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At least 685 records · Page 38

Deep Diversity: Novel Approach to Overcoming the PCR Bias Encountered During Environmental Analysis of Microbial Populations for Alpha-Diversity

Alpha-diversity studies are of crucial importance to environmental microbiologists. The polymerase chain reaction (PCR) method has been paramount for studies interrogating microbial environmental samples for taxon richness. Phylogenetic studies using this technique are based on the amplification and comparison of the 16S rRNA coding regions. PCR, due disproportionate distribution of microbial species in the environment, increasingly favors the amplification of the most predominant phylotypes with every subsequent reaction cycle. The genetic and chemical complexity of environmental samples are intrinsic factors that exacerbate an inherit bias in PCR-based quantitative and qualitative studies of microbial communities. We report that treatment of a genetically complex total genomic environmental DNA extract with Propidium Monoazide (PMA), a DNA intercalating molecule capable of forming a covalent cross-linkage to organic moieties upon light exposure, disproportionally inactivates predominant phylotypes and results in the exponential amplification of previously shadowed microbial ?-diversity quantified as a 19.5% increase in OUTs reported via phylogenetic screening using PhyloChip.

phylogenetic microarray technologies↗

Cerebrovascular Accident Incidence in the NASA Astronaut Population

The development of atherosclerosis is strongly associated with an increased risk for cerebrovascular accidents (CVA), including stroke and transient ischemic attacks (TIA). Certain unique occupational exposures that individuals in the NASA astronaut corps face, specifically high-performance aircraft training, SCUBA training, and spaceflight, are hypothesized to cause changes to the cardiovascular system. These changes, which include (but are not limited to) oxidative damage as a result of radiation exposure and circadian rhythm disturbance, increased arterial stiffness, and increased carotid-intima-media thickness (CIMT), may contribute to the development of atherosclerosis and subsequent CVA. The purpose of this study was to review cases of CVA in the NASA astronaut corps and describe the comorbidities and occupational exposures associated with CVA.

LaPelusa, Michael B.↗

The Foreign Clast Populations of Anomalous Polymict Urelite Almahata Sitta (Asteroid 2008 TC(sub3) and Typical Polymict Ureilites: Implications for Asteroid-Meteorite Connections

Almahata Sitta (AhS) is the first meteorite to originate from an asteroid (2008 TC3) that had been studied in space before it hit Earth [1,2]. It is also unique because the fallen fragments comprise a variety of types: approximately 69% ureilites (achondrites) and 31% chondrites [3]. Two models have been proposed for the origin 2008 TC3: 1) an accretionary model [3,4]; or 2) a regolith model [5,6]. Typical polymict ureilites are interpreted to represent regolith, and contain a few % foreign clasts [7,8]. The most common are dark (CC matrix-like) clasts similar to those in many meteoritic breccias [9]. A variety of other chondrites, as well as achondrites (angrites), have also been reported [7,9,10]. We have been working to determine the full diversity of these clasts [10-13] for comparison with AhS. We discuss implications for mixing of materials in the early solar system and the origin of 2008 TC3.

Goodrich, C. A.↗

Skin-Based DNA Repair Phenotype for Cancer Risk from GCR in Genetically Diverse Populations

Predicting cancer risk associated with cosmic radiation remains a mission-critical challenge for NASA radiation health scientists and mission planners. Epidemiological data are lacking and risk methods do not take individual radiation sensitivity into account. In our approach we hypothesize that genetic factors strongly influence risk of cancer from space radiation and that biomarkers reflecting DNA damage and cell death are ideal tools to predict risk and monitor potential health effects post-flight. At this workshop, we will be reporting the work we have done over the first 9 months of this proposal. Skin cells from 15 different strains of mice already characterized for radiation-induced cancer sensitivity (B6C3F; BALB/cByJ, C57BL/6J, CBA/CaJ, C3H/HeMsNrsf), and 10 strains from the DOE collaborative cross-mouse model were expanded from ear biopsy and cultivated until Passage 3. On average, 3 males and 3 females for each strain were expanded and frozen for further characterization at the NSRL beam line during the NSRL16C run for three LET (350 MeV/n Si, 350 MeV/n Ar and 600 MeV/n Fe) and two ion fluences (1 and 3 particles per cell). The mice work has established new metrics for the usage of Radiation Induced Foci as a marker for various aspect of DNA repair deficiencies. In year 2, we propose to continue characterization of the mouse lines with low LET to identify loci specific to high- versus low- LET and establish genetic linkage for the various DNA repair biomarkers. Correlation with cancer risk from each animals strain and gender will also be investigated. On the human side, we will start characterizing the DNA damage response induced ex-vivo in 200 human's blood donors for radiation sensitivity with a tentative 500 donors by the end of this project. All ex-vivo phenotypic data will be correlated to genetic characterization of each individual human donors using SNP arrays characterization as done for mice. Similarly, ex-vivo phenotypic features from mice will be associated to cancer risk, to identify which biomarkers correlate the most with cancer risk. Genetic traits across humans will also be associated to radiation phenotypic features as a function of age and gender.

radiation space biology↗

Exploring X-Ray Binary Populations in Compact Group Galaxies With Chandra

We obtain total galaxy X-ray luminosities, LX, originating from individually detected point sources in a sample of 47 galaxies in 15 compact groups of galaxies (CGs). For the great majority of our galaxies, we find that the detected point sources most likely are local to their associated galaxy, and are thus extragalactic X-ray binaries (XRBs) or nuclear active galactic nuclei (AGNs). For spiral and irregular galaxies, we find that, after accounting for AGNs and nuclear sources, most CG galaxies are either within the +/-1σ scatter of the Mineo et al. LX-star formation rate (SFR) correlation or have higher LX than predicted by this correlation for their SFR. We discuss how these "excesses" may be due to low metallicities and high interaction levels. For elliptical and S0 galaxies, after accounting for AGNs and nuclear sources, most CG galaxies are consistent with the Boroson et al. LX-stellar mass correlation for low-mass XRBs, with larger scatter, likely due to residual effects such as AGN activity or hot gas. Assuming non-nuclear sources are low- or high-mass XRBs, we use appropriate XRB luminosity functions to estimate the probability that stochastic effects can lead to such extreme LX values. We find that, although stochastic effects do not in general appear to be important, for some galaxies there is a significant probability that high LX values can be observed due to strong XRB variability.

X-rays: binaries↗

Influence of Population Variation of Physiological Parameters in Computational Models of Space Physiology

The earliest manifestations of Visual Impairment and Intracranial Pressure (VIIP) syndrome become evident after months of spaceflight and include a variety of ophthalmic changes, including posterior globe flattening and distension of the optic nerve sheath. Prevailing evidence links the occurrence of VIIP to the cephalic fluid shift induced by microgravity and the subsequent pressure changes around the optic nerve and eye. Deducing the etiology of VIIP is challenging due to the wide range of physiological parameters that may be influenced by spaceflight and are required to address a realistic spectrum of physiological responses. Here, we report on the application of an efficient approach to interrogating physiological parameter space through computational modeling. Specifically, we assess the influence of uncertainty in input parameters for two models of VIIP syndrome: a lumped-parameter model (LPM) of the cardiovascular and central nervous systems, and a finite-element model (FEM) of the posterior eye, optic nerve head (ONH) and optic nerve sheath. Methods: To investigate the parameter space in each model, we employed Latin hypercube sampling partial rank correlation coefficient (LHSPRCC) strategies. LHS techniques outperform Monte Carlo approaches by enforcing efficient sampling across the entire range of all parameters. The PRCC method estimates the sensitivity of model outputs to these parameters while adjusting for the linear effects of all other inputs. The LPM analysis addressed uncertainties in 42 physiological parameters, such as initial compartmental volume and nominal compartment percentage of total cardiac output in the supine state, while the FEM evaluated the effects on biomechanical strain from uncertainties in 23 material and pressure parameters for the ocular anatomy. Results and Conclusion: The LPM analysis identified several key factors including high sensitivity to the initial fluid distribution. The FEM study found that intraocular pressure and intracranial pressure had dominant impact on the peak strains in the ONH and retro-laminar optic nerve, respectively; optic nerve and lamina cribrosa stiffness were also important. This investigation illustrates the ability of LHSPRCC to identify the most influential physiological parameters, which must therefore be well-characterized to produce the most accurate numerical results.

biomechanics↗

SO-QT: Collaborative Tool to Project the Future Space Object Population

Earth orbit gets increasingly congested, a challenge to space operators, both in governments and industry. We present a web tool that provides: 1) data on todays and the historic space object environments, by aggregating object-specific tracking data; and 2) future trends through a collaboration platform to collect information on planed launches. The collaborative platform enables experts to pool and compare their data in order to generate future launch scenarios. The tool is intended to support decision makers and mission designers while they investigate future missions and scholars as they develop strategies for space traffic management.

space debris↗

Air Traffic Simulation Technology for High-Population Metroplexes

IAI's MetroSim optimizes air traffic by simulating departures, arrivals, and activity in air and onthe ground in busy metroplexes, where flights impact each other at a single airport and among traffic at nearby airports. MetroSim evolved out of several NASA SBIR/STTR Awards and has since been used by NASA for flight simulation analysis. MetroSim has also been integrated with FAA and DOT technology, has produced studies for the Port Authority of New York and New Jersey, and is under development to support the Navy

Cannon, Kimberly A.↗

Effect of a Large Population of Seeded Alumina Inclusions on Crack Initiation and Small Crack Fatigue Crack Growth in Udimet 720 Nickel-Base Disk Superalloy

Crack initiation, crack coalescence and small crack growth behavior were monitored for over 400 seeded inclusions during interrupted low cycle fatigue testing conducted on the P/M Udimet 720 nickel disk alloy at 650°C. Two types of seeded alumina inclusions with average sizes of 54 μm and 122 μm were used in the study performed at varying loading conditions resulting in LCF lives ranging from 2,000 cycles to over 1,000,000 cycles. The fatigue behavior was sub-categorized into four groups. Visual maps detailing inclusion size/cycle history were developed. The effect of surface residual stresses on the fatigue life was also investigated.

Superalloys↗

BLOOD-BASED MULTI-SCALE MODEL FOR CANCER RISK FROM GCR IN GENETICALLY DIVERSE POPULATIONS

OBJECTIVES AND METHODS This project addresses the challenge of understanding and predicting individual radiation sensitivity by integrating genetics, demographics and biomarker characteristics across species (mice and humans). We hypothesize that ex vivo DNA repair response to GCR components is a central determinant of cancer risk from space radiation and can serve as a biomarker of radiation risk in combination with genetics. Automated image quantification of 53BP1+ radiation-induced foci (RIF) during the first 4-48 h post-irradiation was performed as a function of dose and LET in non-immortalized primary skin fibroblasts derived from 76 mice across 15 strains (5 inbred reference strains and 10 collaborative-cross strains) exposed to X rays (0.1, 1 and 4 Gy), 350 MeV/n 40Ar and 600 MeV/n 56Fe (1.1 and 3 particles/100μm2), as well as in peripheral blood mononuclear cells (PBMCs) from 768 healthy donors (matched ethnicity, 50/50 male/female, 18-70 years old) exposed to gamma rays (0.1 and 1 Gy), 350 MeV/n 28Si, 350 MeV/n 40Ar and 600 MeV/n 56Fe (1.1 and 3 particles/100μm2). QUANTIFICATION OF 53BP1+ FOCI IN VITRO AND ASSOCIATIONS TO IN VIVO RADIATION SUSCEPTIBILITY IN 15 MOUSE STRAINS We reported in vitro repair kinetic and repairable fractions of RIF for the 15 mouse strains and introduced a mathematical model for RIF as a function of time, dose and LET. We noted that the metabolic activity of cells modulates the RIF response, and we introduced the open access tool terRIFic (Tool for Enhanced Results of RIF In Cells, https://radbiolab.shinyapps.io/terrific/) to correct for such bias using confluence level. Notably, at 4h post-irradiation, RIF/Gy decreased with dose or LET: as the dose or LET increases, so does the proximity of DNA double-strand-breaks (DSB) and our data suggest that proximal DSBs are brought together inside isolated RIF for repair. The RIF/Gy trend was inverted at 24h, suggesting RIF with high DSB content are more difficult to repair. We showed that in vitro metrics correlate with in vivo measurements in the same 15 mouse strains, such as survival levels of immune cells or spontaneous cancer incidence, suggesting a relationship between the efficiency of DSB repair and cancer risk or radiation toxicity. In addition to the efficiency of repair and persistent RIF, the amount of spontaneous foci before irradiation was also found to be strain dependent. Finally, we performed genome-wide association study in the same 15 mouse strains using all RIF phenotypes measured in vitro, identifying genes of interest and validating RIF as an ideal biomarker for individual radiation sensitivity. BASELINE 53BP1+ FOCI PREDICTS INDIVIDUAL HUMAN RESPONSE TO GCR COMPONENTS Based on the analysis of radiation responses of 576 donor PBMCs (using quantification of 53BP1+ foci, oxidative stress and cell death), we observed a wide variability of subject- and LET-dependent radiation responses, with radiation-induced DNA repair foci increasing with LET, though oxidative stress being notably reduced by high-LET irradiation, potentially due to a switch between hydrogen peroxide and oxygen radical-based mechanisms. We identified a relationship between few spontaneous DNA foci at baseline and increased DNA repair after irradiation, accompanied by an alteration in immunoregulatory cytokine secretion, which might be adapted as biomarkers to predict ionizing radiation sensitivity. Among demographic variables, only latent cytomegalovirus infection and age were predictive of high baseline foci formation. Finally, we have performed low-throughput whole genome sequencing of all samples and are currently in the process of identifying the genes and pathways associated with low and high-LET ionizing radiation sensitivity in humans.

53BP1↗