Evolution of Flexible Multibody Dynamics for Simulation Applications Supporting Human Spaceflight

During the course of transition from the Space Shuttle and International Space Station programs to the Orion and Journey to Mars exploration programs, a generic flexible multibody dynamics formulation and associated software implementation has evolved to meet an ever changing set of requirements at the NASA Johnson Space Center (JSC). Challenging problems related to large transitional topologies and robotic free-flyer vehicle capture/ release, contact dynamics, and exploration missions concept evaluation through simulation (e.g., asteroid surface operations) have driven this continued development. Coupled with this need is the requirement to oftentimes support human spaceflight operations in real-time. Moreover, it has been desirable to allow even more rapid prototyping of on-orbit manipulator and spacecraft systems, to support less complex infrastructure software for massively integrated simulations, to yield further computational efficiencies, and to take advantage of recent advances and availability of multi-core computing platforms. Since engineering analysis, procedures development, and crew familiarity/training for human spaceflight is fundamental to JSC's charter, there is also a strong desire to share and reuse models in both the non-realtime and real-time domains, with the goal of retaining as much multibody dynamics fidelity as possible. Three specific enhancements are reviewed here: (1) linked list organization to address large transitional topologies, (2) body level model order reduction, and (3) parallel formulation/implementation. This paper provides a detailed overview of these primary updates to JSC's flexible multibody dynamics algorithms as well as a comparison of numerical results to previous formulations and associated software

Update: Advancement of Contact Dynamics Modeling for Human Spaceflight Simulation Applications

Pong is a new software tool developed at the NASA Johnson Space Center that advances interference-based geometric contact dynamics based on 3D graphics models. The Pong software consists of three parts: a set of scripts to extract geometric data from 3D graphics models, a contact dynamics engine that provides collision detection and force calculations based on the extracted geometric data, and a set of scripts for visualizing the dynamics response with the 3D graphics models. The contact dynamics engine can be linked with an external multibody dynamics engine to provide an integrated multibody contact dynamics simulation. This paper provides a detailed overview of Pong including the overall approach and modeling capabilities, which encompasses force generation from contact primitives and friction to computational performance. Two specific Pong-based examples of International Space Station applications are discussed, and the related verification and validation using this new tool are also addressed

Sex-dependent influence of endogenous estrogen in pulmonary hypertension

Rationale: The incidence of pulmonary arterial hypertension (PAH) is greater in women suggesting estrogens may play a role in the disease pathogenesis. Experimentally, in males exogenously administered estrogen can protect against PH; however in models that display female susceptibility estrogens may play a causative role. Objectives: To clarify the influence of endogenous estrogen and gender in PH and assess the therapeutic potential of a clinically available aromatase inhibitor. Methods: We interrogated the effect of reduced endogenous estrogen in males and females using the aromatase inhibitor, anastrozole, in two models of PH; the hypoxic mouse and Sugen 5416/hypoxic rat. We also determined the effects of gender on pulmonary expression of aromatase in these models and in lungs from PAH patients. Results: Anastrozole attenuated PH in both models studied, but only in females. To verify this effect was due to reduced estrogenic activity we confirmed that in hypoxic mice inhibition of estrogen receptor alpha also has a therapeutic effect specifically in females. Female rodent lung displays increased aromatase and decreased BMPR2 and Id1 expression compared to male. Anastrozole treatment reversed the impaired BMPR2 pathway in females. Increased aromatase expression was also detected in female human pulmonary artery smooth muscle cells compared to male. Conclusions: The unique phenotype of female pulmonary arteries facilitates the therapeutic effects of anastrozole in experimental PH confirming a role for endogenous estrogen in the disease pathogenesis in females and suggests aromatase inhibitors may have therapeutic potential

A Review of Controlling Motivational Strategies from a Self-Determination Theory Perspective: Implications for Sports Coaches

The aim of this paper is to present a preliminary taxonomy of six controlling strategies, primarily based on the parental and educational literatures, which we believe are employed by coaches in sport contexts. Research in the sport and physical education literature has primarily focused on coaches’ autonomysupportive behaviours. Surprisingly, there has been very little research on the use of controlling strategies. A brief overview of the research which delineates each proposed strategy is presented, as are examples of the potential manifestation of the behaviours associated with each strategy in the context of sports coaching. In line with self-determination theory (Deci & Ryan, 1985; Ryan & Deci, 2002), we propose that coach behaviours employed to pressure or control athletes have the potential to thwart athletes’ feelings of autonomy, competence,and relatedness, which, in turn, undermine athletes’ self-determined motivation and contribute to the development of controlled motives. When athletes feel pressured to behave in a certain way, a variety of negative consequences are expected to ensue which are to the detriment of the athletes’ well-being. The purpose of this paper is to raise awareness and interest in the darker side of sport participation and to offer suggestions for future research in this area

Chemical Validation of Methionyl tRNA Synthetase (MetRS) as a Druggable Target in <i>Leishmania donovani</i>

Methionyl-tRNA synthetase (MetRS) has been chemically validated as a drug target in the kinetoplastid parasite Trypanosoma brucei. In the present study we investigate the validity of this target in the related trypanosomatid Leishmania donovani. Following development of a robust highthroughput compatible biochemical assay, a compound screen identified DDD806905 as a highly potent inhibitor of LdMetRS (Ki 18 nM). Crystallography revealed this compound binds to the methionine pocket of MetRS with enzymatic studies confirming DDD806905 displays competitive inhibition with respect to methionine and mixed inhibition with respect to ATP binding. DDD806905 showed activity, albeit with different levels of potency, in various Leishmania cell-based viability assays, with on-target activity observed in both Leishmania promastigote cell assays and a Leishmania tarentolae in vitro translation assay. Unfortunately this compound failed to show efficacy in an animal model of leishmaniasis. We investigated the potential causes for the discrepancies in activity observed in different Leishmania cell assays and the lack of efficacy in the animal model and found that high protein binding as well as sequestration of this dibasic compound into acidic compartments may play a role. Despite medicinal chemistry efforts to address the dibasic nature of DDD806905 and analogues, no progress could be achieved with the current chemical series. Although DDD806905 is not a developable anti-leishmanial compound, MetRS remains an attractive anti-leishmanial drug target

Differences in Respiratory Symptoms and Lung Structure Between Hispanic and Non-Hispanic White Smokers: A Comparative Study

Background: Prior studies have demonstrated that U.S. Hispanic smokers have a lower risk of decline in lung function and chronic obstructive pulmonary disease (COPD) compared with non-Hispanic whites (NHW). This suggests there might be racial-ethnic differences in susceptibility in cigarette smoke-induced respiratory symptoms, lung parenchymal destruction, and airway and vascular disease, as well as in extra-pulmonary manifestations of COPD. Therefore, we aimed to explore respiratory symptoms, lung function, and pulmonary and extra-pulmonary structural changes in Hispanic and NHW smokers. Methods: We compared respiratory symptoms, lung function, and computed tomography (CT) measures of emphysema-like tissue, airway disease, the branching generation number (BGN) to reach a 2-mm-lumen-diameter airway, and vascular pruning as well as muscle and fat mass between 39 Hispanic and 39 sex-, age- and smoking exposure-matched NHW smokers. Results: Hispanic smokers had higher odds of dyspnea than NHW after adjustment for COPD and asthma statuses (odds ratio[OR] = 2.96; 95% confidence interval [CI] 1.09-8.04), but no significant differences were found in lung function and CT measurements. Conclusions: While lung function and CT measures of the lung structure were similar, dyspnea is reported more frequently by Hispanic than matched-NHW smokers. It seems to be an impossible puzzle but it's easy to solve a Rubik' Cube using a few algorithms

"Every structure we're taught goes out the window": General practitioners' experiences of providing help for patients with emotional concerns'

Up to 40% of general practitioners (GP) consultations contain an emotional component. General practitioners (GPs) have to provide care with limited time and resources. This qualitative study aimed to explore how GPs care for patients experiencing emotional concerns within the constraints of busy clinical practice. Seven GPs participated in three focus groups. Groups were recorded, transcribed and analysed thematically. Three themes were identified. (a) Collaboratively negotiated diagnosis: How patients' emotional concerns are understood and managed is the result of a negotiation between patient and GP belief models and the availability of treatments including talking therapy. (b) Doctor as drug: Not only is a continuous relationship between GPs and patients therapeutic in its own right, it is also necessary to effectively diagnose and engage patients in treatment as patients may experience stigma regarding emotional concerns. (c) Personal responsibility and institutional pressure: GPs feel personally responsible for supporting patients through their care journey, however, they face barriers due to lack of time and pressure from guidelines. GPs are forced to prioritise high-risk patients and experience an emotional toll. In conclusion, guidelines focus on diagnosis and a stepped-care model, however, this assumes diagnosis is relatively straightforward. GPs and patients have different models of psychological distress. This and the experience of stigma mean that establishing rapport is an important step before the GP and patient negotiate openly and develop a shared understanding of the problem. This takes time and emotional resources to do well. Longer consultations, continuity of care and formal supervision for GPs could enable them to better support patients

Bioavailability in soils

The consumption of locally-produced vegetables by humans may be an important exposure pathway for soil contaminants in many urban settings and for agricultural land use. Hence, prediction of metal and metalloid uptake by vegetables from contaminated soils is an important part of the Human Health Risk Assessment procedure. The behaviour of metals (cadmium, chromium, cobalt, copper, mercury, molybdenum, nickel, lead and zinc) and metalloids (arsenic, boron and selenium) in contaminated soils depends to a large extent on the intrinsic charge, valence and speciation of the contaminant ion, and soil properties such as pH, redox status and contents of clay and/or organic matter. However, chemistry and behaviour of the contaminant in soil alone cannot predict soil-to-plant transfer. Root uptake, root selectivity, ion interactions, rhizosphere processes, leaf uptake from the atmosphere, and plant partitioning are important processes that ultimately govern the accumulation ofmetals and metalloids in edible vegetable tissues. Mechanistic models to accurately describe all these processes have not yet been developed, let alone validated under field conditions. Hence, to estimate risks by vegetable consumption, empirical models have been used to correlate concentrations of metals and metalloids in contaminated soils, soil physico-chemical characteristics, and concentrations of elements in vegetable tissues. These models should only be used within the bounds of their calibration, and often need to be re-calibrated or validated using local soil and environmental conditions on a regional or site-specific basis.Mike J. McLaughlin, Erik Smolders, Fien Degryse, and Rene Rietr