967 research outputs found
Efficacy and tolerability of the Galanin Analog NAX 5055 in the multiple-hit rat model of symptomatic infantile spasms
Infantile spasms are seizures manifesting in infantile epileptic encephalopathies that are associated with poor epilepsy and cognitive outcomes. The current therapies are not always effective or are associated with serious side effects. Early cessation of spasms has been proposed to improve long-term outcomes. To identify new therapies for infantile spasms with rapid suppression of spasms, we are using the multiple-hit rat model of infantile spasms, which is a model of refractory infantile spasms. Here, we are testing the efficacy and tolerability of a single dose of the galanin receptor 1 preferring analog, NAX 5055, in the multiple-hit model of spasms. To induce the model, postnatal day 3 (PN3) male Sprague-Dawley rats underwent right intracerebral infusions of doxorubicin and lipopolysaccharide; p-chlorophenylalanine was then injected intraperitoneally (i.p.) at PN5. After the onset of spasms at PN4, 11-14 rats/group were injected i.p. with either NAX 5055 (0.5, 1, 2, or 4mg/kg) or vehicle. Video monitoring for spasms included a 1h pre-injection period, followed by 5h of recording post-injection, and two 2h sessions on PN5. The study was conducted in a randomized, blinded manner. Neurodevelopmental reflexes were assessed daily as well as at 2h after injection. Respiratory function, heart rate, pulse distension, oximetry and blood glucose were measured 4h after injection. The relative expression of GalR1 and GalR2 mRNA over ÎČ-actin in the cerebral cortex and hippocampus was determined with real time reverse transcription polymerase chain reaction. There was no acute effect of NAX 5055 on spasm frequency after the single dose of NAX 5055 (n=11-13 rats/group, following exclusions). Neurodevelopmental reflexes, vital signs, blood glucose measured 4h post-injection, and survival were not affected. A reduction in pulse and breath distention of unclear clinical significance was observed with the 7mg/kg NAX 5055 dose. GalR1 mRNA was present in the cerebral cortex and hippocampus of PN4 and adult rats. The hippocampal - but not the cortical - GalR1 mRNA expression was significantly lower in PN4 pups than in adults. GalR1 mRNA was also at least 20 times less abundant in the PN4 cortex than GalR2 mRNA. In conclusion, a single dose of NAX 5055 has no acute efficacy on spasms or toxicity in the multiple hit rat model of medically refractory infantile spasms. Our findings cannot exclude the possibility that repetitive NAX 5055 administration may show efficacy on spasms. The higher expression of GalR2 in the PN4 cortex suggests that GalR2-preferring analogs may be of interest to test for efficacy on spasms
The effect of seasonal host birth rates on disease persistence
In this paper, we add seasonality to the birth rate of an SIR model with density dependence in the death rate. We find that disease persistence can be explained by considering the average value of the seasonal term. If the basic reproductive ratio with this average value then the disease will persist and if with this average value then the disease will die out. However, if the underlying non-seasonal model displays oscillations towards the equilibrium then the dynamics of the seasonal model can become more complex. In this case the seasonality can interact with the underlying oscillations, resonate and the population can display a range of complex behaviours including chaos. We discuss these results in terms of two examples, Cowpox in bank voles and Rabbit Haemorrhagic Disease in rabbits
Timing of surgery following neoadjuvant chemoradiotherapy in locally advanced rectal cancer â A comparison of magnetic resonance imaging at two time points and histopathological responses
Real-space local polynomial basis for solid-state electronic-structure calculations: A finite-element approach
We present an approach to solid-state electronic-structure calculations based
on the finite-element method. In this method, the basis functions are strictly
local, piecewise polynomials. Because the basis is composed of polynomials, the
method is completely general and its convergence can be controlled
systematically. Because the basis functions are strictly local in real space,
the method allows for variable resolution in real space; produces sparse,
structured matrices, enabling the effective use of iterative solution methods;
and is well suited to parallel implementation. The method thus combines the
significant advantages of both real-space-grid and basis-oriented approaches
and so promises to be particularly well suited for large, accurate ab initio
calculations. We develop the theory of our approach in detail, discuss
advantages and disadvantages, and report initial results, including the first
fully three-dimensional electronic band structures calculated by the method.Comment: replacement: single spaced, included figures, added journal referenc
Onset of Superfluidity in 4He Films Adsorbed on Disordered Substrates
We have studied 4He films adsorbed in two porous glasses, aerogel and Vycor,
using high precision torsional oscillator and DC calorimetry techniques. Our
investigation focused on the onset of superfluidity at low temperatures as the
4He coverage is increased. Torsional oscillator measurements of the 4He-aerogel
system were used to determine the superfluid density of films with transition
temperatures as low as 20 mK. Heat capacity measurements of the 4He-Vycor
system probed the excitation spectrum of both non-superfluid and superfluid
films for temperatures down to 10 mK. Both sets of measurements suggest that
the critical coverage for the onset of superfluidity corresponds to a mobility
edge in the chemical potential, so that the onset transition is the bosonic
analog of a superconductor-insulator transition. The superfluid density
measurements, however, are not in agreement with the scaling theory of an onset
transition from a gapless, Bose glass phase to a superfluid. The heat capacity
measurements show that the non-superfluid phase is better characterized as an
insulator with a gap.Comment: 15 pages (RevTex), 21 figures (postscript
Supermassive Black Hole Binaries: The Search Continues
Gravitationally bound supermassive black hole binaries (SBHBs) are thought to
be a natural product of galactic mergers and growth of the large scale
structure in the universe. They however remain observationally elusive, thus
raising a question about characteristic observational signatures associated
with these systems. In this conference proceeding I discuss current theoretical
understanding and latest advances and prospects in observational searches for
SBHBs.Comment: 17 pages, 4 figures. To appear in the Proceedings of 2014 Sant Cugat
Forum on Astrophysics. Astrophysics and Space Science Proceedings, ed.
C.Sopuerta (Berlin: Springer-Verlag
Massive binary black holes in galactic nuclei and their path to coalescence
Massive binary black holes form at the centre of galaxies that experience a
merger episode. They are expected to coalesce into a larger black hole,
following the emission of gravitational waves. Coalescing massive binary black
holes are among the loudest sources of gravitational waves in the Universe, and
the detection of these events is at the frontier of contemporary astrophysics.
Understanding the black hole binary formation path and dynamics in galaxy
mergers is therefore mandatory. A key question poses: during a merger, will the
black holes descend over time on closer orbits, form a Keplerian binary and
coalesce shortly after? Here we review progress on the fate of black holes in
both major and minor mergers of galaxies, either gas-free or gas-rich, in
smooth and clumpy circum-nuclear discs after a galactic merger, and in
circum-binary discs present on the smallest scales inside the relic nucleus.Comment: Accepted for publication in Space Science Reviews. To appear in hard
cover in the Space Sciences Series of ISSI "The Physics of Accretion onto
Black Holes" (Springer Publisher
Social Network Analysis: Recent Achievements and Current Controversies
Network analysis has grown rapidly over the past two decades, but criticisms of the approach have increased as well This article focuses on several accomplishments and unresolved problems of the network approach In the first section. I illustrate the value of the network model in several substantive areas. focusing on studies of centrahty and power, network subgroups, and interorganizational relations I then discuss three issues over which the approach has provoked controversy the relation between network analysis and rational choice theory; the role of norms and culture, and the question of human agency I conclude with some examples of how network theorists are addressing these problemsPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68023/2/10.1177_000169939403700403.pd
Whole genome sequencing and the application of a SNP panel reveal primary evolutionary lineages and genomic variation in the lion (Panthera leo)
Background Previous phylogeographic studies of the lion (Panthera leo) have improved our insight into the distribution of genetic variation, as well as a revised taxonomy which now recognizes a northern (Panthera leo leo) and a southern (Panthera leo melanochaita) subspecies. However, existing whole range phylogeographic studies on lions either consist of very limited numbers of samples, or are focused on mitochondrial DNA and/or a limited set of microsatellites. The geographic extent of genetic lineages and their phylogenetic relationships remain uncertain, clouded by massive sampling gaps, sex-biased dispersal and incomplete lineage sorting. Results In this study we present results of low depth whole genome sequencing and subsequent variant calling in ten lions sampled throughout the geographic range, resulting in the discovery of >150,000 Single Nucleotide Polymorphisms (SNPs). Phylogenetic analyses revealed the same basal split between northern and southern populations, as well as four population clusters on a more local scale. Further, we designed a SNP panel, including 125 autosomal and 14 mitochondrial SNPs, which was tested on >200 lions from across their range. Results allow us to assign individuals to one of these four major clades (West & Central Africa, India, East Africa, or Southern Africa) and delineate these clades in more detail. Conclusions The results presented here, particularly the validated SNP panel, have important applications, not only for studying populations on a local geographic scale, but also for tracing samples of unknown origin for forensic purposes, and for guiding conservation management of ex situ populations. Thus, these genomic resources not only contribute to our understanding of the evolutionary history of the lion, but may also play a crucial role in conservation efforts aimed at protecting the species in its full diversity.Environmental Biolog
Planck intermediate results. VIII. Filaments between interacting clusters
About half of the baryons of the Universe are expected to be in the form of
filaments of hot and low density intergalactic medium. Most of these baryons
remain undetected even by the most advanced X-ray observatories which are
limited in sensitivity to the diffuse low density medium. The Planck satellite
has provided hundreds of detections of the hot gas in clusters of galaxies via
the thermal Sunyaev-Zel'dovich (tSZ) effect and is an ideal instrument for
studying extended low density media through the tSZ effect. In this paper we
use the Planck data to search for signatures of a fraction of these missing
baryons between pairs of galaxy clusters. Cluster pairs are good candidates for
searching for the hotter and denser phase of the intergalactic medium (which is
more easily observed through the SZ effect). Using an X-ray catalogue of
clusters and the Planck data, we select physical pairs of clusters as
candidates. Using the Planck data we construct a local map of the tSZ effect
centered on each pair of galaxy clusters. ROSAT data is used to construct X-ray
maps of these pairs. After having modelled and subtracted the tSZ effect and
X-ray emission for each cluster in the pair we study the residuals on both the
SZ and X-ray maps. For the merging cluster pair A399-A401 we observe a
significant tSZ effect signal in the intercluster region beyond the virial
radii of the clusters. A joint X-ray SZ analysis allows us to constrain the
temperature and density of this intercluster medium. We obtain a temperature of
kT = 7.1 +- 0.9, keV (consistent with previous estimates) and a baryon density
of (3.7 +- 0.2)x10^-4, cm^-3. The Planck satellite mission has provided the
first SZ detection of the hot and diffuse intercluster gas.Comment: Accepted by A&
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