On convergence of higher order schemes for the projective integration method for stiff ordinary differential equations

We present a convergence proof for higher order implementations of the projective integration method (PI) for a class of deterministic multi-scale systems in which fast variables quickly settle on a slow manifold. The error is shown to contain contributions associated with the length of the microsolver, the numerical accuracy of the macrosolver and the distance from the slow manifold caused by the combined effect of micro- and macrosolvers, respectively. We also provide stability conditions for the PI methods under which the fast variables will not diverge from the slow manifold. We corroborate our results by numerical simulations.Comment: 43 pages, 7 figures; accepted for publication in the Journal of Computational and Applied Mathematic

The effect of low volume sprint interval training in patients with non-alcoholic fatty liver disease

Objectives: Exercise is an important part of disease management in patients with non-alcoholic fatty liver disease (NAFLD), but adherence to current exercise recommendations is poor. Novel low-volume sprint interval training (SIT) protocols with total training time commitments of ≤30 min per week have been shown to improve cardiometabolic risk and functional capacity in healthy sedentary participants, but the efficacy of such protocols in the management of NAFLD remains unknown. The aim of the present study was to examine whether a low-volume SIT protocol can be used to improve liver function, insulin resistance, body composition, physical fitness, cognitive function and general well-being in patients with NAFLD.Methods: In the present study, 7 men and 2 women with NAFLD (age: 45±8 y, BMI: 28.7±4.1 kg·m−2) completed a 6-week control period followed by 6 weeks of twice-weekly SIT sessions (5-10×6-s ‘all-out’ cycle sprints). Body composition, blood pressure, liver function, metabolic function, functional capacity, cognitive function and quality of life were assessed at baseline, following the control period, and following the SIT intervention.Results: Walking speed during the walk test (+12%), estimated V̇O2max (+8%), verbal fluency (+44%), and blood platelet count (+12%; all p<0.05) significantly increased during the control period. These measures remained significantly raised compared to baseline following the SIT intervention, but did not significantly change any further compared to the post-control time-point. Diastolic blood pressure decreased from 87±10 to 77±8 mm Hg from the end of the control period to the end of the SIT intervention (p<0.05).Conclusion: This study does not support the use of 6 weeks of a low volume SIT protocol involving twice-weekly sessions with 5-10×6-s ‘all-out’ cycle sprints as an intervention for NAFLD disease management

Positive allosteric modulators of the a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor

L-glutamate is the major excitatory neurotransmitter in the mammalian central nervous system (CNS) and plays a fundamental role in the control of motor function, cognition and mood. The physiological effects of glutamate are mediated through two functionally distinct receptor families. While activation of metabotropic (G-protein coupled) glutamate receptors results in modulation of neuronal excitability and transmission, the ionotropic glutamate receptors (ligand-gated ion channels) are responsible for mediating the fast synaptic response to extracellular glutamate

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

A comparison study of the degradative effects and safety implications of UVC and 405 nm germicidal light sources for endoscope storage

Storage of flexible endoscopes under germicidal ultraviolet (UVC) light has been associated with degradation of device material leading to failure and increased risk to patients. 405 nm germicidal light presents a possible alternative, potentially providing effective bacterial inactivation without material damage. Samples of endoscope material were exposed to UVC and 405 nm germicidal light sources and a broad spectrum light source control. Material properties were monitored using FTIR, AFM, contact angle and confocal microscopy. Significant changes were observed with samples exposed to the UVC source, with variations in FTIR spectra indicative of side chain scission, a decrease in contact angle from 82.6° to 61.4°, an increase in average surface roughness from 2.34 nm to 68.7 nm and visible cracking of the surface. In contrast samples exposed to the 405 nm light source showed little to no changes, with any variations being comparable to those seen on samples exposed to the broad spectrum control. Bacterial adhesion tests on samples showed an 86.8% increase in Pseudomonas aeruginosa adhesion on UVC exposed samples and no significant increase in adhesion with samples exposed to the other light sources. 405 nm germicidal light therefore potentially represents a safer alternative to UVC light for use in flexible endoscope storage

Dynamic changes in lung microRNA profiles during the development of pulmonary hypertension due to chronic hypoxia and monocrotaline

<b>Objective</b>: MicroRNAs (miRNAs) are small noncoding RNAs that have the capacity to control protein production through binding "seed" sequences within a target mRNA. Each miRNA is capable of potentially controlling hundreds of genes. The regulation of miRNAs in the lung during the development of pulmonary arterial hypertension (PAH) is unknown.<p></p> <b>Methods and Results</b>: We screened lung miRNA profiles in a longitudinal and crossover design during the development of PAH caused by chronic hypoxia or monocrotaline in rats. We identified reduced expression of Dicer, involved in miRNA processing, during the onset of PAH after hypoxia. MiR-22, miR-30, and let-7f were downregulated, whereas miR-322 and miR-451 were upregulated significantly during the development of PAH in both models. Differences were observed between monocrotaline and chronic hypoxia. For example, miR-21 and let-7a were significantly reduced only in monocrotaline-treated rats. MiRNAs that were significantly regulated were validated by quantitative polymerase chain reaction. By using in vitro studies, we demonstrated that hypoxia and growth factors implicated in PAH induced similar changes in miRNA expression. Furthermore, we confirmed miR-21 downregulation in human lung tissue and serum from patients with idiopathic PAH.<p></p> <b>Conclusion</b>: Defined miRNAs are regulated during the development of PAH in rats. Therefore, miRNAs may contribute to the pathogenesis of PAH and represent a novel opportunity for therapeutic intervention.<p></p&gt