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At least 289 records · Page 16

Defining Nitrogen Kinetics for Air Break in Prebreathe

Actual tissue nitrogen (N2) kinetics are complex; the uptake and elimination is often approximated with a single half-time compartment in statistical descriptions of denitrogenation [prebreathe (PB)] protocols. Air breaks during PB complicate N2 kinetics. A comparison of symmetrical versus asymmetrical N2 kinetics was performed using the time to onset of hypobaric decompression sickness (DCS) as a surrogate for actual venous N2 tension. Published results of 12 tests involving 179 hypobaric exposures in altitude chambers after PB, with and without air breaks, provide the complex protocols from which to model N2 kinetics. DCS survival time for combined control and air breaks were described with an accelerated log logistic model where N2 uptake and elimination before, during, and after the air break was computed with a simple exponential function or a function that changed half-time depending on ambient N2 partial pressure. P1N2-P2 = delta P defined DCS dose for each altitude exposure, where P2 was the test altitude and P1N2 was computed N2 pressure at the beginning of the altitude exposure. The log likelihood (LL) without DCS dose (null model) was -155.6, and improved (best-fit) to -97.2 when dose was defined with a 240 min half-time for both N2 elimination and uptake during the PB. The description of DCS survival time was less precise with asymmetrical N2 kinetics, for example, LL was -98.9 with 240 min half-time elimination and 120 min half-time uptake. The statistical regression described survival time mechanistically linked to symmetrical N2 kinetics during PBs that also included air breaks. The results are data-specific, and additional data may change the conclusion. The regression is useful to compute additional PB time to compensate for an air break in PB within the narrow range of tested conditions.

Conkin, Johnny↗

Genetic Determinants of Microbial Survival in Space

Space flight agencies envision a future for humankind beyond Earth, including missions back to the Moon and to Mars in the coming decades. Sending humans into space inevitably includes their microbiomes as well, leading to trillions of bacteria being shed in their living areas. These bacteria shape the lives of their hosts as well as their environment; thus, it is crucial to understand the adaptations of these microbial spacefarers in spaceflight conditions. We aimed to elucidate the genetic determinants of microbial survival in space using a pan-genome analysis of 12 genera cultured from the International Space Station (ISS) from 2017 to 2018. Analysis was performed on each of the genera individually with terrestrial analogs to identify the core and accessory genomes of the spaceflight and terrestrial strains. We then compared the flight and terrestrial core and accessory genomes for each genera using a Bray-Curtis index and visualized the resulting dissimilarity using an Non-Metric Dimensional Scaling plot. The core proteins available in only the spaceflight organisms were then manually characterized for function and genomic location. In every core genome comparison in each genus, there was significant dissimilarity in the core of the spaceflight organisms when compared to the terrestrial organisms. This trend was present in some of the accessory genomes, but was not ubiquitous. Functional analysis of the core content of the ISS genomes showed the majority of genes unique to the core were clustered by location. These gene clusters suggested a set of genetic determinants confer survival in spacecraft-built environments, notably through the uptake of extracellular DNA such as bacteriophage and plasmids. The clear difference between spaceflight and terrestrial microorganisms shows that spaceflight conditions are selective, which has long term implications for their human hosts and environments.

MoBE↗

Computational ranking identifies Plexin-B2 in circulating tumor cell clustering with monocytes in breast cancer metastasis

Abstract Multicellular circulating tumor cell (CTC) clusters can be up to 50 times more efficient than single CTCs in mediating viable metastasis. Here, combining computational ranking and functional determination, we identify the transmembrane protein Plexin-B2 (PLXNB2) as one of the top molecular targets associated with unfavorable distant metastasis-free survival, showing enriched expression in CTC clusters versus single CTCs from patients with advanced breast cancer (mostly female). Loss of PLXNB2 (Plxnb2) reduces the formation of homotypic tumor cell clusters and heterotypic tumor-myeloid cell clusters, reducing spontaneous metastases in female mice bearing human (mouse) breast cancer. Interactions of PLXNB2 with its ligands SEMA4C on tumor cells and SEMA4A on myeloid cells (monocytes) promote homotypic and heterotypic CTC cluster formation, respectively, thereby driving lung metastasis. Global proteomic analysis reveals downstream effectors of the PLXNB2 pathway associated with tumor cell clustering. Thus, PLXNB2 is a therapeutic target for preventing new metastasis in breast cancer.

Science & Technology - Other Topics↗

Meron, skyrmion, and vortex crystals in centrosymmetric tetragonal magnets

The recent experimental confirmation of a transformation between meron and skyrmion topological spin textures in the chiral magnet Co 8 Zn 9 Mn 3 confirms that the skyrmion crystals discovered in 2009 are just the tip of the iceberg. Crystals of topological textures, including skyrmions, merons, vortices, and monopoles, can be stabilized by combining simple physical ingredients, such as lattice symmetry, frustration, and spin anisotropy. The current challenge is to find the combinations of these ingredients that produce specific topological spin textures. In this work, we report a simple mechanism for the stabilization of meron, skyrmion, and vortex crystals in centrosymmetric tetragonal magnets. In particular, the meron/skyrmion crystals can form even in absence of magnetic field. The application of magnetic field leads to a rich variety of topological spin textures that survive in the long wavelength limit of the theory. When conduction electrons are coupled to the spins, these topological spin textures twist the electronic wave functions to induce Chern insulators and Weyl semimetals for specific band filling fractions.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Cultivating the Bacterial Microbiota of Populus Roots

Microbial communities play an integral role in the health and survival of their plant hosts. Many studies have identified key members in these communities and led to the use of synthetic communities for elucidating their function; however, these studies are limited by the available cultured bacterial representatives.

16S rRNA gene sequencing↗

Ecosystems and Networks Integrated with Genes and Molecular Assemblies (ENIGMA): Component 5: Imaging Protein Conformations, Shapes & Assemblies in Solution & Administration project (Final Scientific/Technical Report, Subcontract No. 6974584)

We set ambitious goals to examine microorganism communities and measure both their chemical input and output as a read out of specific biochemical activity. These scientific goals are driving the development of sophisticated algorithms to analyze large amounts of experimental measurements made using high throughput technologies to explain and predict how the environment influences biological function at multiple scales and how the microbial systems in tum modify the environment. By examining how bacteria communities rely on symbiotic metabolic relationships for survival and reproductive success, and how these relationships consequently affect their biochemical capabilities. This was accomplished using state-of-the-art mass spectrometry-based methods, and metabolic fingerprinting approaches with a high degree of chemical specificity and sensitivity. During this period the original effort transitioned and was consolidated into what is now ENIGMA, the efforts on technology development expanded to include more untargeted metabolomics and its application to organisms on a systems level.

59 BASIC BIOLOGICAL SCIENCES↗

A co-accretional model of satellite formation

A model of the accumulation process of a satellite about an accreting planet is proposed in order to explain the difference in relative size between the moon and the outer planets' satellites. The parameter that most strongly affects the final mass ratio of the pair in this model is the time at which the secondary embryo is introduced. Thus the difference between terrestrial and outer planet satellite systems is easily understood in terms of the differences in Q (the specific dissipation function of the particles in the circumplanetary cloud) between these planets. The high Q of the outer planets does not allow a satellite embryo to survive a significant portion of the accretion process; therefore only small bodies formed very late in the accumulation of the planet remain as satellites.

Harris, A. W.↗

Differential degradation of Martian impact basins

Among the major problems of martian geologic history are the cause of the highland-lowland dichotomy, and of the scarp separating these two global-scale provinces. These features were formed after much of the early bombardment was completed; consequently, many of the surviving impact basins very likely were present during the creation of the dichotomy, and it is possible that differences in their present morphologies as a function of location and of relative age may provide clues to the tectonic and geomorphic processes responsible for the dichotomy and the scarp.

Stam, M.↗

Crew productivity issues in long-duration space flight

Considerable evidence suggests the importance of teamwork, coordination, and conflict resolution to the performance and survival of isolated, confined groups in high-technology environments. With the advent of long-duration space flight, group-related issues of crew functioning will take on added significance. This paper discusses the influence of crew roles, status, leadership, and norms on the performance of small, confined groups, and offers guidelines and suggestions regarding organizational design, crew selection, training, and team building for crew productivity and social well-being in long-duration spaceflight.

Nicholas, John M.↗

A satellite data terminal for land mobile use

Telesat Mobile Incorporated (TMI) has recently introduced the Mobile Data Service (MDS) into Canada. This paper outlines the system design and some key aspects of the detailed design of the Mobile Earth Terminal (MET) developed by Canadian Aeronautics Limited (CAL) for use with the MDS. The technical requirements for the MET are outlined and the equipment architecture is described. The major design considerations for each functional module are then addressed. Environmental conditions unique to the land mobile service are highlighted, along with the measures taken to ensure satisfactory operation and survival of the MET. Finally, the probable direction of future developments is indicated.

Sutherland, Colin A.↗

A Novel Method for Characterizing Spacesuit Mobility through Metabolic Cost

Spacesuit mobility has historically been defined and characterized by a combination of range of motion and joint torque of the individual anatomical joints when performing isolated motions meant to drive that joint only in a given orthogonal plane. While this has been the standard approach for several decades, there are numerous shortcomings that suit designers and engineers would like to see rectified. First, the lack of a standardized method for collecting both range of motion and joint torque translates to many different test setups, procedures and methods of data analysis. Second, all of these previously used methods for data collection lack some degree of repeatability, even within the same test setup and the same conductor; in addition, attempts at higher fidelity data collection techniques require high overhead and cost with minimal improvement. Lastly, isolated motions in standard anatomical planes are not representative of real‐world tasks that a crewmember would be performing during an EVA, be it microgravity or surface exploration based. To address these shortcomings, options are being explored within the Space Suit and Crew Survival Systems Branch to ascertain the feasibility of an alternative approach to defining mobility - one that is more repeatable, lower overhead, and more tied to functional EVA tasks. This paper serves to document the first attempt at such an alternative option - one that looks at the metabolic energy‐cost of a spacesuit. In other words, can we objectively compare the mobility of a spacesuit by evaluating the metabolic cost of that suit to the wearer while performing a battery of functional EVA tasks?

McFarland, Shane↗

Space Station WP-2 application of LDEF MLI results

The Cascaded Variable Conductance Heat Pipe Experiment, which was developed by Michael Grote of McDonnell Douglas Electronic Systems Company, was located in Tray F-9 of the Long Duration Exposure Facility (LDEF), where it received atomic oxygen almost normal to its surface. The majority of the tray was covered by aluminized Kapton polyimide multilayer insulation (MLI), which showed substantial changes from atomic oxygen erosion. Most of the outermost Kapton layer of the MLI and the polyester scrim cloth under it were lost, and there was evidence of contaminant deposition which discolored the edges of the MLI blanket. Micrometeoroid and orbital debris (MM/OD) hits caused small rips in the MLI layers, and in some cases left cloudy areas where the vapor plume caused by a hit condensed on the next layer. The MLI was bent gradually through 90 deg at the edges to enclose the experiment, and the Kapton that survived along the curved portion showed the effects of atomic oxygen erosion at oblique angles. In spite of space environment effects over the period of the LDEF mission, the MLI blanket remained functional. The results of the analysis of LDEF MLI were used in developing the standard MLI blanket for Space Station Work Package-2 (WP-2). This blanket is expected to last 30 years when exposed to the low Earth orbit (LEO) environment constituents of atomic oxygen and MM/OD, which are the most damaging to MLI materials. The WP-2 standard blanket consists of an outer cover made from Beta-cloth glass fiber fabric which is aluminized on the interior surface, and an inner cover of 0.076-mm (0.003-in) double-side-aluminized perforated Kapton. The inner reflector layers are 0.0076-mm (0.0003-in) double-side aluminized, perforated Kapton separated by layers of Dacron polyester fabric. The outer cover was selected to be resistant to the LEO environment and durable enough to survive in orbit for 30 years. This paper describes the analyses of the LDEF MLI results, and how these results contributed to the selection of the WP-2 MLI blanket materials and configuration.

Smith, Charles A.↗

Immunophenotypic characterization and therapeutics effects of human bone marrow- and umbilical cord-derived mesenchymal stromal cells in an experimental model of sepsis

Highlights: • Mesenchymal stromal cells (MSCs) may be a therapeutic option for sepsis. • Bone marrow (BM) vs. umbilical cord (UC) -MSCs induce different M1/M2 gene profiles. • In a CLP model of sepsis, only BM-MSCs improved survival and bacterial clearance. Sepsis is a complicated multi-system disorder characterized by a dysregulated host response to infection. Despite substantial progress in the understanding of mechanisms of sepsis, translation of these advances into clinically effective therapies remains challenging. Mesenchymal Stromal Cells (MSCs) possess immunomodulatory properties that have shown therapeutic promise in preclinical models of sepsis. The therapeutic effects of MSCs may vary depending on the source and type of these cells. In this comparative study, the gene expression pattern and surface markers of bone marrow-derived MSCs (BM-MSCs) and umbilical cord-derived MSCs (UC-MSCs) as well as their therapeutic effects in a clinically relevant mouse model of polymicrobial sepsis, cecal ligation and puncture (CLP), were investigated. The results showed remarkable differences in gene expression profile, surface markers and therapeutic potency in terms of enhancing survival and pro/anti-inflammatory responses between the two MSC types. BM-MSCs improved survival concomitant with an enhanced systemic bacterial clearance and improved inflammatory profile post CLP surgery. Despite some improvement in the inflammatory profile of the septic animals, treatment with UC-MSCs did not enhance survival or bacterial clearance. Overall, the beneficial therapeutic effects of BM-MSCs over UC-MSCs may likely be attributed to their pro-inflammatory function, and to some extent anti-inflammatory features, reflected in their gene expression pattern enhancing macrophage polarization to M1/M2 phenotypes resulting in a balanced pro- and anti-inflammatory response against polymicrobial sepsis.

60 APPLIED LIFE SCIENCES↗

Ecosystems and Networks Integrated with Genes and Molecular Assemblies (ENIGMA): Integrating Metabolomics into Environmental Systems Biology

Our research endeavors entail ambitious objectives to explore the communities of microorganisms and quantify their chemical input and output to determine specific biochemical activity. To achieve these scientific aims, we are creating advanced algorithms to scrutinize extensive experimental data produced through high-throughput technologies, enabling us to elucidate how biological functions are influenced by environmental factors on various scales, and how microbial systems alter their surroundings. By studying the metabolic interdependence of bacterial communities for their survival and reproductive prosperity, we can gain insights into their biochemical capabilities. To accomplish this, we employed cutting-edge mass spectrometry-based techniques and metabolic fingerprinting methods, which offer high chemical specificity and sensitivity. As our efforts progressed, the project evolved into ENIGMA, encompassing a broader range of technology development, including untargeted metabolomics and its implementation for system-level organism analysis.

54 ENVIRONMENTAL SCIENCES↗

Stand Alone Pressure Measurement Device (SAPMD) for the space shuttle Orbiter, part 1

The specifications for the Stand Alone Pressure Measurement Device (SAPMD) are as follows: the SAPMD shall measure ambient pressure at the surface of the Orbiter TPS in the range of 0 to 15 pounds per square inch absolute (PSIA). Measurement will begin at solid rocket booster (SRB) ignition as sensed by appropriate vibration sensing elements in the SAPMD. Pressure and corresponding real-time data are to be recorded every one tenth second for 140 seconds and at the end of the recording period, the operation will be discontinued with the data preserved for interrogation subsequent to Orbiter re-entry and landing. The type and size of the battery shall be such as to allow the vibration sensing elements and a real-time clock to be initialized a minimum of 30 day prior to launch and still provide power as necessary to perform the 140 second data recording period after SRB ignition. Battery installation shall be in such a manner as to allow battery replacement without removing the SAPMD from its position or removing more than one TPS tile. The SAPMD must be mounted in specific locations under tile of the TPS. To accommodate such mounting, the absolute maximum physical dimensions much not exceed 6.0 inches in length, 1.5 inches in width, and 0.4 inches in height, and the device shall be of such configuration that it can be bonded to the Orbiter skin at the joint line of two TPS tiles with the pressure sensing port at the surface of the tile. The SAPMD must remain operational in the temperature range of -40 to +85 C and survive storage temperature of -55 to +125 C. The pressure port must withstand 934 C without causing damage to the TPS during entry and must remain functional at 262 C during ascent. The accuracy of the pressure measurement must be plus or minus one-half PSIA over a temperature range of 0 to +36 C. All the specifications were met and verified by prototype testing and documented in the enclosed test data. Four flight-qualified models were fabricated and of these, two were delivered and successfully flown in the cargo bay of STS-26.

Tomlinson, Bill↗

Developments in Nano-Satellite Structural Subsystem Design at NASA-GSFC

The NASA-GSFC Nano-satellite Technology Development Program will enable flying constellations of tens to hundreds of nano-satellites for future NASA Space and Earth Science missions. Advanced technology components must be developed to make these future spacecraft compact, lightweight, low-power, low-cost, and survivable to a radiation environment over a two-year mission lifetime. This paper describes the efforts underway to develop lightweight, low cost, and multi-functional structures, serviceable designs, and robust mechanisms. As designs shrink, the integration of various subsystems becomes a vital necessity. This paper also addresses structurally integrated electrical power, attitude control, and thermal systems. These innovations bring associated fabrication, integration, and test challenges. Candidate structural materials and processes are examined and the merits of each are discussed. Design and fabrication processes include flat stock composite construction, cast aluminum-beryllium alloy, and an injection molded fiber-reinforced plastic. A viable constellation deployment scenario is described as well as a Phase-A Nano-satellite Pathfinder study.

Rossoni, Peter↗

The SrrAB two-component system regulates Staphylococcus aureus pathogenicity through redox sensitive cysteines

Staphylococcus aureus infections can lead to diseases that range from localized skin abscess to life-threatening toxic shock syndrome. The SrrAB two-component system (TCS) is a global regulator of S. aureus virulence and critical for survival under environmental conditions such as hypoxic, oxidative, and nitrosative stress found at sites of infection. Despite the critical role of SrrAB in S. aureus pathogenicity, the mechanism by which the SrrAB TCS senses and responds to these environmental signals remains unknown. Bioinformatics analysis showed that the SrrB histidine kinase contains several domains, including an extracellular Cache domain and a cytoplasmic HAMP-PAS-DHp-CA region. In this work, we show that the PAS domain regulates both kinase and phosphatase enzyme activity of SrrB and present the structure of the DHp-CA catalytic core. Importantly, this structure shows a unique intramolecular cysteine disulfide bond in the ATP-binding domain that significantly affects autophosphorylation kinetics. In vitro data show that the redox state of the disulfide bond affects S. aureus biofilm formation and toxic shock syndrome toxin-1 production. Moreover, with the use of the rabbit infective endocarditis model, we demonstrate that the disulfide bond is a critical regulatory element of SrrB function during S. aureus infection. Our data support a model whereby the disulfide bond and PAS domain of SrrB sense and respond to the cellular redox environment to regulate S. aureus survival and pathogenesis.

59 BASIC BIOLOGICAL SCIENCES↗

Growing B Lymphocytes in a Three-Dimensional Culture System

A three-dimensional (3D) culture system for growing long-lived B lymphocytes has been invented. The capabilities afforded by the system can be expected to expand the range of options for immunological research and related activities, including testing of immunogenicity of vaccine candidates in vitro, generation of human monoclonal antibodies, and immunotherapy. Mature lymphocytes, which are the effectors of adaptive immune responses in vertebrates, are extremely susceptible to apoptotic death, and depend on continuous reception of survival-inducing stimulation (in the forms of cytokines, cell-to-cell contacts, and antigen receptor signaling) from the microenvironment. For this reason, efforts to develop systems for long-term culture of functional, non-transformed and non-activated mature lymphocytes have been unsuccessful until now. The bone-marrow microenvironment supports the growth and differentiation of many hematopoietic lineages, in addition to B-lymphocytes. Primary bone-marrow cell cultures designed to promote the development of specific cell types in vitro are highly desirable experimental systems, amenable to manipulation under controlled conditions. However, the dynamic and complex network of stromal cells and insoluble matrix proteins is disrupted in prior plate- and flask-based culture systems, wherein the microenvironments have a predominantly two-dimensional (2D) character. In 2D bone-marrow cultures, normal B-lymphoid cells become progressively skewed toward precursor B-cell populations that do not retain a normal immunophenotype, and such mature B-lymphocytes as those harvested from the spleen or lymph nodes do not survive beyond several days ex vivo in the absence of mitogenic stimulation. The present 3D culture system is a bioreactor that contains highly porous artificial scaffolding that supports the long-term culture of bone marrow, spleen, and lymph-node samples. In this system, unlike in 2D culture systems, B-cell subpopulations developing within 3D cultures that have been modified to foster lymphopoiesis retain an immunophenotype that closely recapitulates cells in fresh bone marrow harvests. The 3D culture system has been found to be capable of supporting long-lived (8 weeks) populations of B and T lymphocytes from peripheral lymphoid organs, in the absence of activation signals, to an extent not achievable by conventional culture techniques. Interestingly, it has been found that 3D-culture B cells display a phenotype that has characteristics of both B1a and B2 cells. These promising preliminary observations suggest that the 3D culture system could be used with success in the study of peripheral-B-lymphocyte biology and in the development of biotechnological techniques and processes.

Wu, J. H. David↗