Extracellular Vesicles and Asthma—More Than Just a Co-Existence

Extracellular vesicles (EVs) are membranous structures, which are secreted by almost every cell type analyzed so far. In addition to their importance for cell-cell communication under physiological conditions, EVs are also released during pathogenesis and mechanistically contribute to this process. Here we summarize their functional relevance in asthma, one of the most common chronic non-communicable diseases. Asthma is a complex persistent inflammatory disorder of the airways characterized by reversible airflow obstruction and, from a long-term perspective, airway remodeling. Overall, mechanistic studies summarized here indicate the importance of different subtypes of EVs and their variable cargoes in the functioning of the pathways underlying asthma, and show some interesting potential for the development of future therapeutic interventions. Association studies in turn demonstrate a good diagnostic potential of EVs in asthma.     

Tetrahydroindoles as Multipurpose Screening Compounds and Novel Sirtuin Inhibitors

Indoles are privileged structures in medicinal and bioorganic chemistry that are particularly well suited to serve as platforms for diversity. Among many other therapeutic areas, the indole scaffold has been used to design aromatic compounds useful to interfere with enzymes engaged in the regulation of substrate acylation status, such as sirtuins. However, the planarity of the indole ring is not necessarily optimal for all target enzymes, especially when functionalization with aromatic side chains is required. Replacement of flat scaffolds by nonplanar molecular cores dominated by sp³ hybridization is a common strategy to avoid the disadvantages associated with poor solubility and high promiscuity, while covering less-well-explored areas of chemical space. Thus, we synthesized fragment-like tetrahydroindoles suitable for fragment-based drug discovery as well as a well-characterized small library intended as multipurpose screening compounds. For proof of principle, these compounds were screened against sirtuins 1–3, enzymes known to be addressable by indoles. We found that 2,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxamides are potent and selective SIRT2 inhibitors. Compound 16 t displayed an IC₅₀ value of 0.98 μm and could serve as exquisite starting point for hit-to-lead profiling.     

Matrix Transformation in Boron Containing High-Temperature Co–Re–Cr Alloys

An addition of boron largely increases the ductility in polycrystalline high-temperature Co–Re alloys. Therefore, the effect of boron on the alloy structural characteristics is of high importance for the stability of the matrix at operational temperatures. Volume fractions of ε (hexagonal close-packed—hcp), γ (face-centered cubic—fcc) and σ (Cr₂Re₃ type) phases were measured at ambient and high temperatures (up to 1500 °C) for a boron-containing Co–17Re–23Cr alloy using neutron diffraction. The matrix phase undergoes an allotropic transformation from ε to γ structure at high temperatures, similar to pure cobalt and to the previously investigated, more complex Co–17Re–23Cr–1.2Ta–2.6C alloy. It was determined in this study that the transformation temperature depends on the boron content (0–1000 wt. ppm). Nevertheless, the transformation temperature did not change monotonically with the increase in the boron content but reached a minimum at approximately 200 ppm of boron. A probable reason is the interplay between the amount of boron in the matrix and the amount of σ phase, which binds hcp-stabilizing elements (Cr and Re). Moreover, borides were identified in alloys with high boron content.     

Results from the ORPHEUS dark matter detector

The ORPHEUS dark matter detector consists of 450 g superconducting tin granules with diameters of 28 and 36 μm. The detector has been operating in the shallow site of the underground laboratory in Bern (70 m.w.e). First preliminary results on WIMP detection sensitivity will be presented.     

Processor membership in asynchronous distributed systems

Presents protocols for determining processor membership in asynchronous distributed systems that are subject to processor and communication faults. These protocols depend on the placement of a total order on broadcast messages. The types of systems for which each of these protocols is applicable are characterized by the properties of the communication mechanisms and by the availability of stable storage. In the absence of stable storage or of a mechanism for distinguishing promptly delivered messages, the authors show that no membership protocol can exist. They also discuss their experience in implementing these membership protocols     

用仿真工具优化车辆动力系统(一)

在本文的第一部分，介绍了一种理想的车辆动力系统的计算机辅助开发过程。它显示了现代仿真技术在产品持续发展过程中的作用，该技术采用硬件回路作非在线的仿真，并通过现代化的试验手段对车辆进行匹配。特别重要的是提供了将电控变速器和发动机控制单元综合的可能性。接着是在线仿真在诸如发动机和变速器模式方面的应用和发展，它是上述开发过程的基础。根据上述的方法论，本文论述了仿真技术已取得的成绩和将来的应用可能性。     

Comparison of Displacement and Mixing Diffusers

In order to cumpare the peformance of different supply diffuers of ventilation air, the airflow passern, temperature stratifiation and contaminant dispersion in a furnitured office ventilated by three kinds of air diffuer were numerically investigated. The air diffuers studied in this paper are a quarter-cylinder displacement diffuer on the floor and mixing diffuers (linear and vortex diffuers) on the ceiling. The heat sources in the of-fice are considered to be 50% convective and 50% radiative. The k-? two-equatwn model of turbulence is employed to predict the turbulent diffusion. The results show that the displacement diffuser provides a rather uniform flow field with low velocify in most areas, and the vertical temperature difference from floor to ceiling is as high as 6 K. With the linear diffuser, the air velociry is high, and the temperature is uniform both horizontally and vertically. The air velocity generated by the vortex diffuser is moderate. The distributions of the temperature and the contaminant are rather uniform.     

Analysis of electrocardiograms during atrial fibrillation

The research discussed in this article is motivated by the search for an optimal classification of the different types of atrial fibrillation (AF) on the basis of recorded atrial signals. This would facilitate the selection of an optimal therapy. This article focuses on the biophysical models of the genesis of ECG waveforms during AF. The model of the electric activity of the atria was found to have sufficient realism to be used to describe the electric sources during AF. The inclusion of the volume conduction model resulted in electrocardiographic signals that are in all aspects similar to those observed clinically. The model is currently applied to solve various problems related to optimal signal preprocessing and extraction of features in AF signals for the classification of AF abnormalities. The biophysical model of the atrial activity is an essential element in this research, since it is capable of describing the electric source specifications derived from different hypotheses relating to the etiology of AF     

Elastic constants of face-centered cubic and L1<Subscript>2</Subscript> Ni-Si alloys: Composition and temperature dependence

The adiabatic elastic stiffness constants C _ij of Ni-Si single-crystal solid-solution alloys of two slightly different compositions, 10.78 and 11.17 at. pct Si, were measured over the temperature range from 20 °C to 900 °C using the rectangular parallelepiped resonance method. The isotropic elastic constants of the polycrystalline ordered intermetallic compound Ni₃Si containing 23 at. pct Si were also measured over this temperature range. Values of the C _ij for Ni₃Si were estimated from the data on the polycrystalline alloy, as well as from published data in the literature on isomorphous ternary ordered intermetallic compounds containing different amounts of Si. Using measured values and previously published data, the stiffness constants of Ni₃Ti were estimated; these are the only available data on this alloy. The estimated single-crystal elastic constants of Ni₃Si, as well as the experimentally measured bulk modulus, are considerably smaller than published values calculated from first-principles methods. The same is true for the C _ij of Ni₃Ti, but the discrepancies are smaller.