1,208 research outputs found
Aberrant seizure-induced neurogenesis in experimental temporal lobe epilepsy
Neurogenesis in the hippocampal dentate gyrus persists throughout life and is increased by seizures. The dentate granule cell (DGC) layer is often abnormal in human and experimental temporal lobe epilepsy, with dispersion of the layer and the appearance of ectopic granule neurons in the hilus. We tested the hypothesis that these abnormalities result from aberrant DGC neurogenesis after seizure-induced injury. Bromodeoxyuridine labeling, in situ hybridization, and immunohistochemistry were used to identify proliferating progenitors and mature DGCs in the adult rat pilocarpine temporal lobe epilepsy model. We also examined dentate gyri from epileptic human hippocampal surgical specimens. Prox-1 immunohistochemistry and pulse-chase bromodeoxyuridine labeling showed that progenitors migrate aberrantly to the hilus and molecular layer after prolonged seizures and differentiate into ectopic DGCs in rat. Neuroblast marker expression indicated the delayed appearance of chainlike progenitor cell formations extending into the hilus and molecular layer, suggesting that seizures alter migratory behavior of DGC precursors. Ectopic putative DGCs also were found in the hilus and molecular layer of epileptic human dentate gyrus. These findings indicate that seizure-induced abnormalities of neuroblast migration lead to abnormal integration of newborn DGCs in the epileptic adult hippocampus, and implicate aberrant neurogenesis in the development or progression of recurrent seizures. Ann Neurol 2005Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49280/1/20699_ftp.pd
Two-Loop Renormalization Group Equations for Soft Supersymmetry-Breaking Couplings
We compute the two-loop renormalization group equations for all soft
supersymmetry-breaking couplings in a general softly broken N=1 supersymmetric
model. We also specialize these results to the Minimal Supersymmetric Standard
Model.Comment: 26 pages. [v4: Signs of equations (4.2) and (4.3) are fixed.
A precision study of the fine tuning in the DiracNMSSM
Recently the DiracNMSSM has been proposed as a possible solution to reduce
the fine tuning in supersymmetry. We determine the degree of fine tuning needed
in the DiracNMSSM with and without non-universal gaugino masses and compare it
with the fine tuning in the GNMSSM. To apply reasonable cuts on the allowed
parameter regions we perform a precise calculation of the Higgs mass. In
addition, we include the limits from direct SUSY searches and dark matter
abundance. We find that both models are comparable in terms of fine tuning,
with the minimal fine tuning in the GNMSSM slightly smaller.Comment: 20 pages + appendices, 10 figure
Transit Timing Observations from Kepler: III. Confirmation of 4 Multiple Planet Systems by a Fourier-Domain Study of Anti-correlated Transit Timing Variations
We present a method to confirm the planetary nature of objects in systems
with multiple transiting exoplanet candidates. This method involves a
Fourier-Domain analysis of the deviations in the transit times from a constant
period that result from dynamical interactions within the system. The
combination of observed anti-correlations in the transit times and mass
constraints from dynamical stability allow us to claim the discovery of four
planetary systems Kepler-25, Kepler-26, Kepler-27, and Kepler-28, containing
eight planets and one additional planet candidate.Comment: Accepted to MNRA
Characteristics of Kepler Planetary Candidates Based on the First Data Set: The Majority are Found to be Neptune-Size and Smaller
In the spring of 2009, the Kepler Mission commenced high-precision photometry
on nearly 156,000 stars to determine the frequency and characteristics of small
exoplanets, conduct a guest observer program, and obtain asteroseismic data on
a wide variety of stars. On 15 June 2010 the Kepler Mission released data from
the first quarter of observations. At the time of this publication, 706 stars
from this first data set have exoplanet candidates with sizes from as small as
that of the Earth to larger than that of Jupiter. Here we give the identity and
characteristics of 306 released stars with planetary candidates. Data for the
remaining 400 stars with planetary candidates will be released in February
2011. Over half the candidates on the released list have radii less than half
that of Jupiter. The released stars include five possible multi-planet systems.
One of these has two Neptune-size (2.3 and 2.5 Earth-radius) candidates with
near-resonant periods.Comment: Paper to accompany Kepler's June 15, 2010 data release; submitted to
Astrophysical Journal Figures 1,2,& 3 revised. Improved labeling on all
figures. Slight changes to planet frequencies in result
Human exploration of space: A review of NASA's 90-day study and alternatives
The National Research Council (NRC) examines the NASA Report of the 90-Day Study on Human Exploration of the Moon and Mars, and alternative concepts. Included in this paper, prepared for the National Space Council, are the answers to a challenging set of questions posed by the Vice President. Concerns addressed include: the appropriate pace, the scope of human exploration, the level of long-term support required, the technology development available and needed, the feasibility of long-duration human spaceflight in a low-gravity environment, scientific objectives, and other considerations such as costs and risks
International criteria for electrocardiographic interpretation in athletes: Consensus statement.
Sudden cardiac death (SCD) is the leading cause of mortality in athletes during sport. A variety of mostly hereditary, structural or electrical cardiac disorders are associated with SCD in young athletes, the majority of which can be identified or suggested by abnormalities on a resting 12-lead electrocardiogram (ECG). Whether used for diagnostic or screening purposes, physicians responsible for the cardiovascular care of athletes should be knowledgeable and competent in ECG interpretation in athletes. However, in most countries a shortage of physician expertise limits wider application of the ECG in the care of the athlete. A critical need exists for physician education in modern ECG interpretation that distinguishes normal physiological adaptations in athletes from distinctly abnormal findings suggestive of underlying pathology. Since the original 2010 European Society of Cardiology recommendations for ECG interpretation in athletes, ECG standards have evolved quickly, advanced by a growing body of scientific data and investigations that both examine proposed criteria sets and establish new evidence to guide refinements. On 26-27 February 2015, an international group of experts in sports cardiology, inherited cardiac disease, and sports medicine convened in Seattle, Washington (USA), to update contemporary standards for ECG interpretation in athletes. The objective of the meeting was to define and revise ECG interpretation standards based on new and emerging research and to develop a clear guide to the proper evaluation of ECG abnormalities in athletes. This statement represents an international consensus for ECG interpretation in athletes and provides expert opinion-based recommendations linking specific ECG abnormalities and the secondary evaluation for conditions associated with SCD
HLA-DM Mediates Epitope Selection by a “Compare-Exchange” Mechanism when a Potential Peptide Pool Is Available
BACKGROUND: HLA-DM (DM) mediates exchange of peptides bound to MHC class II (MHCII) during the epitope selection process. Although DM has been shown to have two activities, peptide release and MHC class II refolding, a clear characterization of the mechanism by which DM facilitates peptide exchange has remained elusive. METHODOLOGY/PRINCIPAL FINDINGS: We have previously demonstrated that peptide binding to and dissociation from MHCII in the absence of DM are cooperative processes, likely related to conformational changes in the peptide-MHCII complex. Here we show that DM promotes peptide release by a non-cooperative process, whereas it enhances cooperative folding of the exchange peptide. Through electron paramagnetic resonance (EPR) and fluorescence polarization (FP) we show that DM releases prebound peptide very poorly in the absence of a candidate peptide for the exchange process. The affinity and concentration of the candidate peptide are also important for the release of the prebound peptide. Increased fluorescence energy transfer between the prebound and exchange peptides in the presence of DM is evidence for a tetramolecular complex which resolves in favor of the peptide that has superior folding properties. CONCLUSION/SIGNIFICANCE: This study shows that both the peptide releasing activity on loaded MHCII and the facilitating of MHCII binding by a candidate exchange peptide are integral to DM mediated epitope selection. The exchange process is initiated only in the presence of candidate peptides, avoiding possible release of a prebound peptide and loss of a potential epitope. In a tetramolecular transitional complex, the candidate peptides are checked for their ability to replace the pre-bound peptide with a geometry that allows the rebinding of the original peptide. Thus, DM promotes a "compare-exchange" sorting algorithm on an available peptide pool. Such a "third party"-mediated mechanism may be generally applicable for diverse ligand recognition in other biological systems
The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe
The preponderance of matter over antimatter in the early Universe, the
dynamics of the supernova bursts that produced the heavy elements necessary for
life and whether protons eventually decay --- these mysteries at the forefront
of particle physics and astrophysics are key to understanding the early
evolution of our Universe, its current state and its eventual fate. The
Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed
plan for a world-class experiment dedicated to addressing these questions. LBNE
is conceived around three central components: (1) a new, high-intensity
neutrino source generated from a megawatt-class proton accelerator at Fermi
National Accelerator Laboratory, (2) a near neutrino detector just downstream
of the source, and (3) a massive liquid argon time-projection chamber deployed
as a far detector deep underground at the Sanford Underground Research
Facility. This facility, located at the site of the former Homestake Mine in
Lead, South Dakota, is approximately 1,300 km from the neutrino source at
Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino
charge-parity symmetry violation and mass ordering effects. This ambitious yet
cost-effective design incorporates scalability and flexibility and can
accommodate a variety of upgrades and contributions. With its exceptional
combination of experimental configuration, technical capabilities, and
potential for transformative discoveries, LBNE promises to be a vital facility
for the field of particle physics worldwide, providing physicists from around
the globe with opportunities to collaborate in a twenty to thirty year program
of exciting science. In this document we provide a comprehensive overview of
LBNE's scientific objectives, its place in the landscape of neutrino physics
worldwide, the technologies it will incorporate and the capabilities it will
possess.Comment: Major update of previous version. This is the reference document for
LBNE science program and current status. Chapters 1, 3, and 9 provide a
comprehensive overview of LBNE's scientific objectives, its place in the
landscape of neutrino physics worldwide, the technologies it will incorporate
and the capabilities it will possess. 288 pages, 116 figure
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