315 research outputs found

    Constructing Dirac linear fermions in terms of non-linear Heisenberg spinors

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    We show that the massive (or massless) neutrinos can be described as special states of Heisenberg nonlinear spinors. As a by-product of this decomposition a particularly attractive consequence appears: the possibility of relating the existence of only three species of mass-less neutrinos to such internal non-linear structure. At the same time it allows the possibility that neutrino oscillation can occurs even for massless neutrinos

    TEV GAMMA-RAYS FROM PROTON BLAZARS

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    Proton acceleration in nearby blazars can be diagnosed measuring their intense TeV γ\gamma-ray emission. Flux predictions for 1101+384 (Mrk421) and 1219+285 (ON231), both strong EGRET sources (0.1-10 GeV), are obtained from model spectra of unsaturated synchrotron pair cascades fitted to publicly available multifrequency data. An experimental effort to confirm the predicted emission in the range 1-10 TeV would be of great importance for the problems of the origin of cosmic rays, the era of galaxy formation and the cosmological distance scale.Comment: 10 pages of latex using Kluwer spacekap.sty, to appear in Space Science Review

    “A Hideous Torture on Himself”: Madness and Self-Mutilation in Victorian Literature

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    This paper suggests that late nineteenth-century definitions of self-mutilation, a new category of psychiatric symptomatology, were heavily influenced by the use of selfinjury as a rhetorical device in the novel, for the literary text held a high status in Victorian psychology. In exploring Dimmesdale’s “self-mutilation” in The Scarlet Letter in conjunction with psychiatric case histories, the paper indicates a number of common techniques and themes in literary and psychiatric texts. As well as illuminating key elements of nineteenth-century conceptions of the self, and the relation of mind and body through ideas of madness, this exploration also serves to highlight the social commentary implicit in many Victorian medical texts. Late nineteenth-century England, like mid-century New England, required the individual to help himself and, simultaneously, others; personal charity and individual philanthropy were encouraged, while state intervention was often presented as dubious. In both novel and psychiatric text, self-mutilation is thus presented as the ultimate act of selfish preoccupation, particularly in cases on the “borderlands” of insanity

    Cyclodextrin Induces Calcium-Dependent Lysosomal Exocytosis

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    Cyclodextrins (CDs) have long been used to manipulate cellular cholesterol levels both in vitro and in vivo, but their direct effects at a cellular level are not well characterized. Recently, CDs have garnered much interest because of their ability to clear stored cholesterol from Niemann Pick Type C (NPC) cells and markedly prolong the life of NPC1 disease mice. Here, we investigate the hypothesis that treatment with 2-hydroxypropyl- β-cyclodextrin (HPB-CD) stimulates lysosomal exocytosis in a calcium-enhanced manner. We propose that this exocytosis is the mechanism by which HPB-CD ameliorates the endolysosomal cholesterol storage phenotype in NPC cells. These findings have significant implications for the use of HPB-CD in biochemical assays and data interpretation as well as for their use for the treatment for NPC and other disorders

    Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

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    The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

    Computational and mathematical approaches to societal transitions

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    After an introduction of the theoretical framework and concepts of transition studies, this article gives an overview of how structural change in social systems has been studied from various disciplinary perspectives. This overview first leads to the conclusion that computational and mathematical approaches and their practical form, modeling, up till now, have been almost absent in the research and theorizing of structural change or transitions in social systems. Second, this review of the social science literature suggests numerous theoretical constructs relevant for transition modeling. Relevant concepts include the conceptualization of the micro-to-macro link, the importance of explaining both stability and change, quantitative and qualitative definitions of structural change, the use of dichotomies, synchronic and diachronic reasoning in explaining structural change, definitions of basic patterns of social change, the conceptualization of resistance to change and intentional and normative aspects of social change. This article employs these theoretical concepts to describe and discuss the models presented in this special issue in order to develop an understanding of what exactly entails a computational or mathematical approach to societal transitions

    Estrus cyclicity of spinogenesis: underlying mechanisms

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    Hippocampal spine density varies with the estrus cycle. The cyclic change in estradiol levels in serum was hypothesized to underlie this phenomenon, since treatment of ovariectomized animals with estradiol induced an increase in spine density in hippocampal dendrites of rats, as compared to ovariectomized controls. In contrast, application of estradiol to hippocampal slice cultures did not promote spinogenesis. In addressing this discrepancy, we found that hippocampal neurons themselves are capable of synthesizing estradiol de novo. Estradiol synthesis can be suppressed by aromatase inhibitors and by knock-down of Steroid Acute Regulatory Protein (StAR) and enhanced by substrates of steroidogenesis. Expression of estrogen receptors (ERs) and synaptic proteins, synaptogenesis, and long-term potentiation (LTP) correlated positively with aromatase activity in hippocampal cultures without any difference between genders. All effects due to inhibition of aromatase activity were rescued by application of estradiol to the cultures. Most importantly, gonadotropin-releasing hormone (GnRH) increased estradiol synthesis dose-dependently via an aromatase-mediated mechanism and consistently increased spine synapse density and spinophilin expression. As a consequence, our data suggest that cyclic fluctuations in spine synapse density result from pulsative release of GnRH from the hypothalamus and its effect on hippocampal estradiol synthesis, rather than from varying levels of serum estradiol. This hypothesis is further supported by higher GnRH receptor (GnRH-R) density in the hippocampus than in the cortex and hypothalamus and the specificity of estrus cyclicity of spinogenesis in the hippocampus, as compared to the cortex

    Chronic Cyclodextrin Treatment of Murine Niemann-Pick C Disease Ameliorates Neuronal Cholesterol and Glycosphingolipid Storage and Disease Progression

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    BACKGROUND:Niemann-Pick type C (NPC) disease is a fatal neurodegenerative disorder caused most commonly by a defect in the NPC1 protein and characterized by widespread intracellular accumulation of unesterified cholesterol and glycosphingolipids (GSLs). While current treatment therapies are limited, a few drugs tested in Npc1(-/-) mice have shown partial benefit. During a combination treatment trial using two such compounds, N-butyldeoxynojirimycin (NB-DNJ) and allopregnanolone, we noted increased lifespan for Npc1(-/-) mice receiving only 2-hydroxypropyl-beta-cyclodextrin (CD), the vehicle for allopregnanolone. This finding suggested that administration of CD alone, but with greater frequency, might provide additional benefit. METHODOLOGY/PRINCIPAL FINDINGS:Administration of CD to Npc1(-/-) mice beginning at either P7 or P21 and continuing every other day delayed clinical onset, reduced intraneuronal cholesterol and GSL storage as well as free sphingosine accumulation, reduced markers of neurodegeneration, and led to longer survival than any previous treatment regime. We reasoned that other lysosomal diseases characterized by cholesterol and GSL accumulation, including NPC disease due to NPC2 deficiency, GM1 gangliosidosis and mucopolysaccharidosis (MPS) type IIIA, might likewise benefit from CD treatment. Treated Npc2(-/-) mice showed benefits similar to NPC1 disease, however, mice with GM1 gangliosidosis or MPS IIIA failed to show reduction in storage. CONCLUSIONS/SIGNIFICANCE:Treatment with CD delayed clinical disease onset, reduced intraneuronal storage and secondary markers of neurodegeneration, and significantly increased lifespan of both Npc1(-/-) and Npc2(-/-) mice. In contrast, CD failed to ameliorate cholesterol or glycosphingolipid storage in GM1 gangliosidosis and MPS IIIA disease. Understanding the mechanism(s) by which CD leads to reduced neuronal storage may provide important new opportunities for treatment of NPC and related neurodegenerative diseases characterized by cholesterol dyshomeostasis
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