PRACTICE OF CAD AND CAE DESIGN IN THE FIELD OF PLASMA TECHNOLOGIES

The effectiveness of automated plasma torch design methods can be improved by integrating design and engineering analysis technologies. The features of CAD and CAE technologies for designing plasma torches are considered. Shows examples of the design of plasma torches for cutting metals and waste treatment with the use of digital technologies.Эффективность автоматизированных методов проектирования плазмотронов можно повысить за счет интеграции технологий проектирования и инженерного анализа. Рассмотрены особенности CAD и CAE технологий проектирования плазмотронов. Показаны примеры проектирования плазмотронов для резки металлов и обезвреживания отходов с применением цифровых технологий

Selenium Nanoparticles as Potential Drug-Delivery Systems for the Treatment of Parkinson’s Disease

The development of efficient drug formulations for Parkinson’s disease (PD) treatment is challenged by achieving pharmacokinetic profiles, reduced side effects, and better permeability through the blood–brain barrier (BBB). As nanoparticles may facilitate the delivery of drugs in the brain due to their high-loading capacity and ability to cross biological barriers, we designed two different types of selenium nanoparticles (SeNPs) that may increase the transport of drugs across the BBB and may act as antioxidants at the site of action. The SeNPs were functionalized with polyvinylpyrrolidone (PVP) and polysorbate 20 (Tween) and characterized in terms of their size, size distribution, shape, surface charge, and colloidal stability in relevant biological media. Their drug-loading capacity was tested using dopamine and l-DOPA as therapeutically active agents for PD. Thermodynamic analysis revealed that binding processes occurred spontaneously through hydrogen bond/van der Waals interactions or electrostatic interactions. The strongest interaction was observed between PVP-SeNPs and l-DOPA or dopamine, which was characterized by a binding constant several orders of magnitude higher than for Tween-SeNPs. However, the addition of human transferrin as a model plasma protein significantly reduced this difference, which indicates the crucial role of protein corona formation in the design of drug nanodelivery systems. In vitro evaluation by cell-free and cellular transwell models showed efficient internalization of SeNP-loaded l-DOPA/dopamine by human endothelial brain cells, while facilitated BBB permeability for l-DOPA, and dopamine was achieved using PVP-SeNPs. Overall, the high potential of SeNPs as drug-delivery vehicles in PD treatment was demonstrated

Selenium Nanoparticles as Potential Drug-Delivery Systems for the Treatment of Parkinson’s Disease

The development of efficient drug formulations for Parkinson’s disease (PD) treatment is challenged by achieving pharmacokinetic profiles, reduced side effects, and better permeability through the blood–brain barrier (BBB). As nanoparticles may facilitate the delivery of drugs in the brain due to their high-loading capacity and ability to cross biological barriers, we designed two different types of selenium nanoparticles (SeNPs) that may increase the transport of drugs across the BBB and may act as antioxidants at the site of action. The SeNPs were functionalized with polyvinylpyrrolidone (PVP) and polysorbate 20 (Tween) and characterized in terms of their size, size distribution, shape, surface charge, and colloidal stability in relevant biological media. Their drug-loading capacity was tested using dopamine and l-DOPA as therapeutically active agents for PD. Thermodynamic analysis revealed that binding processes occurred spontaneously through hydrogen bond/van der Waals interactions or electrostatic interactions. The strongest interaction was observed between PVP-SeNPs and l-DOPA or dopamine, which was characterized by a binding constant several orders of magnitude higher than for Tween-SeNPs. However, the addition of human transferrin as a model plasma protein significantly reduced this difference, which indicates the crucial role of protein corona formation in the design of drug nanodelivery systems. In vitro evaluation by cell-free and cellular transwell models showed efficient internalization of SeNP-loaded l-DOPA/dopamine by human endothelial brain cells, while facilitated BBB permeability for l-DOPA, and dopamine was achieved using PVP-SeNPs. Overall, the high potential of SeNPs as drug-delivery vehicles in PD treatment was demonstrated

Selenium Nanoparticles as Potential Drug-Delivery Systems for the Treatment of Parkinson’s Disease

The development of efficient drug formulations for Parkinson’s disease (PD) treatment is challenged by achieving pharmacokinetic profiles, reduced side effects, and better permeability through the blood–brain barrier (BBB). As nanoparticles may facilitate the delivery of drugs in the brain due to their high-loading capacity and ability to cross biological barriers, we designed two different types of selenium nanoparticles (SeNPs) that may increase the transport of drugs across the BBB and may act as antioxidants at the site of action. The SeNPs were functionalized with polyvinylpyrrolidone (PVP) and polysorbate 20 (Tween) and characterized in terms of their size, size distribution, shape, surface charge, and colloidal stability in relevant biological media. Their drug-loading capacity was tested using dopamine and l-DOPA as therapeutically active agents for PD. Thermodynamic analysis revealed that binding processes occurred spontaneously through hydrogen bond/van der Waals interactions or electrostatic interactions. The strongest interaction was observed between PVP-SeNPs and l-DOPA or dopamine, which was characterized by a binding constant several orders of magnitude higher than for Tween-SeNPs. However, the addition of human transferrin as a model plasma protein significantly reduced this difference, which indicates the crucial role of protein corona formation in the design of drug nanodelivery systems. In vitro evaluation by cell-free and cellular transwell models showed efficient internalization of SeNP-loaded l-DOPA/dopamine by human endothelial brain cells, while facilitated BBB permeability for l-DOPA, and dopamine was achieved using PVP-SeNPs. Overall, the high potential of SeNPs as drug-delivery vehicles in PD treatment was demonstrated

Femtosecond to Millisecond Dynamics of Light Induced Allostery in the <i>Avena sativa</i> LOV Domain

The rational engineering of photosensor proteins underpins the field of optogenetics, in which light is used for spatiotemporal control of cell signaling. Optogenetic elements function by converting electronic excitation of an embedded chromophore into structural changes on the microseconds to seconds time scale, which then modulate the activity of output domains responsible for biological signaling. Using time-resolved vibrational spectroscopy coupled with isotope labeling, we have mapped the structural evolution of the LOV2 domain of the flavin binding phototropin <i>Avena sativa</i> (AsLOV2) over 10 decades of time, reporting structural dynamics between 100 fs and 1 ms after optical excitation. The transient vibrational spectra contain contributions from both the flavin chromophore and the surrounding protein matrix. These contributions are resolved and assigned through the study of four different isotopically labeled samples. High signal-to-noise data permit the detailed analysis of kinetics associated with the light activated structural evolution. A pathway for the photocycle consistent with the data is proposed. The earliest events occur in the flavin binding pocket, where a subpicosecond perturbation of the protein matrix occurs. In this perturbed environment, the previously characterized reaction between triplet state isoalloxazine and an adjacent cysteine leads to formation of the adduct state; this step is shown to exhibit dispersive kinetics. This reaction promotes coupling of the optical excitation to successive time-dependent structural changes, initially in the β-sheet and then α-helix regions of the AsLOV2 domain, which ultimately gives rise to Jα-helix unfolding, yielding the signaling state. This model is tested through point mutagenesis, elucidating in particular the key mediating role played by Q513

Elucidating the Signal Transduction Mechanism of the Blue-Light-Regulated Photoreceptor YtvA: From Photoactivation to Downstream Regulation

The blue-light photoreceptor YtvA from Bacillus subtilis has an N-terminal flavin mononucleotide (FMN)-binding light-oxygen-voltage (LOV) domain that is fused to a C-terminal sulfate transporter and anti-σ factor antagonist (STAS) output domain. To interrogate the signal transduction pathway that leads to photoactivation, the STAS domain was replaced with a histidine kinase, so that photoexcitation of the flavin could be directly correlated with biological activity. N94, a conserved Asn that is hydrogen bonded to the FMN C2O group, was replaced with Ala, Asp, and Ser residues to explore the role of this residue in triggering the structural dynamics that activate the output domain. Femtosecond to millisecond time-resolved multiple probe spectroscopy coupled with a fluorescence polarization assay revealed that the loss of the hydrogen bond between N94 and the C2O group decoupled changes in the protein structure from photoexcitation. In addition, alterations in N94 also decreased the stability of the Cys-FMN adduct formed in the light-activated state by up to a factor of ∼25. Collectively, these studies shed light on the role of the hydrogen bonding network in the LOV β-scaffold in signal transduction