气膜孔角度对动叶前缘冲击/气膜复合冷却的影响

本文针对GE-E3第一级动叶前缘的冲击/气膜复合冷却结构进行了热流耦合数值研究.采用标准k-ω湍流模型,分析了前缘气膜孔对称布置时,其角度对透平动叶前缘冲击/气膜复合冷却特性的影响;在五种冷气质量流量比(MFR=0005,0.010, 0.016, 0.020, 0.025)下,研究了气膜孔在不同角度(β=20°,25...     

The Potential of 2-Substituted Quinolines as Antileishmanial Drug Candidates

There is a need for new, cost-effective drugs to treat leishmaniasis. A strategy based on traditional medicine practiced in Bolivia led to the discovery of the 2-substituted quinoline series as a source of molecules with antileishmanial activity and low toxicity. This review documents the development of the series from the first isolated natural compounds through several hundred synthetized molecules to an optimized compound exhibiting an in vitro IC₅₀ value of 0.2 µM against Leishmania donovani, and a selectivity index value of 187, together with in vivo activity on the L. donovani/hamster model. Attempts to establish structure–activity relationships are described, as well as studies that have attempted to determine the mechanism of action. For the latter, it appears that molecules of this series act on multiple targets, possibly including the immune system, which could explain the observed lack of drug resistance after in vitro drug pressure. We also show how nanotechnology strategies could valorize these drugs through adapted formulations and how a mechanistic targeting approach could generate new compounds with increased activity.     

Treatment of Human Glioblastoma U251 Cells with Sulforaphane and a Peptide Nucleic Acid (PNA) Targeting miR-15b-5p: Synergistic Effects on Induction of Apoptosis

Glioblastoma multiforme (GBM) is a lethal malignant tumor accounting for 42% of the tumors of the central nervous system, the median survival being 15 months. At present, no curative treatment is available for GBM and new drugs and therapeutic protocols are urgently needed. In this context, combined therapy appears to be a very interesting approach. The isothiocyanate sulforaphane (SFN) has been previously shown to induce apoptosis and inhibit the growth and invasion of GBM cells. On the other hand, the microRNA miR-15b is involved in invasiveness and proliferation in GBM and its inhibition is associated with the induction of apoptosis. On the basis of these observations, the objective of the present study was to determine whether a combined treatment using SFN and a peptide nucleic acid interfering with miR-15b-5p (PNA-a15b) might be proposed for increasing the pro-apoptotic effects of the single agents. To verify this hypothesis, we have treated GMB U251 cells with SFN alone, PNA-a15b alone or their combination. The cell viability, apoptosis and combination index were, respectively, analyzed by calcein staining, annexin-V and caspase-3/7 assays, and RT-qPCR for genes involved in apoptosis. The efficacy of the PNA-a15b determined the miR-15b-5p content analyzed by RT-qPCR. The results obtained indicate that SFN and PNA-a15b synergistically act in inducing the apoptosis of U251 cells. Therefore, the PNA-a15b might be proposed in a “combo-therapy” associated with SFN. Overall, this study suggests the feasibility of using combined treatments based on PNAs targeting miRNA involved in GBM and nutraceuticals able to stimulate apoptosis.     

Acoustoelastic effect simulation by time–space finite element formulation based on quadratic interpolation of the acceleration

Acoustoelastic effect describes the change of ultrasound velocity due to the initial stress. Its simulation involves a numerical analysis of nonlinear elastodynamics and requires high accuracy in the time domain. A time–space finite element formulation, derived from the quadratic interpolation of the acceleration within a time segment, is proposed for an accurate simulation of the acoustoelastic effect in the present study. Ten different integration schemes are generated based on this formulation and nine of them are found to be conditionally stable. Among the nine stable schemes, one is found to obtain a spectral radius of one when the normalized step ratio is less than 5.477, indicating no numerical dissipation or numerical divergence. Compared with integration schemes from previous studies, this integration scheme demonstrates better performance in calculation accuracy and energy conservation. A two-stage approach, namely the static stage and the dynamic stage, has been employed in the simulation of the acoustoelastic effect. The former stage is adopted to obtain the initial stress and the latter stage, where the proposed integration scheme is implemented, is adopted to simulate the ultrasound propagation in an initial stress state. The simulation results of the dynamic stage show that the ultrasound velocity increases in a compression stress state and decreases in a tension stress state for aluminum alloy, which is in good agreement with previous experimental studies. Together with the simulation result of the static stage, it is conjectured that the acoustoelastic effect results from the stress-dependent elastic modulus.     

Morris-Lecar系统中通道噪声诱导的自发性动作电位研究

在生物物理学中, 越来越多的现象是由于分段确定性的动力系统与连续时间马氏过程之间的耦合作用而产生的. 因为这种耦合性, 相关的数学模型更适合取为随机混合系统而不是扩散过程(基于It?随机微分方程). 本文从理论上和数值上研究了在弱噪声条件下无鞍点状态的随机混合Morris-Lecar系统中, 由通道噪声诱导的自发性放电现象. 一个动作电位的初始阶段可视为噪声诱导的逃逸事件, 其最优路径和拟势可由辅助Hamilton系统给出. 由于系统不存在鞍点, 因此可选择虚拟分界线(ghost separatrix)为阈值, 研究噪声诱导的自静息态的逃逸事件. 通过计算在阈值处的拟势, 便可发现其值有一个明显的最小值, 其作用类似于鞍点. 通过改进的Monte Carlo模拟方法, 计算了历程概率分布, 其结果对初始阶段和兴奋阶段的理论解均给出了验证. 此外, 基于前人将拟势等高线作为阈值的另一种选择, 我们对两种阈值取法的优劣性进行了比较. 最后, 本文研究了钠离子和钾离子通道噪声的不同组合对最优路径和拟势的影响. 结果表明: 钾离子通道噪声在自发性放电过程中起主导作用, 且两种噪声强度存在一个最优比例能使总的噪声强度达到最小.      

组合式十字形钢管混凝土柱偏压力学性能试验研究

设计了一种由槽钢和方形钢管拼焊形成的组合式十字形钢管混凝土柱,将其灵活地布置在框架结构的中节点,可使柱肢与填充墙等厚,有效地提高建筑使用面积。共制作了6根组合式十字形钢管混凝土柱试件,考虑了偏心距和长细比两种变化参数。通过对其进行偏心受压试验研究,考察了试件的破坏形态和荷载-挠度曲线,并分析了其在不同偏心距和长细比下的荷载-应变曲线发展规律。结果表明:组合式十字形钢管混凝土柱中钢管和槽钢对混凝土的约束作用强,表现为较高的延性系数;偏心距或长细比越大,试件的极限承载力及弹性刚度越小,且偏心距越大延性越好,长细比对延性影响不显著;在受拉侧纵向应变基本上符合平截面假定,在受压侧纵向应变不符合平截面假定。     

原子吸收硫化锌法间接测定精氨酸络合反应的机理研究

通过编程计算精氨酸和锌离子在不同pH条件下的各种存在形式,通过分析拟合分布图,研究了在硫化锌法原子吸收间接测定精氨酸时的pH对原子吸收响应的影响及络合反应的机理.经对不同形态的精氨酸与金属锌离子的共存区域的各种组合探讨,指出在pH 9.0左右最佳测定条件下的pH响应峰是由于精氨酸和锌离子的两种不同存在形式的变化所引起的左右峰边缘,精氨酸是以正一价荷电形态的精氨酸基Arg -与Zn(OH)2形成了可溶性络合离子[HN=CH(NH 3)-NH-(CH2)3-CH(NH 3)-COO]2Zn(OH)2.结果表明,理论分析计算的结果与实验数据得到了基本吻合,确定了硫化锌法原子吸收间接测定精氨酸时的络合物反应机理及络合物的组成结构.     

Biodegradable Black-Phosphorus-Nanosheet-Based Nanoagent for Enhanced Chemo-Photothermal Therapy

Black phosphorus nanosheet (BPNS) is a promising multifunctional material in the biomedical field with biodegradability and low side effects, however its features are always weakened severely owing to its poor stability. Here, a novel method is developed for improving the defect of BPNS based on the effective protection of poly(lactic-co-glycolic acid) (PLGA), which preserves the stable photothermal therapy (PTT) effect of BPNS and biodegradability of the material. Meanwhile, doxorubicin (DOX) is loaded on BPNS/PLGA to get BPNS/PLGA/DOX for further chemotherapy and preventing the recurrence of tumor after PTT. The presented combined therapeutic strategy exploits the strengths and improves the defects of BPNS, thus developing an efficient and safe nanoagent for cancer therapy, which affords and reveals the great potential of BPNS in nanomedicine.     

采用组合引导磁场的多注二极管设计

分析了采用单一同轴磁场时强流相对论多注阴极的侧端发射问题,研究了在不同磁场内半径和多注漂移管长度情况下多注电子束的传输效率。研究发现:由于引导磁场尺寸有限,高压下多注阴极杆及多注阴极柱的电子束发射是影响多注电子束传输效率的主要因素,且该部分电子束对多注漂移管入口管壁的轰击直接影响了多注速调管的重频能力。设计了采用永磁铁和同轴磁场组合工作的强流相对论多注二极管,理论分析和模拟计算证明:基于组合磁场的多注二极管可明显减弱甚至抑制多注阴极发射球头以外的电子束发射,并且组合磁场的磁场位形和强度可满足强流相对论多注电子束的高效、稳定传输。     

Localized enzymolysis and sonochemically modified sunflower protein: Physical,functional and structure attributes

Impacts of localized enzymolysis and sonication on physical, techno-functional, and structure attributes of sunflower meal protein (SMP) and its hydrolysate (SMPH) were studied. SMP was subjected to enzymolysis (using alcalase) to prepare SMPH with various degrees of hydrolysis (6–24% DH). Enzymolysis decreased colour lightness, turbidity, and particle size of unsonicated and sonicated SMP, while it increased the absolute values of zeta potential (P < 0.05). Sonication improved oil absorption capacity and dispersibility over unsonicated samples. Contrarily, sonicated preparations showed a decrease in water holding capacity. Intrinsic fluorescence and FTIR spectral analyses suggested that SMPH had more movable/flexible secondary structures than SMP. Moreover, the changes in sulfhydryl clusters and disulfide linkages following sonication demonstrated limited unfolding of SMP and SMPH structure and decrease in intermolecular interactions. SDS-PAGE profile exhibited significant reduction in molecular weight (MW) of sonicated SMP, whereas did not display differences between unsonicated and sonicated SMPH. From further MW analysis, SMPH was categorized with high proportion of small-sized peptides ≤ 3 kDa fractions, which increased from 78.64 to 93.01% (control) and from 82.3 to 93.88% (sonication) with enzymolysis (6–24DH). Localized enzymolysis and sonication can be utilised to modify the physical and conformational attributes of SMP and SMPH, which could enhance their functionalities and broaden the utilisation area in food industry.