369 research outputs found

    Density fluctuations and the structure of a nonuniform hard sphere fluid

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    We derive an exact equation for density changes induced by a general external field that corrects the hydrostatic approximation where the local value of the field is adsorbed into a modified chemical potential. Using linear response theory to relate density changes self-consistently in different regions of space, we arrive at an integral equation for a hard sphere fluid that is exact in the limit of a slowly varying field or at low density and reduces to the accurate Percus-Yevick equation for a hard core field. This and related equations give accurate results for a wide variety of fields

    Stage-specific control of oligodendrocyte survival and morphogenesis by TDP-43

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    Generation of oligodendrocytes in the adult brain enables both adaptive changes in neural circuits and regeneration of myelin sheaths destroyed by injury, disease, and normal aging. This transformation of oligodendrocyte precursor cells (OPCs) into myelinating oligodendrocytes requires processing of distinct mRNAs at different stages of cell maturation. Although mislocal- ization and aggregation of the RNA-binding protein, TDP-43, occur in both neurons and glia in neurodegenerative diseases, the consequences of TDP-43 loss within different stages of the oligo- dendrocyte lineage are not well understood. By performing stage-specific genetic inactivation of Tardbp in vivo, we show that oligodendrocyte lineage cells are differentially sensitive to loss of TDP- 43. While OPCs depend on TDP-43 for survival, with conditional deletion resulting in cascading cell loss followed by rapid regeneration to restore their density, oligodendrocytes become less sensitive to TDP-43 depletion as they mature. Deletion of TDP-43 early in the maturation process led to even- tual oligodendrocyte degeneration, seizures, and premature lethality, while oligodendrocytes that experienced late deletion survived and mice exhibited a normal lifespan. At both stages, TDP-43- deficient oligodendrocytes formed fewer and thinner myelin sheaths and extended new processes that inappropriately wrapped neuronal somata and blood vessels. Transcriptional analysis revealed that in the absence of TDP-43, key proteins involved in oligodendrocyte maturation and myelination were misspliced, leading to aberrant incorporation of cryptic exons. Inducible deletion of TDP-43 from oligodendrocytes in the adult central nervous system (CNS) induced the same progressive morphological changes and mice acquired profound hindlimb weakness, suggesting that loss of TDP-43 function in oligodendrocytes may contribute to neuronal dysfunction in neurodegenerative disease

    Theory and simulation of short-range models of globular protein solutions

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    We report theoretical and simulation studies of phase coexistence in model globular protein solutions, based on short-range, central, pair potential representations of the interaction among macro-particles. After reviewing our previous investigations of hard-core Yukawa and generalised Lennard-Jones potentials, we report more recent results obtained within a DLVO-like description of lysozyme solutions in water and added salt. We show that a one-parameter fit of this model based on Static Light Scattering and Self-Interaction Chromatography data in the dilute protein regime, yields demixing and crystallization curves in good agreement with experimental protein-rich/protein-poor and solubility envelopes. The dependence of cloud and solubility points temperature of the model on the ionic strength is also investigated. Our findings highlight the minimal assumptions on the properties of the microscopic interaction sufficient for a satisfactory reproduction of the phase diagram topology of globular protein solutions.Comment: 17 pages, 8 figures, Proc. of Conference "Structural Arrest Transitions in Colloidal Systems with Short-Range Attractions", Messina (ITALY) 17-20 December 200

    Качество статистической информации о причинах смерти в Российской Федерации

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    The authors of this article quality assessment of the information collected in the Russian Federation on population mortality in order to ensure reliability and international comparability of data of the important section of demographic statistics. The study was conducted within the framework of the tasks in reforming information support of the implementation of the Russian healthcare modernization program aimed, in particular, at changing the unfavorable trends in morbidity and mortality, which play a major role in the current demographic situation.Авторами статьи дана оценка качества собираемой в Российской Федерации информации о смертности населения с целью обеспечения достоверности и международной сопоставимости данных важного раздела демографической статистики. Исследование осуществлено в рамках задачи реформирования информационного обеспечения реализации российской Программы модернизации здравоохранения, направленной, в частности, и на изменение неблагоприятных тенденций в заболеваемости и смертности, которые играют большую роль в существующей демографической ситуации

    Genotoxic agents promote the nuclear accumulation of annexin A2: role of annexin A2 in mitigating DNA damage

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    Annexin A2 is an abundant cellular protein that is mainly localized in the cytoplasm and plasma membrane, however a small population has been found in the nucleus, suggesting a nuclear function for the protein. Annexin A2 possesses a nuclear export sequence (NES) and inhibition of the NES is sufficient to cause nuclear accumulation. Here we show that annexin A2 accumulates in the nucleus in response to genotoxic agents including gamma-radiation, UV radiation, etoposide and chromium VI and that this event is mediated by the nuclear export sequence of annexin A2. Nuclear accumulation of annexin A2 is blocked by the antioxidant agent N-acetyl cysteine (NAC) and stimulated by hydrogen peroxide (H2O2), suggesting that this is a reactive oxygen species dependent event. In response to genotoxic agents, cells depleted of annexin A2 show enhanced phospho-histone H2AX and p53 levels, increased numbers of p53-binding protein 1 nuclear foci and increased levels of nuclear 8-oxo-2'-deoxyguanine, suggesting that annexin A2 plays a role in protecting DNA from damage. This is the first report showing the nuclear translocation of annexin A2 in response to genotoxic agents and its role in mitigating DNA damage.Natural Sciences and Engineering Research Council of Canada (NSERC); European Union [PCOFUND-GA-2009-246542]; Foundation for Science and Technology of Portugal; Beatrice Hunter Cancer Research Institute; Terry Fox Foundationinfo:eu-repo/semantics/publishedVersio

    Cauda equina entrapment in a pseudomeningocele after lumbar Schwannoma extirpation

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    Incidental or intentional durotomy causing cerebrospinal fluid (CSF) leakage, leading to the formation of a pseudomeningocele is a known complication in spinal surgery. Herniation of nerve roots into such a pseudomeningocele is very rare, but can occur up to years after initial durotomy and has been described to cause permanent neurologic deficit. However, cauda equina fiber herniation and entrapment into a pseudomeningocele has not been reported before. Here, we present a case of symptomatic transdural cauda equina herniation and incarceration into a pseudomeningocele, 3 months after extirpation of a lumbar Schwannoma. A 59-year-old man, who previously underwent intradural Schwannoma extirpation presented 3 months after surgery with back pain, sciatica and loss of bladder filling sensation caused by cauda equina fiber entrapment into a defect in the wall of a pseudomeningocele, diagnosed with magnetic resonance imaging. On re-operation, the pseudomeningocele was resected and the herniated and entrapped cauda fibers were released and replaced intradurally. The dura defect was closed and the patient recovered completely. In conclusion, CSF leakage can cause neurological deficit up to years after durotomy by transdural nerve root herniation and subsequent entrapment. Clinicians should be aware of the possibility of this potentially devastating complication. The present case also underlines the importance of meticulous dura closure in spinal surgery

    Theoretical description of phase coexistence in model C60

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    We have investigated the phase diagram of the Girifalco model of C60 fullerene in the framework provided by the MHNC and the SCOZA liquid state theories, and by a Perturbation Theory (PT), for the free energy of the solid phase. We present an extended assessment of such theories as set against a recent Monte Carlo study of the same model [D. Costa et al, J. Chem. Phys. 118:304 (2003)]. We have compared the theoretical predictions with the corresponding simulation results for several thermodynamic properties. Then we have determined the phase diagram of the model, by using either the SCOZA, or the MHNC, or the PT predictions for one of the coexisting phases, and the simulation data for the other phase, in order to separately ascertain the accuracy of each theory. It turns out that the overall appearance of the phase portrait is reproduced fairly well by all theories, with remarkable accuracy as for the melting line and the solid-vapor equilibrium. The MHNC and SCOZA results for the liquid-vapor coexistence, as well as for the corresponding critical points, are quite accurate. All results are discussed in terms of the basic assumptions underlying each theory. We have selected the MHNC for the fluid and the first-order PT for the solid phase, as the most accurate tools to investigate the phase behavior of the model in terms of purely theoretical approaches. The overall results appear as a robust benchmark for further theoretical investigations on higher order C(n>60) fullerenes, as well as on other fullerene-related materials, whose description can be based on a modelization similar to that adopted in this work.Comment: RevTeX4, 15 pages, 7 figures; submitted to Phys. Rev.

    The liquid-vapor interface of an ionic fluid

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    We investigate the liquid-vapor interface of the restricted primitive model (RPM) for an ionic fluid using a density-functional approximation based on correlation functions of the homogeneous fluid as obtained from the mean-spherical approximation (MSA). In the limit of a homogeneous fluid our approach yields the well-known MSA (energy) equation of state. The ionic interfacial density profiles, which for the RPM are identical for both species, have a shape similar to those of simple atomic fluids in that the decay towards the bulk values is more rapid on the vapor side than on the liquid side. This is the opposite asymmetry of the decay to that found in earlier calculations for the RPM based on a square-gradient theory. The width of the interface is, for a wide range of temperatures, approximately four times the second moment correlation length of the liquid phase. We discuss the magnitude and temperature dependence of the surface tension, and argue that for temperatures near the triple point the ratio of the dimensionless surface tension and critical temperature is much smaller for the RPM than for simple atomic fluids.Comment: 6 postscript figures, submitted to Phys. Rev.

    Nonergodicity transitions in colloidal suspensions with attractive interactions

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    The colloidal gel and glass transitions are investigated using the idealized mode coupling theory (MCT) for model systems characterized by short-range attractive interactions. Results are presented for the adhesive hard sphere and hard core attractive Yukawa systems. According to MCT, the former system shows a critical glass transition concentration that increases significantly with introduction of a weak attraction. For the latter attractive Yukawa system, MCT predicts low temperature nonergodic states that extend to the critical and subcritical region. Several features of the MCT nonergodicity transition in this system agree qualitatively with experimental observations on the colloidal gel transition, suggesting that the gel transition is caused by a low temperature extension of the glass transition. The range of the attraction is shown to govern the way the glass transition line traverses the phase diagram relative to the critical point, analogous to findings for the fluid-solid freezing transition.Comment: 11 pages, 7 figures; to be published in Phys. Rev. E (1 May 1999
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