131 research outputs found

    Isotopic dependence of the giant monopole resonance in the even-A ^{112-124}Sn isotopes and the asymmetry term in nuclear incompressibility

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    The strength distributions of the giant monopole resonance (GMR) have been measured in the even-A Sn isotopes (A=112--124) with inelastic scattering of 400-MeV α\alpha particles in the angular range 00^\circ--8.58.5^\circ. We find that the experimentally-observed GMR energies of the Sn isotopes are lower than the values predicted by theoretical calculations that reproduce the GMR energies in 208^{208}Pb and 90^{90}Zr very well. From the GMR data, a value of Kτ=550±100K_{\tau} = -550 \pm 100 MeV is obtained for the asymmetry-term in the nuclear incompressibility.Comment: Submitted to Physical Review Letters. 10 pages; 4 figure

    Characterization of the thermal and photoinduced reactions of photochromic spiropyrans in aqueous solution

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    Six water-soluble spiropyran derivatives have been characterized with respect to the thermal and photoinduced reactions over a broad pH-interval. A comprehensive kinetic model was formulated including the spiro- and the merocyanine isomers, the respective protonated forms, and the hydrolysis products. The experimental studies on the hydrolysis reaction mechanism were supplemented by calculations using quantum mechanical (QM) models employing density functional theory. The results show that (1) the substitution pattern dramatically influences the pKa-values of the protonated forms as well as the rates of the thermal isomerization reactions, (2) water is the nucleophile in the hydrolysis reaction around neutral pH, (3) the phenolate oxygen of the merocyanine form plays a key role in the hydrolysis reaction. Hence, the nonprotonated merocyanine isomer is susceptible to hydrolysis, whereas the corresponding protonated form is stable toward hydrolytic degradation

    Circadian Clocks in Mouse and Human CD4+ T Cells

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    Though it has been shown that immunological functions of CD4+ T cells are time of day-dependent, the underlying molecular mechanisms remain largely obscure. To address the question whether T cells themselves harbor a functional clock driving circadian rhythms of immune function, we analyzed clock gene expression by qPCR in unstimulated CD4+ T cells and immune responses of PMA/ionomycin stimulated CD4+ T cells by FACS analysis purified from blood of healthy subjects at different time points throughout the day. Molecular clock as well as immune function was further analyzed in unstimulated T cells which were cultured in serum-free medium with circadian clock reporter systems. We found robust rhythms of clock gene expression as well as, after stimulation, IL-2, IL-4, IFN-γ production and CD40L expression in freshly isolated CD4+ T cells. Further analysis of IFN-γ and CD40L in cultivated T cells revealed that these parameters remain rhythmic in vitro. Moreover, circadian luciferase reporter activity in CD4+ T cells and in thymic sections from PER2::LUCIFERASE reporter mice suggest that endogenous T cell clock rhythms are self-sustained under constant culture conditions. Microarray analysis of stimulated CD4+ T cell cultures revealed regulation of the NF-κB pathway as a candidate mechanism mediating circadian immune responses. Collectively, these data demonstrate for the first time that CD4+ T cell responses are regulated by an intrinsic cellular circadian oscillator capable of driving rhythmic CD4+ T cell immune responses

    Short Telomeres Compromise β-Cell Signaling and Survival

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    The genetic factors that underlie the increasing incidence of diabetes with age are poorly understood. We examined whether telomere length, which is inherited and known to shorten with age, plays a role in the age-dependent increased incidence of diabetes. We show that in mice with short telomeres, insulin secretion is impaired and leads to glucose intolerance despite the presence of an intact β-cell mass. In ex vivo studies, short telomeres induced cell-autonomous defects in β-cells including reduced mitochondrial membrane hyperpolarization and Ca2+ influx which limited insulin release. To examine the mechanism, we looked for evidence of apoptosis but found no baseline increase in β-cells with short telomeres. However, there was evidence of all the hallmarks of senescence including slower proliferation of β-cells and accumulation of p16INK4a. Specifically, we identified gene expression changes in pathways which are essential for Ca2+-mediated exocytosis. We also show that telomere length is additive to the damaging effect of endoplasmic reticulum stress which occurs in the late stages of type 2 diabetes. This additive effect manifests as more severe hyperglycemia in Akita mice with short telomeres which had a profound loss of β-cell mass and increased β-cell apoptosis. Our data indicate that short telomeres can affect β-cell metabolism even in the presence of intact β-cell number, thus identifying a novel mechanism of telomere-mediated disease. They implicate telomere length as a determinant of β-cell function and diabetes pathogenesis

    Gene Expression Profiles of Beta-Cell Enriched Tissue Obtained by Laser Capture Microdissection from Subjects with Type 2 Diabetes

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    Background: Changes in gene expression in pancreatic beta-cells from type 2 diabetes (T2D) should provide insights into their abnormal insulin secretion and turnover. Methodology/Principal Findings: Frozen sections were obtained from cadaver pancreases of 10 control and 10 T2D human subjects. Beta-cell enriched samples were obtained by laser capture microdissection (LCM). RNA was extracted, amplified and subjected to microarray analysis. Further analysis was performed with DNA-Chip Analyzer (dChip) and Gene Set Enrichment Analysis (GSEA) software. There were changes in expression of genes linked to glucotoxicity. Evidence of oxidative stress was provided by upregulation of several metallothionein genes. There were few changes in the major genes associated with cell cycle, apoptosis or endoplasmic reticulum stress. There was differential expression of genes associated with pancreatic regeneration, most notably upregulation of members of the regenerating islet gene (REG) family and metalloproteinase 7 (MMP7). Some of the genes found in GWAS studies to be related to T2D were also found to be differentially expressed. IGF2BP2, TSPAN8, and HNF1B (TCF2) were upregulated while JAZF1 and SLC30A8 were downregulated. Conclusions/Significance: This study made possible by LCM has identified many novel changes in gene expression tha

    “Control-Alt-Delete”: Rebooting Solutions for the E-Waste Problem

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    A number of efforts have been launched to solve the global electronic waste (e-waste) problem. The efficiency of e-waste recycling is subject to variable national legislation, technical capacity, consumer participation, and even detoxification. E-waste management activities result in procedural irregularities and risk disparities across national boundaries. We review these variables to reveal opportunities for research and policy to reduce the risks from accumulating e-waste and ineffective recycling. Full regulation and consumer participation should be controlled and reinforced to improve local e-waste system. Aiming at standardizing best practice, we alter and identify modular recycling process and infrastructure in eco-industrial parks that will be expectantly effective in countries and regions to handle the similar e-waste stream. Toxicity can be deleted through material substitution and detoxification during the life cycle of electronics. Based on the idea of "Control-Alt-Delete", four patterns of the way forward for global e-waste recycling are proposed to meet a variety of local situations

    Models and measurements of energy-dependent quenching

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    Energy-dependent quenching (qE) in photosystem II (PSII) is a pH-dependent response that enables plants to regulate light harvesting in response to rapid fluctuations in light intensity. In this review, we aim to provide a physical picture for understanding the interplay between the triggering of qE by a pH gradient across the thylakoid membrane and subsequent changes in PSII. We discuss how these changes alter the energy transfer network of chlorophyll in the grana membrane and allow it to switch between an unquenched and quenched state. Within this conceptual framework, we describe the biochemical and spectroscopic measurements and models that have been used to understand the mechanism of qE in plants with a focus on measurements of samples that perform qE in response to light. In addition, we address the outstanding questions and challenges in the field. One of the current challenges in gaining a full understanding of qE is the difficulty in simultaneously measuring both the photophysical mechanism of quenching and the physiological state of the thylakoid membrane. We suggest that new experimental and modeling efforts that can monitor the many processes that occur on multiple timescales and length scales will be important for elucidating the quantitative details of the mechanism of qE

    Minimum Leadfield-Variance Beamformer with Voxel-Wise Orthonormal Leadfield

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    Abstract-In biomagnetic inverse problem, the estimated signal source distribution is practically required to provide with sharpness, smoothness, bias-free, high resolution, etc. Some of the requirements conflict each other. We propose the newly developed biomagnetic signal source estimation method, the minimum leadfield-variance beamformer (MLVB) with the voxel-wise orthonormal leadfield (VWOL) for compromising the requirements. This method consists of two techniques: VWOL) leadfields are reconstructed for orthonormalization both in signal source space and in MEG data space; and MLVB) the minimum variance beamformer (MVB) is modified with the covariance matrix based on forward model. Simulation was performed for evaluating MLVB with VWOL and for comparing with the weighted minimum L 2 norm (WMN) solution and the standardized low resolution brain electromagnetic tomography (sLORETA) solution. MLVB with VWOL solution was shaper and smoother than WMN solution, and moreover was bias-free. However, MLVB with VWOL dose not produce feasible solutions. Although MLVB with VWOL solution is quite similar to sLORETA solution, MLVB with VWO is apt to slightly emphasize the resolution of the estimated signal source distribution comparing with sLORETA solution. On the other hand, VWOL itself, a modified leadfields, can be used with other biomagnetic inverse techniques. Keywords-biomagnetic inverse problem, leadfield, magnetoencephalography, minimum norm estimation, minimum variance beamformer, standardized low resolution brain electromagnetic tomography
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