Rodent Research Development for Long Duration Studies on the International Space Station

Rodent research in space is needed to advance our understanding of the health risks,consequences and possible countermeasures to protect crew during future, long duration missions. TheAnimal Enclosure Module (AEM) was designed originally to support habitation of rats and mice onrelatively short duration, Shuttle missions (<19 days). The AEM was flown previously on 27 SpaceShuttle missions, and recently was modified extensively to support future long duration space biology andbiomedical research on the International Space Station (ISS). In consultation with a Science WorkingGroup comprised of veterinarians and investigators experienced in rodent spaceflight experimentation inspace, the Rodent Habitat project team at Ames Research Center modified existing hardware, developednew hardware, operations, and science activities, and performed a series of ground-based operational andscience habitat verification tests in preparation for the first validation flight

Advances in Rodent Research Missions on the International Space Station

A Research platform for rodent experiment on the ISS is an essential tool for advancing biomedical research in space. The Rodent Research allows for experiments of much longer duration that experiments on the Shuttle. NASAs Rodent Research (RR)-1 mission was successfully completed, including post-flight analysis and achieved a number of objectives including validation of flight hardware, on-orbit operations, and science capabilities that were developed at the NASA Ames Research Center. Briefly, twenty C57BL/6J adult female mice were launched on the SpX4 Dragon vehicle, which thrived for up to 37 days in microgravity. Daily health checks of the mice were performed during the mission via downlinked video; all animals were healthy and displayed normal behavior without any significant signs of stress. Behavioral analysis demonstrated that Flight and Ground Control mice exhibited the same range of behaviors, including eating, drinking, exploratory behavior, self- and allo-grooming, and social interactions indicative of healthy animals. The animals were euthanized and select tissues were collected from some of the mice on orbit to assess the long-term sample storage capabilities of the ISS. The data obtained from the flight mice were comparable to those from the 3 groups of control mice (baseline, vivarium and ground controls), suggesting that the ISS has adequate capability to support long-duration rodent experimentations. We recovered over 35 tissues from 40 RR1 frozen carcasses, yielded over 3200 aliquots of tissues, and distributed to the scientific community, including NASAs GeneLab and scientists in the U.S. through Biospecimen Sharing Program via Ames Life Science Data Archive. Tissues were also distributed to Russian research colleagues at the Institute for Biomedical Problems. The expression levels of select genes including albumin, catalase, GAPDH, HMGCoA Reductase, and IGF1 were determined using RNA isolated from the livers by qPCR and no significant differences by one factor ANOVA were found between flight and ground control groups. In addition, some of the liver samples were subject to transcriptomics, epigenomics and proteomics. The data are now available to the scientific community through GeneLabs open science data website. Since the RR1 mission, another long duration mission (Rodent Research-2) was completed on the ISS in 2015 in which 20 female C57 BL/6J mice were successfully maintained on the ISS for varying time points, with the last group of 5 animals being on-orbit for 54 days. This second Rodent Research flight expanded the programs capabilities with the introduction of new technologies including blood collection and separation and bone densitometry scanning. Furthermore, we have continued to expand the ISSs capabilities by running a series of ground-based verification testing using male mice. Our next step is to fly male mice for Rodent Research-4 on SpaceX-10 to study the effects of microgravity on bone healing and regeneration. It will be the first long-duration mission using male mice using Rodent Hardware. In addition, the number of mice will increase from 20 mice (on RR-1 and RR-2) to 40 for RR-4. When samples return to Earth, a number of tissues will be dissected from the frozen carcasses and select tissue samples will become available to the scientific community via BSP. Altogether, we have continued to expand our capabilities for performing long-duration missions on the ISS as emphasized in the National Research Councils Decadal Survey released in 2011 and to maximize science return from each mission

One Large Kindred Excludes a Locus for Multiple Endocrine Neoplasia Type 2A from about 25% of the Human Autosomal Genetic Map

This report presents pairwise linkage results from our search for the locus of the gene (MEN2A) for the multiple endocrine neoplasia type 2A (MEN-2A) syndrome in one large kindred (the N kindred), clearly segregating for an autosomal dominant form. About 25% of the autosomal genome is excluded when these new results are combined with those we have published previously. The genetic markers employed are distributed across at least 19 of the 22 autosomes. Seven genetic markers whose chromosomal locations are not yet established have also been studied

Dietary yeast influences ethanol sedation in Drosophila via serotonergic neuron function

Abuse of alcohol is a major clinical problem with far- reaching health consequences. Understanding the environmental and genetic factors that contribute to alcohol- related behaviors is a potential gateway for developing novel therapeutic approaches for patients that abuse the drug. To this end, we have used Drosophila melanogaster as a model to investigate the effect of diet, an environmental factor, on ethanol sedation. Providing flies with diets high in yeast, a routinely used component of fly media, increased their resistance to ethanol sedation. The yeast- induced resistance to ethanol sedation occurred in several different genetic backgrounds, was observed in males and females, was elicited by yeast from different sources, was readily reversible, and was associated with increased nutrient intake as well as decreased internal ethanol levels. Inhibition of serotonergic neuron function using multiple independent genetic manipulations blocked the effect of yeast supplementation on ethanol sedation, nutrient intake, and internal ethanol levels. Our results demonstrate that yeast is a critical dietary component that influences ethanol sedation in flies and that serotonergic signaling is required for the effect of dietary yeast on nutrient intake, ethanol uptake/elimination, and ethanol sedation. Our studies establish the fly as a model for diet- induced changes in ethanol sedation and raise the possibility that serotonin might mediate the effect of diet on alcohol- related behavior in other species.Flies fed a high yeast diet consume more nutrients, have decreased levels of internal ethanol when exposed to ethanol vapor and require longer exposure to ethanol to become sedated (ie, increased ST50). Our studies implicate serotonergic neurons as key regulators of nutrient consumption and therefore, the effect of dietary yeast on ethanol sedation in flies.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155987/1/adb12779.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155987/2/adb12779_am.pd

Overview of the Kepler Science Processing Pipeline

The Kepler Mission Science Operations Center (SOC) performs several critical functions including managing the ~156,000 target stars, associated target tables, science data compression tables and parameters, as well as processing the raw photometric data downlinked from the spacecraft each month. The raw data are first calibrated at the pixel level to correct for bias, smear induced by a shutterless readout, and other detector and electronic effects. A background sky flux is estimated from ~4500 pixels on each of the 84 CCD readout channels, and simple aperture photometry is performed on an optimal aperture for each star. Ancillary engineering data and diagnostic information extracted from the science data are used to remove systematic errors in the flux time series that are correlated with these data prior to searching for signatures of transiting planets with a wavelet-based, adaptive matched filter. Stars with signatures exceeding 7.1 sigma are subjected to a suite of statistical tests including an examination of each star's centroid motion to reject false positives caused by background eclipsing binaries. Physical parameters for each planetary candidate are fitted to the transit signature, and signatures of additional transiting planets are sought in the residual light curve. The pipeline is operational, finding planetary signatures and providing robust eliminations of false positives.Comment: 8 pages, 3 figure

Designing an automated clinical decision support system to match clinical practice guidelines for opioid therapy for chronic pain

Abstract Background Opioid prescribing for chronic pain is common and controversial, but recommended clinical practices are followed inconsistently in many clinical settings. Strategies for increasing adherence to clinical practice guideline recommendations are needed to increase effectiveness and reduce negative consequences of opioid prescribing in chronic pain patients. Methods Here we describe the process and outcomes of a project to operationalize the 2003 VA/DOD Clinical Practice Guideline for Opioid Therapy for Chronic Non-Cancer Pain into a computerized decision support system (DSS) to encourage good opioid prescribing practices during primary care visits. We based the DSS on the existing ATHENA-DSS. We used an iterative process of design, testing, and revision of the DSS by a diverse team including guideline authors, medical informatics experts, clinical content experts, and end-users to convert the written clinical practice guideline into a computable algorithm to generate patient-specific recommendations for care based upon existing information in the electronic medical record (EMR), and a set of clinical tools. Results The iterative revision process identified numerous and varied problems with the initially designed system despite diverse expert participation in the design process. The process of operationalizing the guideline identified areas in which the guideline was vague, left decisions to clinical judgment, or required clarification of detail to insure safe clinical implementation. The revisions led to workable solutions to problems, defined the limits of the DSS and its utility in clinical practice, improved integration into clinical workflow, and improved the clarity and accuracy of system recommendations and tools. Conclusions Use of this iterative process led to development of a multifunctional DSS that met the approval of the clinical practice guideline authors, content experts, and clinicians involved in testing. The process and experiences described provide a model for development of other DSSs that translate written guidelines into actionable, real-time clinical recommendations.http://deepblue.lib.umich.edu/bitstream/2027.42/78267/1/1748-5908-5-26.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/2/1748-5908-5-26.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/3/1748-5908-5-26-S3.TIFFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/4/1748-5908-5-26-S2.TIFFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/5/1748-5908-5-26-S1.TIFFPeer Reviewe

Discovery and Rossiter-McLaughlin Effect of Exoplanet Kepler-8b

We report the discovery and the Rossiter-McLaughlin effect of Kepler-8b, a transiting planet identified by the NASA Kepler Mission. Kepler photometry and Keck-HIRES radial velocities yield the radius and mass of the planet around this F8IV subgiant host star. The planet has a radius RP = 1.419 RJ and a mass, MP = 0.60 MJ, yielding a density of 0.26 g cm^-3, among the lowest density planets known. The orbital period is P = 3.523 days and orbital semima jor axis is 0.0483+0.0006/-0.0012 AU. The star has a large rotational v sin i of 10.5 +/- 0.7 km s^-1 and is relatively faint (V = 13.89 mag), both properties deleterious to precise Doppler measurements. The velocities are indeed noisy, with scatter of 30 m s^-1, but exhibit a period and phase consistent with the planet implied by the photometry. We securely detect the Rossiter-McLaughlin effect, confirming the planet's existence and establishing its orbit as prograde. We measure an inclination between the projected planetary orbital axis and the projected stellar rotation axis of lambda = -26.9 +/- 4.6 deg, indicating a moderate inclination of the planetary orbit. Rossiter-McLaughlin measurements of a large sample of transiting planets from Kepler will provide a statistically robust measure of the true distribution of spin-orbit orientations for hot jupiters in general.Comment: 26 pages, 8 figures, 2 tables; In preparation for submission to the Astrophysical Journa

Intra- and inter-individual genetic differences in gene expression

Genetic variation is known to influence the amount of mRNA produced by a gene. Given that the molecular machines control mRNA levels of multiple genes, we expect genetic variation in the components of these machines would influence multiple genes in a similar fashion. In this study we show that this assumption is correct by using correlation of mRNA levels measured independently in the brain, kidney or liver of multiple, genetically typed, mice strains to detect shared genetic influences. These correlating groups of genes (CGG) have collective properties that account for 40-90% of the variability of their constituent genes and in some cases, but not all, contain genes encoding functionally related proteins. Critically, we show that the genetic influences are essentially tissue specific and consequently the same genetic variations in the one animal may up-regulate a CGG in one tissue but down-regulate the same CGG in a second tissue. We further show similarly paradoxical behaviour of CGGs within the same tissues of different individuals. The implication of this study is that this class of genetic variation can result in complex inter- and intra-individual and tissue differences and that this will create substantial challenges to the investigation of phenotypic outcomes, particularly in humans where multiple tissues are not readily available.&#xd;&#xa;&#xd;&#xa

Kepler Data Release 4 Notes

The Data Analysis Working Group have released long and short cadence materials, including FFIs and Dropped Targets for the Public. The Kepler Science Office considers Data Release 4 to provide "browse quality" data. These notes have been prepared to give Kepler users of the Multimission Archive at STScl (MAST) a summary of how the data were collected and prepared, and how well the data processing pipeline is functioning on flight data. They will be updated for each release of data to the public archive and placed on MAST along with other Kepler documentation, at http://archive.stsci.edu/kepler/documents.html. Data release 3 is meant to give users the opportunity to examine the data for possibly interesting science and to involve the users in improving the pipeline for future data releases. To perform the latter service, users are encouraged to notice and document artifacts, either in the raw or processed data, and report them to the Science Office