2,905 research outputs found

    Irreversible reorganization in a supercooled liquid originates from localised soft modes

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    The transition of a fluid to a rigid glass upon cooling is a common route of transformation from liquid to solid that embodies the most poorly understood features of both phases1,2,3. From the liquid perspective, the puzzle is to understand stress relaxation in the disordered state. From the perspective of solids, the challenge is to extend our description of structure and its mechanical consequences to materials without long range order. Using computer simulations, we show that the localized low frequency normal modes of a configuration in a supercooled liquid are causally correlated to the irreversible structural reorganization of the particles within that configuration. We also demonstrate that the spatial distribution of these soft local modes can persist in spite of significant particle reorganization. The consequence of these two results is that it is now feasible to construct a theory of relaxation length scales in glass-forming liquids without recourse to dynamics and to explicitly relate molecular properties to their collective relaxation.Comment: Published online: 20 July 2008 | doi:10.1038/nphys1025 Available from http://www.nature.com/nphys/journal/v4/n9/abs/nphys1025.htm

    Letters and records of the dissenting congregations: David Crosley, Cripplegate and Baptist Church life

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    The original publication is available at www.springerlink.comInternational audienceThis chapter examines the status and function of letters in manuscript records of dissenting Churches of the post-Toleration years, concentrating on the correspondence of the Baptist Church of Cripplegate. The letters are placed in the context of controversies about Church government and discipline and the rhetoric used during the scandal caused by the excommunication of its Northern minister David Crosley for drinking, lying and adultery is assessed. In doing so, the chapter pays particular attention to the epistolary exchanges between metropolitan and provincial congregations and to what they reveal about conceptions of the Baptist ministry

    Type I IFN induces protein ISGylation to enhance cytokine expression and augments colonic inflammation

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    Type I IFNs have broad activity in tissue inflammation and malignant progression that depends on the expression of IFN-stimulated genes (ISGs). ISG15, one such ISG, can form covalent conjugates to many cellular proteins, a process termed "protein ISGylation." Although type I IFNs are involved in multiple inflammatory disorders, the role of protein ISGylation during inflammation has not been evaluated. Here we report that protein ISGylation exacerbates intestinal inflammation and colitis-associated colon cancer in mice. Mechanistically, we demonstrate that protein ISGylation negatively regulates the ubiquitin-proteasome system, leading to increased production of IFN-induced reactive oxygen species (ROS). The increased cellular ROS then enhances LPS-induced activation of p38 MAP kinase and the expression of inflammation-related cytokines in macrophages. Thus our studies reveal a regulatory role for protein ISGylation in colonic inflammation and its related malignant progression, indicating that targeting ubiquitin-activating enzyme E1 homolog has therapeutic potential in treating inflammatory diseases

    A metal-free organic–inorganic aqueous flow battery

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    As the fraction of electricity generation from intermittent renewable sources—such as solar or wind—grows, the ability to store large amounts of electrical energy is of increasing importance. Solid-electrode batteries maintain discharge at peak power for far too short a time to fully regulate wind or solar power output1,2^{1, 2}. In contrast, flow batteries can independently scale the power (electrode area) and energy (arbitrarily large storage volume) components of the system by maintaining all of the electro-active species in fluid form3,4,5^{3, 4, 5}. Wide-scale utilization of flow batteries is, however, limited by the abundance and cost of these materials, particularly those using redox-active metals and precious-metal electrocatalysts6,7^{6, 7}. Here we describe a class of energy storage materials that exploits the favourable chemical and electrochemical properties of a family of molecules known as quinones. The example we demonstrate is a metal-free flow battery based on the redox chemistry of 9,10-anthraquinone-2,7-disulphonic acid (AQDS). AQDS undergoes extremely rapid and reversible two-electron two-proton reduction on a glassy carbon electrode in sulphuric acid. An aqueous flow battery with inexpensive carbon electrodes, combining the quinone/hydroquinone couple with the Br2/BrBr_2/Br^- redox couple, yields a peak galvanic power density exceeding 0.6 W cm^{−2} at 1.3 A cm^{−2}. Cycling of this quinone–bromide flow battery showed >99 per cent storage capacity retention per cycle. The organic anthraquinone species can be synthesized from inexpensive commodity chemicals8^8. This organic approach permits tuning of important properties such as the reduction potential and solubility by adding functional groups: for example, we demonstrate that the addition of two hydroxy groups to AQDS increases the open circuit potential of the cell by 11% and we describe a pathway for further increases in cell voltage. The use of π-aromatic redox-active organic molecules instead of redox-active metals represents a new and promising direction for realizing massive electrical energy storage at greatly reduced cost.Chemistry and Chemical BiologyEngineering and Applied Science

    High quality and quantity Genome-wide germline genotypes from FFPE normal tissue

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    <p>Abstract</p> <p>Background</p> <p>Although collections of formalin fixed paraffin embedded (FFPE) samples exist, sometimes representing decades of stored samples, they have not typically been utilized to their full potential. Normal tissue from such samples would be extremely valuable for generation of genotype data for individuals who cannot otherwise provide a DNA sample.</p> <p>Findings</p> <p>We extracted DNA from normal tissue identified in FFPE tissue blocks from prostate surgery and obtained complete genome wide genotype data for over 500,000 SNP markers for these samples, and for DNA extracted from whole blood for 2 of the cases, for comparison.</p> <p>Four of the five FFPE samples of varying age and amount of tissue had identifiable normal tissue. We obtained good quality genotype data for between 89 and 99% of all SNP markers for the 4 samples from FFPE. Concordance rates of over 99% were observed for the 2 samples with DNA from both FFPE and from whole blood.</p> <p>Conclusions</p> <p>DNA extracted from normal FFPE tissue provides excellent quality and quantity genome-wide genotyping data representing germline DNA, sufficient for both linkage and association analyses. This allows genetic analysis of informative individuals who are no longer available for sampling in genetic studies.</p

    Peri-Abortion Contraceptive Choices of Migrant Chinese Women: A Retrospective Review of Medical Records

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    BACKGROUND: Migrant Asian women reportedly have low levels of contraceptive use and high rates of abortion in New Zealand. Chinese make up the largest proportion of migrant Asian in New Zealand. This study aimed to describe the contraceptive choices of Chinese women seeking abortion; to examine method choice in relation to demographic characteristics (including length of stay) and to determine whether Chinese women were over-represented among abortion clinic attendees. METHODS: Retrospective review of medical records at a public hospital abortion clinic involving 305 Chinese women. Previously collected data for European (n = 277) and Maori women (n = 128) were used for comparative analyses. Regression analyses explored correlates of contraceptive method choice. Population census data were used to calculate rates of clinic attendance across ethnic groups. RESULTS: Chinese women were not over-represented among clinic attendees, and had similar rates of contraceptive non-use pre-abortion as women in comparison groups. Use of the oral contraceptive pill by Chinese was lower pre-abortion than for other ethnic groups, but choice of this method post-abortion was similar for Chinese (46.9%, 95% CI 41-52.7) and European women (43.7%, 95% CI 37.8-49.7). Post-abortion choice of an intrauterine device did not differ significantly between Chinese (28.9%, 95% CI 23.8-34.3) and Maori women (37%, 95% CI 28.4-45.7), but was higher than uptake of this method by European women (21.7%, 95% CI 17-27.0). Age, parity and previous abortion were significant predictors of post-abortion method choice by Chinese women (p<0.05). CONCLUSIONS: Following contraceptive counseling at the clinic, Chinese women chose more effective contraceptive methods for use post-abortion than they had used previously. As the population of migrant Chinese in New Zealand continues to increase, strategies are urgently needed to provide new arrivals with appropriate information and advice about contraception and where to access it, so women can be better prepared to avoid unplanned pregnancy

    The frequency of osteogenic activities and the pattern of intermittence between periods of physical activity and sedentary behaviour affects bone mineral content: the cross-sectional NHANES study

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    BACKGROUND: Sedentary behaviours, defined as non exercising seated activities, have been shown to have deleterious effects on health. It has been hypothesised that too much sitting time can have a detrimental effect on bone health in youth. The aim of this study is to test this hypothesis by exploring the association between objectively measured volume and patterns of time spent in sedentary behaviours, time spent in specific screen-based sedentary pursuits and bone mineral content (BMC) accrual in youth. METHODS: NHANES 2005–2006 cycle data includes BMC of the femoral and spinal region via dual-energy X-ray absorptiometry (DEXA), assessment of physical activity and sedentary behaviour patterns through accelerometry, self reported time spent in screen based pursuits (watching TV and using a computer), and frequency of vigorous playtime and strengthening activities. Multiple regression analysis, stratified by gender was performed on N = 671 males and N = 677 females aged from 8 to 22 years. RESULTS: Time spent in screen-based sedentary behaviours is negatively associated with femoral BMC (males and females) and spinal BMC (females only) after correction for time spent in moderate and vigorous activity. Regression coefficients indicate that an additional hour per day of screen-based sitting corresponds to a difference of −0.77 g femoral BMC in females [95% CI: -1.31 to −0.22] and of −0.45 g femoral BMC in males [95% CI: -0.83 to −0.06]. This association is attenuated when self-reported engagement in regular (average 5 times per week) strengthening exercise (for males) and vigorous playing (for both males and females) is taken into account. Total sitting time and non screen-based sitting do not appear to have a negative association with BMC, whereas screen based sedentary time does. Patterns of intermittence between periods of sitting and moderate to vigorous activity appears to be positively associated with bone health when activity is clustered in time and inter-spaced with long continuous bouts of sitting. CONCLUSIONS: Some specific sedentary pursuits (screen-based) are negatively associated with bone health in youth. This association is specific to gender and anatomical area. This relationship between screen-based time and bone health is independent of the total amount of physical activity measured objectively, but not independent of self-reported frequency of strengthening and vigorous play activities. The data clearly suggests that the frequency, rather than the volume, of osteogenic activities is important in counteracting the effect of sedentary behaviour on bone health. The pattern of intermittence between sedentary periods and activity also plays a role in bone accrual, with clustered short bouts of activity interspaced with long periods of sedentary behaviours appearing to be more beneficial than activities more evenly spread in time
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