Humans vs Hardware: The Unique World of NASA Human System Risk Assessment

Understanding spaceflight risks to crew health and performance is a crucial aspect of preparing for exploration missions in the future. The research activities of the Human Research Program (HRP) provide substantial evidence to support most risk reduction work. The Human System Risk Board (HSRB), acting on behalf of the Office of Chief Health and Medical Officer (OCHMO), assesses these risks and assigns likelihood and consequence ratings to track progress. Unfortunately, many traditional approaches in risk assessment such as those used in the engineering aspects of spaceflight are difficult to apply to human system risks. This presentation discusses the unique aspects of risk assessment from the human system risk perspective and how these limitations are accommodated and addressed in order to ensure that reasonable inputs are provided to support the OCHMO's overall risk posture for manned exploration missions

On the action potential as a propagating density pulse and the role of anesthetics

The Hodgkin-Huxley model of nerve pulse propagation relies on ion currents through specific resistors called ion channels. We discuss a number of classical thermodynamic findings on nerves that are not contained in this classical theory. Particularly striking is the finding of reversible heat changes, thickness and phase changes of the membrane during the action potential. Data on various nerves rather suggest that a reversible density pulse accompanies the action potential of nerves. Here, we attempted to explain these phenomena by propagating solitons that depend on the presence of cooperative phase transitions in the nerve membrane. These transitions are, however, strongly influenced by the presence of anesthetics. Therefore, the thermodynamic theory of nerve pulses suggests a explanation for the famous Meyer-Overton rule that states that the critical anesthetic dose is linearly related to the solubility of the drug in the membranes.Comment: 13 pages, 8 figure

A mosaic genetic screen for novel mutations affecting Drosophila neuroblast divisions

BACKGROUND: The asymmetric segregation of determinants during cell division is a fundamental mechanism for generating cell fate diversity during development. In Drosophila, neural precursors (neuroblasts) divide in a stem cell-like manner generating a larger apical neuroblast and a smaller basal ganglion mother cell. The cell fate determinant Prospero and its adapter protein Miranda are asymmetrically localized to the basal cortex of the dividing neuroblast and segregated into the GMC upon cytokinesis. Previous screens to identify components of the asymmetric division machinery have concentrated on embryonic phenotypes. However, such screens are reaching saturation and are limited in that the maternal contribution of many genes can mask the effects of zygotic loss of function, and other approaches will be necessary to identify further genes involved in neuroblast asymmetric division. RESULTS: We have performed a genetic screen in the third instar larval brain using the basal localization of Miranda as a marker for neuroblast asymmetry. In addition to the examination of pupal lethal mutations, we have employed the MARCM (Mosaic Analysis with a Repressible Cell Marker) system to generate postembryonic clones of mutations with an early lethal phase. We have screened a total of 2,300 mutagenized chromosomes and isolated alleles affecting cell fate, the localization of basal determinants or the orientation of the mitotic spindle. We have also identified a number of complementation groups exhibiting defects in cell cycle progression and cytokinesis, including both novel genes and new alleles of known components of these processes. CONCLUSION: We have identified four mutations which affect the process of neuroblast asymmetric division. One of these, mapping to the imaginal discs arrested locus, suggests a novel role for the anaphase promoting complex/cyclosome (APC/C) in the targeting of determinants to the basal cortex. The identification and analysis of the remaining mutations will further advance our understanding of the process of asymmetric cell division. We have also isolated a number of mutations affecting cell division which will complement the functional genomics approaches to this process being employed by other laboratories. Taken together, these results demonstrate the value of mosaic screens in the identification of genes involved in neuroblast division

TarO : a target optimisation system for structural biology

This work was funded by the UK Biotechnology and Biological Sciences Research Council (BBSRC) Structural Proteomics of Rational Targets (SPoRT) initiative, (Grant BBS/B/14434). Funding to pay the Open Access publication charges for this article was provided by BBSRC.TarO (http://www.compbio.dundee.ac.uk/taro) offers a single point of reference for key bioinformatics analyses relevant to selecting proteins or domains for study by structural biology techniques. The protein sequence is analysed by 17 algorithms and compared to 8 databases. TarO gathers putative homologues, including orthologues, and then obtains predictions of properties for these sequences including crystallisation propensity, protein disorder and post-translational modifications. Analyses are run on a high-performance computing cluster, the results integrated, stored in a database and accessed through a web-based user interface. Output is in tabulated format and in the form of an annotated multiple sequence alignment (MSA) that may be edited interactively in the program Jalview. TarO also simplifies the gathering of additional annotations via the Distributed Annotation System, both from the MSA in Jalview and through links to Dasty2. Routes to other information gateways are included, for example to relevant pages from UniProt, COG and the Conserved Domains Database. Open access to TarO is available from a guest account with private accounts for academic use available on request. Future development of TarO will include further analysis steps and integration with the Protein Information Management System (PIMS), a sister project in the BBSRC Structural Proteomics of Rational Targets initiative.Publisher PDFPeer reviewe

Engineering biofilms for biocatalysis

Biofilm, friend not foe: Single species biofilms can be engineered to form robust biocatalysts with greater catalytic activity and significantly improved catalytic longevity than purified and immobilised enzymes. We report the engineering, structural analysis and biocatalytic capability of a biofilm that can mediate the conversion of serine and haloindoles to halotryptophans

Apparatus to Determine the Heat Capacity and Thermal Conductivity of a Material From 1 to 300 K in Magnetic Fields Up to 9 T

Magnetic refrigeration is a new technology that potentially offers refrigeration efficiencies > 50% of Carnot, compactness, and high reliability. Studies indicate that approx. 35% of Carnot efficiency is generally the best that is now possible for gas compression/expansion systems and, at that, only for very large plants; for smaller machines, the fraction of Carnot efficiency can become very small, e.g., 1-W refrigerators generally operate at 2 to 8% of Carnot efficiency. For magnetic refrigerators, the compression/expansion processes are replaced by a cycle involving the application/removal of a magnetic field to either a paramagnetic or ferromagnetic material (generally, paramagnets are used below approx. 20K and ferromagnets above). The thermodynamic cycles in gas and magnetic systems are analogous. Central to the development of magnetic refrigerators is the characterization of magnetic working substances. Among the key properties for which we require data are the heat capacity (from which we derive the entropy) and the thermal conductivity as functions of temperature and magnetic field. Accordingly, at the Los Alamos National Laboratory, we have designed and constructed an apparatus to make measurements of these quantities over the range 1 to 300 K at fields up to 9 T. We describe the methodology of these measurements, the versatile apparatus for making them, and results on GdNi, the first sample measured

Adultery and the Rumor Mill: les bourgeois de Molinchart and El gran galeoto

This article seeks to challenge interpretations of the adultery plot as a subversive current in nineteenth-century literature by examining two texts that are often dismissed by contemporary critics: Les bourgeois de Molinchart (1854), a novel by the French writer Champfleury (the pseudonym of Jules Husson), and El gran Galeoto (1881), a play by the Spanish playwright Jos, Echegaray. In each of these works, the rumor of the adultery precedes and to a large extent precipitates the infidelity at the end of the work. In committing adultery, therefore, the protagonists are not rising up against social norms so much as capitulating to the expectations of society, enacting a plot that has been projected upon them. The essay compares and contrasts the treatment of the rumor mill in the two works and examines the literary strategies that the writers use to undercut a transgressive reading of the infidelity plot

Challenges in Integrating Biological Data Sources

this report, we examine the technical challenges to integration, critique the available tools and resources, and compare the cost and advantages of various methodologies. We begin by analyzing the basic steps in strict and complete integration: 1) transformation of the various schemas to a common data model; 2) matching of semantically related schema objects; 3) schema integration; 4) transformation of data to the federated database on demand; and 5) matching of semantically equivalent data. Some progress has been made on generic problems such as (1) and (3) within the wider database community, but issues of semantics (steps (2) and (5)) have only been dealt with any degree of success by domain experts within the biological community. We then look at the solution space of integration strategies as defined by two axes, the "tightness" of federation and the "degree" of instantiation, discuss where various solutions fall on this plane, and examine their cost and advantages/disadvantages. Finally, we examine technical challenges that are not -3- July 12, 199