348 research outputs found
Charge-starved, relativistic jets and blazar variability
High energy emission from blazars is thought to arise in a relativistic jet
launched by a supermassive black hole. The emission site must be far from the
hole and the jet relativistic, in order to avoid absorption of the photons. In
extreme cases, rapid variability of the emission suggests that structures of
length-scale smaller than the gravitational radius of the central black hole
are imprinted on the jet as it is launched, and modulate the radiation released
after it has been accelerated to high Lorentz factor. We propose a mechanism
which can account for the acceleration of the jet, and for the rapid
variability of the radiation, based on the propagation characteristics of
large-amplitude waves in charge-starved, polar jets. Using a two-fluid
(electron-positron) description, we find the outflows exhibit a delayed
acceleration phase, that starts at roughly 1pc, where the inertia associated
with the wave currents becomes important. The time-structure imprinted on the
jet at launch modulates photons produced by the accelerating jet provided the
pair multiplicity in the black-hole magnetosphere is sufficiently small,
suggesting that very rapid variability is confined to sources in which the
electromagnetic cascade in the black-hole magnetosphere is not prolific.Comment: 8 pages, 1 figure. Momentum equation corrected. Conclusions
unchanged. Erratum submitted to Ap
The testosterone-dependent and independent transcriptional networks in the hypothalamus of Gpr54 and Kiss1 knockout male mice are not fully equivalent.
BACKGROUND: Humans and mice with loss of function mutations in GPR54 (KISS1R) or kisspeptin do not progress through puberty, caused by a failure to release GnRH. The transcriptional networks regulated by these proteins in the hypothalamus have yet to be explored by genome-wide methods. RESULTS: We show here, using 1 million exon mouse arrays (Exon 1.0 Affymetrix) and quantitative polymerase chain reaction (QPCR) validation to analyse microdissected hypothalamic tissue from Gpr54 and Kiss1 knockout mice, the extent of transcriptional regulation in the hypothalamus. The sensitivity to detect important transcript differences in microdissected RNA was confirmed by the observation of counter-regulation of Kiss1 expression in Gpr54 knockouts and confirmed by immunohistochemistry (IHC). Since Gpr54 and Kiss1 knockout animals are effectively pre-pubertal with low testosterone (T) levels, we also determined which of the validated transcripts were T-responsive and which varied according to genotype alone. We observed four types of transcriptional regulation (i) genotype only dependent regulation, (ii) T only dependent regulation, (iii) genotype and T-dependent regulation with interaction between these variables, (iv) genotype and T-dependent regulation with no interaction between these variables. The results implicate for the first time several transcription factors (e.g. Npas4, Esr2), proteases (Klk1b22), and the orphan 10-transmembrane transporter TMEM144 in the biology of GPR54/kisspeptin function in the hypothalamus. We show for the neuronal activity regulated transcription factor NPAS4, that distinct protein over-expression is seen in the hypothalamus and hippocampus in Gpr54 knockout mice. This links for the first time the hypothalamic-gonadal axis with this important regulator of inhibitory synapse formation. Similarly we confirm TMEM144 up-regulation in the hypothalamus by RNA in situ hybridization and western blot. CONCLUSIONS: Taken together, global transcriptional profiling shows that loss of GPR54 and kisspeptin are not fully equivalent in the mouse hypothalamus.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are
Mortality following Stroke, the Weekend Effect and Related Factors: Record Linkage Study
Increased mortality following hospitalisation for stroke has been reported from many but not all studies that have investigated a 'weekend effect' for stroke. However, it is not known whether the weekend effect is affected by factors including hospital size, season and patient distance from hospital.To assess changes over time in mortality following hospitalisation for stroke and how any increased mortality for admissions on weekends is related to factors including the size of the hospital, seasonal factors and distance from hospital.A population study using person linked inpatient, mortality and primary care data for stroke from 2004 to 2012. The outcome measures were, firstly, mortality at seven days and secondly, mortality at 30 days and one year.Overall mortality for 37 888 people hospitalised following stroke was 11.6% at seven days, 21.4% at 30 days and 37.7% at one year. Mortality at seven and 30 days fell significantly by 1.7% and 3.1% per annum respectively from 2004 to 2012. When compared with week days, mortality at seven days was increased significantly by 19% for admissions on weekends, although the admission rate was 21% lower on weekends. Although not significant, there were indications of increased mortality at seven days for weekend admissions during winter months (31%), in community (81%) rather than large hospitals (8%) and for patients resident furthest from hospital (32% for distances of >20 kilometres). The weekend effect was significantly increased (by 39%) for strokes of 'unspecified' subtype.Mortality following stroke has fallen over time. Mortality was increased for admissions at weekends, when compared with normal week days, but may be influenced by a higher stroke severity threshold for admission on weekends. Other than for unspecified strokes, we found no significant variation in the weekend effect for hospital size, season and distance from hospital
Accuracy and differential bias in copy number measurement of CCL3L1 in association studies with three auto-immune disorders
Contains fulltext :
97604.pdf (publisher's version ) (Open Access)BACKGROUND: Copy number variation (CNV) contributes to the variation observed between individuals and can influence human disease progression, but the accurate measurement of individual copy numbers is technically challenging. In the work presented here we describe a modification to a previously described paralogue ratio test (PRT) method for genotyping the CCL3L1/CCL4L1 copy variable region, which we use to ascertain CCL3L1/CCL4L1 copy number in 1581 European samples. As the products of CCL3L1 and CCL4L1 potentially play a role in autoimmunity we performed case control association studies with Crohn's disease, rheumatoid arthritis and psoriasis clinical cohorts. RESULTS: We evaluate the PRT methodology used, paying particular attention to accuracy and precision, and highlight the problems of differential bias in copy number measurements. Our PRT methods for measuring copy number were of sufficient precision to detect very slight but systematic differential bias between results from case and control DNA samples in one study. We find no evidence for an association between CCL3L1 copy number and Crohn's disease, rheumatoid arthritis or psoriasis. CONCLUSIONS: Differential bias of this small magnitude, but applied systematically across large numbers of samples, would create a serious risk of false positive associations in copy number, if measured using methods of lower precision, or methods relying on single uncorroborated measurements. In this study the small differential bias detected by PRT in one sample set was resolved by a simple pre-treatment by restriction enzyme digestion
Genome-Wide Association of Bipolar Disorder Suggests an Enrichment of Replicable Associations in Regions near Genes
Although a highly heritable and disabling disease, bipolar disorder's (BD) genetic variants have been challenging to identify. We present new genotype data for 1,190 cases and 401 controls and perform a genome-wide association study including additional samples for a total of 2,191 cases and 1,434 controls. We do not detect genome-wide significant associations for individual loci; however, across all SNPs, we show an association between the power to detect effects calculated from a previous genome-wide association study and evidence for replication (P = 1.5×10−7). To demonstrate that this result is not likely to be a false positive, we analyze replication rates in a large meta-analysis of height and show that, in a large enough study, associations replicate as a function of power, approaching a linear relationship. Within BD, SNPs near exons exhibit a greater probability of replication, supporting an enrichment of reproducible associations near functional regions of genes. These results indicate that there is likely common genetic variation associated with BD near exons (±10 kb) that could be identified in larger studies and, further, provide a framework for assessing the potential for replication when combining results from multiple studies
Double Spin Asymmetry of Electrons from Heavy Flavor Decays in p+p Collisions at sqrt(s)=200 GeV
We report on the first measurement of double-spin asymmetry, A_LL, of
electrons from the decays of hadrons containing heavy flavor in longitudinally
polarized p+p collisions at sqrt(s)=200 GeV for p_T= 0.5 to 3.0 GeV/c. The
asymmetry was measured at mid-rapidity (|eta|<0.35) with the PHENIX detector at
the Relativistic Heavy Ion Collider. The measured asymmetries are consistent
with zero within the statistical errors. We obtained a constraint for the
polarized gluon distribution in the proton of |Delta g/g(log{_10}x=
-1.6^+0.5_-0.4, {mu}=m_T^c)|^2 < 0.033 (1 sigma), based on a leading-order
perturbative-quantum-chromodynamics model, using the measured asymmetry.Comment: 385 authors, 17 pages, 15 figures, 5 tables. Submitted to Phys. Rev.
D. Plain text data tables for the points plotted in figures for this and
previous PHENIX publications are (or will be) publicly available at
http://www.phenix.bnl.gov/papers.htm
Upsilon (1S+2S+3S) production in d+Au and p+p collisions at sqrt(s_NN)=200 GeV and cold-nuclear matter effects
The three Upsilon states, Upsilon(1S+2S+3S), are measured in d+Au and p+p
collisions at sqrt(s_NN)=200 GeV and rapidities 1.2<|y|<2.2 by the PHENIX
experiment at the Relativistic Heavy-Ion Collider. Cross sections for the
inclusive Upsilon(1S+2S+3S) production are obtained. The inclusive yields per
binary collision for d+Au collisions relative to those in p+p collisions
(R_dAu) are found to be 0.62 +/- 0.26 (stat) +/- 0.13 (syst) in the gold-going
direction and 0.91 +/- 0.33 (stat) +/- 0.16 (syst) in the deuteron-going
direction. The measured results are compared to a nuclear-shadowing model,
EPS09 [JHEP 04, 065 (2009)], combined with a final-state breakup cross section,
sigma_br, and compared to lower energy p+A results. We also compare the results
to the PHENIX J/psi results [Phys. Rev. Lett. 107, 142301 (2011)]. The rapidity
dependence of the observed Upsilon suppression is consistent with lower energy
p+A measurements.Comment: 495 authors, 11 pages, 9 figures, 5 tables. Submitted to Phys. Rev.
C. Plain text data tables for the points plotted in figures for this and
previous PHENIX publications are (or will be) publicly available at
http://www.phenix.bnl.gov/papers.htm
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