Rapid Contingency Simulation Modeling of the NASA Crew Launch Vehicle

The NASA Crew Launch Vehicle is a two-stage orbital launcher designed to meet NASA's current as well as future needs for human space flight. In order to free the designers to explore more possibilities during the design phase, a need exists for the ability to quickly perform simulation on both the baseline vehicle as well as the vehicle after proposed changes due to mission planning, vehicle configuration and avionics changes, proposed new guidance and control algorithms, and any other contingencies the designers may wish to consider. Further, after the vehicle is designed and built, the need will remain for such analysis in the event of future mission planning. An easily reconfigurable, modular, nonlinear six-degree-of-freedom simulation matching NASA Marshall's in-house high-fidelity simulator is created with the ability to quickly perform simulation and analysis of the Crew Launch Vehicle throughout the entire launch profile. Simulation results are presented and discussed, and an example comparison fly-off between two candidate controllers is presented

Characterization of T-bet and eomes in peripheral human immune cells.

The T-box transcription factors T-bet and Eomesodermin (Eomes) have been well defined as key drivers of immune cell development and cytolytic function. While the majority of studies have defined the roles of these factors in the context of murine T-cells, recent results have revealed that T-bet, and possibly Eomes, are expressed in other immune cell subsets. To date, the expression patterns of these factors in subsets of human peripheral blood mononuclear cells beyond T-cells remain relatively uncharacterized. In this study, we used multiparametric flow cytometry to characterize T-bet and Eomes expression in major human blood cell subsets, including total CD4(+) and CD8(+) T-cells, γδ T-cells, invariant NKT cells, natural killer cells, B-cells, and dendritic cells. Our studies identified novel cell subsets that express T-bet and Eomes and raise implications for their possible functions in the context of other human immune cell subsets besides their well-known roles in T-cells. The corrigendum regards data and text for the final figure of the manuscript, Figure 7: Subsequent analysis of T-bet levels in human lymphocytes comparing different permeabilization procedures (eBioscience FoxP3 transcription factor kit, BD Pharmingen Cytofix/Cytoperm) has revealed variable findings in the level of T-bet expression detected within certain lymphocyte populations. While this does not change our conclusions for the majority of the populations assessed in this study, B cells in particular show differences under these conditions. Specifically, permeabilization via the eBioscience FoxP3 transcription factor staining buffer set indicates that subpopulations of memory B cells express significantly higher levels of T-bet (MFI) compared to plasmablasts, and that plasmablasts express T-bet only at low levels. Subsequent RNA transcript analysis confirms that plasmablasts express T-bet RNA at a level comparable to naïve B cells. Together, in combination with fluorescence-minus-one and isotype control studies, these new findings suggest that subsets memory B cells, not plasmablasts, express the highest levels of T-bet in the B cell compartment and plasmablasts express T-bet at a lower frequency than is reported in Figure 7. Figure 7 Legend should read: (C) Histograms depicting T-bet expression levels in B-cells and NK cells from a representative donor. Histograms represent the following subsets: naïve B-cells (thick black line), memory B-cells (shaded gray), plasmablasts (thin black line), CD56bright NK cells (gray line), and CD56dim NK cells (shaded black). B-cell results section should be titled T-bet is predominantly expressed in mature memory B-cells and should read: While Eomes was undetectable in B-cells (data not shown), we found T-bet in ~10% of B-cells (Figure 7B). This T-bet expression was largely relegated to memory B-cells, with significantly lower amounts observed in transitional/immature B-cells, naïve B-cells, and plasmablasts (Figure 7B). Greater than 15% of memory B-cells expressed T-bet, a significantly higher frequency than that of all other B-cell populations, suggesting that T-bet may play a particularly important role in memory B-cell function. The discussion related to T-bet expression in plasmablasts should be reconsidered as follows: We found that T-bet is not significantly expressed in transitional/immature B-cells, naïve B-cells, and plasmablasts, but is highly expressed in subsets of memory-B cells. Reduced frequencies of T-bet expression in plasmablasts indicate a specific role for T-bet at the memory B-cell stage of development, which may no longer be necessary after further differentiation to the plasmablast stage. Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest

Embedded Relative Navigation Sensor Fusion Algorithms for Autonomous Rendezvous and Docking Missions

bd Systems (a subsidiary of SAIC) has developed a suite of embedded relative navigation sensor fusion algorithms to enable NASA autonomous rendezvous and docking (AR&D) missions. Translational and rotational Extended Kalman Filters (EKFs) were developed for integrating measurements based on the vehicles' orbital mechanics and high-fidelity sensor error models and provide a solution with increased accuracy and robustness relative to any single relative navigation sensor. The filters were tested tinough stand-alone covariance analysis, closed-loop testing with a high-fidelity multi-body orbital simulation, and hardware-in-the-loop (HWIL) testing in the Marshall Space Flight Center (MSFC) Flight Robotics Laboratory (FRL)

Taxonomic voucher specimens for study of bee communities in intensively managed Douglas-fir forests in the Oregon Coast Range

Understanding how pollinators respond to anthropogenic land use is key to conservation of biodiversity and ecosystem services, but few studies have addressed this topic in coniferous forests, particularly those managed intensively for wood production. This study reports on voucher material generated as part of Zitomer et al. (2023), that assessed changes in wild bee communities with time since harvest in 60 intensively managed Douglas-fir (Pseudotsuga menziesii) stands in the Oregon Coast Range across a gradient in stand age spanning a typical harvest rotation (0-37 years post-harvest). We additionally assessed relationships of bee diversity and community composition to relevant habitat features, including availability of floral resources and nest sites, understory vegetation characteristics, and composition of the surrounding landscape. Specimens were collected using a combination of passive sampling methods-blue vane traps and white, blue, and yellow bowl traps- and hand-netting and were identified to the lowest possible taxonomic level by A.R. Moldenke and L.R. Best. Four hundred and ten taxonomic voucher specimens were deposited into the Oregon State Arthropod Collection (Accession# OSAC_AC_2023_01_09-001-01) to serve as a reference for future research

Structure of the Claudin-binding Domain of Clostridium perfringens Enterotoxin

Clostridium perfringens enterotoxin is a common cause of food-borne and antibiotic-associated diarrhea. The toxin's receptors on intestinal epithelial cells include claudin-3 and -4, members of a large family of tight junction proteins. Toxin-induced cytolytic pore formation requires residues in the NH(2)-terminal half, whereas residues near the COOH terminus are required for binding to claudins. The claudin-binding COOH-terminal domain is not toxic and is currently under investigation as a potential drug absorption enhancer. Because claudin-4 is overexpressed on some human cancers, the toxin is also being investigated for targeting chemotherapy. Our aim was to solve the structure of the claudin-binding domain to advance its therapeutic applications. The structure of a 14-kDa fragment containing residues 194 to the native COOH terminus at position 319 was solved by x-ray diffraction to a resolution of 1.75A. The structure is a nine-strand beta sandwich with previously unappreciated similarity to the receptor-binding domains of several other toxins of spore-forming bacteria, including the collagen-binding domain of ColG from Clostridium histolyticum and the large Cry family of toxins (including Cry4Ba) of Bacillus thuringiensis. Correlations with previous studies suggest that the claudin-4 binding site is on a large surface loop between strands beta8 and beta9 or includes these strands. The sequence that was crystallized (residues 194-319) binds to purified human claudin-4 with a 1:1 stoichiometry and affinity in the submicromolar range similar to that observed for binding of native toxin to cells. Our results provide a structural framework to advance therapeutic applications of the toxin and suggest a common ancestor for several receptor-binding domains of bacterial toxins

Substituting carbohydrate at lunch for added protein increases fat oxidation during subsequent exercise in healthy males

Context How pre-exercise meal composition influences metabolic and health responses to exercise later in the day is currently unclear. Objective Examine the effects of substituting carbohydrate for protein at lunch on subsequent exercise metabolism, appetite, and energy intake. Methods Twelve healthy males completed three trials in randomized, counterbalanced order. Following a standardized breakfast (779 ± 66 kcal; ∼08:15), participants consumed a lunch (1186 ± 140 kcal; ∼13:15) containing either 0.2 g·kg-1 carbohydrate and ∼2 g·kg-1 protein (LO-CARB), 2 g·kg-1 carbohydrate and ∼0.4 g·kg-1 protein (HI-CARB), or fasted (FAST). Participants later cycled at ∼60% V̇O2peak for 1 h (∼16:15) and post-exercise ad-libitum energy intake was measured (∼18:30). Substrate oxidation, subjective appetite, and plasma concentrations of glucose, insulin, non-esterified fatty acids (NEFA), peptide YY (PYY), glucagon-like peptide-1 (GLP-1), and acylated ghrelin (AG) were measured for 5 h post-lunch. Results Fat oxidation was greater during FAST (+11.66 ± 6.63 g) and LO-CARB (+8.00 ± 3.83 g) than HI-CARB (p < 0.001), with FAST greater than LO-CARB (+3.67 ± 5.07 g; p < 0.05). NEFA were lowest in HI-CARB and highest in FAST, with insulin demonstrating the inverse response (all p < 0.01). PYY and GLP-1 demonstrated a stepwise pattern, with LO-CARB greatest and FAST lowest (all p < 0.01). AG was lower during HI-CARB and LO-CARB versus FAST (p < 0.01). Energy intake in LO-CARB was lower than FAST (-383 ± 233 kcal; p < 0.001) and HI-CARB (-313 ± 284 kcal; p < 0.001). Conclusion Substituting carbohydrate for protein in a pre-exercise lunch increased fat oxidation, suppressed subjective and hormonal appetite, and reduced post-exercise energy intake

Class I-restricted T-cell responses to a polymorphic peptide in a gene therapy clinical trial for alpha-1-antitrypsin deficiency

Adeno-associated virus (AAV)-mediated gene therapy is currently being pursued as a treatment for the monogenic disorder alpha-1-antitrypsin (AAT) deficiency. Results from phase I and II studies have shown relatively stable and dose-dependent increases in transgene-derived wild-type AAT after local intramuscular vector administration. In this report we describe the appearance of transgene-specific T-cell responses in two subjects that were part of the phase II trial. The patient with the more robust T-cell response, which was associated with a reduction in transgene expression, was characterized more thoroughly in this study. We learned that the AAT-specific T cells in this patient were cytolytic in phenotype, mapped to a peptide in the endogenous mutant AAT protein that contained a common polymorphism not incorporated into the transgene, and were restricted by a rare HLA class I C alleles present only in this patient. These human studies illustrate the genetic influence of the endogenous gene and HLA haplotype on the outcome of gene therapy

Debris-Collecting Vacuum Machine with Grounded Safety System and Associated Methods

A debris collection machine includes a vacuum system (including a suction source operable to provide suction for pulling debris into a receptacle), a ground reference portion, a ground test portion, and a ground-checking module. The ground reference portion is electrically coupled with an electrically grounded reference point, and the ground test portion is electrically coupled with a portion of the vacuum system. The ground-checking module determines a resistance between from the ground reference portion and the ground test portion and prevents or terminates operation of the suction source of the vacuum system when the resistance exceeds a predetermined threshold value, e.g., which may correspond to a risk condition of spark generation that could ignite material in the receptacle

Periconceptional environment predicts leukocyte telomere length in a cross-sectional study of 7-9 year old rural Gambian children

Early life exposures are important predictors of adult disease risk. Although the underlying mechanisms are largely unknown, telomere maintenance may be involved. This study investigated the relationship between seasonal differences in parental exposures at time of conception and leukocyte telomere length (LTL) in their offspring. LTL was measured in two cohorts of children aged 2 yrs (N = 487) and 7–9 yrs (N = 218). The association between date of conception and LTL was examined using Fourier regression models, adjusted for age, sex, leukocyte cell composition, and other potential confounders. We observed an effect of season in the older children in all models [likelihood ratio test (LRT) χ²2 = 7.1, p = 0.03; fully adjusted model]. LTL was greatest in children conceived in September (in the rainy season), and smallest in those conceived in March (in the dry season), with an effect size (LTL peak–nadir) of 0.60 z-scores. No effect of season was evident in the younger children (LRT χ²2 = 0.87, p = 0.65). The different results obtained for the two cohorts may reflect a delayed effect of season of conception on postnatal telomere maintenance. Alternatively, they may be explained by unmeasured differences in early life exposures, or the increased telomere attrition rate during infancy