1,197 research outputs found
Identification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC
Regulation of cell volume is critical for many cellular and organismal functions, yet the molecular identity of a key player, the volume-regulated anion channel VRAC, has remained unknown. A genome-wide siRNA screen in mammalian cells identified LRRC8A as a VRAC component. LRRC8A formed heteromers with other LRRC8 multispan membrane proteins. Genomic disruption of LRRC8A ablated VRAC currents. Cells with disruption of all five LRRC8 genes required LRRC8A co-transfection with other LRRC8 isoforms to reconstitute VRAC currents. The isoform combination determined VRAC inactivation kinetics. Taurine flux and regulatory volume decrease also depended on LRRC8 proteins. Our work shows that VRAC defines a class of anion channels, suggests that VRAC is identical to the volume-sensitive organic osmolyte/anion channel VSOAC, and explains the heterogeneity of native VRAC currents
Aharonov-Bohm interferences from local deformations in graphene
One of the most interesting aspects of graphene is the tied relation between
structural and electronic properties. The observation of ripples in the
graphene samples both free standing and on a substrate has given rise to a very
active investigation around the membrane-like properties of graphene and the
origin of the ripples remains as one of the most interesting open problems in
the system. The interplay of structural and electronic properties is
successfully described by the modelling of curvature and elastic deformations
by fictitious gauge fields that have become an ex- perimental reality after the
suggestion that Landau levels can form associated to strain in graphene and the
subsequent experimental confirmation. Here we propose a device to detect
microstresses in graphene based on a scanning-tunneling-microscopy setup able
to measure Aharonov-Bohm inter- ferences at the nanometer scale. The
interferences to be observed in the local density of states are created by the
fictitious magnetic field associated to elastic deformations of the sample.Comment: Some bugs fixe
Strain-induced Evolution of Electronic Band Structures in a Twisted Graphene Bilayer
Here we study the evolution of local electronic properties of a twisted
graphene bilayer induced by a strain and a high curvature. The strain and
curvature strongly affect the local band structures of the twisted graphene
bilayer; the energy difference of the two low-energy van Hove singularities
decreases with increasing the lattice deformations and the states condensed
into well-defined pseudo-Landau levels, which mimic the quantization of massive
Dirac fermions in a magnetic field of about 100 T, along a graphene wrinkle.
The joint effect of strain and out-of-plane distortion in the graphene wrinkle
also results in a valley polarization with a significant gap, i.e., the
eight-fold degenerate Landau level at the charge neutrality point is splitted
into two four-fold degenerate quartets polarized on each layer. These results
suggest that strained graphene bilayer could be an ideal platform to realize
the high-temperature zero-field quantum valley Hall effect.Comment: 4 figure
Room-temperature ferromagnetism in graphite driven by 2D networks of point defects
Ferromagnetism in carbon-based materials is appealing for both applications
and fundamental science purposes because carbon is a light and bio-compatible
material that contains only s and p electrons in contrast to traditional
ferromagnets based on 3d or 4f electrons. Here we demonstrate direct evidence
for ferromagnetic order locally at defect structures in highly oriented
pyrolytic graphite (HOPG) with magnetic force microscopy and in bulk
magnetization measurements at room temperature. Magnetic impurities have been
excluded as the origin of the magnetic signal after careful analysis supporting
an intrinsic magnetic behavior of carbon. The observed ferromagnetism has been
attributed to originate from unpaired electron spins localized at grain
boundaries of HOPG. Grain boundaries form two-dimensional arrays of point
defects, where their spacing depends on the mutual orientation of two grains.
Depending on the distance between these point defects, scanning tunneling
spectroscopy of grain boundaries showed two intense split localized states for
small distances between defects (< 4 nm) and one localized state at the Fermi
level for large distances between defects (> 4 nm).Comment: 19 pages, 5 figure
Bianchi Type-II String Cosmological Models in Normal Gauge for Lyra's Manifold with Constant Deceleration Parameter
The present study deals with a spatially homogeneous and anisotropic
Bianchi-II cosmological models representing massive strings in normal gauge for
Lyra's manifold by applying the variation law for generalized Hubble's
parameter that yields a constant value of deceleration parameter. The variation
law for Hubble's parameter generates two types of solutions for the average
scale factor, one is of power-law type and other is of the exponential form.
Using these two forms, Einstein's modified field equations are solved
separately that correspond to expanding singular and non-singular models of the
universe respectively. The energy-momentum tensor for such string as formulated
by Letelier (1983) is used to construct massive string cosmological models for
which we assume that the expansion () in the model is proportional to
the component of the shear tensor . This
condition leads to , where A, B and C are the metric coefficients
and m is proportionality constant. Our models are in accelerating phase which
is consistent to the recent observations. It has been found that the
displacement vector behaves like cosmological term in the
normal gauge treatment and the solutions are consistent with recent
observations of SNe Ia. It has been found that massive strings dominate in the
decelerating universe whereas strings dominate in the accelerating universe.
Some physical and geometric behaviour of these models are also discussed.Comment: 24 pages, 10 figure
Insulin receptor isoform switching in intestinal stem cells, progenitors, differentiated lineages and tumors: evidence that IR-B limits proliferation
Despite evidence for the impact of insulin on intestinal epithelial physiology and pathophysiology, the expression patterns, roles, and regulation of insulin receptor (IR) and IR isoforms in the intestinal epithelium are not well characterized. IR-A is thought to mediate the proliferative effects of insulin or insulin growth factors (IGFs) in fetal or cancer cells. IR-B is considered to be the metabolic receptor for insulin in specialized tissues. This study used a novel Sox9-EGFP reporter mouse that permits isolation of intestinal epithelial stem cells (IESCs), progenitors, enteroendocrine cells and differentiated lineages, the ApcMin/+ mouse model of precancerous adenoma and normal human intestinal and colorectal cancer (CRC) cell lines. We tested the hypothesis that there is differential expression of IR-A or IR-B in stem and tumor cells versus differentiated intestinal epithelial cells (IECs) and that IR-B impacts cell proliferation. Our findings provide evidence that IR-B expression is significantly lower in highly proliferative IESCs and progenitor cells versus post-mitotic, differentiated IECs and in subconfluent and undifferentiated versus differentiated Caco-2 cells. IR-B is also reduced in ApcMin/+ tumors and highly tumorigenic CRC cells. These differences in IR-B were accompanied by altered levels of mRNAs encoding muscleblind-like 2 (MBNL2), a known regulator of IR alternative splicing. Forced IR-B expression in subconfluent and undifferentiated Caco-2 cells reduced proliferation and increased biomarkers of differentiation. Our findings indicate that the impact of insulin on different cell types in the intestinal epithelium might differ depending on relative IR-B∶ IR-A expression levels and provide new evidence for the roles of IR-B to limit proliferation of CRC cells
A New SiC-Whisker-Reinforced Lithium Aluminosilicate Composite
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65747/1/j.1151-2916.1993.tb04016.x.pd
Higher Dimensional Cylindrical or Kasner Type Electrovacuum Solutions
We consider a D dimensional Kasner type diagonal spacetime where metric
functions depend only on a single coordinate and electromagnetic field shares
the symmetries of spacetime. These solutions can describe static cylindrical or
cosmological Einstein-Maxwell vacuum spacetimes. We mainly focus on
electrovacuum solutions and four different types of solutions are obtained in
which one of them has no four dimensional counterpart. We also consider the
properties of the general solution corresponding to the exterior field of a
charged line mass and discuss its several properties. Although it resembles the
same form with four dimensional one, there is a difference on the range of the
solutions for fixed signs of the parameters. General magnetic field vacuum
solution are also briefly discussed, which reduces to Bonnor-Melvin magnetic
universe for a special choice of the parameters. The Kasner forms of the
general solution are also presented for the cylindrical or cosmological cases.Comment: 16 pages, Revtex. Text and references are extended, Published versio
Ataluren delays loss of ambulation and respiratory decline in nonsense mutation Duchenne muscular dystrophy patients
Aim: We investigated the effect of ataluren plus standard of care (SoC) on age at loss of ambulation (LoA) and respiratory decline in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD) versus patients with DMD on SoC alone. / Patients & methods: Study 019 was a long-term Phase III study of ataluren safety in nmDMD patients with a history of ataluren exposure. Propensity score matching identified Study 019 and CINRG DNHS patients similar in disease progression predictors. / Results & conclusion: Ataluren plus SoC was associated with a 2.2-year delay in age at LoA (p = 0.0006), and a 3.0-year delay in decline of predicted forced vital capacity to <60% in nonambulatory patients (p = 0.0004), versus SoC. Ataluren plus SoC delays disease progression and benefits ambulatory and nonambulatory patients with nmDMD. / ClinicalTrials.gov: NCT01557400
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