, type I NKT cells were not necessary for the immune suppression. These unexpected results may now resolve the paradox in the role of CD1d-restricted NKT cells in the regulation of tumor immunity, in that type II NKT cells may be sufficient for negative regulation, whereas protection has been found to be mediated by α-galactosylceramide–responsive type I NKT cells

Mediators of Monocyte Migration in Response to Recovery Modalities following Resistance Exercise

Mediators of monocyte migration, complement receptor-3 (CR3), and chemokine ligand-4 (CCL4) were measured in response to recovery modalities following resistance exercise. Thirty resistance-trained men (23.1 +/- 2.9 y; 175.2 +/- 7.1 cm; 82.1 +/- 8.4 kg) were given neuromuscular electric stimulation (NMES), cold water immersion (CWI), or control (CON) treatments immediately following resistance exercise. Blood samples were obtained preexercise (PRE), immediately (IP), 30 minutes (30 P), 24 hours (24 H), and 48 hours (48 H) after exercise for measurement of circulating CCL4 and CR3 expression on CD14+ monocytes, by assay and flow cytometry. Circulating CCL4 showed no consistent changes. Inferential analysis indicated that CR3 expression was likely greater in CON at 30 P than NMES (90.0%) or CWI (86.8%). NMES was likely lower than CON at 24H (92.9%) and very likely lower at 48H (98.7%). Expression of CR3 following CWI was very likely greater than CON (96.5%) at 24H. The proportion of CR3+ monocytes was likely greater following CWI than NMES (85.8%) or CON (85.2%) at 24 H. The change in proportion of CR3+ monocytes was likely (86.4%) greater following NMES than CON from IP to 30 P. The increased expression of CR3 and increased proportion of CR3+ monocytes following CWI at 24 H indicate a potentially improved ability for monocyte adhesion to the endothelium, possibly improving phagocytosis of damaged tissues

Exploration Technologies for Operations

Although the International Space Station (ISS) assembly has been completed, the Operations support teams continue to seek more efficient and effective ways to prepare for and conduct the ISS operations and future exploration missions beyond low earth orbit. This search for improvement has led to a significant collaboration between the NASA research and advanced software development community at NASA Ames Research Center and the Mission Operations community at NASA Johnson Space Center. Since 2001, NASA Ames Research Center has been developing and applying its advanced intelligent systems and human systems integration research to mission operations tools for several of the unmanned Mars missions operations. Since 2006, NASA Ames Research Center has also been developing and applying its advanced intelligent systems and human systems integration research to mission operations tools for manned operations support with the Mission Operations Directorate at NASA Johnson Space Center. This paper discusses the completion of the development and deployment of a variety of intelligent and human systems technologies adopted for manned mission operations. The technologies associated with the projects include advanced software systems for operations and human-centered computing. Human-centered computing looks to the processes and procedures that people do to perform any given job, then attempts to identify opportunities to improve these processes and procedures. In particular, for mission operations, improvements are quantified by specifically identifying how a tool can increase a persons efficiency, enhance a persons functional capability, andor improve the assurance of a persons decisions. The Ames development team has collaborated with the Mission Operations team to identify areas of efficiencies through technology infusion applications in support of the Plan, Train, and Fly activities of human-spaceflight mission operations. The specific applications discussed in this paper are in the areas of mission planning systems, mission operations design modeling and workflow automation, advanced systems monitoring, mission control technologies, search tools, training management tools, spacecraft solar array management, spacecraft power management, and spacecraft attitude planning. We discuss these specific projects between the Ames Research Center and the Johnson Space Centers Mission Operations Directorate, and how these technologies and projects are enhancing the mission operations support for the International Space Station. We also discuss the challenges, problems, and successes associated with long-distance and multi-year development projects between the research team at Ames and the Mission Operations customers at Johnson Space center. Finally, we discuss how these technology infusion applications and underlying technologies might be used in the future to support on-board operations of the crew and spacecraft systems as human exploration expands beyond low earth orbit to destinations in the solar system where communications delays will require more on-board autonomy and planning by the crew. Longer communications delays will require that the ground mission operations support will be primarily strategic in nature, while the tactical level of planning, systems monitoring and control, and failure analysisisolationrecovery will be the responsibility of both the spacecraft autonomous systems and the crew. Our expectation is that the technologie

Electrochemical Quantification of D-Glucose during the Production of Bioethanol from Thermo-Mechanically Pre-treated Wheat Straw

Mechanical pre-treatment (disc refining) of wheat straw, at both atmospheric and elevated pressure, is shown to be an efficient process to access fermentable monosaccharides, with the potential to integrate within the infrastructure of existing first-generation bioethanol plants. The mild, enzymatic degradation of this sustainable lignocellulosic biomass affords ca. 0.10-0.13 g/g (dry weight) of D-glucose quantifiable voltammetrically in real time, over a two hundred-fold range in experimental laboratory scales (25 mL to 5.0 L), with pressure disc refining of the wheat straw enabling almost twice the amount of D-glucose to be generated during the hydrolysis stage than experiments using atmospheric refining (0.06 – 0.09 g/g dry weight). Fermentation of the resulting hydrolysate affords 0.08 – 0.10 g/g (dry weight) of ethanol over similar scales, with ethanol productivity at ca. 37 mg/(L h). These results demonstrate that minimal cellulose decomposition occurs during pressure refining of wheat straw, in contrast to hemicellulose, and suggest that the development of green, mechanochemical processes for the scalable and cost-effective manufacture of second-generation bioethanol requires improved cellulose decomposition

Preparation and Integration of ALHAT Precision Landing Technology for Morpheus Flight Testing

The Autonomous precision Landing and Hazard Avoidance Technology (ALHAT) project has developed a suite of prototype sensors for enabling autonomous and safe precision land- ing of robotic or crewed vehicles on solid solar bodies under varying terrain lighting condi- tions. The sensors include a Lidar-based Hazard Detection System (HDS), a multipurpose Navigation Doppler Lidar (NDL), and a long-range Laser Altimeter (LAlt). Preparation for terrestrial ight testing of ALHAT onboard the Morpheus free- ying, rocket-propelled ight test vehicle has been in progress since 2012, with ight tests over a lunar-like ter- rain eld occurring in Spring 2014. Signi cant work e orts within both the ALHAT and Morpheus projects has been required in the preparation of the sensors, vehicle, and test facilities for interfacing, integrating and verifying overall system performance to ensure readiness for ight testing. The ALHAT sensors have undergone numerous stand-alone sensor tests, simulations, and calibrations, along with integrated-system tests in special- ized gantries, trucks, helicopters and xed-wing aircraft. A lunar-like terrain environment was constructed for ALHAT system testing during Morpheus ights, and vibration and thermal testing of the ALHAT sensors was performed based on Morpheus ights prior to ALHAT integration. High- delity simulations were implemented to gain insight into integrated ALHAT sensors and Morpheus GN&C system performance, and command and telemetry interfacing and functional testing was conducted once the ALHAT sensors and electronics were integrated onto Morpheus. This paper captures some of the details and lessons learned in the planning, preparation and integration of the individual ALHAT sen- sors, the vehicle, and the test environment that led up to the joint ight tests