188 research outputs found

    On a Classical, Geometric Origin of Magnetic Moments, Spin-Angular Momentum and the Dirac Gyromagnetic Ratio

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    By treating the real Maxwell Field and real linearized Einstein equations as being imbedded in complex Minkowski space, one can interpret magnetic moments and spin-angular momentum as arising from a charge and mass monopole source moving along a complex world line in the complex Minkowski space. In the circumstances where the complex center of mass world-line coincides with the complex center of charge world-line, the gyromagnetic ratio is that of the Dirac electron.Comment: 17 page

    Lack of IL‐6 augments inflammatory response but decreases vascular permeability in bacterial meningitis

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    Interleukin (IL)‐6 is a multifunctional cytokine with diverse actions and has been implicated in the pathophysiology of many neurological and inflammatory disorders. In this study, we investigated the role of IL‐6 in pneumococcal meningitis. Cerebral infection in wild‐type (WT) mice caused an increase in vascular permeability and intracranial pressure (ICP), which were significantly reduced in IL‐6-/- mice. In contrast, meningitis in IL‐6-/- mice was associated with a significant increase in CSF white blood cell count compared with infected WT mice, indicating an enhanced inflammatory response. Analysis of mRNA expression in the brain showed an increase in tumour necrosis factor (TNF)‐α, IL‐1β, and macrophage inflammatory protein 2 (MIP‐2) levels, but decreased expression of granulocyte-macrophage colony‐stimulating factor in infected IL‐6-/- mice compared with infected WT controls. Similar results were obtained when rats challenged with pneumococci were systemically treated with neutralizing anti‐IL‐6 antibodies, resulting in an increased pleocytosis but at the same time a reduction of vascular permeability, brain oedema formation, and ICP, which was not accompanied by a downregulation of matrix metalloproteinases. Our data indicate that IL‐6 plays an important anti‐inflammatory role in bacterial meningitis by reducing leukocyte infiltration but contributes to the rise in intracranial pressure by increasing blood-brain barrier (BBB) permeability. These findings suggest that the migration of leukocytes across the BBB and the increase in vascular permeability are two independent processes during bacterial meningiti

    Planning, implementation and scientific goals of the Studies of Emissions and Atmospheric Composition, Clouds and Climate Coupling by Regional Surveys (SEAC4RS) field mission

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    The Studies of Emissions and Atmospheric Composition, Clouds and Climate Coupling by Regional Surveys (SEAC4RS) field mission based at Ellington Field, Texas, during August and September 2013 employed the most comprehensive airborne payload to date to investigate atmospheric composition over North America. The NASA ER-2, DC-8, and SPEC Inc. Learjet flew 57 science flights from the surface to 20 km. The ER-2 employed seven remote sensing instruments as a satellite surrogate and eight in situ instruments. The DC-8 employed 23 in situ and five remote sensing instruments for radiation, chemistry, and microphysics. The Learjet used 11 instruments to explore cloud microphysics. SEAC4RS launched numerous balloons, augmented AErosol RObotic NETwork, and collaborated with many existing ground measurement sites. Flights investigating convection included close coordination of all three aircraft. Coordinated DC-8 and ER-2 flights investigated the optical properties of aerosols, the influence of aerosols on clouds, and the performance of new instruments for satellite measurements of clouds and aerosols. ER-2 sorties sampled stratospheric injections of water vapor and other chemicals by local and distant convection. DC-8 flights studied seasonally evolving chemistry in the Southeastern U.S., atmospheric chemistry with lower emissions of NOx and SO2 than in previous decades, isoprene chemistry under high and low NOx conditions at different locations, organic aerosols, air pollution near Houston and in petroleum fields, smoke from wildfires in western forests and from agricultural fires in the Mississippi Valley, and the ways in which the chemistry in the boundary layer and the upper troposphere were influenced by vertical transport in convective clouds

    Gentle Perturbations of the Free Bose Gas I

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    It is demonstrated that the thermal structure of the noncritical free Bose Gas is completely described by certain periodic generalized Gaussian stochastic process or equivalently by certain periodic generalized Gaussian random field. Elementary properties of this Gaussian stochastic thermal structure have been established. Gentle perturbations of several types of the free thermal stochastic structure are studied. In particular new models of non-Gaussian thermal structures have been constructed and a new functional integral representation of the corresponding euclidean-time Green functions have been obtained rigorously.Comment: 51 pages, LaTeX fil

    N-Glycosylation of Carnosinase Influences Protein Secretion and Enzyme Activity: Implications for Hyperglycemia

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    OBJECTIVE-The (CTG)(n) polymorphism in the serum carnosinase (CN-1) gene affects CN-1 secretion Since CN-1 is heavily glycosylated and glycosylation might influence protein secretion as well, we tested the role of N-glycosylation for CN-1 secretion and enzyme activity. We also tested whether CN-1 secretion is changed under hyperglycemic conditions. RESULTS-N-glycosylation of CN-1 was either inhibited by tunicamycin in pCSII-CN-1-transfected Cos-7 cells or by stepwise deletion of its three putative N-glycosylation sites. CN-1 protein expression, N-glycosylation, and enzyme activity were assessed in cell extracts and supernatants. The influence of hyperglycemia on CN-1 enzyme activity in human serum was tested in homozygous (CTG)(5) diabetic patients and healthy control subjects Tunicamycin completely inhibited CN-1 secretion Deletion of all N-glycosylation sites was required to reduce CN-1 secretion efficiency. Enzyme activity was already diminished when two sites were deleted. In pCSII-CN-1-transfected Cos-7 cells cultured in medium containing 25 mmol/l D-glucose, the immature 61 kilodaltons (kDa) CN-1 immune reactive band was not detected. This was paralleled by an increased GlcNAc expression in cell lysates and CN-1 expression in the supernatants. Homozygous (CTG)(5) diabetic patients had significantly higher serum CN-1 activity compared with genotype-matched, healthy control subjects CONCLUSIONS-We conclude that apart from the (CTG)(n) polymorphism in the signal peptide of CN-1, N-glycosylation is essential for appropriate secretion and enzyme activity. Since hyperglycemia enhances CN-1 secretion and enzyme activity, our data suggest that poor blood glucose control in diabetic patients might result in an increased CN-1 secretion even in the presence of the (CTG)(5) allele Diabetes 59:1984-1990, 201

    Outcome of preterm twins compared to preterm singleton neonates, a multicenter prospective observational study in Ethiopia

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    Background: In recent decades there has been a major increase in multiple birth rates, and the rate of twining vary from 6-9 per thousand life births to 20 per thousand live births across differ-ent areas of the world. Many studies have demonstrated higher neonatal and perinatal mortality and morbidity rates in twin deliveries compared to singleton births. This study was aimed to com-pare the outcomes of preterm twins and preterm singletons.Methods: A prospective, observational multicenter study was conducted from July 2016 to May 2018 in five tertiary hospitals in Ethiopia. All preterm, liveborn infants born at or transferred at less than 7 days of life to one of the study hospitals with an estimated gestational age below 37 weeks were included.Results: A total of 3,703 preterm neonates admitted to participating neonatal intensive care units were included in the study, of which 1171(31.6%) were twins. After adjusting for birth weight and gestational age, the mortality rate for preterm singletons of 31.0% was higher than the mortality rate for preterm twins of 24.8%, which was statistically significant (p-value = 0.001), OR of 1.37 (95% CI: 1.15 to 1.64). The study also identified an inverse relationship between birth weight and gestational age, and mortality. Male singletons were more likely to die than male twins (440 (32.4%) vs. 141 (23.4%); AOR 1.56 (95% CI: 1.22, 1.99); p=0.001)Conclusion: Our study showed that the mortality of a singleton preterm infant was significantly higher than the mortality of a preterm twin infan

    Mendelian randomization study of B-type natriuretic peptide and type 2 diabetes: evidence of causal association from population studies

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    <p>Background: Genetic and epidemiological evidence suggests an inverse association between B-type natriuretic peptide (BNP) levels in blood and risk of type 2 diabetes (T2D), but the prospective association of BNP with T2D is uncertain, and it is unclear whether the association is confounded.</p> <p>Methods and Findings: We analysed the association between levels of the N-terminal fragment of pro-BNP (NT-pro-BNP) in blood and risk of incident T2D in a prospective case-cohort study and genotyped the variant rs198389 within the BNP locus in three T2D case-control studies. We combined our results with existing data in a meta-analysis of 11 case-control studies. Using a Mendelian randomization approach, we compared the observed association between rs198389 and T2D to that expected from the NT-pro-BNP level to T2D association and the NT-pro-BNP difference per C allele of rs198389. In participants of our case-cohort study who were free of T2D and cardiovascular disease at baseline, we observed a 21% (95% CI 3%-36%) decreased risk of incident T2D per one standard deviation (SD) higher log-transformed NT-pro-BNP levels in analysis adjusted for age, sex, body mass index, systolic blood pressure, smoking, family history of T2D, history of hypertension, and levels of triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The association between rs198389 and T2D observed in case-control studies (odds ratio = 0.94 per C allele, 95% CI 0.91-0.97) was similar to that expected (0.96, 0.93-0.98) based on the pooled estimate for the log-NT-pro-BNP level to T2D association derived from a meta-analysis of our study and published data (hazard ratio = 0.82 per SD, 0.74-0.90) and the difference in NT-pro-BNP levels (0.22 SD, 0.15-0.29) per C allele of rs198389. No significant associations were observed between the rs198389 genotype and potential confounders.</p> <p>Conclusions: Our results provide evidence for a potential causal role of the BNP system in the aetiology of T2D. Further studies are needed to investigate the mechanisms underlying this association and possibilities for preventive interventions.</p&gt

    The unexpected resurgence of Weyl geometry in late 20-th century physics

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    Weyl's original scale geometry of 1918 ("purely infinitesimal geometry") was withdrawn by its author from physical theorizing in the early 1920s. It had a comeback in the last third of the 20th century in different contexts: scalar tensor theories of gravity, foundations of gravity, foundations of quantum mechanics, elementary particle physics, and cosmology. It seems that Weyl geometry continues to offer an open research potential for the foundations of physics even after the turn to the new millennium.Comment: Completely rewritten conference paper 'Beyond Einstein', Mainz Sep 2008. Preprint ELHC (Epistemology of the LHC) 2017-02, 92 pages, 1 figur

    Proteomic analysis of the Plasmodium male gamete reveals the key role for glycolysis in flagellar motility.

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    BACKGROUND: Gametogenesis and fertilization play crucial roles in malaria transmission. While male gametes are thought to be amongst the simplest eukaryotic cells and are proven targets of transmission blocking immunity, little is known about their molecular organization. For example, the pathway of energy metabolism that power motility, a feature that facilitates gamete encounter and fertilization, is unknown. METHODS: Plasmodium berghei microgametes were purified and analysed by whole-cell proteomic analysis for the first time. Data are available via ProteomeXchange with identifier PXD001163. RESULTS: 615 proteins were recovered, they included all male gamete proteins described thus far. Amongst them were the 11 enzymes of the glycolytic pathway. The hexose transporter was localized to the gamete plasma membrane and it was shown that microgamete motility can be suppressed effectively by inhibitors of this transporter and of the glycolytic pathway. CONCLUSIONS: This study describes the first whole-cell proteomic analysis of the malaria male gamete. It identifies glycolysis as the likely exclusive source of energy for flagellar beat, and provides new insights in original features of Plasmodium flagellar organization

    Degradation of p53 by Human Alphapapillomavirus E6 Proteins Shows a Stronger Correlation with Phylogeny than Oncogenicity

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    Human Papillomavirus (HPV) E6 induced p53 degradation is thought to be an essential activity by which high-risk human Alphapapillomaviruses (alpha-HPVs) contribute to cervical cancer development. However, most of our understanding is derived from the comparison of HPV16 and HPV11. These two viruses are relatively distinct viruses, making the extrapolation of these results difficult. In the present study, we expand the tested strains (types) to include members of all known HPV species groups within the Alphapapillomavirus genus.We report the biochemical activity of E6 proteins from 27 HPV types representing all alpha-HPV species groups to degrade p53 in human cells. Expression of E6 from all HPV types epidemiologically classified as group 1 carcinogens significantly reduced p53 levels. However, several types not associated with cancer (e.g., HPV53, HPV70 and HPV71) were equally active in degrading p53. HPV types within species groups alpha 5, 6, 7, 9 and 11 share a most recent common ancestor (MRCA) and all contain E6 ORFs that degrade p53. A unique exception, HPV71 E6 ORF that degraded p53 was outside this clade and is one of the most prevalent HPV types infecting the cervix in a population-based study of 10,000 women. Alignment of E6 ORFs identified an amino acid site that was highly correlated with the biochemical ability to degrade p53. Alteration of this amino acid in HPV71 E6 abrogated its ability to degrade p53, while alteration of this site in HPV71-related HPV90 and HPV106 E6s enhanced their capacity to degrade p53.These data suggest that the alpha-HPV E6 proteins' ability to degrade p53 is an evolved phenotype inherited from a most recent common ancestor of the high-risk species that does not always segregate with carcinogenicity. In addition, we identified an amino-acid residue strongly correlated with viral p53 degrading potential
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