Hybrid propulsion system with a gyro component for economic and dynamic operation

The design of a hybrid drive with gyro components is described and its drive components for a medium class private car are discussed. The gyro component affects the short-period output of the drive by accelerating and slowing down and -- because of the mechanical transfer of kinetic energy between the gyro and the vehicle -- it affects also the energy balance in the case of intermittent operation. Energy can be taken in as desired either in the form of fuel or as fuel and current. A high energy recovery efficiency as well as the favorable operating range of the interval combustion engine makes it possible to reduce the fuel consumption per unit distance travelled to almost half that for a private car with a traditional engine

Numerical Advances in Electrophoretic Deposition in Flow Cells

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The impact of supply disruption on the standing order system in the FMCG supply chain

Purpose: The article aims to present the impact of supply disruption on the FMCG supply chain's standing order system. Design/Methodology/Approach: The research methodology used is the inventory control system's indicators with a fixed order quantity and graphic modeling. Findings: The system with a fixed order quantity requires the determination of the average annual demand for a given good and the determination of the ordering point, which is important for the FMCG branch. Practical Implications: Delivering goods in the right place and time plays an important role in the supply chain of movable goods. Maintaining a safe level of inventory ensures an effective and smooth flow of inventories through the supply chain's links. Originality/value: This article demonstrates the system with a fixed order quantity allows you to determine the size of the average annual demand for a given good and the point of ordering. It was indicated when logistic companies should use this method.peer-reviewe

Analysis of risk factors in an indirect distribution channel

Purpose: The article aims to present an analysis of risk factors in an indirect distribution channel. Design/Methodology/Approach: The research methodology used are indicators that enable the analysis of risk factors in the distribution channel. The results obtained by the FMEA method enabled the use of the preventive mechanisms method in the enterprise. The purpose of using the FMEA method is to characterize the most dangerous risk factors in the surveyed entities, which will be most felt by the organization in enterprises. Findings: Numerous risk factors can arise in a network of indirect distribution channels. The applied FMEA method identified which risk factors are the most dangerous for the organization regarding probability, detectability, and significance of the risk factor. The results obtained from the FMEA method made it possible to develop preventive mechanisms for the examined company and thus reduce the possibility of risk factors. Practical Implications: Over time, new risk factors may appear, so you should constantly monitor and analyze disturbances using the FMEA method that allows you to manage risk factors. Enterprises that are part of an indirect distribution channel should develop preventive mechanisms to ensure an efficiently functioning organization. Originality/value: The studies showed that the magnitude of the effect and the probability of risk factors depend on the first activity performed in the distribution network up to the last link of the supply chain. It is also influenced by the continuity of the consequences of a given occurrence of a risk factor. The obtained data is the basis for risk management for distribution entities.peer-reviewe

Particle-Based Simulations of Electrophoretic Deposition with Adaptive Physics Models

This work represents an extension of mesoscale particle-based modeling of electrophoretic deposition (EPD), which has relied exclusively on pairwise interparticle interactions described by Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. With this standard treatment, particles continuously move and interact via excluded volume and electrostatic pair potentials under the influence of external fields throughout the EPD process. The physics imposed by DLVO theory may not be appropriate to describe all systems, considering the vast material, operational, and application space available to EPD. As such, we present three modifications to standard particle-based models, each rooted in the ability to dynamically change interparticle interactions as simulated deposition progresses. This approach allows simulations to capture charge transfer and/or irreversible adsorption based on tunable parameters. We evaluate and compare simulated deposits formed under new physical assumptions, demonstrating the range of systems that these adaptive physics models may capture.Comment: 34 pages, 10 figure

Development of an online p38α mitogen-activated protein kinase binding assay and integration of LC–HR-MS

A high-resolution screening method was developed for the p38α mitogen-activated protein kinase to detect and identify small-molecule binders. Its central role in inflammatory diseases makes this enzyme a very important drug target. The setup integrates separation by high-performance liquid chromatography with two parallel detection techniques. High-resolution mass spectrometry gives structural information to identify small molecules while an online enzyme binding detection method provides data on p38α binding. The separation step allows the individual assessment of compounds in a mixture and links affinity and structure information via the retention time. Enzyme binding detection was achieved with a competitive binding assay based on fluorescence enhancement which has a simple principle, is inexpensive, and is easy to interpret. The concentrations of p38α and the fluorescence tracer SK&F86002 were optimized as well as incubation temperature, formic acid content of the LC eluents, and the material of the incubation tubing. The latter notably improved the screening of highly lipophilic compounds. For optimization and validation purposes, the known kinase inhibitors BIRB796, TAK715, and MAPKI1 were used among others. The result is a high-quality assay with Z′ factors around 0.8, which is suitable for semi-quantitative affinity measurements and applicable to various binding modes. Furthermore, the integrated approach gives affinity data on individual compounds instead of averaged ones for mixtures

Membrane lipid remodeling modulates γ-secretase processivity

Imbalances in the amounts of amyloid-beta peptides (A beta) generated by the membrane proteases beta- and gamma-secretase are considered as a trigger of Alzheimer's disease (AD). Cell-free studies of gamma-secretase have shown that increasing membrane thickness modulates A beta generation but it has remained unclear if these effects are translatable to cells. Here we show that the very long-chain fatty acid erucic acid (EA) triggers acyl chain remodeling in AD cell models, resulting in substantial lipidome alterations which included increased esterification of EA in membrane lipids. Membrane remodeling enhanced gamma-secretase processivity, resulting in the increased production of the potentially beneficial A beta 37 and/or A beta 38 species in multiple cell lines. Unexpectedly, we found that the membrane remodeling stimulated total A beta secretion by cells expressing WT gamma-secre-tase but lowered it for cells expressing an aggressive familial AD mutant gamma-secretase. We conclude that EA-mediated mod-ulation of membrane composition is accompanied by complex lipid homeostatic changes that can impact amyloidogenic processing in different ways and elicit distinct gamma-secretase re-sponses, providing critical implications for lipid-based AD treatment strategies

On-line electrochemistry–bioaffinity screening with parallel HR-LC-MS for the generation and characterization of modified p38α kinase inhibitors

In this study, an integrated approach is developed for the formation, identification and biological characterization of electrochemical conversion products of p38α mitogen-activated protein kinase inhibitors. This work demonstrates the hyphenation of an electrochemical reaction cell with a continuous-flow bioaffinity assay and parallel LC-HR-MS. Competition of the formed products with a tracer (SKF-86002) that shows fluorescence enhancement in the orthosteric binding site of the p38α kinase is the readout for bioaffinity. Parallel HR-MSn experiments provided information on the identity of binders and non-binders. Finally, the data produced with this on-line system were compared to electrochemical conversion products generated off-line. The electrochemical conversion of 1-{6-chloro-5-[(2R,5S)-4-(4-fluorobenzyl)-2,5-dimethylpiperazine-1-carbonyl]-3aH-indol-3-yl}-2-morpholinoethane-1,2-dione resulted in eight products, three of which showed bioaffinity in the continuous-flow p38α bioaffinity assay used. Electrochemical conversion of BIRB796 resulted, amongst others, in the formation of the reactive quinoneimine structure and its corresponding hydroquinone. Both products were detected in the p38α bioaffinity assay, which indicates binding to the p38α kinase

A squalene-hopene cyclase in Schizosaccharomyces japonicus represents a eukaryotic adaptation to sterol-limited anaerobic environments

Biosynthesis of sterols, which are key constituents of canonical eukaryotic membranes, requires molecular oxygen. Anaerobic protists and deep-branching anaerobic fungi are the only eukaryotes in which a mechanism for sterol-independent growth has been elucidated. In these organisms, tetrahymanol, formed through oxygen-independent cyclization of squalene by a squalene-tetrahymanol cyclase, acts as a sterol surrogate. This study confirms an early report [C. J. E. A. Bulder, Antonie Van Leeuwenhoek, 37, 353-358 (1971)] that Schizosaccharomyces japonicus is exceptional among yeasts in growing anaerobically on synthetic media lacking sterols and unsaturated fatty acids. Mass spectrometry of lipid fractions of anaerobically grown Sch. japonicus showed the presence of hopanoids, a class of cyclic triterpenoids not previously detected in yeasts, including hop-22(29)-ene, hop17(21)-ene, hop-21(22)-ene, and hopan-22-ol. A putative gene in Sch. japonicus showed high similarity to bacterial squalene-hopene cyclase (SHC) genes and in particular to those of Acetobacter species. No orthologs of the putative Sch. japonicus SHC were found in other yeast species. Expression of the Sch. japonicus SHC gene (Sjshc1) in Saccharomyces cerevisiae enabled hopanoid synthesis and stimulated anaerobic growth in sterol-free media, thus indicating that one or more of the hopanoids produced by SjShc1 could at least partially replace sterols. Use of hopanoids as sterol surrogates represents a previously unknown adaptation of eukaryotic cells to anaerobic growth. The fast anaerobic growth of Sch. japonicus in sterol-free media is an interesting trait for developing robust fungal cell factories for application in anaerobic industrial processes.Proteomic