1,033 research outputs found
Somatic PIK3R1 Variation as a Cause of Vascular Malformations and Overgrowth
PurposeSomatic activating variants in the PI3K-AKT pathway cause vascular malformations with and without overgrowth. We previously reported an individual with capillary and lymphatic malformation harboring a pathogenic somatic variant in PIK3R1, which encodes three PI3K complex regulatory subunits. Here, we investigate PIK3R1 in a large cohort with vascular anomalies and identify an additional 16 individuals with somatic mosaic variants in PIK3R1.MethodsAffected tissue from individuals with vascular lesions and overgrowth recruited from a multisite collaborative network was studied. Next-generation sequencing targeting coding regions of cell-signaling and cancer-associated genes was performed followed by assessment of variant pathogenicity.ResultsThe phenotypic and variant spectrum associated with somatic variation in PIK3R1 is reported herein. Variants occurred in the inter-SH2 or N-terminal SH2 domains of all three PIK3R1 protein products. Phenotypic features overlapped those of the PIK3CA-related overgrowth spectrum (PROS). These overlapping features included mixed vascular malformations, sandal toe gap deformity with macrodactyly, lymphatic malformations, venous ectasias, and overgrowth of soft tissue or bone.ConclusionSomatic PIK3R1 variants sharing attributes with cancer-associated variants cause complex vascular malformations and overgrowth. The PIK3R1-associated phenotypic spectrum overlaps with PROS. These data extend understanding of the diverse phenotypic spectrum attributable to genetic variation in the PI3K-AKT pathway
Mutation Screening of Multiple Genes in Spanish Patients with Autosomal Recessive Retinitis Pigmentosa by Targeted Resequencing
Retinitis Pigmentosa (RP) is a heterogeneous group of inherited retinal dystrophies characterised ultimately by the loss of photoreceptor cells. RP is the leading cause of visual loss in individuals younger than 60 years, with a prevalence of about 1 in 4000. The molecular genetic diagnosis of autosomal recessive RP (arRP) is challenging due to the large genetic and clinical heterogeneity. Traditional methods for sequencing arRP genes are often laborious and not easily available and a screening technique that enables the rapid detection of the genetic cause would be very helpful in the clinical practice. The goal of this study was to develop and apply microarray-based resequencing technology capable of detecting both known and novel mutations on a single high-throughput platform. Hence, the coding regions and exon/intron boundaries of 16 arRP genes were resequenced using microarrays in 102 Spanish patients with clinical diagnosis of arRP. All the detected variations were confirmed by direct sequencing and potential pathogenicity was assessed by functional predictions and frequency in controls. For validation purposes 4 positive controls for variants consisting of previously identified changes were hybridized on the array. As a result of the screening, we detected 44 variants, of which 15 are very likely pathogenic detected in 14 arRP families (14%). Finally, the design of this array can easily be transformed in an equivalent diagnostic system based on targeted enrichment followed by next generation sequencing
Measurement of the t(t)over-bar production cross section in the dilepton channel in pp collisions at âs=8 TeV
The top-antitop quark (t (t) over bar) production cross section is measured in proton-proton collisions at root s = 8 TeV with the CMS experiment at the LHC, using a data sample corresponding to an integrated luminosity of 5.3 fb(-1). The measurement is performed by analysing events with a pair of electrons or muons, or one electron and one muon, and at least two jets, one of which is identified as originating from hadronisation of a bottom quark. The measured cross section is 239 +/- 2 (stat.) +/- 11 (syst.) +/- 6 (lum.) pb, for an assumed top-quark mass of 172.5 GeV, in agreement with the prediction of the standard model
Cluster Lenses
Clusters of galaxies are the most recently assembled, massive, bound
structures in the Universe. As predicted by General Relativity, given their
masses, clusters strongly deform space-time in their vicinity. Clusters act as
some of the most powerful gravitational lenses in the Universe. Light rays
traversing through clusters from distant sources are hence deflected, and the
resulting images of these distant objects therefore appear distorted and
magnified. Lensing by clusters occurs in two regimes, each with unique
observational signatures. The strong lensing regime is characterized by effects
readily seen by eye, namely, the production of giant arcs, multiple-images, and
arclets. The weak lensing regime is characterized by small deformations in the
shapes of background galaxies only detectable statistically. Cluster lenses
have been exploited successfully to address several important current questions
in cosmology: (i) the study of the lens(es) - understanding cluster mass
distributions and issues pertaining to cluster formation and evolution, as well
as constraining the nature of dark matter; (ii) the study of the lensed objects
- probing the properties of the background lensed galaxy population - which is
statistically at higher redshifts and of lower intrinsic luminosity thus
enabling the probing of galaxy formation at the earliest times right up to the
Dark Ages; and (iii) the study of the geometry of the Universe - as the
strength of lensing depends on the ratios of angular diameter distances between
the lens, source and observer, lens deflections are sensitive to the value of
cosmological parameters and offer a powerful geometric tool to probe Dark
Energy. In this review, we present the basics of cluster lensing and provide a
current status report of the field.Comment: About 120 pages - Published in Open Access at:
http://www.springerlink.com/content/j183018170485723/ . arXiv admin note:
text overlap with arXiv:astro-ph/0504478 and arXiv:1003.3674 by other author
A review of elliptical and disc galaxy structure, and modern scaling laws
A century ago, in 1911 and 1913, Plummer and then Reynolds introduced their
models to describe the radial distribution of stars in `nebulae'. This article
reviews the progress since then, providing both an historical perspective and a
contemporary review of the stellar structure of bulges, discs and elliptical
galaxies. The quantification of galaxy nuclei, such as central mass deficits
and excess nuclear light, plus the structure of dark matter halos and cD galaxy
envelopes, are discussed. Issues pertaining to spiral galaxies including dust,
bulge-to-disc ratios, bulgeless galaxies, bars and the identification of
pseudobulges are also reviewed. An array of modern scaling relations involving
sizes, luminosities, surface brightnesses and stellar concentrations are
presented, many of which are shown to be curved. These 'redshift zero'
relations not only quantify the behavior and nature of galaxies in the Universe
today, but are the modern benchmark for evolutionary studies of galaxies,
whether based on observations, N-body-simulations or semi-analytical modelling.
For example, it is shown that some of the recently discovered compact
elliptical galaxies at 1.5 < z < 2.5 may be the bulges of modern disc galaxies.Comment: Condensed version (due to Contract) of an invited review article to
appear in "Planets, Stars and Stellar
Systems"(www.springer.com/astronomy/book/978-90-481-8818-5). 500+ references
incl. many somewhat forgotten, pioneer papers. Original submission to
Springer: 07-June-201
Azimuthal anisotropy of charged particles at high transverse momenta in PbPb collisions at sqrt(s[NN]) = 2.76 TeV
The azimuthal anisotropy of charged particles in PbPb collisions at
nucleon-nucleon center-of-mass energy of 2.76 TeV is measured with the CMS
detector at the LHC over an extended transverse momentum (pt) range up to
approximately 60 GeV. The data cover both the low-pt region associated with
hydrodynamic flow phenomena and the high-pt region where the anisotropies may
reflect the path-length dependence of parton energy loss in the created medium.
The anisotropy parameter (v2) of the particles is extracted by correlating
charged tracks with respect to the event-plane reconstructed by using the
energy deposited in forward-angle calorimeters. For the six bins of collision
centrality studied, spanning the range of 0-60% most-central events, the
observed v2 values are found to first increase with pt, reaching a maximum
around pt = 3 GeV, and then to gradually decrease to almost zero, with the
decline persisting up to at least pt = 40 GeV over the full centrality range
measured.Comment: Replaced with published version. Added journal reference and DO
Search for new physics with same-sign isolated dilepton events with jets and missing transverse energy
A search for new physics is performed in events with two same-sign isolated
leptons, hadronic jets, and missing transverse energy in the final state. The
analysis is based on a data sample corresponding to an integrated luminosity of
4.98 inverse femtobarns produced in pp collisions at a center-of-mass energy of
7 TeV collected by the CMS experiment at the LHC. This constitutes a factor of
140 increase in integrated luminosity over previously published results. The
observed yields agree with the standard model predictions and thus no evidence
for new physics is found. The observations are used to set upper limits on
possible new physics contributions and to constrain supersymmetric models. To
facilitate the interpretation of the data in a broader range of new physics
scenarios, information on the event selection, detector response, and
efficiencies is provided.Comment: Published in Physical Review Letter
Compressed representation of a partially defined integer function over multiple arguments
In OLAP (OnLine Analitical Processing) data are analysed in an n-dimensional cube. The cube may be represented as a partially defined function over n arguments. Considering that often the function is not defined everywhere, we ask: is there a known way of representing the function or the points in which it is defined, in a more compact manner than the trivial one
Measurement of jet fragmentation into charged particles in pp and PbPb collisions at sqrt(s[NN]) = 2.76 TeV
Jet fragmentation in pp and PbPb collisions at a centre-of-mass energy of
2.76 TeV per nucleon pair was studied using data collected with the CMS
detector at the LHC. Fragmentation functions are constructed using
charged-particle tracks with transverse momenta pt > 4 GeV for dijet events
with a leading jet of pt > 100 GeV. The fragmentation functions in PbPb events
are compared to those in pp data as a function of collision centrality, as well
as dijet-pt imbalance. Special emphasis is placed on the most central PbPb
events including dijets with unbalanced momentum, indicative of energy loss of
the hard scattered parent partons. The fragmentation patterns for both the
leading and subleading jets in PbPb collisions agree with those seen in pp data
at 2.76 TeV. The results provide evidence that, despite the large parton energy
loss observed in PbPb collisions, the partition of the remaining momentum
within the jet cone into high-pt particles is not strongly modified in
comparison to that observed for jets in vacuum.Comment: Submitted to the Journal of High Energy Physic
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