181 research outputs found

    Statistics of non-linear stochastic dynamical systems under L\'evy noises by a convolution quadrature approach

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    This paper describes a novel numerical approach to find the statistics of the non-stationary response of scalar non-linear systems excited by L\'evy white noises. The proposed numerical procedure relies on the introduction of an integral transform of Wiener-Hopf type into the equation governing the characteristic function. Once this equation is rewritten as partial integro-differential equation, it is then solved by applying the method of convolution quadrature originally proposed by Lubich, here extended to deal with this particular integral transform. The proposed approach is relevant for two reasons: 1) Statistics of systems with several different drift terms can be handled in an efficient way, independently from the kind of white noise; 2) The particular form of Wiener-Hopf integral transform and its numerical evaluation, both introduced in this study, are generalizations of fractional integro-differential operators of potential type and Gr\"unwald-Letnikov fractional derivatives, respectively.Comment: 20 pages, 5 figure

    Multiple and interpersonal trauma are risk factors for both post?traumatic stress disorder and borderline personality disorder: A systematic review on the traumatic backgrounds and clinical characteristics of comorbid post?traumatic stress disorder/borderline personality disorder groups versus single?disorder groups

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    Background: Both BPD and PTSD are associated with exposure to traumatic events and are highly comorbid. No review to date has addressed the clinical presentations and traumatic backgrounds associated with these disorders although this work is essential for the development of effective interventions.Objectives: To systematically explore similarities and differences in traumatic history and clinical presentation in comorbid BPD and PTSD as compared to PTSD or BPD alone.Method: The Web of Science, Cochrane Library, PsychInfo, Medline, and PILOTS databases were searched systematically. Eligible studies included adult populations, compared comorbid BPD/PTSD to a single disorder, and published in English.Results: 10,147 cases across 33 studies were included; 2057 comorbid BPD/PTSD, 2648 BPD only, and 5442 PTSD only. The comorbid group overall reported greater exposure to multiple and interpersonal trauma and elevated emotion dysregulation compared to both single disorder groups. In terms of methodological quality, most papers achieved a Fair rating with improvements required in minimising bias through recruiting adequate and representative samples, and reporting on traumatic exposure.Conclusion: Multiple and interpersonal trauma might have a unique role in the development of comorbid BPD/PTSD features, particularly so for emotion dysregulation. Future research is required to unravel the unique characteristics of interpersonal trauma that can generate BPD and PTSD symptoms.Practitioner Points• Practitioners should routinely assess for interpersonal trauma considering its impact• Tackling emotional regulation difficulties might promote recovery from both PTSD and BPD symptoms• Presence of self-injury might be used to discriminate between PTSD and BPD and offer suitable intervention

    Deconstructing the Late Phase of Vimentin Assembly by Total Internal Reflection Fluorescence Microscopy (TIRFM)

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    Quantitative imaging of intermediate filaments (IF) during the advanced phase of the assembly process is technically difficult, since the structures are several µm long and therefore they exceed the field of view of many electron (EM) or atomic force microscopy (AFM) techniques. Thereby quantitative studies become extremely laborious and time-consuming. To overcome these difficulties, we prepared fluorescently labeled vimentin for visualization by total internal reflection fluorescence microscopy (TIRFM). In order to investigate if the labeling influences the assembly properties of the protein, we first determined the association state of unlabeled vimentin mixed with increasing amounts of labeled vimentin under low ionic conditions by analytical ultracentrifugation. We found that bona fide tetrameric complexes were formed even when half of the vimentin was labeled. Moreover, we demonstrate by quantitative atomic force microscopy and electron microscopy that the morphology and the assembly properties of filaments were not affected when the fraction of labeled vimentin was below 10%. Using fast frame rates we observed the rapid deposition of fluorescently labeled IFs on glass supports by TIRFM in real time. By tracing their contours, we have calculated the persistence length of long immobilized vimentin IFs to 1 µm, a value that is identical to those determined for shorter unlabeled vimentin. These results indicate that the structural properties of the filaments were not affected significantly by the dye. Furthermore, in order to analyze the late elongation phase, we mixed long filaments containing either Alexa 488- or Alexa 647-labeled vimentin. The ‘patchy’ structure of the filaments obtained unambiguously showed the elongation of long IFs through direct end-to-end annealing of individual filaments

    Withaferin A Alters Intermediate Filament Organization, Cell Shape and Behavior

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    Withaferin A (WFA) is a steroidal lactone present in Withania somnifera which has been shown in vitro to bind to the intermediate filament protein, vimentin. Based upon its affinity for vimentin, it has been proposed that WFA can be used as an anti-tumor agent to target metastatic cells which up-regulate vimentin expression. We show that WFA treatment of human fibroblasts rapidly reorganizes vimentin intermediate filaments (VIF) into a perinuclear aggregate. This reorganization is dose dependent and is accompanied by a change in cell shape, decreased motility and an increase in vimentin phosphorylation at serine-38. Furthermore, vimentin lacking cysteine-328, the proposed WFA binding site, remains sensitive to WFA demonstrating that this site is not required for its cellular effects. Using analytical ultracentrifugation, viscometry, electron microscopy and sedimentation assays we show that WFA has no effect on VIF assembly in vitro. Furthermore, WFA is not specific for vimentin as it disrupts the cellular organization and induces perinuclear aggregates of several other IF networks comprised of peripherin, neurofilament-triplet protein, and keratin. In cells co-expressing keratin IF and VIF, the former are significantly less sensitive to WFA with respect to inducing perinuclear aggregates. The organization of microtubules and actin/microfilaments is also affected by WFA. Microtubules become wavier and sparser and the number of stress fibers appears to increase. Following 24 hrs of exposure to doses of WFA that alter VIF organization and motility, cells undergo apoptosis. Lower doses of the drug do not kill cells but cause them to senesce. In light of our findings that WFA affects multiple IF systems, which are expressed in many tissues of the body, caution is warranted in its use as an anti-cancer agent, since it may have debilitating organism-wide effects

    Zea mays iRS1563: A Comprehensive Genome-Scale Metabolic Reconstruction of Maize Metabolism

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    The scope and breadth of genome-scale metabolic reconstructions have continued to expand over the last decade. Herein, we introduce a genome-scale model for a plant with direct applications to food and bioenergy production (i.e., maize). Maize annotation is still underway, which introduces significant challenges in the association of metabolic functions to genes. The developed model is designed to meet rigorous standards on gene-protein-reaction (GPR) associations, elementally and charged balanced reactions and a biomass reaction abstracting the relative contribution of all biomass constituents. The metabolic network contains 1,563 genes and 1,825 metabolites involved in 1,985 reactions from primary and secondary maize metabolism. For approximately 42% of the reactions direct literature evidence for the participation of the reaction in maize was found. As many as 445 reactions and 369 metabolites are unique to the maize model compared to the AraGEM model for A. thaliana. 674 metabolites and 893 reactions are present in Zea mays iRS1563 that are not accounted for in maize C4GEM. All reactions are elementally and charged balanced and localized into six different compartments (i.e., cytoplasm, mitochondrion, plastid, peroxisome, vacuole and extracellular). GPR associations are also established based on the functional annotation information and homology prediction accounting for monofunctional, multifunctional and multimeric proteins, isozymes and protein complexes. We describe results from performing flux balance analysis under different physiological conditions, (i.e., photosynthesis, photorespiration and respiration) of a C4 plant and also explore model predictions against experimental observations for two naturally occurring mutants (i.e., bm1 and bm3). The developed model corresponds to the largest and more complete to-date effort at cataloguing metabolism for a plant species
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