119 research outputs found
Ultra-High Energy Neutrino Fluxes: New Constraints and Implications
We apply new upper limits on neutrino fluxes and the diffuse extragalactic
component of the GeV gamma-ray flux to various scenarios for ultra high energy
cosmic rays and neutrinos. As a result we find that extra-galactic top-down
sources can not contribute significantly to the observed flux of highest energy
cosmic rays. The Z-burst mechanism where ultra-high energy neutrinos produce
cosmic rays via interactions with relic neutrinos is practically ruled out if
cosmological limits on neutrino mass and clustering apply.Comment: 10 revtex pages, 9 postscript figure
A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale
In this era of complete genomes, our knowledge of neuroanatomical circuitry
remains surprisingly sparse. Such knowledge is however critical both for basic
and clinical research into brain function. Here we advocate for a concerted
effort to fill this gap, through systematic, experimental mapping of neural
circuits at a mesoscopic scale of resolution suitable for comprehensive,
brain-wide coverage, using injections of tracers or viral vectors. We detail
the scientific and medical rationale and briefly review existing knowledge and
experimental techniques. We define a set of desiderata, including brain-wide
coverage; validated and extensible experimental techniques suitable for
standardization and automation; centralized, open access data repository;
compatibility with existing resources, and tractability with current
informatics technology. We discuss a hypothetical but tractable plan for mouse,
additional efforts for the macaque, and technique development for human. We
estimate that the mouse connectivity project could be completed within five
years with a comparatively modest budget.Comment: 41 page
Sarcoidosis activates diverse transcriptional programs in bronchoalveolar lavage cells
Abstract
Background
Sarcoidosis is a multisystem immuno-inflammatory disorder of unknown etiology that most commonly involves the lungs. We hypothesized that an unbiased approach to identify pathways activated in bronchoalveolar lavage (BAL) cells can shed light on the pathogenesis of this complex disease.
Methods
We recruited 15 patients with various stages of sarcoidosis and 12 healthy controls. All subjects underwent bronchoscopy with lavage. For each subject, total RNA was extracted from BAL cells and hybridized to an Affymetrix U133A microarray. Rigorous statistical methods were applied to identify differential gene expression between subjects with sarcoidosis vs. controls. To better elucidate pathways differentially activated between these groups, we integrated network and gene set enrichment analyses of BAL cell transcriptional profiles.
Results
Sarcoidosis patients were either non-smokers or former smokers, all had lung involvement and only two were on systemic prednisone. Healthy controls were all non-smokers. Comparison of BAL cell gene expression between sarcoidosis and healthy subjects revealed over 1500 differentially expressed genes. Several previously described immune mediators, such as interferon gamma, were upregulated in the sarcoidosis subjects. Using an integrative computational approach we constructed a modular network of over 80 gene sets that were highly enriched in patients with sarcoidosis. Many of these pathways mapped to inflammatory and immune-related processes including adaptive immunity, T-cell signaling, graft vs. host disease, interleukin 12, 23 and 17 signaling. Additionally, we uncovered a close association between the proteasome machinery and adaptive immunity, highlighting a potentially important and targetable relationship in the pathobiology of sarcoidosis.
Conclusions
BAL cells in sarcoidosis are characterized by enrichment of distinct transcriptional programs involved in immunity and proteasomal processes. Our findings add to the growing evidence implicating alveolar resident immune effector cells in the pathogenesis of sarcoidosis and identify specific pathways whose activation may modulate disease progression
A MISSING-LINK IN THE SUPERNOVA-GRB CONNECTION: THE CASE OF SN 2012ap
Gamma Ray Bursts (GRBs) are characterized by ultra-relativistic outflows,
while supernovae are generally characterized by non-relativistic ejecta. GRB
afterglows decelerate rapidly usually within days, because their low-mass
ejecta rapidly sweep up a comparatively larger mass of circumstellar material.
However supernovae, with heavy ejecta, can be in nearly free expansion for
centuries. Supernovae were thought to have non-relativistic outflows except for
few relativistic ones accompanied by GRBs. This clear division was blurred by
SN 2009bb, the first supernova with a relativistic outflow without an observed
GRB. Yet the ejecta from SN 2009bb was baryon loaded, and in nearly-free
expansion for a year, unlike GRBs. We report the first supernova discovered
without a GRB, but with rapidly decelerating mildly relativistic ejecta, SN
2012ap. We discovered a bright and rapidly evolving radio counterpart driven by
the circumstellar interaction of the relativistic ejecta. However, we did not
find any coincident GRB with an isotropic fluence of more than a sixth of the
fluence from GRB 980425. This shows for the first time that central engines in
type Ic supernovae, even without an observed GRB, can produce both relativistic
and rapidly decelerating outflows like GRBs.Comment: 8 pages, 5 figures, 1 table, accepted for publication in Ap
Brane-World Gravity
The observable universe could be a 1+3-surface (the "brane") embedded in a
1+3+\textit{d}-dimensional spacetime (the "bulk"), with Standard Model
particles and fields trapped on the brane while gravity is free to access the
bulk. At least one of the \textit{d} extra spatial dimensions could be very
large relative to the Planck scale, which lowers the fundamental gravity scale,
possibly even down to the electroweak ( TeV) level. This revolutionary
picture arises in the framework of recent developments in M theory. The
1+10-dimensional M theory encompasses the known 1+9-dimensional superstring
theories, and is widely considered to be a promising potential route to quantum
gravity. At low energies, gravity is localized at the brane and general
relativity is recovered, but at high energies gravity "leaks" into the bulk,
behaving in a truly higher-dimensional way. This introduces significant changes
to gravitational dynamics and perturbations, with interesting and potentially
testable implications for high-energy astrophysics, black holes, and cosmology.
Brane-world models offer a phenomenological way to test some of the novel
predictions and corrections to general relativity that are implied by M theory.
This review analyzes the geometry, dynamics and perturbations of simple
brane-world models for cosmology and astrophysics, mainly focusing on warped
5-dimensional brane-worlds based on the Randall--Sundrum models. We also cover
the simplest brane-world models in which 4-dimensional gravity on the brane is
modified at \emph{low} energies -- the 5-dimensional Dvali--Gabadadze--Porrati
models. Then we discuss co-dimension two branes in 6-dimensional models.Comment: A major update of Living Reviews in Relativity 7:7 (2004)
"Brane-World Gravity", 119 pages, 28 figures, the update contains new
material on RS perturbations, including full numerical solutions of
gravitational waves and scalar perturbations, on DGP models, and also on 6D
models. A published version in Living Reviews in Relativit
X-ray emission from the Sombrero galaxy: discrete sources
We present a study of discrete X-ray sources in and around the
bulge-dominated, massive Sa galaxy, Sombrero (M104), based on new and archival
Chandra observations with a total exposure of ~200 ks. With a detection limit
of L_X = 1E37 erg/s and a field of view covering a galactocentric radius of ~30
kpc (11.5 arcminute), 383 sources are detected. Cross-correlation with Spitler
et al.'s catalogue of Sombrero globular clusters (GCs) identified from HST/ACS
observations reveals 41 X-rays sources in GCs, presumably low-mass X-ray
binaries (LMXBs). We quantify the differential luminosity functions (LFs) for
both the detected GC and field LMXBs, whose power-low indices (~1.1 for the
GC-LF and ~1.6 for field-LF) are consistent with previous studies for
elliptical galaxies. With precise sky positions of the GCs without a detected
X-ray source, we further quantify, through a fluctuation analysis, the GC LF at
fainter luminosities down to 1E35 erg/s. The derived index rules out a
faint-end slope flatter than 1.1 at a 2 sigma significance, contrary to recent
findings in several elliptical galaxies and the bulge of M31. On the other
hand, the 2-6 keV unresolved emission places a tight constraint on the field
LF, implying a flattened index of ~1.0 below 1E37 erg/s. We also detect 101
sources in the halo of Sombrero. The presence of these sources cannot be
interpreted as galactic LMXBs whose spatial distribution empirically follows
the starlight. Their number is also higher than the expected number of cosmic
AGNs (52+/-11 [1 sigma]) whose surface density is constrained by deep X-ray
surveys. We suggest that either the cosmic X-ray background is unusually high
in the direction of Sombrero, or a distinct population of X-ray sources is
present in the halo of Sombrero.Comment: 11 figures, 5 tables, ApJ in pres
f(R) theories
Over the past decade, f(R) theories have been extensively studied as one of
the simplest modifications to General Relativity. In this article we review
various applications of f(R) theories to cosmology and gravity - such as
inflation, dark energy, local gravity constraints, cosmological perturbations,
and spherically symmetric solutions in weak and strong gravitational
backgrounds. We present a number of ways to distinguish those theories from
General Relativity observationally and experimentally. We also discuss the
extension to other modified gravity theories such as Brans-Dicke theory and
Gauss-Bonnet gravity, and address models that can satisfy both cosmological and
local gravity constraints.Comment: 156 pages, 14 figures, Invited review article in Living Reviews in
Relativity, Published version, Comments are welcom
Cell-Autonomous Alterations in Dendritic Arbor Morphology and Connectivity Induced by Overexpression of MeCP2 in Xenopus Central Neurons In Vivo
Methyl CpG binding protein-2 (MeCP2) is an essential epigenetic regulator in human brain development. Mutations in the MeCP2 gene have been linked to Rett syndrome, a severe X-linked progressive neurodevelopmental disorder, and one of the most common causes of mental retardation in females. MeCP2 duplication and triplication have also been found to affect brain development, indicating that both loss of function and gain in MeCP2 dosage lead to similar neurological phenotypes. Here, we used the Xenopus laevis visual system as an in vivo model to examine the consequence of increased MeCP2 expression during the morphological maturation of individual central neurons in an otherwise intact brain. Single-cell overexpression of wild-type human MeCP2 was combined with time-lapse confocal microscopy imaging to study dynamic mechanisms by which MeCP2 influences tectal neuron dendritic arborization. Analysis of neurons co-expressing DsRed2 demonstrates that MeCP2 overexpression specifically interfered with dendritic elaboration, decreasing the rates of branch addition and elimination over a 48 hour observation period. Moreover, dynamic analysis of neurons co-expressing wt-hMeCP2 and PSD95-GFP revealed that even though neurons expressing wt-hMeCP2 possessed significantly fewer dendrites and simpler morphologies than control neurons at the same developmental stage, postsynaptic site density in wt-hMeCP2-expressing neurons was similar to controls and increased at a rate higher than controls. Together, our in vivo studies support an early, cell-autonomous role for MeCP2 during the morphological differentiation of neurons and indicate that perturbations in MeCP2 gene dosage result in deficits in dendritic arborization that can be compensated, at least in part, by synaptic connectivity changes
The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe
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 figuresMajor 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 figuresThe 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
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