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At least 91 records · Page 5

Clinical physiology of bed rest

Maintenance of optimal health in humans requires the proper balance between exercise, rest, and sleep as well as time in the upright position. About one-third of a lifetime is spent sleeping; and it is no coincidence that sleeping is performed in the horizontal position, the position in which gravitational influence on the body is minimal. Although enforced bed rest is necessary for the treatment of some ailments, in some cases it has probably been used unwisely. In addition to the lower hydrostatic pressure with the normally dependent regions of the cardiovascular system, body fuid compartments during bed rest in the horizontal body position, and virtual elimination of compression on the long bones of the skeletal system during bed rest (hypogravia), there is often reduction in energy metabolism due to the relative confinement (hypodynamia) and alteration of ambulatory circadian variations in metabolism, body temperature, and many hormonal systems. If patients are also moved to unfamiliar surroundings, they probably experience some feelings of anxiety and some sociopsychological problems. Adaptive physiological responses during bed rest are normal for that environment. They are attempts by the body to reduce unnecessary energy expenditure, to optimize its function, and to enhance its survival potential. Many of the deconditioning responses begin within the first day or two of bed rest; these early responses have prompted physicians to insist upon early resumption of the upright posture and ambulation of bedridden patients.

Greenleaf, John E.↗

Vibration Test Demonstrated Dynamic Capability of an Operating Stirling Convertor

The NASA Glenn Research Center and the U.S. Department of Energy are currently developing a high-efficiency, long-life, free piston Stirling convertor for use as an advanced spacecraft power system for future NASA missions. As part of this development, a Stirling Technology Demonstrator Converter (TDC), developed by Stirling Technology Company for the Department of Energy, was vibration tested at Glenn's Structural Dynamics Laboratory in November and December 1999. This testing demonstrated that the Stirling TDC is able to withstand the harsh random vibration (20 to 2000 Hz) seen during a typical spacecraft launch and to survive with no structural damage or functional power performance degradation, thereby enabling its use in future spacecraft power systems. Glenn and Stirling personnel conducted tests on a single 55 We TDC. The purpose was to characterize the TDC's structural response to vibration and to determine if the TDC could survive the vibration criteria established by the Jet Propulsion Laboratory for launch environments. The TDC was operated at full-stroke and full power conditions during the vibration testing.

Hughes, William O.↗

Vibration Testing of Stirling Power Convertors

The NASA John H. Glenn Research Center (GRC) and the U.S. Department of Energy (DOE) are currently developing a high efficient, long life, free piston Stirling convertor for use as an advanced spacecraft power system for future NASA missions. As part of this development, a Stirling Technology Demonstrator Convertor (TDC), developed by Stirling Technology Company (STC) for DOE, was vibration tested at GRC s Structural Dynamics Laboratory (SDU7735) in November- December 1999. This testing demonstrated that the Stirling TDC is able to withstand the harsh random vibration (20 to 2000 Hertz) seen during a typical spacecraft launch and survive with no structural damage or functional power performance degradation, thereby enabling its usage in future spacecraft power systems. The Stirling Vibration Test Team at NASA GRC and STC personnel conducted tests on a single 55 electric watt TDC. The purpose was to characterize the TDC s structural response to vibration and determine if the TDC could survive the vibration criteria established by the Jet Propulsion Laboratory (JPL) for launch environments. The TDC was operated at full-stroke and full power conditions during the vibration testing. The TDC was tested in two orientations, with the direction of vibration parallel and perpendicular to the TDC s moving components (displacer and piston). The TDC successfully passed a series of sine and random vibration tests. The most severe test was a 12.3 Grms random vibration test (peak vibration level of 0.2 g2/Hz from 50 to 250 Hertz) with test durations of 3 minutes per axis. The random vibration test levels were chosen to simulate, with margin, the maximum anticipated launch vibration conditions. As a result of this very successful vibration testing and successful evaluations in other key technical readiness areas, the Stirling power system is now considered a viable technology for future application for NASA spacecraft missions. Possible usage of the Stirling power system would be to supply on- board electric spacecraft power for future NASA Deep-Space Missions, performing as an attractive alternative to Radioisotope Thermoelectric Generators (RTG). Usage of the Stirling technology is also being considered as the electric power source for future Mars rovers, whose mission profiles may exclude the use of photovoltaic power systems (such as exploring at high Martian latitudes or for missions of lengthy durations). GRC s Thermo-Mechanical Systems Branch (5490) provides Stirling technology expertise under a Space Act Agreement with the DOE. Additional vibration testing, by GRC s Structural Systems Dynamics Branch (7733, is planned to continue to demonstrate the Stirling power system s vibration capability as its technology and flight system designs progress.

Hughes, Bill↗

Helium-cold induced hypothermia in the white rat.

Hypothermia was induced in white rats by exposing them to low ambient temperatures (about 0 C) and a gaseous atmosphere of 80% helium and 20% oxygen (helox). Biological survival, in which revival from hypothermia to normothermia is achieved, and clinical survival, in which one or more functional attributes are monitored in the hypothermic animal until it dies, are examined. The helium-cold method appears to produce a hypothermic state in the rat quite similar to that resulting from such techniques as ice water immersion or hypercapnia + hypoxia. There is a direct relationship between body weight and percent survival. Despite the fact that they require a longer period to become hypothermic, the heavier animals are better able to survive.

Musacchia, X. J.↗

Cryptococcus neoformans Secretes Small Molecules That Inhibit IL-1 β Inflammasome-Dependent Secretion

Cryptococcus neoformans is an encapsulated yeast that causes disease mainly in immunosuppressed hosts. It is considered a facultative intracellular pathogen because of its capacity to survive and replicate inside phagocytes, especially macrophages. This ability is heavily dependent on various virulence factors, particularly the glucuronoxylomannan (GXM) component of the polysaccharide capsule. Inflammasome activation in phagocytes is usually protective against fungal infections, including cryptococcosis. Nevertheless, recognition of C. neoformans by inflammasome receptors requires specific changes in morphology or the opsonization of the yeast, impairing proper inflammasome function. In this context, we analyzed the impact of molecules secreted by C. neoformans B3501 strain and its acapsular mutant Δcap67 in inflammasome activation in an in vitro model. Our results showed that conditioned media derived from B3501 was capable of inhibiting inflammasome-dependent events (i.e., IL-1β secretion and LDH release via pyroptosis) more strongly than conditioned media from Δcap67, regardless of GXM presence. We also demonstrated that macrophages treated with conditioned media were less responsive against infection with the virulent strain H99, exhibiting lower rates of phagocytosis, increased fungal burdens, and enhanced vomocytosis. Moreover, we showed that the aromatic metabolite DL-Indole-3-lactic acid (ILA) and DL-p-Hydroxyphenyllactic acid (HPLA) were present in B3501’s conditioned media and that ILA alone or with HPLA is involved in the regulation of inflammasome activation by C. neoformans. These results were confirmed by in vivo experiments, where exposure to conditioned media led to higher fungal burdens in Acanthamoeba castellanii culture as well as in higher fungal loads in the lungs of infected mice. Overall, the results presented show that conditioned media from a wild-type strain can inhibit a vital recognition pathway and subsequent fungicidal functions of macrophages, contributing to fungal survival in vitro and in vivo and suggesting that secretion of aromatic metabolites, such as ILA, during cryptococcal infections fundamentally impacts pathogenesis.

60 APPLIED LIFE SCIENCES↗

Divergent trait controls on soluble sugars and starch underlie global strategies of tree carbohydrate storage

Nonstructural carbohydrate (NSC) stores buffer tree metabolism, osmotic regulation, and defense, thereby mediating tolerance and survival under climate extremes. Yet, the functional and evolutionary determinants of interspecific variation in NSC remain elusive, limiting understanding and prediction of forest carbon allocation and mortality under global change. Here, we present a cross-species synthesis of NSC concentrations across multiple organs for 281 woody species from 102 mixed forest communities worldwide, where we quantified species-specific deviations from community means to disentangle intrinsic trait effects from environmental and methodological variation. We found phylogenetic signals in NSC deviations, with coniferous gymnosperms and evergreen species consistently maintaining lower stem soluble sugars and starch concentrations than co-occurring angiosperms and deciduous species, respectively. A global pattern emerged where greater stomatal sensitivity to leaf water potential was associated with declines in the relative concentrations of both sugars and starch. In contrast, xylem hydraulic safety traits showed weak and organ-dependent relationships with NSC concentrations. Sugars increased with photosynthetic capacity and declined with wood density, whereas starch showed the reverse pattern, which aligned with the distinct functional-metabolic roles of sugars and starch. By integrating trait-based ecology with a community-centered framework, our study provides global evidence that stomatal regulation, photosynthetic capacity, specific leaf area, and wood density jointly govern interspecific NSC variation, through contrasting effects on sugars and starch. These are among the most broadly measured traits globally, thus the emergent carbohydrate–trait relationships can have broad applications toward understanding and predicting forest growth and survival under climate change.

tropic system↗

Calculation of dose, dose equivalent, and relative biological effectiveness for high charge and energy ion beams

The Green's function for the transport of ions of high charge and energy is utilized with a nuclear fragmentation database to evaluate dose, dose equivalent, and RBE for C3H10T1/2 cell survival and neo-plastic transformation as function of depth in soft tissue. Such evaluations are useful to estimates of biological risk for high altitude aircraft, space operations, accelerator operations, and biomedical application.

Wilson, J. W.↗

A new algorithm for finding survival coefficients employed in reliability equations

Product reliabilities are predicted from past failure rates and reasonable estimate of future failure rates. Algorithm is used to calculate probability that product will function correctly. Algorithm sums the probabilities of each survival pattern and number of permutations for that pattern, over all possible ways in which product can survive.

Bouricius, W. G.↗

Game-Theoretic Strategies for Cyber-Physical Infrastructures Under Component Disruptions

In this work, networked infrastructures of recursively defined systems composed of discrete cyber and physical components are considered. The components of basic systems at the finest levels can be disrupted by cyber or physical means, and can be reinforced to survive at certain costs. A problem of ensuring the infrastructure performance is formulated as a game between a provider and an attacker, who probabilistically choose components to reinforce and attack, respectively. The disruptions of this infrastructure are characterized using the aggregate failure correlation function that specifies the conditional failure probability of the infrastructure given the failure of an individual system at that level. The survival probabilities of basic systems satisfy simple product-form, first-order differential equations expressed in terms of the multiplier functions. The utility functions of the provider and attacker are composed of the reward and cost terms, both expressed in terms of the component reinforcement and attack probabilities. The Nash equilibrium of this game is characterized, along with the sensitivity functions of the survival probabilities of basic systems that highlight their dependence individually on the cost-benefit terms, the correlation functions, and the multiplier functions. These results are illustrated using simplified models of a distributed cloud servers infrastructure, a 5G data network infrastructure, a high performance computing federation, and a smart energy grid infrastructure.

42 ENGINEERING↗

Insight into molecular basis and dynamics of full-length CRaf kinase in cellular signaling mechanisms

Raf kinases play key roles in signal transduction in cells for regulating proliferation, differentiation, and survival. Despite decades of research into functions and dynamics of Raf kinases with respect to other cytosolic proteins, understanding Raf kinases is limited by the lack of their full-length structures at the atomic resolution. Here, we present the first model of the full-length CRaf kinase obtained from artificial intelligence/machine learning algorithms with a converging ensemble of structures simulated by large-scale temperature replica exchange simulations. Our model is validated by comparing simulated structures with the latest cryo-EM structure detailing close contacts among three key domains and regions of the CRaf. Our simulations identify potentially new epitopes of intramolecule interactions within the CRaf and reveal a dynamical nature of CRaf kinases, in which the three domains can move back and forth relative to each other for regulatory dynamics. The dynamic conformations are then used in a docking algorithm to shed insight into the paradoxical effect caused by vemurafenib in comparison with a paradox breaker PLX7904. In this study, we propose a model of Raf-heterodimer/KRas-dimer as a signalosome based on the dynamics of the full-length CRaf.

59 BASIC BIOLOGICAL SCIENCES↗

Identification of a broadly conserved family of enzymes that hydrolyze (p)ppApp

Bacteria produce a variety of nucleotide second messengers to adapt to their surroundings. Although chemically similar, the nucleotides guanosine penta- and tetraphosphate [(p)ppGpp] and adenosine penta- and tetraphosphate [(p)ppApp] have distinct functions in bacteria. (p)ppGpp mediates survival under nutrient-limiting conditions and its intracellular levels are regulated by synthetases and hydrolases belonging to the RelA-SpoT homolog (RSH) family of enzymes. By contrast, (p)ppApp is not known to be involved in nutrient stress responses and is synthesized by RSH-resembling toxins that inhibit the growth of bacterial cells. However, it remains unclear whether there exists a family of hydrolases that specifically act on (p)ppApp to reverse its toxic effects. Here, we present the structure and biochemical characterization of adenosine 3'-pyrophosphohydrolase 1 (Aph1), the founding member of a monofunctional (p)ppApp hydrolase family of enzymes. Our work reveals that Aph1 adopts a histidine-aspartate (HD)-domain fold characteristic of phosphohydrolase metalloenzymes and its activity mitigates the growth inhibitory effects of (p)ppApp-synthesizing toxins. Using an informatic approach, we identify over 2,000 putative (p)ppApp hydrolases that are widely distributed across bacterial phyla and found in diverse genomic contexts, and we demonstrate that 12 representative members hydrolyze ppApp. In addition, our in silico analyses reveal a unique molecular signature that is specific to (p)ppApp hydrolases, and we show that mutation of two residues within this signature broadens the specificity of Aph1 to promiscuously hydrolyze (p)ppGpp in vitro. Overall, our findings indicate that like (p)ppGpp hydrolases, (p)ppApp hydrolases are widespread in bacteria and may play important and underappreciated role(s) in bacterial physiology.

(p)ppApp↗

Growth–Mortality Coordination Differs Among Xerophytic Versus Mesophytic Tree Species During Severe Drought

ABSTRACT Forest composition is changing, yet the consequences for terrestrial carbon cycling are unclear. In the eastern United States, water‐demanding “mesophytic” tree species are replacing “xerophytic” oaks (Quercusspp.) and hickories (Caryaspp.), raising concerns that forest productivity will become increasingly sensitive to more frequent and severe drought conditions predicted for the region. However, we have a limited understanding of the extent to which the mortality risk of xerophytes versus mesophytes is coordinated with their growth sensitivity during drought. Here, we evaluated growth and mortality dynamics for 20 abundant eastern United States tree species following a severe drought in the summer of 2012. We synthesized data from ~4500 forest inventory plots and used an approach that quantified relative drought responses between co‐located trees to minimize impacts from environmental heterogeneity. We found that mesophytes were just as likely to perish as co‐occurring xerophytes but were more sensitive to drought in terms of diminished growth. These findings suggest that xerophytic decline is likely to lead to reduced carbon uptake during drought and that management efforts to conserve oak‐hickory stands will be decisive to sustain the carbon mitigation potential of these forests. However, we also found that growth‐mortality relationships differed between functional groups. Among xerophytes, growth and survival during drought were decoupled. Among mesophytes, there was a high degree of coordination, where species that experienced greater mortality also experienced greater growth reductions. Therefore, mesophytes with high growth sensitivity to water deficits are likely to be the most vulnerable to drought‐driven die‐off events moving forward.

Biodiversity & Conservation↗

Toward the Instrumentation and Data Acquisition of a Tidal Turbine in Real Site Conditions

The National Renewable Energy Laboratory manufactured, instrumented, and deployed thermoplastic composite blades and a data acquisition system (NDAQ) on one of Verdant Power’s Gen5d 5 m diameter tidal turbines in New York’s East River. The thermoplastic blades had internal strain gages, and the NDAQ was a stand-alone system for monitoring and recording the strain and angular position of the blades. The turbine with thermoplastic blades operated and produced power successfully for 3 months, contributing energy to the New York City electric grid. The NDAQ hardware, instrumentation, and structure all survived the deployment and were still functional upon retrieval of the system, but no data were collected. Even though the data retrieval was not a success, data acquisition for deployed subsea marine renewable structures is a new undertaking, and it is critical to share lessons learned from national laboratory experiences. The successful deployment of thermoplastic composite blades marks a significant advancement toward improved materials for subsea components, as well as an advancement in recyclable composite materials. This article outlines the methodology and lessons learned for the instrumentation and data acquisition system.

16 TIDAL AND WAVE POWER↗

Pseudomonas aeruginosa Dps (PA0962) Functions in H 2 O 2 Mediated Oxidative Stress Defense and Exhibits In Vitro DNA Cleaving Activity

We report the structural, biochemical, and functional characterization of the product of gene PA0962 from Pseudomonas aeruginosa PAO1. The protein, termed Pa Dps, adopts the Dps subunit fold and oligomerizes into a nearly spherical 12-mer quaternary structure at pH 6.0 or in the presence of divalent cations at neutral pH and above. The 12-Mer Pa Dps contains two di-iron centers at the interface of each subunit dimer, coordinated by conserved His, Glu, and Asp residues. In vitro, the di-iron centers catalyze the oxidation of Fe 2+ utilizing H 2 O 2 (not O 2 ) as an oxidant, suggesting Pa Dps functions to aid P. aeruginosa to survive H 2 O 2 -mediated oxidative stress. In agreement, a P. aeruginosa Δdps mutant is significantly more susceptible to H 2 O 2 than the parent strain. The Pa Dps structure harbors a novel network of Tyr residues at the interface of each subunit dimer between the two di-iron centers, which captures radicals generated during Fe 2+ oxidation at the ferroxidase centers and forms di-tyrosine linkages, thus effectively trapping the radicals within the Dps shell. Surprisingly, incubating Pa Dps and DNA revealed unprecedented DNA cleaving activity that is independent of H 2 O 2 or O 2 but requires divalent cations and 12-mer Pa Dps.

59 BASIC BIOLOGICAL SCIENCES↗

Common spaceborne multicomputer operating system and development environment

A preliminary technical specification for a multicomputer operating system is developed. The operating system is targeted for spaceborne flight missions and provides a broad range of real-time functionality, dynamic remote code-patching capability, and system fault tolerance and long-term survivability features. Dataflow concepts are used for representing application algorithms. Functional features are included to ensure real-time predictability for a class of algorithms which require data-driven execution on an iterative steady state basis. The development environment supports the development of algorithm code, design of control parameters, performance analysis, simulation of real-time dataflow applications, and compiling and downloading of the resulting application.

Craymer, L. G.↗

Hydroxycinnamic acid-derived polymers constitute the polyaromatic domain of suberin

Suberin is an abundant, complex, intractable, plant cell wall polymeric network that forms both protective and wound-healing layers. Its function is, therefore, critical to the survival of all vascular plants. Its chemical structure and biosynthesis are poorly defined, although it is known to consist of both aromatic and aliphatic domains. While the composition of the aliphatic component has been fairly well characterized, that of the phenolic component has not. Using a combination of specific carbon-13 labeling techniques, and in situ solid state 13C NMR spectroscopic analysis, we now provide the first direct evidence for the nature of the phenolic domain of suberin and report here that it is almost exclusively comprised of a covalently linked, hydroxycinnamic acid-derived polymeric matrix.

NASA Discipline Plant Biology↗

Understanding of the Dynamics of the Stirling Convertor Advanced by Structural Testing

The NASA Glenn Research Center, the U.S. Department of Energy, and the Stirling Technology Company (STC) are developing a highly efficient, long-life, free-piston Stirling convertor for use as an advanced spacecraft power system for future NASA missions, including deep-space and Mars surface applications. As part of this development, four structural dynamic test programs were recently performed on Stirling Technology Demonstration Convertors (TDC's) that were designed and built by STC under contract to the Department of Energy. This testing was performed in Glenn's Structural Dynamics Laboratory and Microgravity Emissions Laboratory. The first test program, in November and December 1999, demonstrated that the Stirling TDC could withstand the harsh random vibration experienced during a typical spacecraft launch and survive with no structural damage or functional power performance degradation. This was a critical step in enabling the use of Stirling convertors for future spacecraft power systems. The most severe test was a 12.3grms random vibration test, with test durations of 3 min per axis. The random vibration test levels were chosen to simulate, with margin, the maximum anticipated launch vibration conditions. The Microgravity Emissions Laboratory is typically used to measure the dynamics produced by operating space experiments and the resulting impact to the International Space Station's microgravity environment. For the second Stirling dynamic test program, performed in January 2001, the Microgravity Emissions Laboratory was used to characterize the structure-borne disturbances produced by the normal operation of a pair of Stirling convertors. The forces and moments produced by the normal operation of a Stirling system must be recognized and controlled, if necessary, so that other nearby spacecraft components, such as cameras, are not adversely affected. The Stirling convertor pair emitted relatively benign tonal forces at its operational frequency and associated harmonics. Therefore, Stirling power systems will not disturb spacecraft science experiments if minimal appropriate mounting efforts are made. The third test program, performed in February and May 2001, resulted in a modal characterization of a Stirling convertor. Since the deflection of the TDC piston rod, under vibration excitation, was of particular interest, the outer pressure shell was removed to allow access to the rod. Through this testing, the Stirling TDC's natural frequencies and modes were identified. This knowledge advanced our understanding of the successful 1999 vibration test and may be utilized to optimize the output power of future Stirling designs. The fourth test program, in April 2001, was conducted to characterize the structural response of a pair of Stirling convertors, as a function of their mounting interface stiffness. The test results provide guidance for the Stirling power package interface design. Properly designed, the interface may lead to increased structural capability and power performance beyond what was demonstrated in the successful 1999 vibration test. Dynamic testing performed to date at Glenn has shown that the Stirling convertors can withstand liftoff random vibration environments and meet "good neighbor" vibratory emission requirements. Furthermore, the future utilization of the information obtained during the tests will allow the corporation selected to be the Stirling system integrator to optimize their convertor and system interfaces designs. Glenn's Thermo-Mechanical Systems Branch provides Stirling technology expertise under a Space Act Agreement with the Department of Energy. Additional vibration testing by Glenn's Structural Systems Dynamics Branch is planned to continue to demonstrate the Stirling power system's vibration capability as its technology and flight system designs progress.

Hughes, William O.↗

Importance of mitral valve repair associated with left ventricular reconstruction for patients with ischemic cardiomyopathy: a real-time three-dimensional echocardiographic study

BACKGROUND: Left ventricular (LV) reconstruction surgery leads to early improvement in LV function in ischemic cardiomyopathy (ICM) patients. This study was designed to evaluate the impact of mitral valve (MV) repair associated with LV reconstruction on LV function 1-year after surgery in ICM patients assessed by real-time 3-dimensional echocardiography (3DE). METHODS AND RESULTS: Sixty ICM patients who underwent the combination surgery (LV reconstruction in 60, MV repair in 30, and revascularization in 52 patients) were studied. Real-time 3DE was performed and LV volumes were obtained at baseline, discharge, 6-month and >or=12-month follow-up. Reduction in end-diastolic volumes (EDV) by 29% and in end-systolic volumes by 38% were demonstrated immediately after surgery and remained at subsequent follow-up (P<0.0001). The LV ejection fraction significantly increased by about 10% at discharge and was maintained >or=12-month (P<0.0001). Although the LV volumes were significantly larger in patients with MV repair before surgery (EDV, 235+/-87 mL versus 193+/-67 mL, P<0.05), they were similar to LV volumes of the patients without MV repair at subsequent follow-ups. However, the EDV increased from 139+/-24 mL to 227+/-79 mL (P<0.01) in 7 patients with recurrent mitral regurgitation (MR). Improvement in New York Heart Association functional class occurred in 81% patients during late follow-up. CONCLUSIONS: Real-time 3DE demonstrates that LV reconstruction provides significant reduction in LV volumes and improvement in LV function which is sustained throughout the 1-year follow-up with 84% cardiac event free survival. If successful, MV repair may prevent LV redilation, while recurrent MR is associated with increased LV volumes.

Clinical Trial↗