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.     

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     

Numerical study on PEMFC’s geometrical parameters under different humidifying conditions

Steady-state and three-dimensional simulations were carried out to study the influences of geometrical parameters on the performance of PEMFC under different hydrating conditions. Flow fields, species transport, transport of water in polymer membrane and movement of liquid water in cathode and anode porous layers were determined, in order to accomplish a complete estimation of ohmic and concentration losses of PEMFC power. The geometrical parameters were thickness of the polymer membrane, cathode catalyst layer as well as gas channel to rib width ratio. Every simulation was made under different relative humidities of inlet flows (50 and 100%) for every change of characteristic length. Results show that the influence of the geometrical parameters on ohmic and concentration losses is of considerable importance. The performance of PEMFC is seriously affected under dehydrating conditions. However, such performance may be considerably improved by using suitable geometrical parameters. Cathode and anode liquid saturation may not only affect the transport of species, but also the polymer electrolyte water content. These results show the importance of simultaneously calculating both the water absorption and desorption through the polymer electrolyte and the liquid saturation in the cathode and anode porous mediums to obtain an actual view of ohmic and concentration losses of the PEMFC performance.     

All year power supply with off-grid photovoltaic system and clean seasonal power storage

The objective of the project is an all-year secure supply of alternating current based on a solar energy island grid consisting of serial components and seasonal energy storage. Photovoltaic modules, inverters, electrolysers, batteries, hydrogen stores and fuel cells form the basis of the independent power supply system. For this, selected load profiles were analysed and evaluated in theory and practice.The analysis is based on the results of the test runs of the system and the simulations, in which the combined hydrogen-battery-system is compared to the battery system.It was revealed that it is sensible to complement an island grid operating on lead batteries for shortterm energy supply with hydrogen as a long-term store. This ensures a year-round supply security based on solar energy and the extension of the life span of the batteries required for hydrogen-based power stores. The systems based purely on batteries can not provide perfect supply security during long periods of low solar radiation since they do not possess energy stores which allow long-term energy storage.Hence a seasonal energy store, such as hydrogen, is required to guarantee reliable power supply for every day of the year.Autonomous power supply systems with long-term energy stores operate independently from the public grid system and can be implemented without elaborate intelligent energy management. For this, however, the costs of the serial components must be reduced and the efficiency of the system must be improved.     

The absence of corpus luteum formation alters the endocrine profile and affects follicular development during the first follicular wave in cattle

We previously established a bovine experimental model showing that the corpus luteum (CL) does not appear following aspiration of the preovulatory follicle before the onset of LH surge. Using this model, the present study aimed to determine the profile of follicular development and the endocrinological environment in the absence of CL with variable nadir circulating progesterone (P(4)) concentrations during the oestrous cycle in cattle. Luteolysis was induced in heifers and cows and they were assigned either to have the dominant follicle aspirated (CL-absent) or ovulation induced (CL-present). Ultrasound scanning to observe the diameter of each follicle and blood collection was performed from the day of follicular aspiration or ovulation and continued for 6 days. The CL-absent cattle maintained nadir circulating P(4) throughout the experimental period and showed a similar diameter between the largest and second largest follicle, resulting in co-dominant follicles. Oestradiol (E(2)) concentrations were greater in the CL-absent cows than in the CL-present cows at day -1, day 1 and day 2 from follicular deviation. The CL-absent cows had a higher basal concentration, area under the curve (AUC), pulse amplitude and pulse frequency of LH than the CL-present cows. After follicular deviation, the CL-absent cows showed a greater basal concentration, AUC and pulse amplitude of growth hormone (GH) than the CL-present cows. These results suggest that the absence of CL accompanying nadir circulating P(4) induces an enhancement of LH pulses, which involves the growth of the co-dominant follicles. Our results also suggest that circulating levels of P(4) and E(2) affect pulsatile GH secretion in cattle.