Telescience testbedding: An implementation approach

Telescience is the term used to describe a concept being developed by NASA's Office of Space Science and Applications (OSSA) under the Science and Applications Information System (SAIS) Program. This concept focuses on the development of an ability for all OSSA users to be remotely interactive with all provided information system services for the Space Station era. This concept includes access to services provided by both flight and ground components of the system and emphasizes the accommodation of users from their home institutions. Key to the development of the telescience capability is an implementation approach called rapid-prototype testbedding. This testbedding is used to validate the concept and test the applicability of emerging technologies and operational methodologies. Testbedding will be used to first determine the feasibility of an idea and then the applicability to real science usage. Once a concept is deemed viable, it will be integrated into the operational system for real time support. It is believed that this approach will greatly decrease the expense of implementing the eventual system and will enhance the resultant capabilities of the delivered system

Participation in Special Olympics and Change in Athlete Self-Concept Over 42 Months

The present study investigated changes in the self-concept of 49 athletes with intellectual disabilities participating in traditional Special Olympics over a 42-month period. Athletes were interviewed to assess their perceived general self-worth, physical competence and social acceptance, and involvement in Special Olympics, which was operationalized through an overall standard score combining a number of components. After controlling for baseline levels of self-worth and involvement in Special Olympics, changes in involvement in Special Olympics predicted improved general self-worth. After adjustment for baseline levels of perceived physical competence and involvement in Special Olympics, changes in involvement in Special Olympics predicted perceived physical competence at 42 months.Special Olympics Canada, Canadian Institutes of Health Researc

Dissipation in Compressible MHD Turbulence

We report results of a three dimensional, high resolution (up to 512^3) numerical investigation of supersonic compressible magnetohydrodynamic turbulence. We consider both forced and decaying turbulence. The model parameters are appropriate to conditions found in Galactic molecular clouds. We find that the dissipation time of turbulence is of order the flow crossing time or smaller, even in the presence of strong magnetic fields. About half the dissipation occurs in shocks. Weak magnetic fields are amplified and tangled by the turbulence, while strong fields remain well ordered.Comment: 5 pages, 3 Postscript figures, LaTeX, accepted by Ap.J.Let

Deducing topology of protein-protein interaction networks from experimentally measured sub-networks.

BackgroundProtein-protein interaction networks are commonly sampled using yeast two hybrid approaches. However, whether topological information reaped from these experimentally-measured sub-networks can be extrapolated to complete protein-protein interaction networks is unclear.ResultsBy analyzing various experimental protein-protein interaction datasets, we found that they are not random samples of the parent networks. Based on the experimental bait-prey behaviors, our computer simulations show that these non-random sampling features may affect the topological information. We tested the hypothesis that a core sub-network exists within the experimentally sampled network that better maintains the topological characteristics of the parent protein-protein interaction network. We developed a method to filter the experimentally sampled network to result in a core sub-network that more accurately reflects the topology of the parent network. These findings have fundamental implications for large-scale protein interaction studies and for our understanding of the behavior of cellular networks.ConclusionThe topological information from experimental measured networks network as is may not be the correct source for topological information about the parent protein-protein interaction network. We define a core sub-network that more accurately reflects the topology of the parent network

The Ca2+ transient as a feedback sensor controlling cardiomyocyte ionic conductances in mouse populations.

Conductances of ion channels and transporters controlling cardiac excitation may vary in a population of subjects with different cardiac gene expression patterns. However, the amount of variability and its origin are not quantitatively known. We propose a new conceptual approach to predict this variability that consists of finding combinations of conductances generating a normal intracellular Ca2+ transient without any constraint on the action potential. Furthermore, we validate experimentally its predictions using the Hybrid Mouse Diversity Panel, a model system of genetically diverse mouse strains that allows us to quantify inter-subject versus intra-subject variability. The method predicts that conductances of inward Ca2+ and outward K+ currents compensate each other to generate a normal Ca2+ transient in good quantitative agreement with current measurements in ventricular myocytes from hearts of different isogenic strains. Our results suggest that a feedback mechanism sensing the aggregate Ca2+ transient of the heart suffices to regulate ionic conductances

Nonlinear analysis of the heartbeats in public patient ECGs using an automated PD2i algorithm for risk stratification of arrhythmic death

Heart rate variability (HRV) reflects both cardiac autonomic function and risk of arrhythmic death (AD). Reduced indices of HRV based on linear stochastic models are independent risk factors for AD in post-myocardial infarct cohorts. Indices based on nonlinear deterministic models have a significantly higher sensitivity and specificity for predicting AD in retrospective data. A need exists for nonlinear analytic software easily used by a medical technician. In the current study, an automated nonlinear algorithm, the time-dependent point correlation dimension (PD2i), was evaluated. The electrocardiogram (ECG) data were provided through an National Institutes of Health-sponsored internet archive (PhysioBank) and consisted of all 22 malignant arrhythmia ECG files (VF/VT) and 22 randomly selected arrhythmia files as the controls. The results were blindly calculated by automated software (Vicor 2.0, Vicor Technologies, Inc., Boca Raton, FL) and showed all analyzable VF/VT files had PD2i < 1.4 and all analyzable controls had PD2i > 1.4. Five VF/VT and six controls were excluded because surrogate testing showed the RR-intervals to contain noise, possibly resulting from the low digitization rate of the ECGs. The sensitivity was 100%, specificity 85%, relative risk > 100; p < 0.01, power > 90%. Thus, automated heartbeat analysis by the time-dependent nonlinear PD2i-algorithm can accurately stratify risk of AD in public data made available for competitive testing of algorithms

Place of birth, duration of residence, neighborhood immigrant composition and body mass index in New York City

<p>Abstract</p> <p>Background</p> <p>Past research has suggested that changes in culture explain the substantial weight gain seen in many immigrant groups with length of residence in the U.S. and across generations of residence in the U.S. However, it has been theorized that those settling in immigrant and co-ethnic neighborhoods may be buffered against this acculturative process and will be more likely to maintain home country dietary and physical activity patterns. To investigate this theory we incorporated measures of neighborhood immigrant composition into analyses of individual's body mass index (BMI) and generation of immigration and duration of residence in the U.S.</p> <p>Methods</p> <p>Multilevel analyses were performed using objectively measured height and weight and survey data on diet and physical activity from a sample of 13,011 residents of New York City. Census data were used to calculate the proportion of foreign-born residents and extent of household linguistic isolation in a ½ mile radial buffer around the subject's home.</p> <p>Results</p> <p>Foreign birth was associated with a significantly lower BMI (-1.09 BMI units, P < 0.001). This association was weakest among Asians (-0.66 BMI units, P = 0.08) and strongest among Black-Caribbeans (-1.41 BMI units, P = 0.07). After controlling for individual level variables, neighborhood proportion foreign-born was not associated with BMI, but increasing neighborhood linguistic isolation was inversely associated with BMI among Hispanics (-2.97 BMI units, P = 0.03). Furthermore among Hispanics, the association between foreign birth and BMI was stronger in low linguistic isolation neighborhoods (-1.36 BMI units, P < 0.0001) as compared to in high linguistic isolation levels (-0.42 BMI units, P = 0.79). Increasing duration of residence in the U.S. was significantly associated with higher BMI overall and among Hispanics.</p> <p>Conclusion</p> <p>The analyses suggest that acculturation is associated with weight gain, and that neighborhood characteristics are only associated with BMI among Hispanics. However, we suggest that changes in body size currently interpreted as post-migration effects of acculturation to U.S. norms may in fact reflect changes in norms that are taking place internationally.</p

Targeting the vasopressin type-2 receptor for renal cell carcinoma therapy.

Arginine vasopressin (AVP) and its type-2 receptor (V2R) play an essential role in the regulation of salt and water homeostasis by the kidneys. V2R activation also stimulates proliferation of renal cell carcinoma (RCC) cell lines in vitro. The current studies investigated V2R expression and activity in human RCC tumors, and its role in RCC tumor growth. Examination of the cancer genome atlas (TCGA) database, and analysis of human RCC tumor tissue microarrays, cDNA arrays and tumor biopsy samples demonstrated V2R expression and activity in clear cell RCC (ccRCC). In vitro, V2R antagonists OPC31260 and Tolvaptan, or V2R gene silencing reduced wound closure and cell viability of 786-O and Caki-1 human ccRCC cell lines. Similarly in mouse xenograft models, Tolvaptan and OPC31260 decreased RCC tumor growth by reducing cell proliferation and angiogenesis, while increasing apoptosis. In contrast, the V2R agonist dDAVP significantly increased tumor growth. High intracellular cAMP levels and ERK1/2 activation were observed in human ccRCC tumors. In mouse tumors and Caki-1 cells, V2R agonists reduced cAMP and ERK1/2 activation, while dDAVP treatment had the reverse effect. V2R gene silencing in Caki-1 cells also reduced cAMP and ERK1/2 activation. These results provide novel evidence for a pathogenic role of V2R signaling in ccRCC, and suggest that inhibitors of the AVP-V2R pathway, including the FDA-approved drug Tolvaptan, could be utilized as novel ccRCC therapeutics

Gene expression in Leishmania is regulated predominantly by gene dosage

ABSTRACT Leishmania tropica, a unicellular eukaryotic parasite present in North and East Africa, the Middle East, and the Indian subcontinent, has been linked to large outbreaks of cutaneous leishmaniasis in displaced populations in Iraq, Jordan, and Syria. Here, we report the genome sequence of this pathogen and 7,863 identified protein-coding genes, and we show that the majority of clinical isolates possess high levels of allelic diversity, genetic admixture, heterozygosity, and extensive aneuploidy. By utilizing paired genome-wide high-throughput DNA sequencing (DNA-seq) with RNA-seq, we found that gene dosage, at the level of individual genes or chromosomal “somy” (a general term covering disomy, trisomy, tetrasomy, etc.), accounted for greater than 85% of total gene expression variation in genes with a 2-fold or greater change in expression. High gene copy number variation (CNV) among membrane-bound transporters, a class of proteins previously implicated in drug resistance, was found for the most highly differentially expressed genes. Our results suggest that gene dosage is an adaptive trait that confers phenotypic plasticity among natural Leishmania populations by rapid down- or upregulation of transporter proteins to limit the effects of environmental stresses, such as drug selection. IMPORTANCE Leishmania is a genus of unicellular eukaryotic parasites that is responsible for a spectrum of human diseases that range from cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL) to life-threatening visceral leishmaniasis (VL). Developmental and strain-specific gene expression is largely thought to be due to mRNA message stability or posttranscriptional regulatory networks for this species, whose genome is organized into polycistronic gene clusters in the absence of promoter-mediated regulation of transcription initiation of nuclear genes. Genetic hybridization has been demonstrated to yield dramatic structural genomic variation, but whether such changes in gene dosage impact gene expression has not been formally investigated. Here we show that the predominant mechanism determining transcript abundance differences (>85%) in Leishmania tropica is that of gene dosage at the level of individual genes or chromosomal somy