Microstructure and mechanical properties of vanadium alloys after thermomechanical treatments

The results of investigation of dispersion strengthening effect on parameters of structural-phase states and characteristics of short-term strength and ductility of vanadium alloys of V–4Ti–4Cr, V–2.4Zr–0.25C, V–1.2Zr–8.8Cr and V–1.7Zr–4.2Cr–7.6W systems with different concentration of interstitial elements after optimized thermomechanical treatment mode were summarized. It was shown that for effective realization of dispersion strengthening by Orowan-type mechanism at least 25–50% of the initial volume fraction of coarse particles should be transformed into fine-disperse state and redistributed over the volume of material

Analysis of the Dynamics of Heat Exchange at Different Power of the Unit Continuous Combined Casting and Pressing Aluminum Alloy

Приведены результаты численного исследования непрерывного совмещенного литья и прессования опытного алюминиевого сплава АК12 при различной производительности установки с горизонтальным карусельным кристаллизатором. Дана количественная оценка влияния темпа разогрева кристаллизатора на температурно-временные характеристики в период переходного теплового процесса. Определены теплотехнические зоны, характеризующиеся различной интенсивностью теплообмена между расплавом и стенками кристаллизатора. Показано, что увеличение производительности установки сокращает продолжительность переходного теплового процесса при пуске установки из холодного состояния до достижения ею стационарного теплового режима. Получена зависимость времени выхода установки на стационарный тепловой режим от скорости вращения колеса-кристаллизатораA numerical study of the process of continuous combined casting and pressing of experimental aluminum alloy AK12 at various capacities of the continuous combined casting and pressing semi-industrial unit was carried out. A quantitative assessment of the influence of the heating rate of the crystallizer on the temperature and time characteristics during the transition thermal process is given. The heat engineering zones characterized by different intensity of heat exchange between the melt and the walls of the crystallizer are determined. It is shown that increasing the semi-industrial unit performance reduces the duration of the transient thermal process when starting from a cold state until it reaches a stationary thermal mode. The dependence of the time when the unit reaches a stationary thermal mode on the rotation speed of the horizontal crystallizer is obtaine

Computer Model Heat Exchange of the Continuous Casting and Extrusion Non-Ferrous Metals

На основе программного комплекса Ansys CFX разработана трехмерная компьютерная модель сложного теплообмена в установке непрерывного литья и прессования цветных металлов. Рассмотрены особенности построения расчетной сетки и решения системы дифференциальных уравнений энергии для обрабатываемого металла и элементов установки. Изучена динамика процесса литья и прессования алюминиевого сплава на опытной лабораторной установке. Определены расчетные температуры металла и элементов опытного образца установки. Проведена экспериментальная оценка достоверности результатов моделирования и показана адекватность разработанной компьютерной моделиBased on the software complex Ansys CFX, a three-dimensional computer model of complex heat transfer in a continuous casting and pressing of non-ferrous metals has been developed. The features of constructing a computational grid and solving the system of differential energy equations for the processed metal and the elements of the installation are considered. The dynamics of the process of casting and pressing of aluminum alloy on an experimental laboratory installation is studied. Calculated temperatures of the metal and elements of the prototype of the installation are determined. An experimental estimation of reliability of modeling results is carried out and adequacy of the developed computer model is show

Computer Model Heat Exchange of the Continuous Casting and Extrusion Non-Ferrous Metals

На основе программного комплекса Ansys CFX разработана трехмерная компьютерная модель сложного теплообмена в установке непрерывного литья и прессования цветных металлов. Рассмотрены особенности построения расчетной сетки и решения системы дифференциальных уравнений энергии для обрабатываемого металла и элементов установки. Изучена динамика процесса литья и прессования алюминиевого сплава на опытной лабораторной установке. Определены расчетные температуры металла и элементов опытного образца установки. Проведена экспериментальная оценка достоверности результатов моделирования и показана адекватность разработанной компьютерной моделиBased on the software complex Ansys CFX, a three-dimensional computer model of complex heat transfer in a continuous casting and pressing of non-ferrous metals has been developed. The features of constructing a computational grid and solving the system of differential energy equations for the processed metal and the elements of the installation are considered. The dynamics of the process of casting and pressing of aluminum alloy on an experimental laboratory installation is studied. Calculated temperatures of the metal and elements of the prototype of the installation are determined. An experimental estimation of reliability of modeling results is carried out and adequacy of the developed computer model is show

Microstructure and mechanical properties of vanadium alloys after thermomechanical treatments

The results of investigation of dispersion strengthening effect on parameters of structural-phase states and characteristics of short-term strength and ductility of vanadium alloys of V–4Ti–4Cr, V–2.4Zr–0.25C, V–1.2Zr–8.8Cr and V–1.7Zr–4.2Cr–7.6W systems with different concentration of interstitial elements after optimized thermomechanical treatment mode were summarized. It was shown that for effective realization of dispersion strengthening by Orowan-type mechanism at least 25–50% of the initial volume fraction of coarse particles should be transformed into fine-disperse state and redistributed over the volume of material

Protective effect of Growth Hormone-Releasing Hormone agonist in bacterial toxin-induced pulmonary barrier dysfunction

Rationale: Antibiotic treatment of patients infected with G(−) or G(+) bacteria promotes release of the toxins lipopolysaccharide (LPS) and pneumolysin (PLY) in their lungs. Growth Hormone-releasing Hormone (GHRH) agonist JI-34 protects human lung microvascular endothelial cells (HL-MVEC), expressing splice variant 1 (SV-1) of the receptor, from PLY-induced barrier dysfunction. We investigated whether JI-34 also blunts LPS-induced hyperpermeability. Since GHRH receptor (GHRH-R) signaling can potentially stimulate both cAMP-dependent barrier-protective pathways as well as barrier-disruptive protein kinase C pathways, we studied their interaction in GHRH agonist-treated HL-MVEC, in the presence of PLY, by means of siRNA-mediated protein kinase A (PKA) depletion. Methods: Barrier function measurements were done in HL-MVEC monolayers using Electrical Cell substrate Impedance Sensing (ECIS) and VE-cadherin expression by Western blotting. Capillary leak was assessed by Evans Blue dye (EBD) incorporation. Cytokine generation in broncho-alveolar lavage fluid (BALF) was measured by multiplex analysis. PKA and PKC-α activity were assessed by Western blotting. Results: GHRH agonist JI-34 significantly blunts LPS-induced barrier dysfunction, at least in part by preserving VE-cadherin expression, while not affecting inflammation. In addition to activating PKA, GHRH agonist also increases PKC-α activity in PLY-treated HL-MVEC. Treatment with PLY significantly decreases resistance in control siRNA-treated HL-MVEC, but does so even more in PKA-depleted monolayers. Pretreatment with GHRH agonist blunts PLY-induced permeability in control siRNA-treated HL-MVEC, but fails to improve barrier function in PKA-depleted PLY-treated monolayers. Conclusions: GHRH signaling in HL-MVEC protects from both LPS and PLY-mediated endothelial barrier dysfunction and concurrently induces a barrier-protective PKA-mediated and a barrier-disruptive PKC-α-induced pathway in the presence of PLY, the former of which dominates the latter

Apolipoprotein M and Sphingosine-1-Phosphate Receptor 1 Promote the Transendothelial Transport of High-Density Lipoprotein

Objective: ApoM enriches S1P (sphingosine-1-phosphate) within HDL (high-density lipoproteins) and facilitates the activation of the S1P1 (S1P receptor type 1) by S1P, thereby preserving endothelial barrier function. Many protective functions exerted by HDL in extravascular tissues raise the question of how S1P regulates transendothelial HDL transport. Approach and Results: HDL were isolated from plasma of wild-type mice, Apom knockout mice, human apoM transgenic mice or humans and radioiodinated to trace its binding, association, and transport by bovine or human aortic endothelial cells. We also compared the transport of fluorescently-labeled HDL or Evans Blue, which labels albumin, from the tail vein into the peritoneal cavity of apoE-haploinsufficient mice with (apoE-haploinsufficient mice with endothelium-specific knockin of S1P1) or without (control mice, ie, apoE-haploinsufficient mice without endothelium-specific knockin of S1P1) endothelium-specific knockin of S1P1. The binding, association, and transport of HDL from Apom knockout mice and human apoM-depleted HDL by bovine aortic endothelial cells was significantly lower than that of HDL from wild-type mice and human apoM-containing HDL, respectively. The binding, uptake, and transport of 125I-HDL by human aortic endothelial cells was increased by an S1P1 agonist but decreased by an S1P1 inhibitor. Silencing of SR-BI (scavenger receptor BI) abrogated the stimulation of 125I-HDL transport by the S1P1 agonist. Compared with control mice, that is, apoE-haploinsufficient mice without endothelium-specific knockin of S1P1, apoE-haploinsufficient mice with endothelium-specific knockin of S1P1 showed decreased transport of Evans Blue but increased transport of HDL from blood into the peritoneal cavity and SR-BI expression in the aortal endothelium. Conclusions: ApoM and S1P1 promote transendothelial HDL transport. Their opposite effect on transendothelial transport of albumin and HDL indicates that HDL passes endothelial barriers by specific mechanisms rather than passive filtration. Keywords: apolipoprotein; endothelium; lipoprotein; mice; sphingosine-1-phosphate

Apolipoprotein M and Sphingosine-1-Phosphate Receptor 1 Promote the Transendothelial Transport of High-Density Lipoprotein

OBJECTIVE: Apolipoprotein M (ApoM) enriches sphingosine-1-phosphate (S1P) within high density lipoproteins (HDL) and facilitates the activation of the S1P(1) receptor by S1P, thereby preserving endothelial barrier function. Many protective functions exerted by HDL in extravascular tissues raise the question how S1P regulates transendothelial HDL transport. APPROACH AND RESULTS: HDL were isolated from plasma of wild type mice, Apom knock-out mice, human apoM transgenic mice or humans and radioiodinated to trace its binding, association, and transport by bovine or human aortic endothelial cells (BAECs and HAECs, respectively). We also compared the transport of fluorescently-labeled HDL or Evan’s Blue, which labels albumin, from the tail vein into the peritoneal cavity of apoE-haploinsufficient mice with (S1P(1)-iECKI) or without (CTRL) endothelium specific knock-in of S1P(1). The binding, association, and transport of HDL from Apom knock-out mice and human apoM-depleted HDL by BAECs was significantly lower than that of HDL from wild type mice and human apoM containing HDL, respectively. The binding, uptake, and transport of (125)I-HDL by HAECs was increased by an S1P(1) agonist but decreased by an S1P(1) inhibitor. Silencing of scavenger receptor BI (SR-BI) abrogated the stimulation of (125)I-HDL transport by the S1P(1) agonist. Compared to CTRL, S1P(1)-iECKI showed decreased transport of Evan’s Blue but increased transport of HDL from blood into the peritoneal cavity and SR-BI expression in the aortal endothelium. CONCLUSIONS: ApoM and S1P(1) promote transendothelial HDL transport. Their opposite effect on transendothelial transport of albumin and HDL indicates that HDL passes endothelial barriers by specific mechanisms rather than passive filtration

Edoxaban versus warfarin in patients with atrial fibrillation

Contains fulltext : 125374.pdf (publisher's version ) (Open Access)BACKGROUND: Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. METHODS: We conducted a randomized, double-blind, double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation (median follow-up, 2.8 years). The primary efficacy end point was stroke or systemic embolism. Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period. The principal safety end point was major bleeding. RESULTS: The annualized rate of the primary end point during treatment was 1.50% with warfarin (median time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban (hazard ratio, 0.79; 97.5% confidence interval [CI], 0.63 to 0.99; P<0.001 for noninferiority) and 1.61% with low-dose edoxaban (hazard ratio, 1.07; 97.5% CI, 0.87 to 1.31; P=0.005 for noninferiority). In the intention-to-treat analysis, there was a trend favoring high-dose edoxaban versus warfarin (hazard ratio, 0.87; 97.5% CI, 0.73 to 1.04; P=0.08) and an unfavorable trend with low-dose edoxaban versus warfarin (hazard ratio, 1.13; 97.5% CI, 0.96 to 1.34; P=0.10). The annualized rate of major bleeding was 3.43% with warfarin versus 2.75% with high-dose edoxaban (hazard ratio, 0.80; 95% CI, 0.71 to 0.91; P<0.001) and 1.61% with low-dose edoxaban (hazard ratio, 0.47; 95% CI, 0.41 to 0.55; P<0.001). The corresponding annualized rates of death from cardiovascular causes were 3.17% versus 2.74% (hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), and 2.71% (hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P=0.008), and the corresponding rates of the key secondary end point (a composite of stroke, systemic embolism, or death from cardiovascular causes) were 4.43% versus 3.85% (hazard ratio, 0.87; 95% CI, 0.78 to 0.96; P=0.005), and 4.23% (hazard ratio, 0.95; 95% CI, 0.86 to 1.05; P=0.32). CONCLUSIONS: Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes. (Funded by Daiichi Sankyo Pharma Development; ENGAGE AF-TIMI 48 ClinicalTrials.gov number, NCT00781391.)