4,009 research outputs found

    Non-Perturbative Renormalization Group for Simple Fluids

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    We present a new non perturbative renormalization group for classical simple fluids. The theory is built in the Grand Canonical ensemble and in the framework of two equivalent scalar field theories as well. The exact mapping between the three renormalization flows is established rigorously. In the Grand Canonical ensemble the theory may be seen as an extension of the Hierarchical Reference Theory (L. Reatto and A. Parola, \textit{Adv. Phys.}, \textbf{44}, 211 (1995)) but however does not suffer from its shortcomings at subcritical temperatures. In the framework of a new canonical field theory of liquid state developed in that aim our construction identifies with the effective average action approach developed recently (J. Berges, N. Tetradis, and C. Wetterich, \textit{Phys. Rep.}, \textbf{363} (2002))

    Serum 25-hydroxyvitamin D and cognitive decline in the very old: the Newcastle 85+ Study.

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    This is the final version of the article. Available from Wiley via the DOI in this record.BACKGROUND AND PURPOSE: Studies investigating the association between 25-hydroxyvitamin D [25(OH)D] and cognition in the very old (85+) are lacking. METHODS: Cross-sectional (baseline) and prospective data (up to 3 years follow-up) from 775 participants in the Newcastle 85+ Study were analysed for global (measured by the Standardized Mini-Mental State Examination) and attention-specific (measured by the attention battery of the Cognitive Drug Research test) cognitive performance in relation to season-specific 25(OH)D quartiles. RESULTS: Those in the lowest and highest season-specific 25(OH)D quartiles had an increased risk of impaired prevalent (1.66, 95% confidence interval 1.06-2.60, P = 0.03; 1.62, 95% confidence interval 1.02-2.59, P = 0.04, respectively) but not incident global cognitive functioning or decline in functioning compared with those in the middle quartiles adjusted for sociodemographic, health and lifestyle confounders. Random effects models showed that participants belonging to the lowest and highest 25(OH)D quartiles, compared with those in the middle quartiles, had overall slower (log-transformed) attention reaction times for Choice Reaction Time (lowest, β = 0.023, P = 0.01; highest, β = 0.021, P = 0.02), Digit Vigilance Task (lowest, β = 0.009, P = 0.05; highest, β = 0.01, P = 0.02) and Power of Attention (lowest, β = 0.017, P = 0.02; highest, β = 0.022, P = 0.002) and greater Reaction Time Variability (lowest, β = 0.021, P = 0.02; highest, β = 0.02, P = 0.03). The increased risk of worse global cognition and attention amongst those in the highest quartile was not observed in non-users of vitamin D supplements/medication. CONCLUSION: Low and high season-specific 25(OH)D quartiles were associated with prevalent cognitive impairment and poorer overall performance in attention-specific tasks over 3 years in the very old, but not with global cognitive decline or incident impairment.This work was supported by the National Institute for Health Research Newcastle Biomedical Research Centre based at Newcastle Hospitals Foundation Trust and Newcastle University (AG). The Newcastle 85+ Study has been funded by the Medical Research Council, Biotechnology and Biological Sciences Research Council and the Dunhill Medical Trust. Additional work has also been funded by the British Heart Foundation, Unilever Corporate Research, Newcastle University and National Health Service (NHS) North of Tyne (Newcastle Primary Care Trust). The views expressed in this paper are those of the authors and not necessarily those of the National Health Service, UK. We acknowledge the operational support of NHS North of Tyne, the local general practitioners and their staff, the research nurses, laboratory technicians, data management and clerical team, as well as many colleagues for their expert advice. Thanks are due especially to the study participants

    Amyloid β 1-42 induces hypometabolism in human stem cell-derived neuron and astrocyte networks

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    Alzheimer's disease (AD) is the most common form of dementia, affecting more than 35 million people worldwide. Brain hypometabolism is a major feature of AD, appearing decades before cognitive decline and pathologic lesions. To date, the majority of studies on hypometabolism in AD have used transgenic animal models or imaging studies of the human brain. As it is almost impossible to validate these findings using human tissue, alternative models are required. In this study, we show that human stem cell-derived neuron and astrocyte cultures treated with oligomers of amyloid beta 1-42 (Aβ1-42) also display a clear hypometabolism, particularly with regard to utilization of substrates such as glucose, pyruvate, lactate, and glutamate. In addition, a significant increase in the glycogen content of cells was also observed. These changes were accompanied by changes in NAD+ /NADH, ATP, and glutathione levels, suggesting a disruption in the energy-redox axis within these cultures. The high energy demands associated with neuronal functions such as memory formation and protection from oxidative stress put these cells at particular risk from Aβ-induced hypometabolism. Further research using this model may elucidate the mechanisms associated with Aβ-induced hypometabolism

    MalHaploFreq: A computer programme for estimating malaria haplotype frequencies from blood samples

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    <p>Abstract</p> <p>Background</p> <p>Molecular markers, particularly those associated with drug resistance, are important surveillance tools that can inform policy choice. People infected with <it>falciparum </it>malaria often contain several genetically-distinct clones of the parasite; genotyping the patients' blood reveals whether or not the marker is present (i.e. its prevalence), but does not reveal its frequency. For example a person with four malaria clones may contain both mutant and wildtype forms of a marker but it is not possible to distinguish the relative frequencies of the mutant and wildtypes i.e. 1:3, 2:2 or 3:1.</p> <p>Methods</p> <p>An appropriate method for obtaining frequencies from prevalence data is by Maximum Likelihood analysis. A computer programme has been developed that allows the frequency of markers, and haplotypes defined by up to three codons, to be estimated from blood phenotype data.</p> <p>Results</p> <p>The programme has been fully documented [see Additional File <supplr sid="S1">1</supplr>] and provided with a user-friendly interface suitable for large scale analyses. It returns accurate frequencies and 95% confidence intervals from simulated dataset sets and has been extensively tested on field data sets.</p> <suppl id="S1"> <title> <p>Additional File 1</p> </title> <text> <p>User manual for MalHaploFreq.</p> </text> <file name="1475-2875-7-130-S1.pdf"> <p>Click here for file</p> </file> </suppl> <p>Conclusion</p> <p>The programme is included [see Additional File <supplr sid="S2">2</supplr>] and/or may be freely downloaded from <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>. It can then be used to extract molecular marker and haplotype frequencies from their prevalence in human blood samples. This should enhance the use of frequency data to inform antimalarial drug policy choice.</p> <suppl id="S2"> <title> <p>Additional File 2</p> </title> <text> <p>executable programme compiled for use on DOS or windows</p> </text> <file name="1475-2875-7-130-S2.exe"> <p>Click here for file</p> </file> </suppl

    Misconceptions about Aerobic and Anaerobic Energy Expenditure

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    The measurement of gas exchange has played an invaluable role in metabolic interpretation. The uptake of 1 liter of oxygen is often converted into an energy expenditure estimate of 21.1 kilojoules (e.g., 1 L O2 = 21.1 kJ or ~5 kcal). This article demonstrates both the importance of such a conversion and the potential for misinterpretation. Oxygen uptake during heavy and severe exercise will also be discussed

    Spatial and topological organization of DNA chains induced by gene co-localization

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    Transcriptional activity has been shown to relate to the organization of chromosomes in the eukaryotic nucleus and in the bacterial nucleoid. In particular, highly transcribed genes, RNA polymerases and transcription factors gather into discrete spatial foci called transcription factories. However, the mechanisms underlying the formation of these foci and the resulting topological order of the chromosome remain to be elucidated. Here we consider a thermodynamic framework based on a worm-like chain model of chromosomes where sparse designated sites along the DNA are able to interact whenever they are spatially close-by. This is motivated by recurrent evidence that there exists physical interactions between genes that operate together. Three important results come out of this simple framework. First, the resulting formation of transcription foci can be viewed as a micro-phase separation of the interacting sites from the rest of the DNA. In this respect, a thermodynamic analysis suggests transcription factors to be appropriate candidates for mediating the physical interactions between genes. Next, numerical simulations of the polymer reveal a rich variety of phases that are associated with different topological orderings, each providing a way to increase the local concentrations of the interacting sites. Finally, the numerical results show that both one-dimensional clustering and periodic location of the binding sites along the DNA, which have been observed in several organisms, make the spatial co-localization of multiple families of genes particularly efficient.Comment: Figures and Supplementary Material freely available on http://dx.doi.org/10.1371/journal.pcbi.100067

    Do female association preferences predict the likelihood of reproduction?

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    Sexual selection acting on male traits through female mate choice is commonly inferred from female association preferences in dichotomous mate choice experiments. However, there are surprisingly few empirical demonstrations that such association preferences predict the likelihood of females reproducing with a particular male. This information is essential to confirm association preferences as good predictors of mate choice. We used green swordtails (&lt;i&gt;Xiphophorus helleri&lt;/i&gt;) to test whether association preferences predict the likelihood of a female reproducing with a male. Females were tested for a preference for long- or short-sworded males in a standard dichotomous choice experiment and then allowed free access to either their preferred or non-preferred male. If females subsequently failed to produce fry, they were provided a second unfamiliar male with similar sword length to the first male. Females were more likely to reproduce with preferred than non-preferred males, but for those that reproduced, neither the status (preferred/non-preferred) nor the sword length (long/short) of the male had an effect on brood size or relative investment in growth by the female. There was no overall preference based on sword length in this study, but male sword length did affect likelihood of reproduction, with females more likely to reproduce with long- than short-sworded males (independent of preference for such males in earlier choice tests). These results suggest that female association preferences are good indicators of female mate choice but that ornament characteristics of the male are also important

    Analysis of factors influencing the ultrasonic fetal weight estimation

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    Objective: The aim of our study was the evaluation of sonographic fetal weight estimation taking into consideration 9 of the most important factors of influence on the precision of the estimation. Methods: We analyzed 820 singleton pregnancies from 22 to 42 weeks of gestational age. We evaluated 9 different factors that potentially influence the precision of sonographic weight estimation ( time interval between estimation and delivery, experts vs. less experienced investigator, fetal gender, gestational age, fetal weight, maternal BMI, amniotic fluid index, presentation of the fetus, location of the placenta). Finally, we compared the results of the fetal weight estimation of the fetuses with poor scanning conditions to those presenting good scanning conditions. Results: Of the 9 evaluated factors that may influence accuracy of fetal weight estimation, only a short interval between sonographic weight estimation and delivery (0-7 vs. 8-14 days) had a statistically significant impact. Conclusion: Of all known factors of influence, only a time interval of more than 7 days between estimation and delivery had a negative impact on the estimation

    First-principles design and subsequent synthesis of a material to search for the permanent electric dipole moment of the electron

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    We describe the first-principles design and subsequent synthesis of a new material with the specific functionalities required for a solid-state-based search for the permanent electric dipole moment of the electron. We show computationally that perovskite-structure europium barium titanate should exhibit the required large and pressure-dependent ferroelectric polarization, local magnetic moments, and absence of magnetic ordering even at liquid helium temperature. Subsequent synthesis and characterization of Eu0.5_{0.5}Ba0.5_{0.5}TiO3_3 ceramics confirm the predicted desirable properties.Comment: Nature Materials, in pres

    Low pH immobilizes and kills human leukocytes and prevents transmission of cell-associated HIV in a mouse model

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    BACKGROUND: Both cell-associated and cell-free HIV virions are present in semen and cervical secretions of HIV-infected individuals. Thus, topical microbicides may need to inactivate both cell-associated and cell-free HIV to prevent sexual transmission of HIV/AIDS. To determine if the mild acidity of the healthy vagina and acid buffering microbicides would prevent transmission by HIV-infected leukocytes, we measured the effect of pH on leukocyte motility, viability and intracellular pH and tested the ability of an acidic buffering microbicide (BufferGel(®)) to prevent the transmission of cell-associated HIV in a HuPBL-SCID mouse model. METHODS: Human lymphocyte, monocyte, and macrophage motilities were measured as a function of time and pH using various acidifying agents. Lymphocyte and macrophage motilities were measured using video microscopy. Monocyte motility was measured using video microscopy and chemotactic chambers. Peripheral blood mononuclear cell (PBMC) viability and intracellular pH were determined as a function of time and pH using fluorescent dyes. HuPBL-SCID mice were pretreated with BufferGel, saline, or a control gel and challenged with HIV-1-infected human PBMCs. RESULTS: Progressive motility was completely abolished in all cell types between pH 5.5 and 6.0. Concomitantly, at and below pH 5.5, the intracellular pH of PBMCs dropped precipitously to match the extracellular medium and did not recover. After acidification with hydrochloric acid to pH 4.5 for 60 min, although completely immotile, 58% of PBMCs excluded ethidium homodimer-1 (dead-cell dye). In contrast, when acidified to this pH with BufferGel, a microbicide designed to maintain vaginal acidity in the presence of semen, only 4% excluded dye at 10 min and none excluded dye after 30 min. BufferGel significantly reduced transmission of HIV-1 in HuPBL-SCID mice (1 of 12 infected) compared to saline (12 of 12 infected) and a control gel (5 of 7 infected). CONCLUSION: These results suggest that physiologic or microbicide-induced acid immobilization and killing of infected white blood cells may be effective in preventing sexual transmission of cell-associated HIV
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