Johnson Space Center's regenerative life support systems test bed

The Regenerative Life Support System (RLSS) Test Bed at NASA's Johnson Space Center is an atmospherically closed, controlled environment facility for the evaluation of regenerative life support systems using higher plants in conjunction with physicochemical life support systems. When completed, the facility will be comprised of two large scale plant growth chambers, each with approximately 10 m(exp 2) growing area. One of the two chambers, the Variable Pressure Growth Chamber (VPGC), will be capable of operating at lower atmospheric pressures to evaluate a range of environments that may be used in Lunar or Martian habitats; the other chamber, the Ambient Pressure Growth Chamber (APGC) will operate at ambient atmospheric pressure. The root zone in each chamber will be configurable for hydroponic or solid state media systems. Research will focus on: (1) in situ resource utilization for CELSS systems, in which simulated lunar soils will be used in selected crop growth studies; (2) integration of biological and physicochemical air and water revitalization systems; (3) effect of atmospheric pressure on system performance; and (4) monitoring and control strategies

Indeterminacy and instability in Petschek reconnection

We explain two puzzling aspects of Petschek's model for fast reconnection. One is its failure to occur in plasma simulations with uniform resistivity. The other is its inability to provide anything more than an upper limit for the reconnection rate. We have found that previously published analytical solutions based on Petschek's model are structurally unstable if the electrical resistivity is uniform. The structural instability is associated with the presence of an essential singularity at the X-line that is unphysical. By requiring that such a singularity does not exist, we obtain a formula that predicts a specific rate of reconnection. For uniform resistivity, reconnection can only occur at the slow, Sweet-Parker rate. For nonuniform resistivity, reconnection can occur at a much faster rate provided that the resistivity profile is not too flat near the X-line. If this condition is satisfied, then the scale length of the nonuniformity determines the reconnection rate

The Mouse INO80 Chromatin-Remodeling Complex Is an Essential Meiotic Factor for Spermatogenesis1

The ability to faithfully transmit genetic information across generations via the germ cells is a critical aspect of mammalian reproduction. The process of germ cell development requires a number of large-scale modulations of chromatin within the nucleus. One such occasion arises during meiotic recombination, when hundreds of DNA double-strand breaks are induced and subsequently repaired, enabling the transfer of genetic information between homologous chromosomes. The inability to properly repair DNA damage is known to lead to an arrest in the developing germ cells and sterility within the animal. Chromatin-remodeling activity, and in particular the BRG1 subunit of the SWI/SNF complex, has been shown to be required for successful completion of meiosis. In contrast, remodeling complexes of the ISWI and CHD families are required for postmeiotic processes. Little is known regarding the contribution of the INO80 family of chromatin-remodeling complexes, which is a particularly interesting candidate due to its well described functions during DNA double-strand break repair. Here we show that INO80 is expressed in developing spermatocytes during the early stages of meiotic prophase I. Based on this information, we used a conditional allele to delete the INO80 core ATPase subunit, thereby eliminating INO80 chromatin-remodeling activity in this lineage. The loss of INO80 resulted in an arrest during meiosis associated with a failure to repair DNA damage during meiotic recombination

Aerosols in the tropical and subtropical UT/LS: in-situ measurements of submicron particle abundance and volatility

Processes occurring in the tropical upper troposphere and lower stratosphere (UT/LS) are of importance for the global climate, for the stratospheric dynamics and air chemistry, and they influence the global distribution of water vapour, trace gases and aerosols. The mechanisms underlying cloud formation and variability in the UT/LS are of scientific concern as these still are not adequately described and quantified by numerical models. Part of the reasons for this is the scarcity of detailed in-situ measurements in particular from the Tropical Transition Layer (TTL) within the UT/LS. In this contribution we provide measurements of particle number densities and the amounts of non-volatile particles in the submicron size range present in the UT/LS over Southern Brazil, West Africa, and Northern Australia. The data were collected in-situ on board of the Russian high altitude research aircraft M-55 "Geophysica" using the specialised COPAS (COndensation PArticle counting System) instrument during the TROCCINOX (Araçatuba, Brazil, February 2005), the SCOUT-O3 (Darwin, Australia, December 2005), and SCOUT-AMMA (Ouagadougou, Burkina Faso, August 2006) campaigns. The vertical profiles obtained are compared to those from previous measurements from the NASA DC-8 and NASA WB-57F over Costa Rica and other tropical locations between 1999 and 2007. The number density of the submicron particles as function of altitude was found to be remarkably constant (even back to 1987) over the tropical UT/LS altitude band such that a parameterisation suitable for models can be extracted from the measurements. At altitudes corresponding to potential temperatures above 430 K a slight increase of the number densities from 2005/2006 results from the data in comparison to the 1987 to 2007 measurements. The origins of this increase are unknown. By contrast the data from Northern hemispheric mid latitudes do not exhibit such an increase between 1999 and 2006. Vertical profiles of the non-volatile fraction of the submicron particles were also measured by a COPAS channel and are presented here. The resulting profiles of the non-volatile number density fraction show a pronounced maximum of 50% in the tropical TTL over Australia and West Africa. Below and above this fraction is much lower attaining values of 10% and smaller. In the lower stratosphere the fine particles mostly consist of sulphuric acid which is reflected in the low numbers of non-volatile residues measured by COPAS. Without detailed chemical composition measurements the reason for the increase of non-volatile particle fractions cannot yet be given. The long distance transfer flights to Brazil, Australia and West-Africa were executed during a time window of 17 months within a period of relative volcanic quiescence. Thus the data measured during these transfers represent a "snapshot picture" documenting the status of a significant part of the global UT/LS aerosol (with sizes below 1 μm) at low concentration levels 15 years after the last major (i.e., the 1991 Mount Pinatubo) eruption. The corresponding latitudinal distributions of the measured particle number densities are also presented in this paper in order to provide input on the UT/LS background aerosol for modelling purposes

Fast imaging of filaments in the X-point region of Alcator C-Mod

A rich variety of field-aligned fluctuations has been revealed using fast imaging of Dαemission from Alcator C-Mod's lower X-point region. Field-aligned filamentary fluctuations are observed along the inner divertor leg, within the Private-Flux-Zone (PFZ), in the Scrape-Off Layer (SOL) outside the outer divertor leg, and, under some conditions, at or above the X-point. The locations and dynamics of the filaments in these regions are strikingly complex in C-Mod. Changes in the filaments’ generation appear to be ordered by plasma density and magnetic configuration. Filaments are not observed for plasmas with n/nGreenwald≲ 0.12 nor are they observed in Upper Single Null configurations. In a Lower Single Null with 0.12 ≲ n/nGreenwald ≲ 0.45 and Bx∇B directed down, filaments typically move up the inner divertor leg toward the X-point. Reversing the field direction results in the appearance of filaments outside of the outer divertor leg. With the divertor targets “detached”, filaments inside the LCFS are seen. These studies were motivated by observations of filaments in the X-point and PFZ regions in MAST, and comparisons with those observations are made. Keywords: Alcator C-Mod; Turbulence; Divertor; X-point; Filament

Factors Associated With Ordering Laboratory Monitoring Of High-Risk Medications

Background Knowledge about factors associated with provider ordering of appropriate testing is limited. Objective To determine physician factors correlated with ordering of recommended laboratory monitoring tests for high-risk medications, accounting for patient characteristics. Methods Analysis of the administrative claims and electronic medical records of patients prescribed a high-risk medication requiring laboratory monitoring in a large multispecialty group practice between January 1, 2008 and December 31, 2008. The outcome is a physician order for each recommended laboratory test for each prescribed medication. Key predictor variables include physician characteristics, including age, gender, specialty training, years since completing training, and prescribing volume. We used multivariable logistic regression to identify the independent association of physician and patient characteristics with ordering of laboratory tests to monitor medications after adjustment for potential confounders, taking into account clustering of drugs within patients and patients within providers. Results Physician orders for laboratory testing varied across drug-test pairs and ranged from 9% (Primidone–Phenobarbital level) to 97% (Azathioprine–CBC) with 50% of drug-test pairs in the 85-91% ordered range. Failure to order a test was associated with lower provider prescribing volume for study drugs and whether the physician was a specialist (primary care providers were more likely to order tests than specialists). Patients with lower patient comorbidity burden and younger patients were less likely to have appropriate tests ordered. Drug-test combinations with black box warnings were more likely to have tests ordered. Conclusions Interventions targeting providers should be addressed at those subgroups with the greatest potential for improvement: providers with lower frequencies of prescribing high-risk medications, and healthier and younger patients. Drug-test combinations with black box warnings have higher ordering rates, but many medications without such warnings also have evidence of harm, thus efforts to improve testing are necessary for all medications shown to be high-risk

Neurobehavioral deficits of mice expressing a low level of G127V mutant frataxin.

Friedreich’s ataxia (FRDA) is a neurodegenerative disease caused by reduced expression of the mitochondrial protein frataxin (FXN). Most FRDA patients are homozygous for large expansions of GAA repeats in intron 1 of FXN, while some are compound heterozygotes with an expanded GAA tract in one allele and a missense or nonsense mutation in the other. A missense mutation, changing a glycine to valine at position 130 (G130V), is prevalent among the clinical variants. We and others have demonstrated that levels of mature FXN protein in FRDA G130V samples are reduced below those detected in samples harboring homozygous repeat expansions. Little is known regarding expression and function of endogenous FXN-G130V protein due to lack of reagents and models that can distinguish the mutant FXN protein from the wild-type FXN produced from the GAA-expanded allele. We aimed to determine the effect of the G130V (murine G127V) mutation on Fxn expression and to define its multi-system impact in vivo. We used CRISPR/Cas9 to introduce the G127V missense mutation in the Fxn coding sequence and generated homozygous mice (FxnG127V/G127V). We also introduced the G127V mutation into a GAA repeat expansion FRDA mouse model (FxnGAA230/KO; KIKO) to generate a compound heterozygous strain (FxnG127V/GAA230). We performed neurobehavioral tests on cohorts of WT and Fxn mutant animals at three-month intervals for one year, and collected tissue samples to analyze molecular changes during that time. The endogenous Fxn G127V protein is detected at much lower levels in all tissues analyzed from FxnG127V/G127V mice compared to age and sex-matched WT mice without differences in Fxn transcript levels. FxnG127V/G127V mice are significantly smaller than WT counterparts, but perform similarly in most neurobehavioral tasks. RNA sequencing analysis revealed reduced expression of genes in oxidative phosphorylation and protein synthesis, underscoring the metabolic consequences in our mouse model expressing extremely low levels of Fxn. Results of these studies provide insight into the unique pathogenic mechanism of the FXN G130V mechanism and the tolerable limit of Fxn/FXN expression in vivo

Polymorphisms of MUC16 (CA125) and MUC1 (CA15.3) in Relation to Ovarian Cancer Risk and Survival

Objective: To examine single nucleotide polymorphism (SNPs) in MUC16 (CA125) and MUC1 (CA15.3) in relation to ovarian cancer risk and survival. Methods: We genotyped germline variants of MUC16 (rs2547065, rs1559168, rs12984471, rs2121133) and MUC1 (rs2070803, rs4072037, rs1045253) using samples collected from 758 ovarian cancer cases and 788 controls enrolled in the New England Case-Control Study between 2003 and 2008. We calculated age-adjusted odds ratios (OR) and 95% confidence intervals (CIs) for disease risk using unconditional and polytomous logistic regression and hazard ratios (HR) for survival using Cox proportional hazard ratios. In a subset of cases, we compared log-normalized CA125 values by genotype using generalized linear models. Results: Cases homozygous for the variant allele of MUC16 SNP, rs12984471, had poorer overall survival (log-rank p = 0.03) and higher CA125 levels, especially cases over age 65 (p = 0.01). For MUC1 SNP, rs4072037, women homozygous for the G variant had a non-significantly decreased risk for serous invasive types but elevated risk for serous borderline tumors, mucinous borderline and invasive tumors, and endometrioid tumors. Women with the variant allele of MUC16 SNP, rs2547065, especially those who were homozygous had an elevated risk for ovarian cancer; but this association was not confirmed in an independent dataset. Conclusion: This targeted screen of seven polymorphisms of MUC16 and MUC1 genes failed to identify and confirm effects on ovarian cancer risk overall. However, there may be effects of MUC16 rs12984471 on survival and MUC1 rs4072037 on risk for histologic types of ovarian cancer other than invasive serous. Further study is warranted

Aerosols in the tropical and subtropical UT/LS: in-situ measurements of submicron particle abundance and volatility

Processes occurring in the tropical upper troposphere (UT), the Tropical Transition Layer (TTL), and the lower stratosphere (LS) are of importance for the global climate, for stratospheric dynamics and air chemistry, and for their influence on the global distribution of water vapour, trace gases and aerosols. In this contribution we present aerosol and trace gas (in-situ) measurements from the tropical UT/LS over Southern Brazil, Northern Australia, and West Africa. The instruments were operated on board of the Russian high altitude research aircraft M-55 "Geophysica" and the DLR Falcon-20 during the campaigns TROCCINOX (Araçatuba, Brazil, February 2005), SCOUT-O3 (Darwin, Australia, December 2005), and SCOUT-AMMA (Ouagadougou, Burkina Faso, August 2006). The data cover submicron particle number densities and volatility from the COndensation PArticle counting System (COPAS), as well as relevant trace gases like N2O, ozone, and CO. We use these trace gas measurements to place the aerosol data into a broader atmospheric context. Also a juxtaposition of the submicron particle data with previous measurements over Costa Rica and other tropical locations between 1999 and 2007 (NASA DC-8 and NASA WB-57F) is provided. The submicron particle number densities, as a function of altitude, were found to be remarkably constant in the tropical UT/LS altitude band for the two decades after 1987. Thus, a parameterisation suitable for models can be extracted from these measurements. Compared to the average levels in the period between 1987 and 2007 a slight increase of particle abundances was found for 2005/2006 at altitudes with potential temperatures, theta, above 430 K. The origins of this increase are unknown except for increases measured during SCOUT-AMMA. Here the eruption of the Soufrière Hills volcano in the Caribbean caused elevated particle mixing ratios. The vertical profiles from Northern hemispheric mid-latitudes between 1999 and 2006 also are compact enough to derive a parameterisation. The tropical profiles all show a broad maximum of particle mixing ratios (between theta ~ 340 K and 390 K) which extends from below the TTL to above the thermal tropopause. Thus these particles are a "reservoir" for vertical transport into the stratosphere. The ratio of non-volatile particle number density to total particle number density was also measured by COPAS. The vertical profiles of this ratio have a maximum of 50% above 370 K over Australia and West Africa and a pronounced minimum directly below. Without detailed chemical composition measurements a reason for the increase of non-volatile particle fractions cannot yet be given. However, half of the particles from the tropical "reservoir" contain compounds other than sulphuric acid and water. Correlations of the measured aerosol mixing ratios with N2O and ozone exhibit compact relationships for the tropical data from SCOUT-AMMA, TROCCINOX, and SCOUT-O3. Correlations with CO are more scattered probably because of the connection to different pollution source regions. We provide additional data from the long distance transfer flights to the campaign sites in Brazil, Australia, and West-Africa. These were executed during a time window of 17 months within a period of relative volcanic quiescence. Thus the data represent a "snapshot picture" documenting the status of a significant part of the global UT/LS fine aerosol at low concentration levels 15 years after the last major (i.e., the 1991 Mount Pinatubo) eruption. The corresponding latitudinal distributions of the measured particle number densities are presented in this paper to provide data of the UT/LS background aerosol for modelling purposes