Аналіз впливу мотивуючих факторів на результати діяльності машинобудівних підприємств

У статті обґрунтовано вибір інструментарію факторного аналізу для оцінки впливу мотивуючих чинників на результативні показники діяльності машинобудівних підприємств. Розраховані коефіцієнти кореляції для досліджуваних підприємств. Встановлена ступінь зв’язку факторів з результативним показником.В статье обоснован выбор инструментария факторного анализа для оценки влияния мотивирующих факторов на результативные показатели деятельности машиностроительных предприятий. Рассчитаны коэффициенты корреляции для исследуемых предприятий. Установлена степень связи факторов с результативным показателем.In the article the choice of tool of factor analysis is grounded for the estimation of influence of explaining factors on effective performance of machine-building enterprises indicators. The coefficients of correlation are expected for the probed enterprises. The degree of connection of factors is set with an effective index

FEM-based comparison of models to predict dynamic recrystallization during orthogonal cutting of AISI 4140

Machining processes induce a thermo-mechanical load collective on the surface layer, which leads to grain refinement of varying depths depending on several factors apart from the workpiece. The size relation of the cutting edge radius to the cutting depth (relative roundness) as well as the cutting edge microgeometry influence the generation of nanocrystalline layers. In this work several models to predict dynamic recrystallization during orthogonal cutting of AISI 4140 are compared using 2D FEM-models considering both, relative roundness and cutting edge microgeometry

Influence of anisotropy of additively manufactured AlSi10Mg parts on chip formation during orthogonal cutting

Anisotropic behavior of metals can influence manufacturing processes including acting thermo-mechanical loads and resulting surface layer states. In additive manufacturing, the build-up direction influences material states like microstructure, density distribution and stress fields, possibly leading to anisotropic behavior. In this work, additively manufactured AlSi10Mg is characterized in tension tests in order to determine the anisotropic material deformation behavior due to the build-up procedure. This was implemented in 2D cutting simulations using finite element method. Additionally, orthogonal cutting experiments were performed in order to determine process forces and chip formation, which finally were used in order to validate simulations

Milling parameter and tool wear dependent surface quality in micro-milling of brass

Short life-time and high tool costs still remain major constraints for the micro-milling process. Understanding the wear mechanisms and their effects on the workpiece quality is essential for efficient tool usage. Usually, wear increases the cutting forces and reduces the emerging surface quality during the micro-milling process. Due to high tool costs, cutting parameters are usually chosen for optimal tool lifetime and/or process time rather than optimal surface quality. The scope of this paper is to investigate the correlation of the process parameters, strategy and wear status of the tool on the resulting surface topography. To reach this goal, micro-milling experiments were conducted, in which several grooves were milled using two end milling tools, new and worn, with a diameter of 1.5 mm and four cutting edges. The cutting speed and feed were varied, as well as the cutting direction. Brass was chosen as workpiece material to ensure a constant wear state of the tools during the experiments. During the cutting process the process forces were recorded and examined for their magnitude and frequency response. Furthermore, the grooves were analyzed optically for their surface roughness. The roughness shows in most cases slightly higher values for the specimen manufactured with the worn tool than the ones done with the new tool. The biggest influence on the surface roughness results from the feed rate, while cutting speed and milling strategy have a smaller influence. The measured cutting forces show similar tendencies, than the resulting surface roughness. The results show also a significant influence of tool wear on the vibration behavior during the process, while the influence of feed rate is mostly negligible. This results partly from the greater tool runout and bigger deviation of the cutting edges

Measurement of reaction kinetics of [177Lu]Lu-DOTA-TATE using a microfluidic system

Microfluidic synthesis techniques can offer improvement over batch syntheses which are currently used for radiopharmaceutical production. These improvements are, for example, better mixing of reactants, more efficient energy transfer, less radiolysis, faster reaction optimization, and overall improved reaction control. However, scale-up challenges hinder the routine clinical use, so the main advantage is currently the ability to optimize reactions rapidly and with low reactant consumption. Translating those results to clinical systems could be done based on calculations, if kinetic constants and diffusion coefficients were known. This study describes a microfluidic system with which it was possible to determine the kinetic association rate constants for the formation of [177Lu]Lu-DOTA-TATE under conditions currently used for clinical production. The kinetic rate constants showed a temperature dependence that followed the Arrhenius equation, allowing the determination of Arrhenius parameters for a Lu-DOTA conjugate (A = 1.24 ± 0.05 × 1019 M-1 s-1, EA = 109.5 ± 0.1 × 103 J mol-1) for the first time. The required reaction time for the formation of [177Lu]Lu-DOTA-TATE (99% yield) at 80 °C was 44 s in a microfluidic channel (100 μm). Simulations done with COMSOL Multiphysics® indicated that processing clinical amounts (3 mL reaction solution) in less than 12 min is possible in a micro- or milli-fluidic system, if the diameter of the reaction channel is increased to over 500 μm. These results show that a continuous, microfluidic system can become a viable alternative to the conventional, batch-wise radiolabelling technique

Human Sterol Regulatory Element-Binding Protein 1a Contributes Significantly to Hepatic Lipogenic Gene Expression

Background/Aims:Sterol regulatory element-binding protein (SREBP) 1, the master regulator of lipogenesis, was shown to be associated with non-alcoholic fatty liver disease, which is attributed to its major isoform SREBP1c. Based on studies in mice, the minor isoform SREBP1a is regarded as negligible for hepatic lipogenesis. This study aims to elucidate the expression and functional role of SREBP1a in human liver. Methods: mRNA expression of both isoforms was quantified in cohorts of human livers and primary human hepatocytes. Hepatocytes were treated with PF-429242 to inhibit the proteolytic activation of SREBP precursor protein. SREBP1a-specific and pan-SREBP1 knock-down were performed by transfection of respective siRNAs. Lipogenic SREBP-target gene expression was analyzed by real-time RT-PCR. Results: In human liver, SREBP1a accounts for up to half of the total SREBP1 pool. Treatment with PF-429242 indicated SREBP-dependent auto-regulation of SREBP1a, which however was much weaker than of SREBP1c. SREBP1a-specific knock-down also reduced significantly the expression of SREBP1c and of SREBP-target genes. Regarding most SREBP-target genes, simultaneous knock-down of both isoforms resulted in effects of only similar extent as SREBP1a-specific knock-down. Conclusion: We here showed that SREBP1a is significantly contributing to the human hepatic SREBP1 pool and has a share in human hepatic lipogenic gene expression. Copyright (C) 2015 S. Karger AG, Base

A systems biology approach to dynamic modeling and inter-subject variability of statin pharmacokinetics in human hepatocytes

A dynamic model for the biotransformation of atorvastatin has been developed using quantitative metabolite measurements in primary human hepatocytes. The model comprises kinetics for transport processes and metabolic enzymes as well as population liver expression data allowing us to assess the impact of inter-individual variability of concentrations of key proteins. Application of computational tools for parameter sensitivity analysis enabled us to considerably improve the validity of the model and to create a consistent framework for precise computer-aided simulations in toxicology

Coordinating Role of RXR alpha in Downregulating Hepatic Detoxification during Inflammation Revealed by Fuzzy-Logic Modeling

During various inflammatory processes circulating cytokines including IL-6, IL-1 beta, and TNF alpha elicit a broad and clinically relevant impairment of hepatic detoxification that is based on the simultaneous downregulation of many drug metabolizing enzymes and transporter genes. To address the question whether a common mechanism is involved we treated human primary hepatocytes with IL-6, the major mediator of the acute phase response in liver, and characterized acute phase and detoxification responses in quantitative gene expression and (phospho-)proteomics data sets. Selective inhibitors were used to disentangle the roles of JAK/STAT, MAPK, and PI3K signaling pathways. A prior knowledge-based fuzzy logic model comprising signal transduction and gene regulation was established and trained with perturbation-derived gene expression data from five hepatocyte donors. Our model suggests a greater role of MAPK/PI3K compared to JAK/STAT with the orphan nuclear receptor RXR alpha playing a central role in mediating transcriptional downregulation. Validation experiments revealed a striking similarity of RXRa gene silencing versus IL-6 induced negative gene regulation (r(s) = 0.79;P<0.0001). These results concur with RXRa functioning as obligatory heterodimerization partner for several nuclear receptors that regulate drug and lipid metabolism

Cliophysics: Socio-political Reliability Theory, Polity Duration and African Political (In)stabilities

Quantification of historical sociological processes have recently gained attention among theoreticians in the effort of providing a solid theoretical understanding of the behaviors and regularities present in sociopolitical dynamics. Here we present a reliability theory of polity processes with emphases on individual political dynamics of African countries. We found that the structural properties of polity failure rates successfully capture the risk of political vulnerability and instabilities in which 87.50%, 75%, 71.43%, and 0% of the countries with monotonically increasing, unimodal, U-shaped and monotonically decreasing polity failure rates, respectively, have high level of state fragility indices. The quasi-U-shape relationship between average polity duration and regime types corroborates historical precedents and explains the stability of the autocracies and democracies.Comment: 4 pages, 3 figures, 1 tabl