Worst case analysis: Earth sensor assembly for the tropical rainfall measuring mission observatory

This worst case analysis verifies that the TRMMESA electronic design is capable of maintaining performance requirements when subjected to worst case circuit conditions. The TRMMESA design is a proven heritage design and capable of withstanding the most worst case and adverse of circuit conditions. Changes made to the baseline DMSP design are relatively minor and do not adversely effect the worst case analysis of the TRMMESA electrical design

Peptide Antigen Concentration Modulates Digital NFAT1 Activation in Primary Mouse Naive CD8(+) T Cells as Measured by Flow Cytometry of Isolated Cell Nuclei

Circulating naive T cells exist in a quiescent state. After TCR contact with the cognate peptide presented by APCs in secondary lymphoid structures, T cells undergo a period of rapid transcriptional changes that set the stage for fate-determining effector or memory programming. We describe a novel method to analyze TCR signaling pathway activation in nuclei isolated from primary mouse naive T cells after stimulation with natural peptide Ags. We prelabeled cells with cell tracking dye to easily distinguish CD8(+) T cell nuclei from APC nuclei by conventional flow cytometry. Using this approach, we observed clear digital activation of NFAT1 transcription factor in OT-I T cells stimulated with OVA peptide presented by bulk splenocytes. OVA concentration had discrete control over the fraction of the cells that translocated NFAT1, indicating that a distinct threshold amount of TCR signaling is required to switch on NFAT1 in naive T cells. This behavior was cell contact dependent and qualitatively more exact than the NFAT1 response in ionomycin-stimulated naive T cells. These data contribute to our understanding of the digital behavior of TCR signaling components documented in other studies and indicate how T cells might discriminate log-fold changes in Ag availability during an actual infection. Overall, these results highlight the potential of this coculture nuclei isolation protocol to address stimulation-dependent translocation of proteins in primary lymphocytes

NASA advanced design program: Analysis, design, and construction of a solar powered aircraft

Increase in energy demands coupled with rapid depletion of natural energy resources have deemed solar energy as the most logical alternative source of power. The major objective of this project was to build a solar powered remotely controlled aircraft to demonstrate the feasibility of solar energy as an effective, alternate source of power. The final design was optimized for minimum weight and maximum strength of the structure. These design constraints necessitated a carbon fiber composite structure. Surya is a lightweight, durable aircraft capable of achieving level flight powered entirely by solar cells

Interpretation of Genetic Association Studies: Markers with Replicated Highly Significant Odds Ratios May Be Poor Classifiers

Recent successful discoveries of potentially causal single nucleotide polymorphisms (SNPs) for complex diseases hold great promise, and commercialization of genomics in personalized medicine has already begun. The hope is that genetic testing will benefit patients and their families, and encourage positive lifestyle changes and guide clinical decisions. However, for many complex diseases, it is arguable whether the era of genomics in personalized medicine is here yet. We focus on the clinical validity of genetic testing with an emphasis on two popular statistical methods for evaluating markers. The two methods, logistic regression and receiver operating characteristic (ROC) curve analysis, are applied to our age-related macular degeneration dataset. By using an additive model of the CFH, LOC387715, and C2 variants, the odds ratios are 2.9, 3.4, and 0.4, with p-values of 10−13, 10−13, and 10−3, respectively. The area under the ROC curve (AUC) is 0.79, but assuming prevalences of 15%, 5.5%, and 1.5% (which are realistic for age groups 80 y, 65 y, and 40 y and older, respectively), only 30%, 12%, and 3% of the group classified as high risk are cases. Additionally, we present examples for four other diseases for which strongly associated variants have been discovered. In type 2 diabetes, our classification model of 12 SNPs has an AUC of only 0.64, and two SNPs achieve an AUC of only 0.56 for prostate cancer. Nine SNPs were not sufficient to improve the discrimination power over that of nongenetic predictors for risk of cardiovascular events. Finally, in Crohn's disease, a model of five SNPs, one with a quite low odds ratio of 0.26, has an AUC of only 0.66. Our analyses and examples show that strong association, although very valuable for establishing etiological hypotheses, does not guarantee effective discrimination between cases and controls. The scientific community should be cautious to avoid overstating the value of association findings in terms of personalized medicine before their time

The Tec kinase ITK differentially optimizes NFAT, NF-κB, and MAPK signaling during early T cell activation to regulate graded gene induction [preprint]

The strength of peptide:MHC interactions with the T cell receptor (TCR) is correlated with the time to first cell division, the relative scale of the effector cell response, and the graded expression of activation-associated proteins like IRF4. To regulate T cell activation programming, the TCR and the TCR proximal kinase ITK simultaneously trigger many biochemically separate TCR signaling cascades. T cells lacking ITK exhibit selective impairments in effector T cell responses after activation, but under the strongest signaling conditions ITK activity is dispensable. To gain insight into whether TCR signal strength and ITK activity tune observed graded gene expression through unequal activation of disparate signaling pathways, we examined Erk1/2 activation and NFAT, NF-κB translocation in naive OT-I CD8+ cell nuclei. We observed consistent digital activation of NFAT1 and Erk-MAPK, but NF-κB displayed dynamic, graded activation in response to variation in TCR signal strength and was tunable by treatment with an ITK inhibitor. Inhibitor-treated cells showed dampened induction of AP-1 factors Fos and Fosb, NF-κB response gene transcripts, and survival factor Il2 transcripts. ATAC-seq analysis also revealed genomic regions most sensitive to ITK inhibition were enriched for NF-κB and AP-1 motifs. Specific inhibition of NF-κB during peptide stimulation tuned expression of early gene products like c-Fos. Together, these data indicate a key role for ITK in orchestrating optimal activation of separate TCR downstream pathways, specifically aiding NF-κB activation. More broadly, we revealed a mechanism by which variation in TCR signal strength can produce patterns of graded gene expression in activated T cells

Endophenotypes for Age-Related Macular Degeneration: Extending Our Reach into the Preclinical Stages of Disease.

The key to reducing the individual and societal burden of age-related macular degeneration (AMD)-related vision loss, is to be able to initiate therapies that slow or halt the progression at a point that will yield the maximum benefit while minimizing personal risk and cost. There is a critical need to find clinical markers that, when combined with the specificity of genetic testing, will identify individuals at the earliest stages of AMD who would benefit from preventive therapies. These clinical markers are endophenotypes for AMD, present in those who are likely to develop AMD, as well as in those who have clinical evidence of AMD. Clinical characteristics associated with AMD may also be possible endophenotypes if they can be detected before or at the earliest stages of the condition, but we and others have shown that this may not always be valid. Several studies have suggested that dynamic changes in rhodopsin regeneration (dark adaptation kinetics and/or critical flicker fusion frequencies) may be more subtle indicators of AMD-associated early retinal dysfunction. One can test for the relevance of these measures using genetic risk profiles based on known genetic risk variants. These functional measures may improve the sensitivity and specificity of predictive models for AMD and may also serve to delineate clinical subtypes of AMD that may differ with respect to prognosis and treatment

Type Ia Supernova Light Curve Inference: Hierarchical Bayesian Analysis in the Near Infrared

We present a comprehensive statistical analysis of the properties of Type Ia SN light curves in the near infrared using recent data from PAIRITEL and the literature. We construct a hierarchical Bayesian framework, incorporating several uncertainties including photometric error, peculiar velocities, dust extinction and intrinsic variations, for coherent statistical inference. SN Ia light curve inferences are drawn from the global posterior probability of parameters describing both individual supernovae and the population conditioned on the entire SN Ia NIR dataset. The logical structure of the hierarchical model is represented by a directed acyclic graph. Fully Bayesian analysis of the model and data is enabled by an efficient MCMC algorithm exploiting the conditional structure using Gibbs sampling. We apply this framework to the JHK_s SN Ia light curve data. A new light curve model captures the observed J-band light curve shape variations. The intrinsic variances in peak absolute magnitudes are: sigma(M_J) = 0.17 +/- 0.03, sigma(M_H) = 0.11 +/- 0.03, and sigma(M_Ks) = 0.19 +/- 0.04. We describe the first quantitative evidence for correlations between the NIR absolute magnitudes and J-band light curve shapes, and demonstrate their utility for distance estimation. The average residual in the Hubble diagram for the training set SN at cz > 2000 km/s is 0.10 mag. The new application of bootstrap cross-validation to SN Ia light curve inference tests the sensitivity of the model fit to the finite sample and estimates the prediction error at 0.15 mag. These results demonstrate that SN Ia NIR light curves are as effective as optical light curves, and, because they are less vulnerable to dust absorption, they have great potential as precise and accurate cosmological distance indicators.Comment: 24 pages, 15 figures, 4 tables. Accepted for publication in ApJ. Corrected typo, added references, minor edit