Identification and Structure–Activity Relationship Studies of Small‐Molecule Inhibitors of the Methyllysine Reader Protein Spindlin1

The methyllysine reader protein Spindlin1 has been implicated in the tumorigenesis of several types of cancer and may be an attractive novel therapeutic target. Small‐molecule inhibitors of Spindlin1 should be valuable as chemical probes as well as potential new therapeutics. We applied an iterative virtual screening campaign, encompassing structure‐ and ligand‐based approaches, to identify potential Spindlin1 inhibitors from databases of commercially available compounds. Our in silico studies coupled with in vitro testing were successful in identifying novel Spindlin1 inhibitors. Several 4‐aminoquinazoline and quinazolinethione derivatives were among the active hit compounds, which indicated that these scaffolds represent promising lead structures for the development of Spindlin1 inhibitors. Subsequent lead optimization studies were hence carried out, and numerous derivatives of both lead scaffolds were synthesized. This resulted in the discovery of novel inhibitors of Spindlin1 and helped explore the structure–activity relationships of these inhibitor series.     

轴流风机叶尖泄漏流动的大涡模拟（英文）

本文采用大涡模拟(LES)的方法研究了在基于外壳直径的雷诺数为9.36×105条件下5叶片的轴流式风扇的流动特性,并且着重分析了叶尖泄漏的流动现象。本文使用了基于有限体积法和分层笛卡尔网格的可压流求解器进行数值计算,并应用了体积守恒的切割网格方法处理风扇几何结构的浸入式边界。同时开发了用于笛卡尔网格的旋转周期性边界条件,这样只需分析由2.5亿网格构造的包含一片叶片的72°区域。该研究首先对网格质量进行了分析,之后讨论了瞬态和时均流场的特性,并与使用RANS的5叶片模拟结果进行了对比。RANS和LES模拟结果的主要不同之处体现在叶尖泄漏涡尾流中的湍流动能。本文进而研究了叶尖间隙对叶尖泄漏涡的影响。研究表明,间隙的大小会影响叶尖泄漏涡的大小形状。此外,间隙中更多的分离现象和反向旋转涡会导致较低的湍流动能。     

How Different Characterization Techniques Elucidate the Nature of the Gold Species in a Polycrystalline Au/TiO2 Catalyst

TiO₂‐supported gold species were prepared via the deposition‐precipitation route, with conservation of the initial speciation by freeze‐drying. The structural and electronic properties of the Au species were investigated by X‐ray absorption spectroscopy, electron microscopy, and IR spectroscopy of adsorbed CO in four states. Exclusively Au^III was deposited on the TiO₂ surface in patches ranging from isolated Au ions to three‐dimensional clusters. This paper illustrates in detail the unique contributions of all characterization techniques to this structural model.     

Photo-vulcanization using thiol-ene chemistry: Film formation,morphology and network characteristics of UV crosslinked rubber latices

The photo-vulcanization with versatile thiol-ene chemistry represents an innovative approach to crosslink diene-rubber materials both in latex and in solid film state. In this work, the structure of elastomer-based thiol-ene networks and the morphology after film formation are studied in detail using electron microscopic techniques, atomic force microscopy and multiple-quantum solid-state NMR spectroscopy. Additionally, film formation properties and corresponding macroscopic properties of photo-vulcanized natural rubber (NR) latex and its synthetic counterpart, isoprene rubber (IR) latex, are determined in dependence on the curing procedure (pre- and post-vulcanization). The results reveal that thiol-ene cured elastomers comprise homogenously distributed crosslinks with a low amount of short chain defects. Whilst photochemically pre-cured NR latex particles provide coherent films, the film formation and mechanical properties of IR are strongly governed by the crosslink density of the latex particles. In film state, photo-vulcanization promotes narrow crosslink distributions and excellent tensile properties of both NR and IR.     

大型X射线光学仪器:单层镜和多层镜的制造与表征

150~500 mm长度的各种X射线光学元件可用于光束导引,光束调整,以及单色化。本文介绍了两种不同的大型X射线反射镜。第一种为单层反射镜,这种反射镜以2°掠入射角在软X射线区(50~200 eV)起全反射镜作用,可用于自由电子激光器,如德国汉堡的FLASH。第二种是多层镜,由于它的布喇格反射特性,适于作为反射镜以0.4~1°的入射角用于硬X射线区(20~50 keV),如层析光束线的同步辐射存储环中。两种反射镜都用最新物理汽相淀积法制备,并用磁控溅射来实现X射线光学应用所需要的优良光学品质。这一淀积工艺使不同批次的镀膜稳定性良好,有利于实际反射镜在优质衬底上的最后淀积。单层镜和多层镜在它们的相关能量范围内都有很高的反射率,表面粗糙度也很低,且在整个光学波长区这些特性表现均匀。文中所叙相关研究都是借助X射线反射计量(XRR)法,透射电子显微镜(TEM)、光学轮廓仪(OP),以及原子力显微镜(AFM)完成的。     

SOAT1: A Suitable Target for Therapy in High-Grade Astrocytic Glioma?

Targeting molecular alterations as an effective treatment for isocitrate dehydrogenase-wildtype glioblastoma (GBM) patients has not yet been established. Sterol-O-Acyl Transferase 1 (SOAT1), a key enzyme in the conversion of endoplasmic reticulum cholesterol to esters for storage in lipid droplets (LD), serves as a target for the orphan drug mitotane to treat adrenocortical carcinoma. Inhibition of SOAT1 also suppresses GBM growth. Here, we refined SOAT1-expression in GBM and IDH-mutant astrocytoma, CNS WHO grade 4 (HGA), and assessed the distribution of LD in these tumors. Twenty-seven GBM and three HGA specimens were evaluated by multiple GFAP, Iba1, IDH1 R132H, and SOAT1 immunofluorescence labeling as well as Oil Red O staining. To a small extent SOAT1 was expressed by tumor cells in both tumor entities. In contrast, strong expression was observed in glioma-associated macrophages. Triple immunofluorescence labeling revealed, for the first time, evidence for SOAT1 colocalization with Iba1 and IDH1 R132H, respectively. Furthermore, a notable difference in the amount of LD between GBM and HGA was observed. Therefore, SOAT1 suppression might be a therapeutic option to target GBM and HGA growth and invasiveness. In addition, the high expression in cells related to neuroinflammation could be beneficial for a concomitant suppression of protumoral microglia/macrophages.     

Illusion—creating a mock reality

Photorealistic computer animation sequences have become more important in recent years in visualization and presentation techniques as well as in fine arts. Some aspects of creating a photorealistic computer animation are demonstrated by the following example of the film Illusion that was created by the computer graphics team at the University of Karlsruhe. An overview of modelling methods, some special effects and details on how to administrate a large computer animation project are presented.