An Atomistic Understanding of Allosteric Inhibition of Glutamate Racemase: a Dampening of Native Activation Dynamics

Glutamate racemases (GR) are members of the family of bacterial enzymes known as cofactor-independent racemases and epimerases and catalyze the stereoinversion of glutamate. D-amino acids are universally important for the proper construction of viable bacterial cell walls, and thus have been repeatedly validated as attractive targets for novel antimicrobial drug design. Significant aspects of the mechanism of this challenging stereoinversion remain unknown. The current study employs a combination of MD and QM/MM computational approaches to show that the GR from H. pylori must proceed via a pre-activation step, which is dependent on the enzyme's flexibility. This mechanism is starkly different from previously proposed mechanisms. These findings have immediate pharmaceutical relevance, as the H. pylori GR enzyme is a very attractive allosteric drug target. The results presented in this study offer a distinctly novel understanding of how AstraZeneca's lead series of inhibitors cripple the H. pylori GR's native motions, via prevention of this critical chemical pre-activation step. Our experimental studies, using SPR, fluorescence and NMR WaterLOGSY, show that H. pylori GR is not inhibited by the uncompetitive mechanism originally put forward by Lundqvist et al.. The current study supports a deep connection between native enzyme motions and chemical reactivity, which has strong relevance to the field of allosteric drug discovery.     

Cellular/dendritic transition,dendritic growth and microhardness in directionally solidified monophasic Sn-2%Sb alloy

Horizontal directional solidification experiments were carried out with a monophasic Sn-2%Sb (mass fraction) alloy to analyze the influence of solidification thermal parameters on the morphology and length scale of the microstructure. Continuous temperature measurements were made during solidification at different positions along the length of the casting and these temperature data were used to determine solidification thermal parameters, including the growth rate (V_L) and the cooling rate (T_R). High cooling rate cells and dendrites are shown to characterize the microstructure in different regions of the casting, with a reverse dendrite-to-cell transition occurring for T_R>5.0 K/s. Cellular (l_c) and primary dendrite arm spacings (l₁) are determined along the length of the directionally-solidified casting. Experimental growth laws relating l_c and l₁ to V_L and T_R are proposed, and a comparative analysis with results from a vertical upward directional solidification experiment is carried out. The influence of morphology and length scale of the microstructure on microhardness is also analyzed.     

PEG修饰的镍钴层状双氢氧化物微球抗菌及溶血性能研究

双氧水作为常用的活性氧试剂广泛应用于清洗创面、去除痂皮、清洗带恶臭的创伤。但是由于其具有强烈刺激性,常采用表面涂抹的方式应用,不可注入体内。并且其常用的浓度高于生理水平,会对健康组织有一定毒性,甚至会延迟伤口愈合。为了解决这个问题,设计了一种利用聚乙二醇修饰的生物相容性好的镍钴层状双氢氧化物微球PEG-Ni/Co-LDHs,使得其具有较高的抑菌效果,同时能减少双氧水的用量。采用一步沉淀法合成了PEG-Ni/Co-LDHs,使用SEM、TEM、XRD等方法对PEG-Ni/Co-LDHs的结构进行表征,结果显示该材料的分散性能好,粒径约为470 nm,微球呈花状结构,由薄层似花瓣结构层层组装而成。PEG-Ni/Co-LDHs具有过氧化物酶的活性,这使得在双氧水的作用下能有效产生羟基自由基,高效抑制革兰氏阴性菌(大肠杆菌)和革兰氏阳性菌(金黄色葡萄球菌)增殖,高浓度时与双氧水联合作用,细菌成活率分别为32%和19%。采集大鼠血细胞对纳米材料PEG-Ni/Co-LDHs进行溶血性能研究,发现在高浓度时,其溶血率低于12%,未出现明显的溶血作用,具有很好的生物相容性。研究结果表明,PEG-Ni/Co-LDHs具有高抗菌活性和低溶血毒性的特点,为其今后作为抗菌剂在生物体内应用奠定了研究基础。     

Hybrid sonochemic urea-nitrate combustion preparation of CuO/ZnO/Al2O3 nanocatalyst used in fuel cell-grade hydrogen production from methanol: Effect of sonication and fuel/nitrate ratio

Fuel cell-grade hydrogen production has been studied via steam reforming of methanol (SRM) over a series of CuO/ZnO/Al₂O₃ nanocatalysts fabricated by the combustion method. The effect of sonication and urea/nitrate ratio on the characteristics and catalytic properties of the prepared catalysts has been investigated. The synthesized catalysts were characterized by x-ray diffraction (XRD), field emission scanning electron microscope (FESEM), Particle Size Distribution (PSD), energy dispersive x-ray (EDX), Brunauer-Emmett-Teller (BET) and FTIR analyses XRD patterns showed positive influence of urea/nitrate ratio on CuO and ZnO crystallite sizes. The ultrasonic mixing of primary gel compared with conventional mixing led to lower crystallite size. FESEM images showed that the sample mixed by sonication with a urea/nitrate ratio of 1 had more homogeneous morphology with narrow particle size distribution. EDX results proved the presence of all metals on the surface of the nanocatalysts and better consistence between the gel and surface composition of elements in samples prepared by sonication. Catalytic performance showed that sonication during the mixing of primary gel dramatically increased the methanol conversion. It was also proved that increasing the amount of urea led to lower catalytic activity. The ultrasound-treated nanocatalyst with urea/nitrate?=?1 was the best sample in terms of activity and selectivity. It was stable in the SRM for 1200?min without considerable change in methanol conversion and product selectivity.     

The thermodynamic characteristics of a Stirling/pulse tube hybrid cryocooler

A Stirling/pulse tube hybrid cryocooler (SPC), comprised of a Stirling cryocooler as the first stage and a pulse tube cryocooler as the second stage, features the ability of shifting cooling capacity between stages by adjusting the movement of the displacer in the first stage. Such an ability allows an SPC to accommodate itself to time-varying heat loads at different temperatures, which makes it a competitive candidate in space applications. However, due to the gas coupling, there exists a significant mutual effect between stages which endows an SPC with special thermodynamic characteristics and has a significant effect on the SPC’s capability of shifting cooling capacity between stages. With the phasor analysis and the thermodynamic analysis, this paper establishes an idealized model of an SPC. The model is then used to study the effect of the second stage on the first stage and reveal the condition that an SPC is able to shift cooling capacity between stages. Also, the model is compared with a Sage numerical model and the two models are consistent on the overall trend. Though it is unable to reflect reality precisely, the idealized model can interpret the mechanism and highlight some of the essential nature of an SPC, which will eventually benefit the appropriate design of an SPC.     

伞帽用高铬铸铁在热强碱腐蚀环境下的磨损分析

针对氧化铝行业中常用的Cr28和Cr20高铬铸铁伞帽在相同工况条件下的磨损机理进行分析,并对比研究了实际生产中两种失效材料的成分、组织及性能。结果表明,伞帽部件在高温强碱腐蚀条件下受到外界冲刷时,磨损量由微切削磨损与变形磨损这两种机制共同决定。含铬量较高的Cr28高铬铸铁,其冲刷和抗腐蚀磨损性能均优于Cr20高铬铸铁。伞帽服役寿命主要受浆料和表层的铸铁材料两大因素影响。两种试验材料经淬火+回火处理后,基体组织中主要为回火马氏体+M₇C3</sub>型碳化物+少量残留奥氏体,其中含铬量较高的Cr28高铬铸铁中共晶碳化物含量更高,且分布更加弥散,其平均硬度值为64.0 HRC,高于Cr20高铬铸铁的60.2 HRC。最终确定Cr28高铬铸铁作为伞帽材质更能满足氧化铝生产及设备检修周期的需要。</sub>     

Performance analysis of hybrid/single nanofluids on augmentation of heat transport in lid-driven undulated cavity

This numerical study reveals the heat transfer performance of hybrid/single nanofluids inside a lid-driven sinusoidal trapezoidal-shaped enclosure. The right and left inclined surfaces of the trapezium have been considered as insulated, whereas the bottom sinusoidal wavy and the flat top surfaces of the enclosure as hot and cold, respectively. The governing partial differential equations of fluid's velocity and temperature have been resolved by applying the finite element method. The implications of Prandtl number (4.2-6.2), Richardson number (0.1-10.0), undulation number (0-3), nanoparticles volume fraction (0%-3%), and nanofluid/base fluid (water, water–copper (Cu), water–Cu–carbon nanotube, water–Cu–copper oxide (CuO), water–Cu–TiO₂, and water–Cu–Al₂O₃) on the velocity and temperature profiles have been studied. Simulated findings have been represented by means of streamlines, isothermal lines, and average Nusselt number of above-mentioned hybrid nanofluids for varying the governing parameters. The comparison of heat transfer rates using hybrid nanofluids and pure water has been also shown. The heat transfer rate is increased about 15% for varying Richardson number from 0.1 to 10.0. Blending of two nanoparticles suspension in base fluid has a higher heat transfer rate—approximately 5% than a mononanoparticle. Moreover, a higher average Nusselt number is obtained by 14.7% using the wavy surface than the flat surface of the enclosure. Thus, this study showed that applying hybrid nanofluid may be beneficial to obtain expected thermal performance.     

Shape optimization of bi-directional flow passage components based on a genetic algorithm and computational fluid dynamics

The inlet/outlet is an important part of a water conveyance system in a pumped storage power station (PSPS). Its hydraulic characteristics are directly related to the operation and economic benefit of the PSPS. Frequent changes between inflow and outflow operations pose significant challenges in the design of the inlet/outlet diffusion segment shape. In this study, an effective optimization method, including three-dimensional parametric modelling, computational fluid dynamics and a genetic algorithm, is introduced and coupled to the design of the diffusion segment shape. The hydraulic characteristics of bi-directional flow, including the head loss, velocity uneven distribution and uneven discharge distribution, are selected as the objective function in the optimization method. Using this method, the recommended shape of the inlet/outlet is studied and its hydraulic characteristics are discussed. The results indicate that the optimized inlet/outlet has better performance.     

Hybrid make-to-stock and make-to-order systems: a taxonomic review

Production planning and control (PPC) systems that employ aspects from both make-to-order (MTO) and make-to-stock (MTS) production control are known as hybrid MTS/MTO systems. While both MTO and MTS separately have been studied extensively, their combined use has received less attention. However, the literature on this topic is growing and this paper shows that the review performed in this paper is an important addition to the field. We categorise relevant literature according to a novel taxonomy and show that hybrid MTS/MTO production control can be used in different contexts. In addition, an overview of the modelling techniques and methods used in these papers is provided. Based on the reviewed literature, relevant research questions and directions for future research are identified. Finally, it is shown that hybrid MTS/MTO production control is prevalent in practice by discussing research with industrial applications. The paper contains an overview of research on hybrid MTS/MTO production control to be used as reference for researchers active in the field, and provides managerial insights and directions for future research on this topic.