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.     

Copper-zirconium tungstate composites exhibiting low and negative thermal expansion influenced by reinforcement phase transformations

A fully-dense Cu-75 vol pct ZrW₂O₈ metal matrix composite was fabricated by hot isostatic pressing of Cu-coated ZrW₂O₈ particles. A small amount of the high-pressure γ-ZrW₂O₈ phase was created during the cooldown and depressurization following densification; near complete transformation to γ-ZrW₂O₈ was achieved by subsequent cold isostatic pressing. The thermal expansion behavior of the composite between 25°C and 325°C was altered by the cold isostatic pressing treatment, and also depended on the length of time that had passed between thermal cycles. The measured thermal expansion coefficients within specific temperature ranges varied from −6·10⁻⁶ K⁻¹ to far above the thermal expansion coefficient of the copper matrix. The complex temperature-dependent expansion/contraction behavior could be justified by considering the evolution of phase transformations taking place in the ZrW₂O₈ phase, which were observed by in-situ synchrotron X-ray diffraction measurements.     

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     

A critical assessment and thermodynamic calculation of the boron-carbon-titanium (B-C-Ti) ternary system

The B-C-Ti system has been critically assessed and calculated in the temperature region of 1400 °C up to the melting range employing the Thermocalc program system. The liquid phase is described using a substitutional model. The ternary solid solubility of boron in titanium carbide has been taken into account by using a two-sublattice model (Ti)₁(B,C,Va),. The calculated isotherms and isopleths are presented and compared with the experimental information. The B-C-Ti reaction scheme is presented including the Ti₃B₄ phase.     

Investigation of wetting behaviour of hardenable copper based-alloys for brazing applications

ABSTRACT

Tools for machining are exposed to high loads, wear, and elevated temperatures. Commonly, such tools consist of cemented carbides and tool steel. To combine the advantages of both materials, high-quality-joints with high strengths are desired. When brazing these materials, the main challenge is the mismatch of the Coefficient of Thermal Expansion (CTE) and the poor wettability of cemented carbides by molten filler alloys. In this regard, the feasibility of two custom-made alloys (CuNi12Si5, CuNi12Si5B0.4) was analysed. Besides being a cost-efficient alternative, these alloys offer the possibility to modify their mechanical properties by precipitation hardening to reduce stresses within the final joints. Thus, this paper shows that a temperature of 1060°C is suitable for wetting and brazing tests on different substrates.