MODELING OF 2LIBH4 PLUS MGH2 HYDROGEN STORAGE SYSTEM ACCIDENT SCENARIOS USING EMPIRICAL AND THEORETICAL THERMODYNAMICS

It is important to understand and quantify the potential risk resulting from accidental environmental exposure of condensed phase hydrogen storage materials under differing environmental exposure scenarios. This paper describes a modeling and experimental study with the aim of predicting consequences of the accidental release of 2LiBH{sub 4}+MgH{sub 2} from hydrogen storage systems. The methodology and results developed in this work are directly applicable to any solid hydride material and/or accident scenario using appropriate boundary conditions and empirical data. The ability to predict hydride behavior for hypothesized accident scenarios facilitates an assessment of the of risk associated with the utilization of a particular hydride. To this end, an idealized finite volume model was developed to represent the behavior of dispersed hydride from a breached system. Semiempirical thermodynamic calculations and substantiating calorimetric experiments were performed in order to quantify the energy released, energy release rates and to quantify the reaction products resulting from water and air exposure of a lithium borohydride and magnesium hydride combination. The hydrides, LiBH{sub 4} and MgH{sub 2}, were studied individually in the as-received form and in the 2:1 'destabilized' mixture. Liquid water hydrolysis reactions were performed in a Calvet calorimeter equipped with a mixing cell using neutral water. Water vapor and oxygen gas phase reactivity measurements were performed at varying relative humidities and temperatures by modifying the calorimeter and utilizing a gas circulating flow cell apparatus. The results of these calorimetric measurements were compared with standardized United Nations (UN) based test results for air and water reactivity and used to develop quantitative kinetic expressions for hydrolysis and air oxidation in these systems. Thermodynamic parameters obtained from these tests were then inputted into a computational fluid dynamics model to predict both the hydrogen generation rates and concentrations along with localized temperature distributions. The results of these numerical simulations can be used to predict ignition events and the resultant conclusions will be discussed

Visual, Motor and Attentional Influences on Proprioceptive Contributions to Perception of Hand Path Rectilinearity during Reaching

We examined how proprioceptive contributions to perception of hand path straightness are influenced by visual, motor and attentional sources of performance variability during horizontal planar reaching. Subjects held the handle of a robot that constrained goal-directed movements of the hand to the paths of controlled curvature. Subjects attempted to detect the presence of hand path curvature during both active (subject driven) and passive (robot driven) movements that either required active muscle force production or not. Subjects were less able to discriminate curved from straight paths when actively reaching for a target versus when the robot moved their hand through the same curved paths. This effect was especially evident during robot-driven movements requiring concurrent activation of lengthening but not shortening muscles. Subjects were less likely to report curvature and were more variable in reporting when movements appeared straight in a novel “visual channel” condition previously shown to block adaptive updating of motor commands in response to deviations from a straight-line hand path. Similarly, compromised performance was obtained when subjects simultaneously performed a distracting secondary task (key pressing with the contralateral hand). The effects compounded when these last two treatments were combined. It is concluded that environmental, intrinsic and attentional factors all impact the ability to detect deviations from a rectilinear hand path during goal-directed movement by decreasing proprioceptive contributions to limb state estimation. In contrast, response variability increased only in experimental conditions thought to impose additional attentional demands on the observer. Implications of these results for perception and other sensorimotor behaviors are discussed

Steady-state modulation of voltage-gated K+ channels in rat arterial smooth muscle by cyclic AMP-dependent protein kinase and protein phosphatase 2B

Voltage-gated potassium channels (Kv) are important regulators of membrane potential in vascular smooth muscle cells, which is integral to controlling intracellular Ca2+ concentration and regulating vascular tone. Previous work indicates that Kv channels can be modulated by receptor-driven alterations of cyclic AMP-dependent protein kinase (PKA) activity. Here, we demonstrate that Kv channel activity is maintained by tonic activity of PKA. Whole-cell recording was used to assess the effect of manipulating PKA signalling on Kv and ATP-dependent K+ channels of rat mesenteric artery smooth muscle cells. Application of PKA inhibitors, KT5720 or H89, caused a significant inhibition of Kv currents. Tonic PKA-mediated activation of Kv appears maximal as application of isoprenaline (a β-adrenoceptor agonist) or dibutyryl-cAMP failed to enhance Kv currents. We also show that this modulation of Kv by PKA can be reversed by protein phosphatase 2B/calcineurin (PP2B). PKA-dependent inhibition of Kv by KT5720 can be abrogated by pre-treatment with the PP2B inhibitor cyclosporin A, or inclusion of a PP2B auto-inhibitory peptide in the pipette solution. Finally, we demonstrate that tonic PKA-mediated modulation of Kv requires intact caveolae. Pre-treatment of the cells with methyl-β-cyclodextrin to deplete cellular cholesterol, or adding caveolin-scaffolding domain peptide to the pipette solution to disrupt caveolae-dependent signalling each attenuated PKA-mediated modulation of the Kv current. These findings highlight a novel, caveolae-dependent, tonic modulatory role of PKA on Kv channels providing new insight into mechanisms and the potential for pharmacological manipulation of vascular tone

Molecular Adaptations for Sensing and Securing Prey and Insight into Amniote Genome Diversity from the Garter Snake Genome

Colubridae represents the most phenotypically diverse and speciose family of snakes, yet no well-assembled and annotated genome exists for this lineage. Here, we report and analyze the genome of the garter snake, Thamnophis sirtalis, a colubrid snake that is an important model species for research in evolutionary biology, physiology, genomics, behavior, and the evolution of toxin resistance. Using the garter snake genome, we show how snakes have evolved numerous adaptations for sensing and securing prey, and identify features of snake genome structure that provide insight into the evolution of amniote genomes. Analyses of the garter snake and other squamate reptile genomes highlight shifts in repeat element abundance and expansion within snakes, uncover evidence of genes under positive selection, and provide revised neutral substitution rate estimates for squamates. Our identification of Z and W sex chromosome-specific scaffolds provides evidence for multiple origins of sex chromosome systems in snakes and demonstrates the value of this genome for studying sex chromosome evolution. Analysis of gene duplication and loss in visual and olfactory gene families supports a dim-light ancestral condition in snakes and indicates that olfactory receptor repertoires underwent an expansion early in snake evolution. Additionally, we provide some of the first links between secreted venom proteins, the genes that encode them, and their evolutionary origins in a rear-fanged colubrid snake, together with new genomic insight into the coevolutionary arms race between garter snakes and highly toxic newt prey that led to toxin resistance in garter snakes

Structural Mechanism of Laforin Function in Glycogen Dephosphorylation and Lafora Disease

Glycogen is the major mammalian glucose storage cache and is critical for energy homeostasis. Glycogen synthesis in neurons must be tightly controlled due to neuronal sensitivity to perturbations in glycogen metabolism. Lafora disease (LD) is a fatal, congenital, neurodegenerative epilepsy. Mutations in the gene encoding the glycogen phosphatase laforin result in hyperphosphorylated glycogen that forms water-insoluble inclusions called Lafora bodies (LBs). LBs induce neuronal apoptosis and are the causative agent of LD. The mechanism of glycogen dephosphorylation by laforin and dysfunction in LD is unknown. We report the crystal structure of laforin bound to phosphoglucan product, revealing its unique integrated tertiary and quaternary structure. Structure-guided mutagenesis combined with biophysical and biochemical analyses reveal the basis for normal function of laforin in glycogen metabolism. Analyses of LD patient mutations define the mechanism by which subsets of mutations disrupt laforin function. These data provide fundamental insights connecting glycogen metabolism to neurodegenerative disease

Phenotypic Detection of Clonotypic B Cells in Multiple Myeloma by Specific Immunoglobulin Ligands Reveals their Rarity in Multiple Myeloma

In multiple myeloma, circulating “clonotypic” B cells, that express the immunoglobulin rearrangement of the malignant plasma cell clone, can be indirectly detected by PCR. Their role as potential “feeder” cells for the malignant plasma cell pool remains controversial. Here we established for the first time an approach that allows direct tracking of such clonotypic cells by labeling with patient-specific immunoglobulin ligands in 15 patients with myeloma. Fifty percent of patients showed evidence of clonotypic B cells in blood or bone marrow by PCR. Epitope-mimicking peptides from random libraries were selected on each patient's individual immunoglobulin and used as ligands to trace cells expressing the idiotypic immunoglobulin on their surface. We established a flow cytometry and immunofluorescence protocol to track clonotypic B cells and validated it in two independent monoclonal B cell systems. Using this method, we found clonotypic B cells in only one out of 15 myeloma patients. In view of the assay's validated sensitivity level of 10−3, this surprising data suggests that the abundance of such cells has been vastly overestimated in the past and that they apparently represent a very rare population in myeloma. Our novel tracing approach may open perspectives to isolate and analyze clonotypic B cells and determine their role in myeloma pathobiology

Inclusive cross section and single-transverse-spin asymmetry for very forward neutron production in polarized p+p collisions at sqrt(s)=200 GeV

The energy dependence of the single-transverse-spin asymmetry, A_N, and the cross section for neutron production at very forward angles were measured in the PHENIX experiment at RHIC for polarized p+p collisions at sqrt(s)=200 GeV. The neutrons were observed in forward detectors covering an angular range of up to 2.2 mrad. We report results for neutrons with momentum fraction of x_F=0.45 to 1.0. The energy dependence of the measured cross sections were consistent with x_F scaling, compared to measurements by an ISR experiment which measured neutron production in unpolarized p+p collisions at sqrt(s)=30.6--62.7 GeV. The cross sections for large x_F neutron production for p+p collisions, as well as those in e+p collisions measured at HERA, are described by a pion exchange mechanism. The observed forward neutron asymmetries were large, reaching A_N=-0.08+/-0.02 for x_F=0.8; the measured backward asymmetries, for negative x_F, were consistent with zero. The observed asymmetry for forward neutron production is discussed within the pion exchange framework, with interference between the spin-flip amplitude due to the pion exchange and nonflip amplitudes from all Reggeon exchanges. Within the pion exchange description, the measured neutron asymmetry is sensitive to the contribution of other Reggeon exchanges even for small amplitudes.Comment: 383 authors, 16 pages, 18 figures, 6 tables. Submitted to Phys. Rev. D. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Transverse momentum and centrality dependence of dihadron correlations in Au+Au collisions at sqrt(s_NN)=200 GeV: Jet-quenching and the response of partonic matter

Azimuthal angle \Delta\phi correlations are presented for charged hadrons from dijets for 0.4 < p_T < 10 GeV/c in Au+Au collisions at sqrt(s_NN) = 200 GeV. With increasing p_T, the away-side distribution evolves from a broad to a concave shape, then to a convex shape. Comparisons to p+p data suggest that the away-side can be divided into a partially suppressed "head" region centered at Delta\phi ~ \pi, and an enhanced "shoulder" region centered at Delta\phi ~ \pi +/- 1.1. The p_T spectrum for the "head" region softens toward central collisions, consistent with the onset of jet quenching. The spectral slope for the "shoulder" region is independent of centrality and trigger p_T, which offers constraints on energy transport mechanisms and suggests that the "shoulder" region contains the medium response to energetic jets.Comment: 420 authors from 58 institutions, 6 pages, 4 figures. Submitted to Physical Review Letters. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Observation of direct-photon collective flow in sqrt(s_NN)=200 GeV Au+Au collisions

The second Fourier component v_2 of the azimuthal anisotropy with respect to the reaction plane was measured for direct photons at midrapidity and transverse momentum (p_T) of 1--13 GeV/c in Au+Au collisions at sqr(s_NN)=200 GeV. Previous measurements of this quantity for hadrons with p_T < 6 GeV/c indicate that the medium behaves like a nearly perfect fluid, while for p_T > 6 GeV/c a reduced anisotropy is interpreted in terms of a path-length dependence for parton energy loss. In this measurement with the PHENIX detector at the Relativistic Heavy Ion Collider we find that for p_T > 4 GeV/c the anisotropy for direct photons is consistent with zero, as expected if the dominant source of direct photons is initial hard scattering. However, in the p_T < 4 GeV/c region dominated by thermal photons, we find a substantial direct photon v_2 comparable to that of hadrons, whereas model calculations for thermal photons in this kinematic region significantly underpredict the observed v_2.Comment: 384 authors, 6 pages, 3 figures, and 1 table. Submitted to Phys. Rev. Lett. v2 has minor changes to match the submission version. Plain text data tables for the points plotted in the figures are publicly available at http://www.phenix.bnl.gov/phenix/WWW/info/data/ppg126_data.htm