Effect of Microstructure and Hydrogen Pores on the Mechanical Behavior of an Al7%Si0.3%Mg Alloy Studied by a Combined Phase‐Field and Micromechanical Approach

A combination of the phase‐field method for the simulation of the microstructure evolution during solidification with subsequent finite element simulation of fracture appearance in the final solidification structure is proposed for the prediction of the mechanical behavior of Al? Si based casting alloys, including the effect of solidification porosity caused by hydrogen. Metallographic investigations and computer tomographic observations of the as cast microstructure of an Al7%Si0.3%Mg alloy together with the data obtained from mechanical tensile testing are used to compare and validate the simulation results to demonstrate the capabilities as well as current limitations in micromechanical modeling of void containing materials. In micromechanical simulations with the element elimination technique (EET) it is shown that porosity influences the crack path as well as crack propagation by connecting the pores. In the eutectic microstructure without porosity, failure starts to develop in silicon lamellae and proceeds in the ductile matrix. However, in the presence of pores fracture also initiates in silicon, and in the later stages of loading, porosity affects the path of the crack and results in additional crack nucleation, and thus, these pores also influence crack propagation in the matrix.     

CYP51: A Major Drug Target in the Cytochrome P450 Superfamily

The cytochrome P540 (CYP) superfamily currently includes about 9000 proteins forming more than 800 families. The enzymes catalyze monooxygenation of a vast array of compounds and play essentially two roles. They provide biodefense (detoxification of xenobiotics, antibiotic production) and participate in biosynthesis of important endogenous molecules, particularly steroids. Based on these two roles, sterol 14/*alpha*/-demethylases (CYP51) belong to the second group of P450s. The CYP51 family, however, is very special as its members preserve strict functional conservation in enzyme activity in all biological kingdoms. At amino acid identity across the kingdoms as low as 25-30%, they all catalyze essentially the same three-step reaction of oxidative removal of the 14/*alpha*/-methyl group from the lanostane frame. This reaction is the required step in sterol biosynthesis of pathogenic microbes. We have shown that specific inhibition of protozoan CYP51 can potentially provide treatment for human trypanosomiases. Three sets of CYP51 inhibitors tested in vitro and in trypanosomal cells in this study include azoles [best results being 50% cell growth inhibition at <1 and at 1.3 muM for Trypanosoma cruzi (TC) and Trypanosoma brucei (TB), respectively], non-azole compounds (50% TC cell growth inhibition at 5 microM) and substrate analogs of the 14/*alpha*/-demethylase reaction. 32-Methylene cyclopropyl lanost-7-enol exhibited selectivity toward TC with 50% cell growth inhibition at 3 microM.     

Design of novel FN3 domains with high stability by a consensus sequence approach

The use of consensus design to produce stable proteins has been applied to numerous structures and classes of proteins. Here, we describe the engineering of novel FN3 domains from two different proteins, namely human fibronectin and human tenascin-C, as potential alternative scaffold biotherapeutics. The resulting FN3 domains were found to be robustly expressed in Escherichia coli, soluble and highly stable, with melting temperatures of 89 and 78°C, respectively. X-ray crystallography was used to confirm that the consensus approach led to a structure consistent with the FN3 design despite having only low-sequence identity to natural FN3 domains. The ability of the Tenascin consensus domain to withstand mutations in the loop regions connecting the β-strands was investigated using alanine scanning mutagenesis demonstrating the potential for randomization in these regions. Finally, rational design was used to produce point mutations that significantly increase the stability of one of the consensus domains. Together our data suggest that consensus FN3 domains have potential utility as alternative scaffold therapeutics.     

The Kiss-and-Run Model of Intra-Golgi Transport

The Golgi apparatus (GA) is the main station along the secretory pathway. Mechanisms of intra-Golgi transport remain unresolved. Three models compete with each other for the right to be defined as the paradigm. The vesicular model cannot explain the following: (1) lipid droplets and aggregates of procollagen that are larger than coatomer I (COPI)-dependent vesicles are transported across the GA; and (2) most anterograde cargoes are depleted in COPI vesicles. The compartment progression/maturation model has the following problems: (1) most Golgi-resident proteins are depleted in COPI vesicles; (2) there are no COPI vesicles for the recycling of the resident proteins in the trans-most-Golgi cisterna; and (3) different proteins have different rates of intra-Golgi transport. The diffusion model based on permanent inter-cisternal connections cannot explain the existence of lipid, ionic and protein gradients across the Golgi stacks. In contrast, the kiss-and-run model has the potential to explain most of the experimental observations. The kiss-and-run model can be symmetric when fusion and then fission occurs in the same place, and asymmetric when fusion takes place in one location, whereas fission takes place in another. The asymmetric kiss-and-run model resembles the carrier maturation mechanism, and it can be used to explain the transport of large cargo aggregates.     

Support nanostructure boosts oxygen transfer to catalytically active platinum nanoparticles

Interactions of metal particles with oxide supports can radically enhance the performance of supported catalysts. At the microscopic level, the details of such metal-oxide interactions usually remain obscure. This study identifies two types of oxidative metal-oxide interaction on well-defined models of technologically important Pt-ceria catalysts: (1) electron transfer from the Pt nanoparticle to the support, and (2) oxygen transfer from ceria to Pt. The electron transfer is favourable on ceria supports, irrespective of their morphology. Remarkably, the oxygen transfer is shown to require the presence of nanostructured ceria in close contact with Pt and, thus, is inherently a nanoscale effect. Our findings enable us to detail the formation mechanism of the catalytically indispensable Pt-O species on ceria and to elucidate the extraordinary structure-activity dependence of ceria-based catalysts in general.     

天然与合成紫晶的3 543 cm-1红外吸收谱带及其鉴定价值

重点对3 800～3 000 cm-1范围的红外吸收光谱在鉴别天然与合成紫晶中的适用性和局限性进行了研究.3 680, 3 664, 3 630 cm-1处吸收带的存在可以确认紫晶为人工合成的, 但仅指那些在近中性NH4F溶液中合成的紫晶.相反, 商业上大量的合成紫晶是在碱性K2CO3溶液中合成的, 这些紫晶的红外吸收光谱并无明显的鉴定特征.前人的研究发现了在近3 595, 3 543 cm-1处吸收带的潜在鉴定价值.3 595 cm-1吸收带在合成紫晶的红外吸收光谱中并未出现, 在一些天然紫晶中也常常缺失.3 543 cm-1吸收带出现在绝大多数碱性溶液中合成紫晶的红外吸收光谱中, 但有时也在天然紫晶中出现.因此, 它只是鉴别合成紫晶的临时性证据.3 543 cm-1吸收带在有些类型的合成紫晶中缺失.要准确地鉴定天然与合成紫晶一定要根据其红外光谱、内部生长结构(包括双晶)和包裹体特征综合判断.