786 research outputs found

    Coordinated grid and place cell replay during rest

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    Hippocampal replay has been hypothesized to underlie memory consolidation and navigational planning, yet the involvement of grid cells in replay is unknown. During replay we found grid cells to be spatially coherent with place cells, encoding locations 11 ms delayed relative to the hippocampus, with directionally modulated grid cells and forward replay exhibiting the greatest coherence with the CA1 area of the hippocampus. This suggests grid cells are engaged during the consolidation of spatial memories to the neocortex

    Genetic analysis of amyotrophic lateral sclerosis identifies contributing pathways and cell types

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    Despite the considerable progress in unraveling the genetic causes of amyotrophic lateral sclerosis (ALS), we do not fully understand the molecular mechanisms underlying the disease. We analyzed genome-wide data involving 78,500 individuals using a polygenic risk score approach to identify the biological pathways and cell types involved in ALS. This data-driven approach identified multiple aspects of the biology underlying the disease that resolved into broader themes, namely, neuron projection morphogenesis, membrane trafficking, and signal transduction mediated by ribonucleotides. We also found that genomic risk in ALS maps consistently to GABAergic interneurons and oligodendrocytes, as confirmed in human single-nucleus RNA-seq data. Using two-sample Mendelian randomization, we nominated six differentially expressed genes (ATG16L2, ACSL5, MAP1LC3A, MAPKAPK3, PLXNB2, and SCFD1) within the significant pathways as relevant to ALS. We conclude that the disparate genetic etiologies of this fatal neurological disease converge on a smaller number of final common pathways and cell types

    Health care utilization and mortality among elderly patients with myelodysplastic syndromes

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    Background: Mortality in patients with myelodysplastic syndromes (MDS) is high, and patients are likely to require hospitalizations, emergency department (ED) visits, and transfusions. The relationships between these events and the MDS complications of anemia, neutropenia, and thrombocytopenia are not well understood

    Heatshield for Extreme Entry Environment Technology (HEEET) TPS for Ice Giants Probe Missions

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    This poster provides an overview of the requirements, design, development and testing of the 3D Woven TPS being developed under NASAs Heatshield for Extreme Entry Environment Technology (HEEET) project. Under this current program, NASA is working to develop a Thermal Protection System (TPS) capable of surviving entry into Saturn. A primary goal of the project is to build and test an Engineering Test Unit (ETU) to establish a Technical Readiness Level (TRL) of 6 for this technology by 2018. Poster also discusses use of HEEET TPS for probe missions to the Ice Giants, Uranus and Neptune

    Ray-parameter based stacking and enhanced pre-conditioning for stable inversion of receiver function data

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    While inversion of seismic velocity from receiver function data could be instable due to its intrinsic non-linearity and non-uniqueness, improper stacking of receiver function could also introduce significant biases to the resulting velocity structure. In a distance section of receiver functions, the Moho Ps conversion and the two reverberations possess a positive and negative moveout, respectively. Stacking receiver functions without moveout correction could significantly reduce and distort the amplitude and waveform of these phases. Inversion with these incorrectly stacked receiver functions will thus inevitably introduce artefacts to the resulting velocity structure. In this study, we have improved the inversion procedure in two ways. First, we introduce a ray-parameter based (RPB) stacking method to correctly construct receiver function data for inversion. Specifically we develop a ‘four-pin’ method that accounts for the moveout effect of the converted and reverberated phases in stacking individual receiver functions recorded at various distances. Secondly, we divide the receiver function trace into conversion and reverberation windows and assign different weights between the two windows in the inversion. More weight is given to the Ps conversion window in resolving the shallow structure, which can be nearly fixed in the successive inversion of deeper structure. We also employ other pre-conditioning proposed by previous studies, such as balancing the receiver function data being filtered with different Gaussian filters, smoothing the velocity model and further regulating the model based on existing information. We compute synthetic receiver functions at distances between 30◦ and 90◦ from a target model and then use the RPB stacking method to generate the input data for various inversions (iterative linear) with different initial models. Our inversions with enhanced pre-conditioning and RPB stacked data demonstrate a good capability in recovering the target model from generally more stable iterations. Applying these techniques to two broad-band stations in China indicates that the improvements on data stacking and inversion can eliminate potential stacking-induced artefacts, and yield models more consistent with surface geology

    Measurement of the Charged Multiplicities in b, c and Light Quark Events from Z0 Decays

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    Average charged multiplicities have been measured separately in bb, cc and light quark (u,d,su,d,s) events from Z0Z^0 decays measured in the SLD experiment. Impact parameters of charged tracks were used to select enriched samples of bb and light quark events, and reconstructed charmed mesons were used to select cc quark events. We measured the charged multiplicities: nˉuds=20.21±0.10(stat.)±0.22(syst.)\bar{n}_{uds} = 20.21 \pm 0.10 (\rm{stat.})\pm 0.22(\rm{syst.}), nˉc=21.28±0.46(stat.)0.36+0.41(syst.)\bar{n}_{c} = 21.28 \pm 0.46(\rm{stat.}) ^{+0.41}_{-0.36}(\rm{syst.}) nˉb=23.14±0.10(stat.)0.37+0.38(syst.)\bar{n}_{b} = 23.14 \pm 0.10(\rm{stat.}) ^{+0.38}_{-0.37}(\rm{syst.}), from which we derived the differences between the total average charged multiplicities of cc or bb quark events and light quark events: Δnˉc=1.07±0.47(stat.)0.30+0.36(syst.)\Delta \bar{n}_c = 1.07 \pm 0.47(\rm{stat.})^{+0.36}_{-0.30}(\rm{syst.}) and Δnˉb=2.93±0.14(stat.)0.29+0.30(syst.)\Delta \bar{n}_b = 2.93 \pm 0.14(\rm{stat.})^{+0.30}_{-0.29}(\rm{syst.}). We compared these measurements with those at lower center-of-mass energies and with perturbative QCD predictions. These combined results are in agreement with the QCD expectations and disfavor the hypothesis of flavor-independent fragmentation.Comment: 19 pages LaTex, 4 EPS figures, to appear in Physics Letters

    A Search for Jet Handedness in Hadronic Z0Z^0 Decays

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    We have searched for signatures of polarization in hadronic jets from Z0qqˉZ^0 \to q \bar{q} decays using the ``jet handedness'' method. The polar angle asymmetry induced by the high SLC electron-beam polarization was used to separate quark jets from antiquark jets, expected to be left- and right-polarized, respectively. We find no evidence for jet handedness in our global sample or in a sample of light quark jets and we set upper limits at the 95% C.L. of 0.063 and 0.099 respectively on the magnitude of the analyzing power of the method proposed by Efremov {\it et al.}Comment: Revtex, 8 pages, 2 figure

    Dysfunction in the βII Spectrin-Dependent Cytoskeleton Underlies Human Arrhythmia.

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    Background: The cardiac cytoskeleton plays key roles in maintaining myocyte structural integrity in health and disease. In fact, human mutations in cardiac cytoskeletal elements are tightly linked with cardiac pathologies including myopathies, aortopathies, and dystrophies. Conversely, the link between cytoskeletal protein dysfunction in cardiac electrical activity is not well understood, and often overlooked in the cardiac arrhythmia field. Methods and Results: Here, we uncover a new mechanism for the regulation of cardiac membrane excitability. We report that βII spectrin, an actin-associated molecule, is essential for the post-translational targeting and localization of critical membrane proteins in heart. βII spectrin recruits ankyrin-B to the cardiac dyad, and a novel human mutation in the ankyrin-B gene disrupts the ankyrin-B/βII spectrin interaction leading to severe human arrhythmia phenotypes. Mice lacking cardiac βII spectrin display lethal arrhythmias, aberrant electrical and calcium handling phenotypes, and abnormal expression/localization of cardiac membrane proteins. Mechanistically, βII spectrin regulates the localization of cytoskeletal and plasma membrane/sarcoplasmic reticulum protein complexes that include the Na/Ca exchanger, RyR2, ankyrin-B, actin, and αII spectrin. Finally, we observe accelerated heart failure phenotypes in βII spectrin-deficient mice. Conclusions: Our findings identify βII spectrin as critical for normal myocyte electrical activity, link this molecule to human disease, and provide new insight into the mechanisms underlying cardiac myocyte biology
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