503 research outputs found
Ferromagnetism in Fe-substituted spinel semiconductor ZnGaO
Motivated by the recent experimental observation of long range ferromagnetic
order at a relatively high temperature of 200K in the Fe-doped ZnGaO
semiconducting spinel, we propose a possible mechanism for the observed
ferromagnetism in this system. We show, supported by band structure
calculations, how a model similar to the double exchange model can be written
down for this system and calculate the ground state phase diagram for the two
cases where Fe is doped either at the tetrahedral position or at the octahedral
position. We find that in both cases such a model can account for a stable
ferromagnetic phase in a wide range of parameter space. We also argue that in
the limit of high Fe concentration at the tetrahedral positions a
description in terms of a two band model is essential. The two orbitals
and the hopping between them play a crucial role in stabilizing the
ferromagnetic phase in this limit. The case when Fe is doped simultaneously at
both the tetrahedral and the octahedral position is also discussed.Comment: 10 pages, 9 figures, added text, J. Phys. Cond. Mat. (to appear
Dilute ferrimagnetic semiconductors in Fe-substituted spinel ZnGaO
Solid solutions of nominal composition
[ZnGaO][FeO], of the semiconducting spinel
ZnGaO with the ferrimagnetic spinel FeO have been prepared with
= 0.05, 0.10, and 0.15. All samples show evidence for long-range magnetic
ordering with ferromagnetic hysteresis at low temperatures. Magnetization as a
function of field for the = 0.15 sample is S-shaped at temperatures as high
as 200 K. M\"ossbauer spectroscopy on the = 0.15 sample confirms the
presence of Fe, and spontaneous magnetization at 4.2 K. The magnetic
behavior is obtained without greatly affecting the semiconducting properties of
the host; diffuse reflectance optical spectroscopy indicates that Fe
substitution up to = 0.15 does not affect the position of the band edge
absorption. These promising results motivate the possibility of dilute
ferrimagnetic semiconductors which do not require carrier mediation of the
magnetic moment.Comment: 9 pages and 6 figure
pH and rate of ‘dark’ events in toad retinal rods : test of a hypothesis on the molecular origin of photoreceptor noise
Thermal activation of the visual pigment constitutes a fundamental constraint on visual sensitivity.
Its electrical correlate in the membrane current of dark-adapted rods are randomly occurring
discrete ‘dark events’ indistinguishable from responses to single photons. It has been proposed that
thermal activation occurs in a small subpopulation of rhodopsin molecules where the Schiff base
linking the chromophore to the protein part is unprotonated. On this hypothesis, rates of thermal
activation should increase strongly with rising pH. The hypothesis has been tested by measuring the
effect of pH changes on the frequency of discrete dark events in red rods of the common toad Bufo
bufo. Dark noise was recorded from isolated rods using the suction pipette technique. Changes in
cytoplasmic pH upon manipulations of extracellular pH were quantified by measuring, using
fast single-cell microspectrophotometry, the pH-dependent metarhodopsin I–metarhodopsin II
equilibrium and subsequent metarhodopsin III formation. These measurements show that, in the
conditions of the electrophysiological experiments, changing perfusion pH from 6.5 to 9.3 resulted
in a cytoplasmic pH shift from 7.6 to 8.5 that was readily sensed by the rhodopsin. This shift, which
implies an 8-fold decrease in cytoplasmic [H+], did not increase the rate of dark events. The results
contradict the hypothesis that thermal pigment activation depends on prior deprotonation of the
Schiff base
Optimised Traffic Flow at a Single Intersection: Traffic Responsive signalisation
We propose a stochastic model for the intersection of two urban streets. The
vehicular traffic at the intersection is controlled by a set of traffic lights
which can be operated subject to fix-time as well as traffic adaptive schemes.
Vehicular dynamics is simulated within the framework of the probabilistic
cellular automata and the delay experienced by the traffic at each individual
street is evaluated for specified time intervals. Minimising the total delay of
both streets gives rise to the optimum signalisation of traffic lights. We
propose some traffic responsive signalisation algorithms which are based on the
concept of cut-off queue length and cut-off density.Comment: 10 pages, 11 eps figs, to appear in J. Phys.
Inert coupling of IRDye800CW to monoclonal antibodies for clinical optical imaging of tumor targets
Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas
Prodrug Strategy for PSMA-targeted Delivery of TGX-221 to Prostate Cancer Cells
TGX-221 is a potent, selective, and cell membrane permeable inhibitor of the PI3K p110β catalytic subunit. Recent studies showed that TGX-221 has anti-proliferative activity against PTEN-deficient tumor cell lines including prostate cancers. The objective of this study was to develop an encapsulation system for parenterally delivering TGX-221 to the target tissue through a prostate-specific membrane aptamer (PSMAa10) with little or no side effects. In this study, PEG-PCL micelles were formulated to encapsulate the drug, and a prodrug strategy was pursued to improve the stability of the carrier system. Fluorescence imaging studies demonstrated that the cellular uptake of both drug and nanoparticles were significantly improved by targeted micelles in a PSMA positive cell line. The area under the plasma concentration time curve of the micelle formulation in nude mice was 2.27-fold greater than the naked drug, and the drug clearance rate was 17.5-fold slower. These findings suggest a novel formulation approach for improving site-specific drug delivery of a molecular-targeted prostate cancer treatment
Mapping Dynamic Histone Acetylation Patterns to Gene Expression in Nanog-depleted Murine Embryonic Stem Cells
Embryonic stem cells (ESC) have the potential to self-renew indefinitely and
to differentiate into any of the three germ layers. The molecular mechanisms
for self-renewal, maintenance of pluripotency and lineage specification are
poorly understood, but recent results point to a key role for epigenetic
mechanisms. In this study, we focus on quantifying the impact of histone 3
acetylation (H3K9,14ac) on gene expression in murine embryonic stem cells. We
analyze genome-wide histone acetylation patterns and gene expression profiles
measured over the first five days of cell differentiation triggered by
silencing Nanog, a key transcription factor in ESC regulation. We explore the
temporal and spatial dynamics of histone acetylation data and its correlation
with gene expression using supervised and unsupervised statistical models. On a
genome-wide scale, changes in acetylation are significantly correlated to
changes in mRNA expression and, surprisingly, this coherence increases over
time. We quantify the predictive power of histone acetylation for gene
expression changes in a balanced cross-validation procedure. In an in-depth
study we focus on genes central to the regulatory network of Mouse ESC,
including those identified in a recent genome-wide RNAi screen and in the
PluriNet, a computationally derived stem cell signature. We find that compared
to the rest of the genome, ESC-specific genes show significantly more
acetylation signal and a much stronger decrease in acetylation over time, which
is often not reflected in an concordant expression change. These results shed
light on the complexity of the relationship between histone acetylation and
gene expression and are a step forward to dissect the multilayer regulatory
mechanisms that determine stem cell fate.Comment: accepted at PLoS Computational Biolog
A genome-wide association study identifies protein quantitative trait loci (pQTLs)
There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al
Genomic Signature-Based Identification of Influenza A Viruses Using RT-PCR/Electro-Spray Ionization Mass Spectrometry (ESI-MS) Technology
BACKGROUND: The emergence and rapid spread of the 2009 H1N1 pandemic influenza A virus (H1N1pdm) in humans highlights the importance of enhancing the capability of existing influenza surveillance systems with tools for rapid identification of emerging and re-emerging viruses. One of the new approaches is the RT-PCR electrospray ionization mass spectrometry (RT-PCR/ESI-MS) technology, which is based on analysis of base composition (BC) of RT-PCR amplicons from influenza "core" genes. Combination of the BC signatures represents a "genomic print" of an influenza A virus. METHODOLOGY/PRINCIPAL FINDINGS: Here, 757 samples collected between 2006 and 2009 were tested, including 302 seasonal H1N1, 171 H3N2, 7 swine triple reassortants, and 277 H1N1pdm viruses. Of the 277 H1N1pdm samples, 209 were clinical specimens (throat, nasal and nasopharyngeal swabs, nasal washes, blood and sputum). BC signatures for the clinical specimen from one of the first cases of the 2009 pandemic, A/California/04/2009, confirmed it as an unusual, previously unrecognized influenza A virus, with "core" genes related to viruses of avian, human and swine origins. Subsequent analysis of additional 276 H1N1pdm samples revealed that they shared the genomic print of A/California/04/2009, which differed from those of North American swine triple reassortant viruses, seasonal H1N1 and H3N2 and other viruses tested. Moreover, this assay allowed distinction between "core" genes of co-circulating groups of seasonal H1N1, such as clades 2B, 2C, and their reassortants with dual antiviral resistance to adamantanes and oseltamivir. CONCLUSIONS/SIGNIFICANCE: The RT-PCR/ESI-MS assay is a broad range influenza identification tool that can be used directly on clinical specimens for rapid and accurate detection of influenza virus genes. The assay differentiates the H1N1pdm from seasonal and other nonhuman hosts viruses. Although not a diagnostic tool, this assay demonstrates its usefulness and robustness in influenza virus surveillance and detection of novel and unusual viruses with previously unseen genomic prints
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