481 research outputs found
Breakdown of the adiabatic limit in low dimensional gapless systems
It is generally believed that a generic system can be reversibly transformed
from one state into another by sufficiently slow change of parameters. A
standard argument favoring this assertion is based on a possibility to expand
the energy or the entropy of the system into the Taylor series in the ramp
speed. Here we show that this argumentation is only valid in high enough
dimensions and can break down in low-dimensional gapless systems. We identify
three generic regimes of a system response to a slow ramp: (A) mean-field, (B)
non-analytic, and (C) non-adiabatic. In the last regime the limits of the ramp
speed going to zero and the system size going to infinity do not commute and
the adiabatic process does not exist in the thermodynamic limit. We support our
results by numerical simulations. Our findings can be relevant to
condensed-matter, atomic physics, quantum computing, quantum optics, cosmology
and others.Comment: 11 pages, 5 figures, to appear in Nature Physics (originally
submitted version
Ethnic Variation in Inflammatory Profile in Tuberculosis
PMCID: PMC3701709This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Associations of vitamin D pathway genes with circulating 25-hydroxyvitamin-D, 1,25-dihydroxyvitamin-D, and prostate cancer:a nested case-control study
Vitamin D pathway single nucleotide polymorphisms (SNPs) are potentially useful proxies for investigating whether circulating vitamin D metabolites [total 25-hydroxyvitamin-D, 25(OH)D; 1,25-dihydroxyvitamin, 1,25(OH)2D] are causally related to prostate cancer. We investigated associations of sixteen SNPs across seven genes with prostate-specific antigen-detected prostate cancer
Vitamin D Binding Protein and Monocyte Response to 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D: Analysis by Mathematical Modeling
Vitamin D binding protein (DBP) plays a key role in the bioavailability of active 1,25-dihydroxyvitamin D (1,25(OH)2D) and its precursor 25-hydroxyvitamin D (25OHD), but accurate analysis of DBP-bound and free 25OHD and 1,25(OH)2D is difficult. To address this, two new mathematical models were developed to estimate: 1) serum levels of free 25OHD/1,25(OH)2D based on DBP concentration and genotype; 2) the impact of DBP on the biological activity of 25OHD/1,25(OH)2D in vivo. The initial extracellular steady state (eSS) model predicted that 50 nM 25OHD and 100 pM 1,25(OH)2D), <0.1% 25OHD and <1.5% 1,25(OH)2D are βfreeβ in vivo. However, for any given concentration of total 25OHD, levels of free 25OHD are higher for low affinity versus high affinity forms of DBP. The eSS model was then combined with an intracellular (iSS) model that incorporated conversion of 25OHD to 1,25(OH)2D via the enzyme CYP27B1, as well as binding of 1,25(OH)2D to the vitamin D receptor (VDR). The iSS model was optimized to 25OHD/1,25(OH)2D-mediated in vitro dose-responsive induction of the vitamin D target gene cathelicidin (CAMP) in human monocytes. The iSS model was then used to predict vitamin D activity in vivo (100% serum). The predicted induction of CAMP in vivo was minimal at basal settings but increased with enhanced expression of VDR (5-fold) and CYP27B1 (10-fold). Consistent with the eSS model, the iSS model predicted stronger responses to 25OHD for low affinity forms of DBP. Finally, the iSS model was used to compare the efficiency of endogenously synthesized versus exogenously added 1,25(OH)2D. Data strongly support the endogenous model as the most viable mode for CAMP induction by vitamin D in vivo. These novel mathematical models underline the importance of DBP as a determinant of vitamin D βstatusβ in vivo, with future implications for clinical studies of vitamin D status and supplementation
Lattice Boltzmann simulations of soft matter systems
This article concerns numerical simulations of the dynamics of particles
immersed in a continuum solvent. As prototypical systems, we consider colloidal
dispersions of spherical particles and solutions of uncharged polymers. After a
brief explanation of the concept of hydrodynamic interactions, we give a
general overview over the various simulation methods that have been developed
to cope with the resulting computational problems. We then focus on the
approach we have developed, which couples a system of particles to a lattice
Boltzmann model representing the solvent degrees of freedom. The standard D3Q19
lattice Boltzmann model is derived and explained in depth, followed by a
detailed discussion of complementary methods for the coupling of solvent and
solute. Colloidal dispersions are best described in terms of extended particles
with appropriate boundary conditions at the surfaces, while particles with
internal degrees of freedom are easier to simulate as an arrangement of mass
points with frictional coupling to the solvent. In both cases, particular care
has been taken to simulate thermal fluctuations in a consistent way. The
usefulness of this methodology is illustrated by studies from our own research,
where the dynamics of colloidal and polymeric systems has been investigated in
both equilibrium and nonequilibrium situations.Comment: Review article, submitted to Advances in Polymer Science. 16 figures,
76 page
LRP5 Is Required for Vascular Development in Deeper Layers of the Retina
Background: The low-density lipoprotein receptor-related protein 5 (LRP5) plays an important role in the development of retinal vasculature. LRP5 loss-of-function mutations cause incomplete development of retinal vessel network in humans as well as in mice. To understand the underlying mechanism for how LRP5 mutations lead to retinal vascular abnormalities, we have determined the retinal cell types that express LRP5 and investigated specific molecular and cellular functions that may be regulated by LRP5 signaling in the retina. Methods and Findings: We characterized the development of retinal vasculature in LRP5 mutant mice using specific retinal cell makers and a GFP transgene expressed in retinal endothelial cells. Our data revealed that retinal vascular endothelial cells predominantly formed cell clusters in the inner-plexiform layer of LRP5 mutant retina rather than sprouting out or migrating into deeper layers to form normal vascular network in the retina. The IRES-b-galactosidase (LacZ) report gene under the control of the endogenous LRP5 promoter was highly expressed in MΓΌller cells and was also weakly detected in endothelial cells of the retinal surface vasculature. Moreover, the LRP5 mutant mice had a reduction of a MΓΌller cell-specific glutamine transporter, Slc38a5, and showed a decrease in b-wave amplitude of electroretinogram. Conclusions: LRP5 is not only essential for vascular endothelial cells to sprout, migrate and/or anastomose in the deeper plexus during retinal vasculature development but is also important for the functions of MΓΌller cells and retina
Visual Information Alone Changes Behavior and Physiology during Social Interactions in a Cichlid Fish (Astatotilapia burtoni)
Social behavior can influence physiological systems dramatically yet the sensory
cues responsible are not well understood. Behavior of male African cichlid fish,
Astatotilapia burtoni, in their natural habitat suggests
that visual cues from conspecifics contribute significantly to regulation of
social behavior. Using a novel paradigm, we asked whether visual cues alone from
a larger conspecific male could influence behavior, reproductive physiology and
the physiological stress response of a smaller male. Here we show that just
seeing a larger, threatening male through a clear barrier can suppress dominant
behavior of a smaller male for up to 7 days. Smaller dominant males being
βattackedβ visually by larger dominant males through a clear barrier
also showed physiological changes for up to 3 days, including up-regulation of
reproductive- and stress-related gene expression levels and lowered plasma
11-ketotestesterone concentrations as compared to control animals. The smaller
males modified their appearance to match that of non-dominant males when exposed
to a larger male but they maintained a physiological phenotype similar to that
of a dominant male. After 7 days, reproductive- and stress- related gene
expression, circulating hormone levels, and gonad size in the smaller males
showed no difference from the control group suggesting that the smaller male
habituated to the visual intruder. However, the smaller male continued to
display subordinate behaviors and assumed the appearance of a subordinate male
for a full week despite his dominant male physiology. These data suggest that
seeing a larger male alone can regulate the behavior of a smaller male but that
ongoing reproductive inhibition depends on additional sensory cues. Perhaps,
while experiencing visual social stressors, the smaller male uses an
opportunistic strategy, acting like a subordinate male while maintaining the
physiology of a dominant male
Predictors of 25(OH)D half-life and plasma 25(OH)D concentration in The Gambia and the UK
Summary: Predictors of 25(OH)D3 half-life were factors associated with vitamin D metabolism, but were different between people in The Gambia and the UK. Country was the strongest predictor of plasma 25(OH)D concentration, probably as a marker of UVB exposure. 25(OH)D3 half-life may be applied as a tool to investigate vitamin D expenditure.Β Introduction: The aim of this study was to investigate predictors of 25(OH)D3 half-life and plasma 25(OH)D concentration.Β Methods: Plasma half-life of an oral tracer dose of deuterated-25(OH)D3 was measured in healthy men aged 24β39 years, resident in The Gambia, West Africa (nβ=β18) and in the UK during the winter (nβ=β18), countries that differ in calcium intake and vitamin D status. Plasma and urinary markers of vitamin D, calcium, phosphate and bone metabolism, nutrient intakes and anthropometry were measured.Β Results: Normally distributed data are presented as mean (SD) and non-normal data as geometric mean (95 % CI). Gambian compared to UK men had higher plasma concentrations of 25(OH)D (69 (13) vs. 29 (11)βnmol/L; Pβ<β0.0001); 1,25(OH)2D (181 (165, 197) vs. 120 (109, 132)βpmol/L; Pβ<β0.01); and parathyroid hormone (PTH) (50 (42, 60) vs. 33 (27, 39); Pβ<β0.0001). There was no difference in 25(OH)D3 half-life (14.7 (3.5)βdays vs. 15.6 (2.5)βdays) between countries (Pβ=β0.2). In multivariate analyses, 25(OH)D, 1,25(OH)2D, vitamin D binding protein and albumin-adjusted calcium (Caalb) explained 79 % of variance in 25(OH)D3 half-life in Gambians, but no significant predictors were found in UK participants. For the countries combined, Caalb, PTH and plasma phosphate explained 39 % of half-life variability. 1,25(OH)2D, weight, PTH and country explained 81 % of variability in 25(OH)D concentration; however, country alone explained 74 %.Β Conclusion: Factors known to affect 25(OH)D metabolism predict 25(OH)D3 half-life, but these differed between countries. Country predicted 25(OH)D, probably as a proxy measure for UVB exposure and vitamin D supply. This study supports the use of 25(OH)D half-life to investigate vitamin D metabolism
Modeling of longitudinal polytomous outcome from complex survey data - application to investigate an association between mental distress and non-malignant respiratory diseases
<p>Abstract</p> <p>Background</p> <p>The data from longitudinal complex surveys based on multi-stage sampling designs contain cross-sectional dependencies among units due to clustered nature of the data and within-subject dependencies due to repeated measurements. Special statistical methods are required to analyze longitudinal complex survey data.</p> <p>Methods</p> <p>Statistics Canada's longitudinal National Population Health Survey (NPHS) dataset from the first five cycles (1994/1995 to 2002/2003) was used to investigate the effects of demographic, social, life-style, and health-related factors on the longitudinal changes of mental distress scores among the NPHS participants who self-reported physician diagnosed respiratory diseases, specifically asthma and chronic bronchitis. The NPHS longitudinal sample includes 17,276 persons of all ages. In this report, participants 15 years and older (n = 14,713) were considered for statistical analysis. Mental distress, an ordinal outcome variable (categories: no/low, moderate, and high) was examined. Ordered logistic regression models based on the weighted generalized estimating equations approach were fitted to investigate the association between respiratory diseases and mental distress adjusting for other covariates of interest. Variance estimates of regression coefficients were computed by using bootstrap methods. The final model was used to predict the probabilities of prevalence of no/low, moderate or high mental distress scores.</p> <p>Results</p> <p>Accounting for design effects does not vary the significance of the coefficients of the model. Participants suffering with chronic bronchitis were significantly at a higher risk (OR<sub>adj </sub>= 1.37; 95% CI: 1.12-1.66) of reporting high levels of mental distress compared to those who did not self-report chronic bronchitis. There was no significant association between asthma and mental distress. There was a significant interaction between sex and self-perceived general health status indicating a dose-response relationship. Among females, the risk of mental distress increases with increasing deteriorating (from excellent to very poor) self-perceived general health.</p> <p>Conclusions</p> <p>A positive association was observed between the physician diagnosed self-reported chronic bronchitis and an increased prevalence of mental distress when adjusted for important covariates. Variance estimates of regression coefficients obtained from the sandwich estimator (i.e. not accounting for design effects) were similar to bootstrap variance estimates (i.e. accounting for design effects). Even though these two sets of variance estimates are similar, it is more appropriate to use bootstrap variance estimates.</p
Effects of Ionomycin on Egg Activation and Early Development in Starfish
Ionomycin is a Ca2+-selective ionophore that is widely used to increase intracellular Ca2+ levels in cell biology laboratories. It is also occasionally used to activate eggs in the clinics practicing in vitro fertilization. However, neither the precise molecular action of ionomycin nor its secondary effects on the eggs' structure and function is well known. In this communication we have studied the effects of ionomycin on starfish oocytes and zygotes. By use of confocal microscopy, calcium imaging, as well as light and transmission electron microscopy, we have demonstrated that immature oocytes exposed to ionomycin instantly increase intracellular Ca2+ levels and undergo structural changes in the cortex. Surprisingly, when microinjected into the cells, ionomycin produced no Ca2+ increase. The ionomycin-induced Ca2+ rise was followed by fast alteration of the actin cytoskeleton displaying conspicuous depolymerization at the oocyte surface and in microvilli with concomitant polymerization in the cytoplasm. In addition, cortical granules were disrupted or fused with white vesicles few minutes after the addition of ionomycin. These structural changes prevented cortical maturation of the eggs despite the normal progression of nuclear envelope breakdown. At fertilization, the ionomycin-pretreated eggs displayed reduced Ca2+ response, no elevation of the fertilization envelope, and the lack of orderly centripetal translocation of actin fibers. These alterations led to difficulties in cell cleavage in the monospermic zygotes and eventually to a higher rate of abnormal development. In conclusion, ionomycin has various deleterious impacts on egg activation and the subsequent embryonic development in starfish. Although direct comparison is difficult to make between our findings and the use of the ionophore in the in vitro fertilization clinics, our results call for more defining investigations on the issue of a potential risk in artificial egg activation
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