1,512 research outputs found
Targeting Chromatin Readers
Modulation of gene expression through epigenetic signaling has recently emerged as a novel approach in treating human disease. Specifically, chromatin reader proteins, which mediate protein–protein interactions via binding to modified lysine residues, are gaining traction as potential therapeutic targets. Herein, we review recent efforts to understand and modulate the activity of chromatin reader proteins with small-molecule ligands
Path integral evaluation of Dbrane amplitudes
We extend Polchinski's evaluation of the measure for the one-loop closed
string path integral to open string tree amplitudes with boundaries and
crosscaps embedded in Dbranes. We explain how the nonabelian limit of
near-coincident Dbranes emerges in the path integral formalism. We give a
careful path integral derivation of the cylinder amplitude including the
modulus dependence of the volume of the conformal Killing group.Comment: Extended version replacing hep-th/9903184, includes discussion of
nonabelian limit, Latex, 10 page
CLASH-VLT: Insights on the mass substructures in the Frontier Fields Cluster MACS J0416.1-2403 through accurate strong lens modeling
We present a detailed mass reconstruction and a novel study on the
substructure properties in the core of the CLASH and Frontier Fields galaxy
cluster MACS J0416.1-2403. We show and employ our extensive spectroscopic data
set taken with the VIMOS instrument as part of our CLASH-VLT program, to
confirm spectroscopically 10 strong lensing systems and to select a sample of
175 plausible cluster members to a limiting stellar mass of log(M_*/M_Sun) ~
8.6. We reproduce the measured positions of 30 multiple images with a
remarkable median offset of only 0.3" by means of a comprehensive strong
lensing model comprised of 2 cluster dark-matter halos, represented by cored
elliptical pseudo-isothermal mass distributions, and the cluster member
components. The latter have total mass-to-light ratios increasing with the
galaxy HST/WFC3 near-IR (F160W) luminosities. The measurement of the total
enclosed mass within the Einstein radius is accurate to ~5%, including
systematic uncertainties. We emphasize that the use of multiple-image systems
with spectroscopic redshifts and knowledge of cluster membership based on
extensive spectroscopic information is key to constructing robust
high-resolution mass maps. We also produce magnification maps over the central
area that is covered with HST observations. We investigate the galaxy
contribution, both in terms of total and stellar mass, to the total mass budget
of the cluster. When compared with the outcomes of cosmological -body
simulations, our results point to a lack of massive subhalos in the inner
regions of simulated clusters with total masses similar to that of MACS
J0416.1-2403. Our findings of the location and shape of the cluster dark-matter
halo density profiles and on the cluster substructures provide intriguing tests
of the assumed collisionless, cold nature of dark matter and of the role played
by baryons in the process of structure formation.Comment: 26 pages, 22 figures, 7 tables; accepted for publication in the
Astrophysical Journal. A high-resolution version is available at
https://sites.google.com/site/vltclashpublic/publications/Grillo_etal_2014.pd
RELICS: The Reionization Lensing Cluster Survey and the Brightest High-z Galaxies
Massive foreground galaxy clusters magnify and distort the light of objects behind them, permitting a view into both the extremely distant and intrinsically faint galaxy populations. We present here the z ~ 6-8 candidate high-redshift galaxies from the Reionization Lensing Cluster Survey (RELICS), a Hubble and Spitzer Space Telescope survey of 41 massive galaxy clusters spanning an area of ≈200 arcmin². These clusters were selected to be excellent lenses, and we find similar high-redshift sample sizes and magnitude distributions as the Cluster Lensing And Supernova survey with Hubble (CLASH). We discover 257, 57, and eight candidate galaxies at z ~ 6, 7, and 8 respectively, (322 in total). The observed (lensed) magnitudes of the z ~ 6 candidates are as bright as AB mag ~23, making them among the brightest known at these redshifts, comparable with discoveries from much wider, blank-field surveys. RELICS demonstrates the efficiency of using strong gravitational lenses to produce high-redshift samples in the epoch of reionization. These brightly observed galaxies are excellent targets for follow-up study with current and future observatories, including the James Webb Space Telescope
Mutation in NSUN2, which Encodes an RNA Methyltransferase, Causes Autosomal-Recessive Intellectual Disability
Causes of autosomal-recessive intellectual disability (ID) have, until very recently, been under researched because of the high degree of genetic heterogeneity. However, now that genome-wide approaches can be applied to single multiplex consanguineous families, the identification of genes harboring disease-causing mutations by autozygosity mapping is expanding rapidly. Here, we have mapped a disease locus in a consanguineous Pakistani family affected by ID and distal myopathy. We genotyped family members on genome-wide SNP microarrays and used the data to determine a single 2.5 Mb homozygosity-by-descent (HBD) locus in region 5p15.32–p15.31; we identified the missense change c.2035G>A (p.Gly679Arg) at a conserved residue within NSUN2. This gene encodes a methyltransferase that catalyzes formation of 5-methylcytosine at C34 of tRNA-leu(CAA) and plays a role in spindle assembly during mitosis as well as chromosome segregation. In mouse brains, we show that NSUN2 localizes to the nucleolus of Purkinje cells in the cerebellum. The effects of the mutation were confirmed by the transfection of wild-type and mutant constructs into cells and subsequent immunohistochemistry. We show that mutation to arginine at this residue causes NSUN2 to fail to localize within the nucleolus. The ID combined with a unique profile of comorbid features presented here makes this an important genetic discovery, and the involvement of NSUN2 highlights the role of RNA methyltransferase in human neurocognitive development
First Results from The GlueX Experiment
The GlueX experiment at Jefferson Lab ran with its first commissioning beam
in late 2014 and the spring of 2015. Data were collected on both plastic and
liquid hydrogen targets, and much of the detector has been commissioned. All of
the detector systems are now performing at or near design specifications and
events are being fully reconstructed, including exclusive production of
, and mesons. Linearly-polarized photons were
successfully produced through coherent bremsstrahlung and polarization transfer
to the has been observed.Comment: 8 pages, 6 figures, Invited contribution to the Hadron 2015
Conference, Newport News VA, September 201
Feedback and metal enrichment in cosmological SPH simulations I. A model for chemical enrichment
We discuss a model for treating chemical enrichment by SNII and SNIa
explosions in simulations of cosmological structure formation. Our model
includes metal-dependent radiative cooling and star formation in dense
collapsed gas clumps. Metals are returned into the diffuse interstellar medium
by star particles using a local SPH smoothing kernel. A variety of chemical
abundance patterns in enriched gas arise in our treatment owing to the
different yields and lifetimes of SNII and SNIa progenitor stars. In the case
of SNII chemical production, we adopt metal-dependent yields. Because of the
sensitive dependence of cooling rates on metallicity, enrichment of galactic
haloes with metals can in principle significantly alter subsequent gas infall
and the build up of the stellar components. Indeed, in simulations of isolated
galaxies we find that a consistent treatment of metal-dependent cooling
produces 25% more stars outside the central region than simulations with a
primordial cooling function. In the highly-enriched central regions, the
evolution of baryons is however not affected by metal cooling, because here the
gas is always dense enough to cool. A similar situation is found in
cosmological simulations because we include no strong feedback processes which
could spread metals over large distances and mix them into unenriched diffuse
gas. We demonstrate this explicitly with test simulations which adopt
super-solar cooling functions leading to large changes both in the stellar mass
and in the metal distributions. We also find that the impact of metallicity on
the star formation histories of galaxies may depend on their particular
evolutionary history. Our results hence emphasise the importance of feedback
processes for interpreting the cosmic metal enrichment.Comment: 15 pages, 15 figures, MNRAS, modified to match published versio
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