46 research outputs found
Binary black hole merger dynamics and waveforms
We study dynamics and radiation generation in the last few orbits and merger
of a binary black hole system, applying recently developed techniques for
simulations of moving black holes. Our analysis of the gravitational radiation
waveforms and dynamical black hole trajectories produces a consistent picture
for a set of simulations with black holes beginning on circular-orbit
trajectories at a variety of initial separations. We find profound agreement at
the level of one percent among the simulations for the last orbit, merger and
ringdown. We are confident that this part of our waveform result accurately
represents the predictions from Einstein's General Relativity for the final
burst of gravitational radiation resulting from the merger of an astrophysical
system of equal-mass non-spinning black holes. The simulations result in a
final black hole with spin parameter a/m=0.69. We also find good agreement at a
level of roughly 10 percent for the radiation generated in the preceding few
orbits.Comment: 11 pages, 11 figures, submitted to PRD, update citations, minor
change
Evolving a puncture black hole with fixed mesh refinement
We present an algorithm for treating mesh refinement interfaces in numerical
relativity. We detail the behavior of the solution near such interfaces located
in the strong field regions of dynamical black hole spacetimes, with particular
attention to the convergence properties of the simulations. In our applications
of this technique to the evolution of puncture initial data with vanishing
shift, we demonstrate that it is possible to simultaneously maintain second
order convergence near the puncture and extend the outer boundary beyond 100M,
thereby approaching the asymptotically flat region in which boundary condition
problems are less difficult and wave extraction is meaningful.Comment: 18 pages, 12 figures. Minor changes, final PRD versio
Report of Third Annual Seminar on Estate Planning
Reports from the UK/CLE Third Annual Seminar on Estate Planning held July 23-24, 1976
Testing gravitational-wave searches with numerical relativity waveforms: Results from the first Numerical INJection Analysis (NINJA) project
The Numerical INJection Analysis (NINJA) project is a collaborative effort
between members of the numerical relativity and gravitational-wave data
analysis communities. The purpose of NINJA is to study the sensitivity of
existing gravitational-wave search algorithms using numerically generated
waveforms and to foster closer collaboration between the numerical relativity
and data analysis communities. We describe the results of the first NINJA
analysis which focused on gravitational waveforms from binary black hole
coalescence. Ten numerical relativity groups contributed numerical data which
were used to generate a set of gravitational-wave signals. These signals were
injected into a simulated data set, designed to mimic the response of the
Initial LIGO and Virgo gravitational-wave detectors. Nine groups analysed this
data using search and parameter-estimation pipelines. Matched filter
algorithms, un-modelled-burst searches and Bayesian parameter-estimation and
model-selection algorithms were applied to the data. We report the efficiency
of these search methods in detecting the numerical waveforms and measuring
their parameters. We describe preliminary comparisons between the different
search methods and suggest improvements for future NINJA analyses.Comment: 56 pages, 25 figures; various clarifications; accepted to CQ
Brainhack: a collaborative workshop for the open neuroscience community
International audienceBrainhack events offer a novel workshop format with participant-generated content that caters to the rapidly growing open neuroscience community. Including components from hackathons and unconferences, as well as parallel educational sessions, Brainhack fosters novel collaborations around the interests of its attendees. Here we provide an overview of its structure, past events, and example projects. Additionally, we outline current innovations such as regional events and post-conference publications. Through introducing Brainhack to the wider neuroscience community, we hope to provide a unique conference format that promotes the features of collaborative, open science
Glioma Through the Looking GLASS: Molecular Evolution of Diffuse Gliomas and the Glioma Longitudinal AnalySiS Consortium
Adult diffuse gliomas are a diverse group of brain neoplasms that inflict a high emotional toll on patients and their families. The Cancer Genome Atlas (TCGA) and similar projects have provided a comprehensive understanding of the somatic alterations and molecular subtypes of glioma at diagnosis. However, gliomas undergo significant cellular and molecular evolution during disease progression. We review the current knowledge on the genomic and epigenetic abnormalities in primary tumors and after disease recurrence, highlight the gaps in the literature, and elaborate on the need for a new multi-institutional effort to bridge these knowledge gaps and how the Glioma Longitudinal AnalySiS Consortium (GLASS) aims to systemically catalog the longitudinal changes in gliomas. The GLASS initiative will provide essential insights into the evolution of glioma toward a lethal phenotype, with the potential to reveal targetable vulnerabilities, and ultimately, improved outcomes for a patient population in need
Mapping H4K20me3 onto the chromatin landscape of senescent cells indicates a function in control of cell senescence and tumor suppression through preservation of genetic and epigenetic stability
Background:
Histone modification H4K20me3 and its methyltransferase SUV420H2 have been implicated in suppression of tumorigenesis. The underlying mechanism is unclear, although H4K20me3 abundance increases during cellular senescence, a stable proliferation arrest and tumor suppressor process, triggered by diverse molecular cues, including activated oncogenes. Here, we investigate the function of H4K20me3 in senescence and tumor suppression.
Results:
Using immunofluorescence and ChIP-seq we determine the distribution of H4K20me3 in proliferating and senescent human cells. Altered H4K20me3 in senescence is coupled to H4K16ac and DNA methylation changes in senescence. In senescent cells, H4K20me3 is especially enriched at DNA sequences contained within specialized domains of senescence-associated heterochromatin foci (SAHF), as well as specific families of non-genic and genic repeats. Altered H4K20me3 does not correlate strongly with changes in gene expression between proliferating and senescent cells; however, in senescent cells, but not proliferating cells, H4K20me3 enrichment at gene bodies correlates inversely with gene expression, reflecting de novo accumulation of H4K20me3 at repressed genes in senescent cells, including at genes also repressed in proliferating cells. Although elevated SUV420H2 upregulates H4K20me3, this does not accelerate senescence of primary human cells. However, elevated SUV420H2/H4K20me3 reinforces oncogene-induced senescence-associated proliferation arrest and slows tumorigenesis in vivo.
Conclusions:
These results corroborate a role for chromatin in underpinning the senescence phenotype but do not support a major role for H4K20me3 in initiation of senescence. Rather, we speculate that H4K20me3 plays a role in heterochromatinization and stabilization of the epigenome and genome of pre-malignant, oncogene-expressing senescent cells, thereby suppressing epigenetic and genetic instability and contributing to long-term senescence-mediated tumor suppression
Failure of human rhombic lip differentiation underlies medulloblastoma formation
Medulloblastoma (MB) comprises a group of heterogeneous paediatric embryonal neoplasms of the hindbrain with strong links to early development of the hindbrain 1â4. Mutations that activate Sonic hedgehog signalling lead to Sonic hedgehog MB in the upper rhombic lip (RL) granule cell lineage 5â8. By contrast, mutations that activate WNT signalling lead to WNT MB in the lower RL 9,10. However, little is known about the more commonly occurring group 4 (G4) MB, which is thought to arise in the unipolar brush cell lineage 3,4. Here we demonstrate that somatic mutations that cause G4 MB converge on the core binding factor alpha (CBFA) complex and mutually exclusive alterations that affect CBFA2T2, CBFA2T3, PRDM6, UTX and OTX2. CBFA2T2 is expressed early in the progenitor cells of the cerebellar RL subventricular zone in Homo sapiens, and G4 MB transcriptionally resembles these progenitors but are stalled in developmental time. Knockdown of OTX2 in model systems relieves this differentiation blockade, which allows MB cells to spontaneously proceed along normal developmental differentiation trajectories. The specific nature of the split human RL, which is destined to generate most of the neurons in the human brain, and its high level of susceptible EOMES +KI67 + unipolar brush cell progenitor cells probably predisposes our species to the development of G4 MB
The influences of task difficulty and response correctness on neural systems supporting fluid reasoning
This functional magnetic resonance imaging (fMRI) study examined neural contributions to managing task difficulty and response correctness during fluid reasoning. Previous studies investigate reasoning by independently varying visual complexity or task difficulty, or the specific domain. Under natural conditions these factors interact in a complex manner to support dynamic combinations of perceptual and conceptual processes. This study investigated fluid reasoning under circumstances that would represent the cognitive flexibility of real life decision-making. Results from a mixed effects analysis corrected for multiple comparisons indicate involvement of cortical and subcortical areas during fluid reasoning. A 2Â ĂÂ 2 ANOVA illustrates activity related to variances in task difficulty correlated with increased blood oxygenation level-dependent (BOLD)-signal in the left middle frontal gyrus (BA6). Activity related to response correctness correlated with increased BOLD-signal in a larger, distributed system including right middle frontal gyrus (BA6), right superior parietal lobule (BA7), left inferior parietal lobule (BA40), left lingual gyrus (BA19), and left cerebellum (Lobule VI). The dissociation of function in left BA 6 for task difficulty and right BA6 for response correctness and the involvement of a more diffuse network involving the left cerebellum in response correctness extends knowledge about contributions of classic motor and premotor areas supporting higher level cognition
Attentionârelated modulation of activity in primary and secondary auditory cortex
WE investigated the effects of auditory attention on brain activity using functional magnetic resonance imaging. Subjects listened to three word lists, three times each, and were instructed to count the number of times they heard a target word during two of these presentations. For the third, they listened to the words without counting. All subjects showed significant areas of activation in auditory cortex during the listening conditions compared to rest. There was significantly more activation and a larger area of activation, particularly in association cortex, in the left temporal lobe during counting of targets compared to the no-target conditions, with a similar trend in the right hemisphere. These results provide evidence of an attention-related enhancement of both activation magnitude and extent in auditory cortex