250 research outputs found

    Using a virtual cortical module implementing a neural field model to modulate brain rhythms in Parkinson’s disease

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    We propose a new method for selective modulation of cortical rhythms based on neural field theory, in which the activity of a cortical area is extensively monitored using a two-dimensional microelectrode array. The example of Parkinson’s disease illustrates the proposed method, in which a neural field model is assumed to accurately describe experimentally recorded activity. In addition, we propose a new closed-loop stimulation signal that is both space- and time- dependent. This method is especially designed to specifically modulate a targeted brain rhythm, without interfering with other rhythms. A new class of neuroprosthetic devices is also proposed, in which the multielectrode array is seen as an artificial neural network interacting with biological tissue. Such a bio-inspired approach may provide a solution to optimize interactions between the stimulation device and the cortex aiming to attenuate or augment specific cortical rhythms. The next step will be to validate this new approach experimentally in patients with Parkinson’s disease

    Design of a sensor cell line based on the germline version of the Hivspecific broadly neutralizing antibody 10E8

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    Identification of antigens driving affinity maturation of broadly neutralizing antibodies is one of the most challenging endeavors in the HIV vaccine development field. In order to isolate such candidate immunogens and to analyze whether they may activate B-cells expressing BCRs based on immature/germline forms of broadly neutralizing antibodies, a robust test system that faithfully recapitulates human B-cell biology would be indispensable. Thus, developing a human В-cell sensor line with surface expression of a germline variant of broadly neutralizing antibody 10E8 may represent one of the possible solutions

    Activity-based models to predict kinetics of levulinic acid esterification

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    The solvent is of prime importance in biomass conversion as it influences dissolution, reaction kinetics, catalyst activity and thermodynamic equilibrium of the reaction system. So far, activity-based models were developed to predict kinetics and equilibria, but the influence of the catalyst on kinetics has not been succesfully predicted by thermodynamic models. In this work, the thermodynamic model ePC-SAFT advanced was used to predict the activities of the reactants and of the catalyst at various conditions (temperature, reactant concentrations, γ-valerolactone GVL cosolvent addition, catalyst concentration) for the homogeneously acid-catalyzed esterification of levulinic acid (LA) with ethanol. Different kinetic models were applied, and it was found that the catalyst influence on kinetics could be predicted correctly by simultaneously solving the dissociation equilibrium of H2SO4 catalyst along the reaction coordinate and by relating reaction kinetics to proton activity. ePC-SAFT advanced model parameters were only fitted to reaction-independent phase equilibrium data. The key reaction properties were determined by applying ePC-SAFT advanced to one experimental kinetic curve for a set of temperatures, yielding the reaction enthalpy at standard state urn:x-wiley:14394235:media:cphc202200729:cphc202200729-math-0001 , activation energy urn:x-wiley:14394235:media:cphc202200729:cphc202200729-math-0002 and the intrinsic reaction rate constant k=0.011 s−1 at 323 K, which is independent of catalyst concentration. The new procedure allowed an a-priori identification of the effects of catalyst, solvent and reactant concentration on LA esterification

    Технологическая подготовка производства изготовления детали "Фланец" на станках с ЧПУ

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    В данной работе рассматривается вопрос технологической подготовки производства детали "Фланец", в ходе которой осуществляется создание технологического процесса изготовления детали, разработка необходимой оснастки, расчет применяемых ресурсов, а также разработка необходимой технологической документации. Кроме того, осуществляется разработка управляющей программы для станков с ЧПУ.In this paper, the issue of technological preparation of the production of the Flange component is considered, during which the technological process of manufacturing parts is developed, the necessary equipment is developed, the applied resources are calculated, and the necessary technological documentation is developed. In addition, a control program for CNC machines is being developed

    Synthesis and characterization of polymers for nonlinear optical applications

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    International audienceA difunctional NLO Azo-Dye chromophore has been synthesized and polymerization has been performed with a comonomer bearing a side-chain epoxy group. Deposition of the polymer on glass substrates was performed by spin-coating, resulting in uniform films up to 2 µm thickness. The orientation of the chromophore was performed under a " pin-to-plane " positive corona discharge followed by a heat-treatment in order to obtain reticulation of the films. Molecular orientation has been investigated using UV-Vis. and Raman spectroscopy. Poling of the films results in a decay of absorbency as well as in a blue shift of the spectrum. At the same time, the 1600 cm-1 band disappears from the Raman spectra, indicating orientation of the chromophores. Cross-linking has been studied by FTIR and all-optical poling and showed an improved stability of the electro-optic thin films

    Heterologous Expression and Purification Systems for Structural Proteomics of Mammalian Membrane Proteins

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    Membrane proteins (MPs) are responsible for the interface between the exterior and the interior of the cell. These proteins are implicated in numerous diseases, such as cancer, cystic fibrosis, epilepsy, hyperinsulinism, heart failure, hypertension and Alzheimer's disease. However, studies on these disorders are hampered by a lack of structural information about the proteins involved. Structural analysis requires large quantities of pure and active proteins. The majority of medically and pharmaceutically relevant MPs are present in tissues at very low concentration, which makes heterologous expression in large-scale production-adapted cells a prerequisite for structural studies. Obtaining mammalian MP structural data depends on the development of methods that allow the production of large quantities of MPs. This review focuses on the different heterologous expression systems, and the purification strategies, used to produce large amounts of pure mammalian MPs for structural proteomics

    Eicosanoid Release Is Increased by Membrane Destabilization and CFTR Inhibition in Calu-3 Cells

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    The antiinflammatory protein annexin-1 (ANXA1) and the adaptor S100A10 (p11), inhibit cytosolic phospholipase A2 (cPLA2α) by direct interaction. Since the latter is responsible for the cleavage of arachidonic acid at membrane phospholipids, all three proteins modulate eicosanoid production. We have previously shown the association of ANXA1 expression with that of CFTR, the multifactorial protein mutated in cystic fibrosis. This could in part account for the abnormal inflammatory status characteristic of this disease. We postulated that CFTR participates in the regulation of eicosanoid release by direct interaction with a complex containing ANXA1, p11 and cPLA2α. We first analyzed by plasmon surface resonance the in vitro binding of CFTR to the three proteins. A significant interaction between p11 and the NBD1 domain of CFTR was found. We observed in Calu-3 cells a rapid and partial redistribution of all four proteins in detergent resistant membranes (DRM) induced by TNF-α. This was concomitant with increased IL-8 synthesis and cPLA2α activation, ultimately resulting in eicosanoid (PGE2 and LTB4) overproduction. DRM destabilizing agent methyl-β-cyclodextrin induced further cPLA2α activation and eicosanoid release, but inhibited IL-8 synthesis. We tested in parallel the effect of short exposure of cells to CFTR inhibitors Inh172 and Gly-101. Both inhibitors induced a rapid increase in eicosanoid production. Longer exposure to Inh172 did not increase further eicosanoid release, but inhibited TNF-α-induced relocalization to DRM. These results show that (i) CFTR may form a complex with cPLA2α and ANXA1 via interaction with p11, (ii) CFTR inhibition and DRM disruption induce eicosanoid synthesis, and (iii) suggest that the putative cPLA2/ANXA1/p11/CFTR complex may participate in the modulation of the TNF-α-induced production of eicosanoids, pointing to the importance of membrane composition and CFTR function in the regulation of inflammation mediator synthesis
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