9,039 research outputs found
Characterization of whole blood gene expression profiles as a sequel to globin mRNA reduction in patients with sickle cell disease
Global transcriptome analysis of whole blood RNA using microarrays has been proven to be challenging due to the high abundance of globin transcripts that constitute 70% of whole blood mRNA. This is a particular problem in patients with sickle cell disease, secondary to the high abundance of globin-expressing nucleated red blood cells and reticulocytes in the circulation. In order to accurately measure the steady state blood transcriptome in sickle cell patients we evaluated the efficacy of reducing globin transcripts in PAXgene stabilized RNA for genome-wide transcriptome analyses using microarrays. We demonstrate here by both microarrays and Q-PCR that the globin mRNA depletion method resulted in 55-65 fold reduction in globin transcripts in whole blood collected from healthy volunteers and sickle cell disease patients. This led to an improvement in microarray data quality by reducing data variability, with increased detection rate of expressed genes and improved overlap with the expression signatures of isolated peripheral blood mononuclear (PBMC) preparations. Analysis of differences between the whole blood transcriptome and PBMC transcriptome revealed important erythrocyte genes that participate in sickle cell pathogenesis and compensation. The combination of globin mRNA reduction after whole-blood RNA stabilization represents a robust clinical research methodology for the discovery of biomarkers for hematologic diseases
Identifying cis- and trans-acting single-nucleotide polymorphisms controlling lymphocyte gene expression in humans
Assuming multiple loci play a role in regulating the expression level of a single phenotype, we propose a new approach to identify cis- and trans-acting loci that regulate gene expression. Using the Problem 1 data set made available for Genetic Analysis Workshop 15 (GAW15), we identified many expression phenotypes that have significant evidence of association and linkage to one or more chromosomal regions. In particular, six of ten phenotypes that we found to be regulated by cis- and trans-acting loci were also mapped by a previous analysis of these data in which a total of 27 phenotypes were identified with expression levels regulated by cis-acting determinants. However, in general, the p-values associated with these regulators identified in our study were larger than in their studies, since we had also identified other factors regulating expression. In fact, we found that most of the gene expression phenotypes are influenced by at least one trans-acting locus. Our study also shows that much of the observable heritability in the phenotypes could be explained by simple single-nucleotide polymorphism associations; residual heritability was reduced and the remaining heritability may represent complex regulation systems with interactions or noise
Recursive partitioning models for linkage in COGA data
We have developed a recursive-partitioning (RP) algorithm for identifying phenotype and covariate groupings that interact with the evidence for linkage. This data-mining approach for detecting gene × environment interactions uses genotype and covariate data on affected relative pairs to find evidence for linkage heterogeneity across covariate-defined subgroups. We adapted a likelihood-ratio based test of linkage parameterized with relative risks to a recursive partitioning framework, including a cross-validation based deviance measurement for choosing optimal tree size and a bootstrap sampling procedure for choosing robust tree structure. ALDX2 category 5 individuals were considered affected, categories 1 and 3 unaffected, and all others unknown. We sampled non-overlapping affected relative pairs from each family; therefore, we used 144 affected pairs in the RP model. Twenty pair-level covariates were defined from smoking status, maximum drinks, ethnicity, sex, and age at onset. Using the all-pairs score in GENEHUNTER, the nonparametric linkage tests showed no regions with suggestive linkage evidence. However, using the RP model, several suggestive regions were found on chromosomes 2, 4, 6, 14, and 20, with detection of associated covariates such as sex and age at onset
Serum adiponectin levels are predictive of carotid intima-medial thickness in a 5-year community-based prospective study
Poster PresentationINTRODUCTION: Hypoadiponectinaemia has been shown to predict the development of type 2 diabetes, hypertension, and myocardial infarction in prospective studies. We have previously reported that hypoadiponectinaemia is associated with impaired endothelium-dependent vasodilation both in healthy controls and diabetic subjects. In this community-based prospective cohort study, we examined the predictive value of serum adiponectin levels on carotid intima-medial thickness, a marker of …published_or_final_versionThe 17th Medical Research Conference, The University of Hong Kong, Hong Kong, 14 January 2012. In Hong Kong Medical Journal, 2012, v. 18 suppl. 1, p. 32, abstract no. 4
Hypoadiponectinemia As an Independent Predictor for the Progression of Carotid Atherosclerosis: A 5-Year Prospective Study
published_or_final_versio
Use of a porous membrane for gas bubble removal in microfluidic channels: physical mechanisms and design criteria
We demonstrate and explain a simple and efficient way to remove gas bubbles
from liquid-filled microchannels, by integrating a hydrophobic porous membrane
on top of the microchannel. A prototype chip is manufactured in hard,
transparent polymer with the ability to completely filter gas plugs out of a
segmented flow at rates up to 7.4 microliter/s per mm2 of membrane area. The
device involves a bubble generation section and a gas removal section. In the
bubble generation section, a T-junction is used to generate a train of gas
plugs into a water stream. These gas plugs are then transported towards the gas
removal section, where they slide along a hydrophobic membrane until complete
removal. The system has been successfully modeled and four necessary operating
criteria have been determined to achieve a complete separation of the gas from
the liquid. The first criterion is that the bubble length needs to be larger
than the channel diameter. The second criterion is that the gas plug should
stay on the membrane for a time sufficient to transport all the gas through the
membrane. The third criterion is that the gas plug travel speed should be lower
than a critical value: otherwise a stable liquid film between the bubble and
the membrane prevents mass transfer. The fourth criterion is that the pressure
difference across the membrane should not be larger than the Laplace pressure
to prevent water from leaking through the membrane
Mathematical modeling of the metastatic process
Mathematical modeling in cancer has been growing in popularity and impact
since its inception in 1932. The first theoretical mathematical modeling in
cancer research was focused on understanding tumor growth laws and has grown to
include the competition between healthy and normal tissue, carcinogenesis,
therapy and metastasis. It is the latter topic, metastasis, on which we will
focus this short review, specifically discussing various computational and
mathematical models of different portions of the metastatic process, including:
the emergence of the metastatic phenotype, the timing and size distribution of
metastases, the factors that influence the dormancy of micrometastases and
patterns of spread from a given primary tumor.Comment: 24 pages, 6 figures, Revie
Carbon-fiber tips for scanning probe microscopes and molecular electronics experiments
We fabricate and characterize carbon-fiber tips for their use in combined
scanning tunneling and force microscopy based on piezoelectric quartz tuning
fork force sensors. An electrochemical fabrication procedure to etch the tips
is used to yield reproducible sub-100-nm apex. We also study electron transport
through single-molecule junctions formed by a single octanethiol molecule
bonded by the thiol anchoring group to a gold electrode and linked to a carbon
tip by the methyl group. We observe the presence of conductance plateaus during
the stretching of the molecular bridge, which is the signature of the formation
of a molecular junction.Comment: Conference Proceeding (Trends in NanoTechnology 2011, Tenerife
SPAIN); Nanoscale Research Letters, (2012) 7:25
Graviton emission in Einstein-Hilbert gravity
The five-point amplitude for the scattering of two distinct scalars with the
emission of one graviton in the final state is calculated in exact kinematics
for Einstein-Hilbert gravity. The result, which satisfies the Steinmann
relations, is expressed in Sudakov variables, finding that it corresponds to
the sum of two gauge invariant contributions written in terms of a new two
scalar - two graviton effective vertex. A similar calculation is carried out in
Quantum Chromodynamics (QCD) for the scattering of two distinct quarks with one
extra gluon in the final state. The effective vertices which appear in both
cases are then evaluated in the multi-Regge limit reproducing the well-known
result obtained by Lipatov where the Einstein-Hilbert graviton emission vertex
can be written as the product of two QCD gluon emission vertices, up to
corrections to preserve the Steinmann relations.Comment: 28 pages, LaTeX, feynmf. v2: typos corrected, reference added. Final
version to appear in Journal of High Energy Physic
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