50 research outputs found
Determination of the characteristic directions of lossless linear optical elements
We show that the problem of finding the primary and secondary characteristic
directions of a linear lossless optical element can be reformulated in terms of
an eigenvalue problem related to the unimodular factor of the transfer matrix
of the optical device. This formulation makes any actual computation of the
characteristic directions amenable to pre-implemented numerical routines,
thereby facilitating the decomposition of the transfer matrix into equivalent
linear retarders and rotators according to the related Poincare equivalence
theorem. The method is expected to be useful whenever the inverse problem of
reconstruction of the internal state of a transparent medium from optical data
obtained by tomographical methods is an issue.Comment: Replaced with extended version as published in JM
Is “incidental finding” the best term?: a study of patients’ preferences
There is debate within the genetics community about the optimal term to describe genetic variants unrelated to the test indication, but potentially important for health. Given the lack of consensus and the importance of adopting terminology that promotes effective clinical communication, we sought the opinion of clinical genetics patients
Role of Heparanase on Hepatic Uptake of Intestinal Derived Lipoprotein and Fatty Streak Formation in Mice
BACKGROUND: Heparanase modulates the level of heparan sulfate proteoglycans (HSPGs) which have an important role in multiple cellular processes. Recent studies indicate that HSPGs have an important function in hepatic lipoprotein handling and processes involving removal of lipoprotein particles. PRINCIPAL FINDINGS: To determine the effects of decreased HSPGs chain length on lipoprotein metabolism and atherosclerosis, transgenic mice over-expressing the human heparanase gene were studied. Hepatic lipid uptake in hpa-Tg mice were evaluated by giving transgenic mice oral fat loads and labeled retinol. Sections of aorta from mice over-expressing heparanase (hpa-Tg) and controls (C57/BL6) fed an atherogenic diet were examined for evidence of atherosclerosis. Heparanase over-expression results in reduced hepatic clearance of postprandial lipoproteins and higher levels of fasting and postprandial serum triglycerides. Heparanase over-expression also induces formation of fatty streaks in the aorta. The mean lesion cross-sectional area in heparanase over-expressing mice was almost 6 times higher when compared to control mice (23,984 µm(2)±5,922 vs. 4,189 µm(2)±1,130, p<0.001). CONCLUSIONS: Over-expression of heparanase demonstrates the importance of HSPGs for the uptake of intestinal derived lipoproteins and its role in the formation of fatty streaks
Neutrino Mixing and Neutrino Telescopes
Measuring flux ratios of ultra-high energy neutrinos is an alternative method
to determine the neutrino mixing angles and the CP phase delta. We conduct a
systematic analysis of the neutrino mixing probabilities and of various flux
ratios measurable at neutrino telescopes. The considered cases are neutrinos
from pion, neutron and muon-damped sources. Explicit formulae in case of mu-tau
symmetry and its special case tri-bimaximal mixing are obtained, and the
leading corrections due to non-zero theta_{13} and non-maximal theta_{23} are
given. The first order correction is universal as it appears in basically all
ratios. We study in detail its dependence on theta_{13}, theta_{23} and the CP
phase, finding that the dependence on theta_{23} is strongest. The flavor
compositions for the considered neutrino sources are evaluated in terms of this
correction. A measurement of a flux ratio is a clean measurement of the
universal correction (and therefore of theta_{13}, theta_{23} and delta) if the
zeroth order ratio does not depend on theta_{12}. This favors pion sources over
the other cases, which in turn are good candidates to probe theta_{12}. The
only situations in which the universal correction does not appear are certain
ratios in case of a neutron and muon-damped source, which depend mainly on
theta_{12} and receive only quadratic corrections from the other parameters. We
further show that there are only two independent neutrino oscillation
probabilities, give the allowed ranges of the considered flux ratios and of all
probabilities, and show that none of the latter can be zero or one.Comment: 29 pages, 8 figures. Minor changes, to appear in JCA
Heparan Sulfate Regrowth Profiles Under Laminar Shear Flow Following Enzymatic Degradation
The local hemodynamic shear stress waveforms present in an artery dictate the endothelial cell phenotype. The observed decrease of the apical glycocalyx layer on the endothelium in atheroprone regions of the circulation suggests that the glycocalyx may have a central role in determining atherosclerotic plaque formation. However, the kinetics for the cells’ ability to adapt its glycocalyx to the environment have not been quantitatively resolved. Here we report that the heparan sulfate component of the glycocalyx of HUVECs increases by 1.4-fold following the onset of high shear stress, compared to static cultured cells, with a time constant of 19 h. Cell morphology experiments show that 12 h are required for the cells to elongate, but only after 36 h have the cells reached maximal alignment to the flow vector. Our findings demonstrate that following enzymatic degradation, heparan sulfate is restored to the cell surface within 12 h under flow whereas the time required is 20 h under static conditions. We also propose a model describing the contribution of endocytosis and exocytosis to apical heparan sulfate expression. The change in HS regrowth kinetics from static to high-shear EC phenotype implies a differential in the rate of endocytic and exocytic membrane turnover.National Heart, Lung, and Blood Institute (Grant HL090856-01)Singapore-MIT Allianc
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Human BDNF/TrkB variants impair hippocampal synaptogenesis and associate with neurobehavioural abnormalities
Abstract: Brain-derived neurotrophic factor (BDNF) signals through its high affinity receptor Tropomyosin receptor kinase-B (TrkB) to regulate neuronal development, synapse formation and plasticity. In rodents, genetic disruption of Bdnf and TrkB leads to weight gain and a spectrum of neurobehavioural phenotypes. Here, we functionally characterised a de novo missense variant in BDNF and seven rare variants in TrkB identified in a large cohort of people with severe, childhood-onset obesity. In cells, the E183K BDNF variant resulted in impaired processing and secretion of the mature peptide. Multiple variants in the kinase domain and one variant in the extracellular domain of TrkB led to a loss of function through multiple signalling pathways, impaired neurite outgrowth and dominantly inhibited glutamatergic synaptogenesis in hippocampal neurons. BDNF/TrkB variant carriers exhibited learning difficulties, impaired memory, hyperactivity, stereotyped and sometimes, maladaptive behaviours. In conclusion, human loss of function BDNF/TrkB variants that impair hippocampal synaptogenesis may contribute to a spectrum of neurobehavioural disorders
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Human BDNF/TrkB variants impair hippocampal synaptogenesis and associate with neurobehavioural abnormalities
Abstract: Brain-derived neurotrophic factor (BDNF) signals through its high affinity receptor Tropomyosin receptor kinase-B (TrkB) to regulate neuronal development, synapse formation and plasticity. In rodents, genetic disruption of Bdnf and TrkB leads to weight gain and a spectrum of neurobehavioural phenotypes. Here, we functionally characterised a de novo missense variant in BDNF and seven rare variants in TrkB identified in a large cohort of people with severe, childhood-onset obesity. In cells, the E183K BDNF variant resulted in impaired processing and secretion of the mature peptide. Multiple variants in the kinase domain and one variant in the extracellular domain of TrkB led to a loss of function through multiple signalling pathways, impaired neurite outgrowth and dominantly inhibited glutamatergic synaptogenesis in hippocampal neurons. BDNF/TrkB variant carriers exhibited learning difficulties, impaired memory, hyperactivity, stereotyped and sometimes, maladaptive behaviours. In conclusion, human loss of function BDNF/TrkB variants that impair hippocampal synaptogenesis may contribute to a spectrum of neurobehavioural disorders
Prevailing-frequency approximation of the coupling ray theory for electromagnetic waves or elastic S waves
Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine
Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine