786 research outputs found
Coordinated grid and place cell replay during rest
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
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
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
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
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
Average charged multiplicities have been measured separately in , and
light quark () events from decays measured in the SLD experiment.
Impact parameters of charged tracks were used to select enriched samples of
and light quark events, and reconstructed charmed mesons were used to select
quark events. We measured the charged multiplicities:
,
, from
which we derived the differences between the total average charged
multiplicities of or quark events and light quark events: and . 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 Decays
We have searched for signatures of polarization in hadronic jets from 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.
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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