87 research outputs found
Simulation model of Permanent Magnet Synchronous Motor in phase loss operation mode
There is a need to prevent technological accidents and minimize irreparable economic losses at important critical technologies and hazardous production facilities (HEP). The requirements for operational safety which could limit the risks of undesirable modes during the operation of nuclear, chemical, construction, metallurgical and other facilities are determining factors in the survivability criteria of the main technological equipment. Thus, in the production of defense products, there are rigorous conditions for the implementation of technological processes when creating products: "a particularly responsible technological process, as a technological process, a violation of which can lead to the failure of defense products or to a change (loss) in its functional properties
ХАРАКТЕРИСТИКИ БОКОВОЙ РЕАКЦИИ ПРИ ИЗМЕНЕНИИ ТЕХНИЧЕСКОГО СОСТОЯНИЯ АМОРТИЗАТОРА
The article presents an analytical study of the influence of the technical condition of the shock absorber on the characteristics of lateral reaction change in the spot of contact of the elastic tire with the support surface. The process of moving the car around a circle with passing along a single road ledge is the object of research. The change in lateral reaction over time is a diagnostic parameter for monitoring the technical condition of the damper. Sensitivity and unambiguity of diagnostic parameter are calculated.Purpose. The theoretical justification for the method of diagnosing a car’s suspension depending on changes in lateral reactions at the point of contact of the wheel with the road.Methodology includes numerical methods for solving differential equations, methods of mathematical modeling and mathematical analysis.Results: the mathematical apparatus for an analytical research of sensitivity and unambiguity of lateral reactions of the car at change of parameters of technical condition of shock absorbers.Practical implications: organizations and institutions that develop vehicle diagnostic techniques can use the results.В статье представлено аналитическое исследование влияния технического состояния амортизатора на характеристики изменения боковой реакции в пятне контакта эластичной шины с опорной поверхностью. Исследуется процесс движения автомобиля по окружности с переездом единичной неровности. Предложено использовать зависимость боковой реакции от времени в качестве диагностического параметра для контроля технического состояния амортизатора. Выполнена оценка чувствительности и однозначности рассматриваемой зависимости.Цель – теоретическое обоснование метода диагностирования подвески автомобиля по изменению боковых реакций в пятне контакта колеса с дорогой.Методы проведения работы: использованы численные методы решения дифференциальных уравнений, методы математического моделирования и математического анализа.Результаты: разработан математический аппарат для аналитического исследования чувствительности и однозначности боковых реакций автомобиля при изменении параметров технического состояния амортизаторов.Область применения результатов: результаты могут быть использованы организациями и учреждениями, занимающихся разработкой методов диагностирования автотранспортных средств
МАТЕМАТИЧЕСКАЯ МОДЕЛЬ ПРОЦЕССА ДВИЖЕНИЯ АВТОМОБИЛЯ ПО ПОПЕРЕЧНОМУ УКЛОНУ
The article presents an analytical study of the influence of the technical state of the suspension system on the stability parameters of the vehicle. The process of movement along the transverse slope with the disturbed state of the suspension is investigated. It is proposed to use the values of the lateral displacement, the angle of rotation and the time of the transient process of the angular velocity as the estimated parameters of motion stability.Purpose – Theoretical substantiation of the method for diagnosing the suspension by the kinematic parameters of the vehicle.Мethodology includes methods of mathematical modeling and numerical methods for solving differential equations.Results: a mathematical apparatus was developed for the analytical study of the process of vehicle movement when changing the parameters of the technical state of shock absorbers.Practical implications: the results can be used by organizations and institutions involved in the development of diagnostic methods for vehicles. В статье представлено аналитическое исследование влияния технического состояния системы подрессоривания на параметры устойчивости автомобиля. Исследуется процесс движения по поперечному уклону при возмущенном состоянии подвески. В качестве оценочных параметров устойчивости движения предложено использовать величины бокового смещения, угла поворота и времени переходного процесса угловой скорости.Цель – Теоретическое обоснование метода диагностирования подвески по кинематическим параметрам автомобиля.Методы проведения работы: использованы методы математического моделирования и численные методы решения дифференциальных уравнений.Результаты: разработан математический аппарат для аналитического исследования процесса движения автомобиля при изменении параметров технического состояния амортизаторов.Область применения результатов: результаты могут быть использованы организациями и учреждениями, занимающихся разработкой методов диагностирования автотранспортных средств
Resistance to thyroid hormone caused by a mutation in thyroid hormone receptor (TR)alpha 1 and TR alpha 2: clinical, biochemical, and genetic analyses of three related patients
Background
The thyroid hormone receptor α gene (THRA) transcript is alternatively spliced to generate either thyroid hormone receptor (TR)α1 or a non-hormone-binding variant protein, TRα2, the function of which is unknown. Here, we describe the first patients identified with a mutation in THRA that affects both TRα1 and TRα2, and compare them with patients who have resistance to thyroid hormone owing to a mutation affecting only TRα1, to delineate the relative roles of TRα1 and TRα2.
Methods
We did clinical, biochemical, and genetic analyses of an index case and her two sons. We assessed physical and radiological features, thyroid function, physiological and biochemical markers of thyroid hormone action, and THRA sequence.
Findings
The patients presented in childhood with growth failure, developmental delay, and constipation, which improved after treatment with thyroxine, despite normal concentrations of circulating thyroid hormones. They had similar clinical (macrocephaly, broad faces, skin tags, motor dyspraxia, slow speech), biochemical (subnormal ratio of free thyroxine:free tri-iodothyronine [T3], low concentration of total reverse T3, high concentration of creatine kinase, mild anaemia), and radiological (thickened calvarium) features to patients with TRα1-mediated resistance to thyroid hormone, although our patients had a heterozygous mis-sense mutation (Ala263Val) in both TRα1 and TRα2 proteins. The Ala263Val mutant TRα1 inhibited the transcriptional function of normal receptor in a dominant-negative fashion. By contrast, function of Ala263Val mutant TRα2 matched its normal counterpart. In vitro, high concentrations of T3 restored transcriptional activity of Ala263Val mutant TRα1, and reversed the dominant-negative inhibition of its normal counterpart. High concentrations of T3 restored expression of thyroid hormone-responsive target genes in patient-derived blood cells.
Interpretation
TRα1 seems to be the principal functional product of the THRA gene. Thyroxine treatment alleviates hormone resistance in patients with mutations affecting this gene, possibly ameliorating the phenotype. These findings will help the diagnosis and treatment of other patients with resistance to thyroid hormone resulting from mutations in THRA.
Funding
Wellcome Trust, NIHR Cambridge Biomedical Research Centre, Marie Curie Actions, Foundation for Development of Internal Medicine in Europe
Fas Activated Serine-Threonine Kinase Domains 2 (FASTKD2) mediates apoptosis of breast and prostate cancer cells through its novel FAST2 domain
Identification of a Phosphorylation-Dependent Nuclear Localization Motif in Interferon Regulatory Factor 2 Binding Protein 2
Background - Interferon regulatory factor 2 binding protein 2 (IRF2BP2) is a muscle-enriched transcription factor required to activate vascular endothelial growth factor-A (VEGFA) expression in muscle. IRF2BP2 is found in the nucleus of cardiac and skeletal muscle cells. During the process of skeletal muscle differentiation, some IRF2BP2 becomes relocated to the cytoplasm, although the functional significance of this relocation and the mechanisms that control nucleocytoplasmic localization of IRF2BP2 are not yet known. // Methodology/Principal Findings - Here, by fusing IRF2BP2 to green fluorescent protein and testing a series of deletion and site-directed mutagenesis constructs, we mapped the nuclear localization signal (NLS) to an evolutionarily conserved sequence 354ARKRKPSP361 in IRF2BP2. This sequence corresponds to a classical nuclear localization motif bearing positively charged arginine and lysine residues. Substitution of arginine and lysine with negatively charged aspartic acid residues blocked nuclear localization. However, these residues were not sufficient because nuclear targeting of IRF2BP2 also required phosphorylation of serine 360 (S360). Many large-scale phosphopeptide proteomic studies had reported previously that serine 360 of IRF2BP2 is phosphorylated in numerous human cell types. Alanine substitution at this site abolished IRF2BP2 nuclear localization in C2C12 myoblasts and CV1 cells. In contrast, substituting serine 360 with aspartic acid forced nuclear retention and prevented cytoplasmic redistribution in differentiated C2C12 muscle cells. As for the effects of these mutations on VEGFA promoter activity, the S360A mutation interfered with VEGFA activation, as expected. Surprisingly, the S360D mutation also interfered with VEGFA activation, suggesting that this mutation, while enforcing nuclear entry, may disrupt an essential activation function of IRF2BP2. // Conclusions/Significance - Nuclear localization of IRF2BP2 depends on phosphorylation near a conserved NLS. Changes in phosphorylation status likely control nucleocytoplasmic localization of IRF2BP2 during muscle differentiation
Sex-dependent changes in neuroactive steroid concentrations in the rat brain following acute swim stress
Sex differences in hypothalamo-pituitary-adrenal (HPA) axis activity are well established in rodents. In addition to glucocorticoids, stress also stimulates secretion of progesterone and deoxycorticosterone (DOC) from the adrenal gland. Neuroactive steroid metabolites of these precursors can modulate HPA axis function; however it is not known whether levels of these steroids differ between male and females following stress. Here we aimed to establish whether neuroactive steroid concentrations in the brain display sex- and/or region-specific differences under basal conditions and following exposure to acute stress.
Brains were collected from male and female rats killed under non-stress conditions or following exposure to forced swimming. Liquid chromatography-mass spectrometry was used to quantify 8 steroids: corticosterone, DOC, dihydrodeoxycorticosterone (DHDOC), pregnenolone, progesterone, dihydroprogesterone (DHP), allopregnanolone and testosterone in plasma and 5 brain regions (frontal cortex, hypothalamus, hippocampus, amygdala and brainstem).
Corticosterone, DOC and progesterone concentrations were significantly greater in the plasma and brain of both sexes following stress; however the responses in plasma were greater in females compared to males. This sex difference was also observed in the majority of brain regions for DOC and progesterone, but not for corticosterone. Despite observing no stress-induced changes in circulating concentrations of pregnenolone, DHDOC or DHP, concentrations were significantly greater in the brain, and this effect was more pronounced in females than males. Basal plasma and brain concentrations of allopregnanolone were significantly higher in females; moreover, stress had a greater impact on central allopregnanolone concentrations in females. Stress had no effect on circulating or brain concentrations of testosterone in males.
These data indicate sex and regional differences in the generation of neuroactive steroids in the brain following acute stress, especially for the 5α-reduced steroids, and further suggest sex-specific expression of steroidogenic enzymes in the brain. Thus, differential neurosteroidogenesis may contribute to sex differences in HPA axis responses to stress
Analysis of the minimal specificity of caspase-2 and identification of Ac-VDTTD-AFC as a caspase-2-selective peptide substrate
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