493 research outputs found
Pairing, Charge, and Spin Correlations in the Three-Band Hubbard Model
Using the Constrained Path Monte Carlo (CPMC) method, we simulated the
two-dimensional, three-band Hubbard model to study pairing, charge, and spin
correlations as a function of electron and hole doping and the Coulomb
repulsion between charges on neighboring Cu and O lattice sites. As a
function of distance, both the -wave and extended s-wave pairing
correlations decayed quickly. In the charge-transfer regime, increasing
decreased the long-range part of the correlation functions in both
channels, while in the mixed-valent regime, it increased the long-range part of
the s-wave behavior but decreased that of the d-wave behavior. Still the d-wave
behavior dominated. At a given doping, increasing increased the
spin-spin correlations in the charge-transfer regime but decreased them in the
mixed-valent regime. Also increasing suppressed the charge-charge
correlations between neighboring Cu and O sites. Electron and hole doping away
from half-filling was accompanied by a rapid suppression of anti-ferromagnetic
correlations.Comment: Revtex, 8 pages with 15 figure
Revisiting the Local Scaling Hypothesis in Stably Stratified Atmospheric Boundary Layer Turbulence: an Integration of Field and Laboratory Measurements with Large-eddy Simulations
The `local scaling' hypothesis, first introduced by Nieuwstadt two decades
ago, describes the turbulence structure of stable boundary layers in a very
succinct way and is an integral part of numerous local closure-based numerical
weather prediction models. However, the validity of this hypothesis under very
stable conditions is a subject of on-going debate. In this work, we attempt to
address this controversial issue by performing extensive analyses of turbulence
data from several field campaigns, wind-tunnel experiments and large-eddy
simulations. Wide range of stabilities, diverse field conditions and a
comprehensive set of turbulence statistics make this study distinct
Chromosome 7 gain and DNA hypermethylation at the HOXA10 locus are associated with expression of a stem cell related HOX-signature in glioblastoma.
BACKGROUND: HOX genes are a family of developmental genes that are expressed neither in the developing forebrain nor in the normal brain. Aberrant expression of a HOX-gene dominated stem-cell signature in glioblastoma has been linked with increased resistance to chemo-radiotherapy and sustained proliferation of glioma initiating cells. Here we describe the epigenetic and genetic alterations and their interactions associated with the expression of this signature in glioblastoma.
RESULTS: We observe prominent hypermethylation of the HOXA locus 7p15.2 in glioblastoma in contrast to non-tumoral brain. Hypermethylation is associated with a gain of chromosome 7, a hallmark of glioblastoma, and may compensate for tumor-driven enhanced gene dosage as a rescue mechanism by preventing undue gene expression. We identify the CpG island of the HOXA10 alternative promoter that appears to escape hypermethylation in the HOX-high glioblastoma. An additive effect of gene copy gain at 7p15.2 and DNA methylation at key regulatory CpGs in HOXA10 is significantly associated with HOX-signature expression. Additionally, we show concordance between methylation status and presence of active or inactive chromatin marks in glioblastoma-derived spheres that are HOX-high or HOX-low, respectively.
CONCLUSIONS: Based on these findings, we propose co-evolution and interaction between gene copy gain, associated with a gain of chromosome 7, and additional epigenetic alterations as key mechanisms triggering a coordinated, but inappropriate, HOX transcriptional program in glioblastoma
A pleurocidin analogue with greater conformational flexibility, enhanced antimicrobial potency and in vivo therapeutic efficacy.
Antimicrobial peptides (AMPs) are a potential alternative to classical antibiotics that are yet to achieve a therapeutic breakthrough for treatment of systemic infections. The antibacterial potency of pleurocidin, an AMP from Winter Flounder, is linked to its ability to cross bacterial plasma membranes and seek intracellular targets while also causing membrane damage. Here we describe modification strategies that generate pleurocidin analogues with substantially improved, broad spectrum, antibacterial properties, which are effective in murine models of bacterial lung infection. Increasing peptide-lipid intermolecular hydrogen bonding capabilities enhances conformational flexibility, associated with membrane translocation, but also membrane damage and potency, most notably against Gram-positive bacteria. This negates their ability to metabolically adapt to the AMP threat. An analogue comprising D-amino acids was well tolerated at an intravenous dose of 15âmg/kg and similarly effective as vancomycin in reducing EMRSA-15 lung CFU. This highlights the therapeutic potential of systemically delivered, bactericidal AMPs
SETD2 haploinsufficiency for microtubule methylation is an early driver of genomic instability in renal cell carcinoma
Loss of the short arm of chromosome 3 (3p) occurs early in >95% of clear cell renal cell carcinoma (ccRCC). Nearly ubiquitous 3p loss in ccRCC suggests haploinsufficiency for 3p tumor suppressors as early drivers of tumorigenesis. We previously reported methyltransferase SETD2, which trimethylates H3 histones on lysine 36 (H3K36me3) and is located in the 3p deletion, to also trimethylate microtubules on lysine 40 (aTubK40me3) during mitosis, with aTubK40me3 required for genomic stability. We now show that monoallelic, Setd2-deficient cells retaining H3K36me3, but not aTubK40me3, exhibit a dramatic increase in mitotic defects and micronuclei count, with increased viability compared with biallelic loss. In SETD2-inactivated human kidney cells, rescue with a pathogenic SETD2 mutant deficient for microtubule (aTubK40me3), but not histone (H3K36me3) methylation, replicated this phenotype. Genomic instability (micronuclei) was also a hallmark of patient-derived cells from ccRCC. These data show that the SETD2 tumor suppressor displays a haploinsufficiency phenotype disproportionately impacting microtubule methylation and serves as an early driver of genomic instability. Significance: Loss of a single allele of a chromatin modifier plays a role in promoting oncogenesis, underscoring the growing relevance of tumor suppressor haploinsufficiency in tumorigenesis
Grain Surface Models and Data for Astrochemistry
AbstractThe cross-disciplinary field of astrochemistry exists to understand the formation, destruction, and survival of molecules in astrophysical environments. Molecules in space are synthesized via a large variety of gas-phase reactions, and reactions on dust-grain surfaces, where the surface acts as a catalyst. A broad consensus has been reached in the astrochemistry community on how to suitably treat gas-phase processes in models, and also on how to present the necessary reaction data in databases; however, no such consensus has yet been reached for grain-surface processes. A team of âź25 experts covering observational, laboratory and theoretical (astro)chemistry met in summer of 2014 at the Lorentz Center in Leiden with the aim to provide solutions for this problem and to review the current state-of-the-art of grain surface models, both in terms of technical implementation into models as well as the most up-to-date information available from experiments and chemical computations. This review builds on the results of this workshop and gives an outlook for future directions
Effects of dietary sulphur sources on concentrations of hydrogen sulphide in the rumen head-space gas of dairy cows
Multidisciplinary design optimization of blended-wing-body transport aircraft with distributed propulsion
Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV
Results are presented from a search for a W' boson using a dataset
corresponding to 5.0 inverse femtobarns of integrated luminosity collected
during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV.
The W' boson is modeled as a heavy W boson, but different scenarios for the
couplings to fermions are considered, involving both left-handed and
right-handed chiral projections of the fermions, as well as an arbitrary
mixture of the two. The search is performed in the decay channel W' to t b,
leading to a final state signature with a single lepton (e, mu), missing
transverse energy, and jets, at least one of which is tagged as a b-jet. A W'
boson that couples to fermions with the same coupling constant as the W, but to
the right-handed rather than left-handed chiral projections, is excluded for
masses below 1.85 TeV at the 95% confidence level. For the first time using LHC
data, constraints on the W' gauge coupling for a set of left- and right-handed
coupling combinations have been placed. These results represent a significant
improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe
- âŚ