Walk on Floor Eyes Closed Test as a Measure of Postflight Ataxia

INTRODUCTION: Astronauts returning from space flight universally exhibit impaired posture and locomotion. Measurement of this impairment is an evolving process. The walk on the floor line test with the eyes closed (WOFEC) provides a unique procedure for quantifying postflight ataxia. Data from a modified WOFEC were obtained as part of an ongoing NASA interdisciplinary pre- and postflight study (Functional Task Test, FTT) designed to evaluate astronaut postflight functional performance. METHODS: Seven astronauts (5 short duration with flights of 12-16 days; 2 long duration crewmembers with flights of 6 months) were tested twice before flight, on landing day (short duration only), and 1, 6, and 30 days after flight. The WOFEC consisted of walking for 10 steps (repeated twice) with the feet heel to toe in tandem, arms folded across the chest and the eyes closed. The performance metric (scored by three examiners from video) was the percentage of correct steps completed over the three trials. A step was not counted as correct if the crewmember sidestepped, opened their eyes, or paused for more than three seconds between steps. RESULTS/ CONCLUSIONS: There was a significant decrease in percentage of correct steps on landing day (short duration crew) and on first day following landing (long duration) with partial recovery the following day, and full recovery beginning on day sixth after flight. Both short and long duration fliers appeared to be unaware of foot position relative to their bodies or the floor. Postflight, deviation from a straight path was common, and the test for two crewmembers elicited motion sickness symptoms. These data clearly demonstrate the sensorimotor challenges facing crewmembers after returning from spaceflight. The WOFEC test has value providing the investigator or crew surgeon with a simple method to quantify vestibular ataxia, as well as providing instant feedback of postural ataxia without the use of complex test equipment

Designing a therapeutic hepatitis B vaccine to circumvent immune tolerance

An effective prophylactic hepatitis B virus (HBV) vaccine has long been available but is ineffective for chronic infection. The primary cause of chronic hepatitis B (CHB) and greatest impediment for a therapeutic vaccine is the direct and indirect effects of immune tolerance to HBV antigens. The resulting defective CD4+/CD8+ T cell response, poor cytokine production, insufficient neutralizing anti-body (nAb) and poor response to HBsAg vaccination characterize CHB infection. The objective of this study was to develop virus-like-particles (VLPs) that elicit nAb to prevent viral spread and prime CD4+/CD8+ T cells to eradicate intracellular HBV. Eight neutralizing B cell epitopes from the envelope PreS1 region were consolidated onto a species-variant of the HBV core protein, the woodchuck hepatitis core antigen (WHcAg). PreS1-specific B cell epitopes were chosen because of preferential expression on HBV virions. Because WHcAg and HBcAg are not crossreactive at the B cell level and only partially cross-reactive at the CD4+/CD8+ T cell level, CD4+ T cells specific for WHcAg-unique T cell sites can provide cognate T-B cell help for anti-PreS1 Ab production that is not curtailed by immune tolerance. Immunization of immune tolerant HBV transgenic (Tg) mice with PreS1-WHc VLPs elicited levels of high titer anti-PreS1 nAbs equivalent to wildtype mice. Passive transfer of PreS1 nAbs into human-liver chimeric mice prevented acute infection and cleared serum HBV from mice previously infected with HBV in a model of CHB. At the T cell level, PreS1-WHc VLPs and hybrid WHcAg/HBcAg DNA immunogens elicited HBcAg-specific CD4+ Th and CD8+ CTL responses

Introduction of Empirical Topology in Construction of Relationship Networks of Informative Objects

Understanding the structure of relationships between objects in a given database is one of the most important problems in the field of data mining. The structure can be defined for a set of single objects (clustering) or a set of groups of objects (network mapping). We propose a method for discovering relationships between individuals (single or groups) that is based on what we call the empirical topology, a system-theoretic measure of functional proximity. To illustrate the suitability and efficiency of the method, we apply it to an astronomical data base

What's wrong with the scrum laws in rugby union? - Judgment, truth and refereeing

Officiating and the role of officials in sport are crucial and often decisive factors in sports contests. Notable contributions in philosophy of sport include Collins (2012), Russell (1997; 1999), McFee (2011) & Mumford (2006) have brought a sharp philosophical focus to highlight that justice and desert of sport contests, in part, rely on officiating truths (performances) that arise from an appropriate admixture of epistemic (judgments) and metaphysical (actions) ingredients. This paper provides a rigorous and original philosophical analysis of the problems of obeying the rules and of applying the rules of sport. The paper focuses on a particular phase of play in rugby union, namely the scrum. It is fair to say that the scrum has become a focus of criticism and bewilderment. Elite televised rugby is damaged as a spectacle because too much time is wasted setting and re-setting scrums. Furthermore, our trust in the fairness of games is eroded because the scrum is a ‘lottery’ when it comes to officiating. In this paper, we identify two fundamental structural problems which contribute to the scrum controversy. First, drawing on Mumford (2006) and Collins (2012) we argue that officials cannot make reliable judgments about scrums because they cannot see what they need to see. Secondly, we argue that players cannot follow the laws of the scrum even if they have a strong desire to do so. Laws which can’t be followed are, according to Fuller (2000) defective. Consequently, the scrum is not only potentially dangerous but also flawed in terms of its capacity to actualize an intended part of the game

Elicitin genes in Phytophthora infestans are clustered and interspersed with various transposon-like elements

Sequencing and annotation of a contiguous stretch of genomic DNA (112.3 kb) from the oomycete plant pathogen Phytophthora infestans revealed the order, spacing and genomic context of four members of the elicitin (inf) gene family. Analysis of the GC content at the third codon position (GC3) of six genes encoded in the region, and a set of randomly selected coding regions as well as random genomic regions, showed that a high GC3 value is a general feature of Phytophthora genes that can be exploited to optimize gene prediction programs for Phytophthora species. At least one-third of the annotated 112.3-kb P. infestans sequence consisted of transposons or transposon-like elements. The most prominent were four Tc3/gypsy and Tc1/copia type retrotransposons and three DNA transposons that belong to the Tc1/mariner, Pogo and PiggyBac groups, respectively. Comparative analysis of other available genomic sequences suggests that transposable elements are highly heterogeneous and ubiquitous in the P. infestans genome

Self-organized model of cascade spreading

We study simultaneous price drops of real stocks and show that for high drop thresholds they follow a power-law distribution. To reproduce these collective downturns, we propose a minimal self-organized model of cascade spreading based on a probabilistic response of the system elements to stress conditions. This model is solvable using the theory of branching processes and the mean-field approximation. For a wide range of parameters, the system is in a critical state and displays a power-law cascade-size distribution similar to the empirically observed one. We further generalize the model to reproduce volatility clustering and other observed properties of real stocks.Comment: 8 pages, 6 figure

A whole-blood transcriptome meta-analysis identifies gene expression signatures of cigarette smoking

Cigarette smoking is a leading modifiable cause of death worldwide. We hypothesized that cigarette smoking induces extensive transcriptomic changes that lead to target-organ damage and smoking-related diseases. We performed a metaanalysis of transcriptome-wide gene expression using whole blood-derived RNA from 10,233 participants of European ancestry in six cohorts (including 1421 current and 3955 former smokers) to identify associations between smoking and altered gene expression levels. At a false discovery rate (FDR) < 0.1, we identified 1270 differentially expressed genes in current vs. never smokers, and 39 genes in former vs. never smokers. Expression levels of 12 genes remained elevated up to 30 years after smoking cessation, suggesting that the molecular consequence of smoking may persist for decades. Gene ontology analysis revealed enrichment of smoking-related genes for activation of platelets and lymphocytes, immune response, and apoptosis. Many of the top smoking-related differentially expressed genes, including LRRN3 and GPR15, have DNA methylation loci in promoter regions that were recently reported to be hypomethylated among smokers. By linking differential gene expression with smoking-related disease phenotypes, we demonstrated that stroke and pulmonary function show enrichment for smoking-related gene expression signatures. Mediation analysis revealed the expression of several genes (e.g. ALAS2) to be putative mediators of the associations between smoking and inflammatory biomarkers (IL6 and C-re

Arches and contact forces in a granular pile

Assemblies of granular particles mechanically stable under their own weight contain arches. These are structural units identified as sets of mutually stable grains. It is generally assumed that these arches shield the weight above them and should bear most of the stress in the system. We test such hypothesis by studying the stress born by in-arch and out-of-arch grains. We show that, indeed, particles in arches withstand larger stresses. In particular, the isotropic stress tends to be larger for in-arch-grains whereas the anisotropic component is marginally distinguishable between the two types of particles. The contact force distributions demonstrate that an exponential tail (compatible with the maximization of entropy under no extra constraints) is followed only by the out-of-arch contacts. In-arch contacts seem to be compatible with a Gaussian distribution consistent with a recently introduced approach that takes into account constraints imposed by the local force balance on grains.Comment: 7 pages, 7 figures, major revisio