175 research outputs found

    Analysis of Parameters Influencing in-plant Milk Run Design for Production Supply

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    In-plant milk-run systems are a transport concept for in-plant material delivery which is becoming more and more applicable especially in the automotive industry. This is due to the system characteristic of providing materials in small lot sizes and with high frequency. As there is a number of different milk run concepts applied and there are several parameters influencing the efficiency and stability of these systems, this paper aims at presenting an overview of common concepts and their properties together with key figures based on an empirical study. The concepts are further analyzed and evaluated with respect to resulting lead times and stability

    Detecting Determinism in High Dimensional Chaotic Systems

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    A method based upon the statistical evaluation of the differentiability of the measure along the trajectory is used to identify in high dimensional systems. The results show that the method is suitable for discriminating stochastic from deterministic systems even if the dimension of the latter is as high as 13. The method is shown to succeed in identifying determinism in electro-encephalogram signals simulated by means of a high dimensional system.Comment: 8 pages (RevTeX 3 style), 5 EPS figures, submitted to Phys. Rev. E (25 apr 2001

    Inhibition of 26S proteasome activity by α-synuclein is mediated by the proteasomal chaperone Rpn14/PAAF1

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    \ua9 2024 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.Parkinson\u27s disease (PD) is characterized by aggregation of α-synuclein (α-syn) into protein inclusions in degenerating brains. Increasing amounts of aggregated α-syn species indicate significant perturbation of cellular proteostasis. Altered proteostasis depends on α-syn protein levels and the impact of α-syn on other components of the proteostasis network. Budding yeast Saccharomyces cerevisiae was used as eukaryotic reference organism to study the consequences of α-syn expression on protein dynamics. To address this, we investigated the impact of overexpression of α-syn and S129A variant on the abundance and stability of most yeast proteins using a genome-wide yeast library and a tandem fluorescent protein timer (tFT) reporter as a measure for protein stability. This revealed that the stability of in total 377 cellular proteins was altered by α-syn expression, and that the impact on protein stability was significantly enhanced by phosphorylation at Ser129 (pS129). The proteasome assembly chaperone Rpn14 was identified as one of the top candidates for increased protein stability by expression of pS129 α-syn. Elevated levels of Rpn14 enhanced the growth inhibition by α-syn and the accumulation of ubiquitin conjugates in the cell. We found that Rpn14 interacts physically with α-syn and stabilizes pS129 α-syn. The expression of α-syn along with elevated levels of Rpn14 or its human counterpart PAAF1 reduced the proteasome activity in yeast and in human cells, supporting that pS129 α-syn negatively affects the 26S proteasome through Rpn14. This comprehensive study into the alternations of protein homeostasis highlights the critical role of the Rpn14/PAAF1 in α-syn-mediated proteasome dysfunction

    Constitutive model for fibre reinforced composites with progressive damage based on the spectral decomposition of material stiffness tensor

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    Copyright © 2022 The Authors. Complex nature of the fibre reinforced composites, their non-homogeneity and anisotropy make their modelling a challenging task. Although the linear – elastic behaviour of the composites is well understood, there is still a significant uncertainty regarding prediction of damage initiation, damage evolution and material failure especially for a general loading case characterised with triaxial state of stress or strain. Consequently, simplifying assumptions are often unavoidable in development of constitutive models capable of accurately predicting damage. The approach used in this work uses decomposition of the strain energy based on spectral decomposition of the material stiffness tensor and an assumption that each strain energy component represent free energy for a characteristic deformation mode. The criteria for damage initiation are based on an assumption that the damage corresponding to a deformation mode is triggered when the strain energy for that mode exceeds a specified critical limit. In the proposed model the deformation modes are not interacting at continuum scale due to orthogonality of the eigenvectors, i.e. the stiffness tensor symmetry. Damage and its evolution are modelled by reduction of the principal material stiffness based on the effective stress concept and the hypothesis of strain energy equivalence. The constitutive model was implemented into Lawrence Livermore National Laboratory (LLNL) Dyna3d explicit hydrocode and coupled with a vector shock Equation of State. The modelling approach was verified and validated in a series of single element tests, plate impact test and high velocity impact of hard projectile impact on an aerospace grade carbon fibre reinforced plastic. The model accurately predicted material response to impact loading including the test cases characterised by presence of shock waves, e.g. the plate impact test. It was also demonstrated that the model was capable of predicting damage and delamination development in the simulation of the high velocity impact tests, where the numerical results were within 5% of the post impact experimental measurements

    Thermal and chemical unfolding and refolding of a eukaryotic sodium channel

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    Voltage-gated sodium channels are dynamic membrane proteins essential for signaling in nervous and muscular systems. They undergo substantial conformational changes associated with the closed, open and inactivated states. However, little information is available regarding their conformational stability. In this study circular dichroism spectroscopy was used to investigate the changes in secondary structure accompanying chemical and thermal denaturation of detergent-solubilised sodium channels isolated from Electrophorus electricus electroplax. The proteins appear to be remarkably resistant to either type of treatment, with "denatured" channels, retaining significant helical secondary structure even at 77 degrees C or in 10% SDS. Further retention of helical secondary structure at high temperature was observed in the presence of the channel-blocking tetrodotoxin. It was possible to refold the thermally-denatured (but not chemically-denatured) channels in vitro. The correctly refolded channels were capable of undergoing the toxin-induced conformational change indicative of ligand binding. In addition, flux measurements in liposomes showed that the thermally-denatured (but not chemically-denatured) proteins were able to re-adopt native, active conformations. These studies suggest that whilst sodium channels must be sufficiently flexible to undergo major conformational changes during their functional cycle, the proteins are highly resistant to unfolding, a feature that is important for maintaining structural integrity during dynamic processes. (c) 2009 Elsevier B.V. All rights reserved

    Inverse Modeling for MEG/EEG data

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    We provide an overview of the state-of-the-art for mathematical methods that are used to reconstruct brain activity from neurophysiological data. After a brief introduction on the mathematics of the forward problem, we discuss standard and recently proposed regularization methods, as well as Monte Carlo techniques for Bayesian inference. We classify the inverse methods based on the underlying source model, and discuss advantages and disadvantages. Finally we describe an application to the pre-surgical evaluation of epileptic patients.Comment: 15 pages, 1 figur

    Evaluating tephrochronology in the permafrost peatlands of Northern Sweden

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    Tephrochronology is an increasingly important tool for the dating of sediment and peat profiles for palaeoecological, palaeoclimatic and archaeological research. However, although much work has been done on tephra in temperate peatlands, there have been very few in-depth investigations of permafrost peatlands. Here we present the analysis of nine peatland cores from Abisko, northern Sweden, and show that the presence of tephra layers may be highly variable even over a scale of <10 km. Using electron probe microanalysis (EPMA) combined with age-depth profiles compiled from radiocarbon (14C) and 210Pb dating of peat records, we identify the Hekla 1104, Hekla 1158, Hekla-Selsund and the Hekla 4 tephra layers. We also infer the presence of the Askja 1875 tephra, in addition to an unassigned tephra dating from between 1971–1987 AD in two separate cores. Five of the nine analysed cores do not contain distinct tephra layers. Volcanic ash deposits in northern Scandinavia are subject to both regional-scale variations in climate and atmospheric circulation, and local-scale variations on the order of tens of kilometres in topography, vegetation, snow cover, and ground permeability. The extreme inconsistency of tephra preservation within a small study area (∼3000 km2) brings into question the reliability of tephrochronology within permafrost peatlands, and highlights the necessity of alternative methods for dating peat profiles in this region

    Drivers of HIV self-testing among female sex workers: Findings from a multi-state study in Malaysia

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    BackgroundAlthough research on HIV self-testing (HIVST) has rapidly increased, few studies have explored HIVST uptake in female sex workers (FSW), and none in Malaysia. Therefore, we endeavored to assess the willingness to use HIVST in this at-risk, vulnerable population.MethodsA cross-sectional survey study was conducted among 113 HIV-negative Malaysian FSW in 2017. Participants were recruited using advertisements on social media, flyers, and direct referrals from community-based organizations. Data were collected using self-administered surveys. Multivariable logistic regression was used to identify correlates of willingness to use HIVST.ResultsNearly a third of participants (30.1%) reported they would be willing to use HIVST. Multivariable analyses adjusting for Malay ethnicity, stable housing, living in Kuala Lumpur (KL), years in sex work, age of first sex work, childhood sexual assault, history of HIV testing, and previously in prison indicated that living in KL [adjusted odds ratio (aOR) = 5.214, p = 0.0137] was associated with a greater willingness to use HIVST. In contrast, having stable housing (aOR = 0.100, p = 0.0064) was negatively associated with willingness to use HIVST.ConclusionsOur results indicate that HIVST may potentially enhance the uptake of HIV testing among FSWs living in an urban environment and experiencing unstable housing, but an overall willingness to use HIVST is low. These findings highlight the need for efforts to increase awareness of HIVST among FSWs and additional research on the effective implementation of HIVST for FSW
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