In vitro and in vivo Staining Characteristics of Small,Fluorescent, Aβ42‐Binding D‐Enantiomeric Peptides in Transgenic AD Mouse Models

Plaque visualisation : We identified three different D ‐enantiomeric peptides that bind to Alzheimer's amyloid β (Aβ1‐42). As there is currently no definitive pre‐mortem diagnosis for Alzheimer's disease, we investigated the peptides' suitability as molecular probes for in vivo imaging in transgenic mouse models.

     

Discovery of Riociguat (BAY 63‐2521): A Potent,Oral Stimulator of Soluble Guanylate Cyclase for the Treatment of Pulmonary Hypertension

Direct stimulation of soluble guanylate cyclase (sGC) represents a promising therapeutic strategy for the treatment of a range of diseases, including the severely disabling pulmonary hypertension (PH). Optimization of the unfavorable DMPK profile of previous sGC stimulators provided riociguat, which is currently being investigated in phase III clinical trials for the oral treatment of PH.

     

Inhibitors of inducible NO synthase expression: total synthesis of (S)-curvularin and its ring homologues

(S)-Curvularin and its 13-, 14-, and 16-membered lactone homologues were synthesized through a uniform strategy in which a Kochi oxidative decarboxylation and ring-closing metathesis reactions constitute the key processes. In the evaluation of the anti-inflammatory effects of the synthesized compounds in assays using cells stably transfected with a human iNOS promoter-luciferase reporter gene construct, the 14- and 16-membered homologues showed a slightly higher inhibitory effect towards iNOS promoter activity than curvularin itself. However, the larger ring homologues also exhibited higher cytotoxicity, manifest in downregulated eNOS promoter activity. In contrast, the di-O-acetyl and 4-chloro derivatives of (S)-curvularin showed higher inhibitory efficiency towards induction of the iNOS promoter and less negative effect on eNOS promoter activity than curvularin.     

Microstructure and Creep Behavior of Silicon Nitride and SiAlONs

Microstructural evolution of silicon nitride (Si₃N₄) and SiAlON materials and its influence on creep resistance is reviewed. Grain size, grain morphology, and the ratio of α- to β-phase grains play a part in resistance to creep. The glassy, intergranular phase typically has the strongest influence on creep. Creep data are usually obtained using uniaxial tensile or compressive tests, where creep in tension is controlled by cavitation and grain boundary sliding controls creep in compression. The impression creep methodology is also reviewed. An additional creep mechanism, dilation of the SiAlON grain structure, was found to be active in impression creep.     

采用新型焊接电弧提高焊接生产的经济效益和焊缝质量

通过在传统的短路过渡电弧和射流过渡电弧的基础上进行创新,发展新型的焊接电弧,可以显著地提高电弧焊接在金属连接中的优越性。两种新的焊接电弧,forceArc~杂志焊接电弧和coldArc~焊接电弧可以在一个焊接电源上实现,对焊接生产具有现实意义。了解和掌握这些新型电弧的工艺特点,可以有效地将其应用到生产中,以此提高焊接产品的质量和焊接生产的经济效益。新型焊接电弧的出现使现有的有关焊前焊接接头准备的标准和规定,特别是有关坡口角度和焊接位置,需要重新考虑。新型焊接电弧可以应用于各种金属加工工业中的焊接生产,是对弧焊工艺的一个创新。     

Particle In-Flight and Coating Properties of Fe-Based Feedstock Materials Sprayed with Modern Thermal Spray Systems

New developments in the field of thermal spraying systems (increased particle velocities, enhanced process stability) are leading to improved coatings. Innovations in the field of feedstock materials are supporting this trend. The combination of both has led to a renaissance of Fe-based feedstocks. Using modern APS or HVOF systems, it is now possible to compete with classical materials for wear and corrosion applications like Ni-basis or metal-matrix composites. This study intends to give an analysis of the in-flight particle and spray jet properties achievable with two different modern thermal spraying systems using Fe-based powders. The velocity fields are measured with the Laser Doppler Anemometry. Resulting coatings are analyzed and a correlation with the particle in-flight properties is given. The experiments are accompanied by computational fluid dynamics simulations of spray jet and particle velocities, leading to a comprehensive analysis of the achievable particle properties with state-of-the-art HVOF and APS systems.     

Synthesis of peptides onto the surface of poly(ethylene terephthalate) particle track membranes

In this article, we describe the synthesis of polypeptides onto the whole specific surface of poly(ethylene terephthalate) particle track membranes. In this case, initial functionalization is necessary. It had been done by an optimized surface oxidation in accordance with the method of Marchant‐Brynaert, J.; Deldime, M.; Dupont, I.; Dewez, J.‐L.; Schneider, Y.‐J. (J Colloid Interface Sci 1995, 173, 236). Subsequent activation with carbodiimide and reaction with multifunctional amines yielded an aminated surface. The synthesis of peptides was carried out by two different means: first, by the coupling of single amino acids analogous to the method of Merrifield, and second, by coupling of presynthesized polypeptides consisting of 18 helix‐forming amino acids. Analytical characterization was carried out by fluorescence spectroscopy by using the label Fluram® and confirmed by the results of X‐ray photoelectron (XP) spectroscopy. Only the stepwise synthesis led to a dense surface functionalization with peptides, whereas the coupling of fragments resulted in lower yields of coupling. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 74: 1669–1674, 1999     

3D-FE-Analysis of CT-specimens including viscoplastic material behavior and nonlocal damage

In order to describe the time-dependent inelastic behavior of steel structures up to failure, a material model is developed within the framework of thermodynamics considering viscoplastic material behavior, isotropic hardening, softening, and isotropic ductile damage. Since softening and damage lead to localization of deformations, the model is extended by a non-local implicit gradient formulation. An additional gradient equation is formulated for the local damage variable in order to achieve results independent of the finite-element discretization. The approach is verified by 3D-structural analysis of CT-specimens.     

Flexural behaviour and strength of cold-formed steel L-headers

Cold-formed steel headers are structural components used over wall openings in cold-formed steel residential and light commercial construction. Recently, there has been an increased interest in cold-formed L-headers among homebuilders primarily due to their ease of installation and low material cost. The findings from an extensive laboratory testing program, of full-scale single and double cold-formed steel L-headers are presented in this paper. The objective of the research was to investigate the flexural behaviour and strength of L-headers under both gravity and uplift loads. Based on the results improved ultimate strength design expressions and new deflection expressions for a wide range of L-header assemblies have been proposed.