EVs from BALF—Mediators of Inflammation and Potential Biomarkers in Lung Diseases

Extracellular vesicles (EVs) have been identified as key messengers of intracellular communication in health and disease, including the lung. EVs that can be found in bronchoalveolar lavage fluid (BALF) are released by multiple cells of the airways including bronchial epithelial cells, endothelial cells, alveolar macrophages, and other immune cells, and they have been shown to mediate proinflammatory signals in many inflammatory lung diseases. They transfer complex molecular cargo, including proteins, cytokines, lipids, and nucleic acids such as microRNA, between structural cells such as pulmonary epithelial cells and innate immune cells such as alveolar macrophages, shaping mutually their functions and affecting the alveolar microenvironment homeostasis. Here, we discuss this distinct molecular cargo of BALF-EVs in the context of inducing and propagating inflammatory responses in particular acute and chronic lung disorders. We present different identified cellular interactions in the inflammatory lung via EVs and their role in lung pathogenesis. We also summarize the latest studies on the potential use of BALF-EVs as diagnostic and prognostic biomarkers of lung diseases, especially of lung cancer.     

Ultrafine-grained nickel refined by dislocation activities at intermediate strain rate impact: deformation microstructure and mechanical properties

This article presents an application of the impact-induced deformation in effective grain refinement in polycrystalline nickel. Ultrafine-grained microstructure was processed by means of Dynamic Plastic Deformation at room temperature using a falling impactor with a maximum impact velocity of 10 m s⁻¹. The commercially pure (98.4 wt%) starting material was characterised by a coarse-grained (~25 μm) microstructure. Electron backscattering diffraction and transmission electron microscopy studies showed that the initial equiaxed grains evolved into a laminar structure of submicron size narrow domains delineated by high-angle grain boundaries. The texture after deformation exhibits preferential orientations including a strong 〈220〉 fibre texture. The mechanical behaviour under quasi-static compression at room temperature and at a strain rate of 2 × 10⁻³ s⁻¹ was investigated in directions parallel and perpendicular to the impact axis. Stress–strain responses showed an increased yield strength (440–520 MPa) compared with the initial state (90 MPa). The strain-hardening behaviour was found to strongly depend on the orientation of the compression axis.     

Criterion for microcrack resistance of multi-phase steels based on property gradient maps

A novel criterion for microcrack resistance of multi-phase steels based on property gradient maps is proposed. Two industrial sheets of steel were processed to obtain dual-phase and complex-phase microstructures with exactly the same chemical composition. Experimental investigations showed characteristic differences for the tensile tests, hole expansion and the local plastic behavior during deformation. An innovative full-field modeling approach that explicitly predicts mechanical property gradients as a function of microstructural gradients during forming was developed and validated. This allowed to form a new criterion for evaluation of structure–property relationship in nano-structured multi-phase steels and can reveal the formability limitations.     

Optimization of band structure and quantum-size-effect tuning for two-photon absorption enhancement in quantum dots

The two-photon absorption, 2PA, cross sections of PbS quantum dots, QDs, are theoretically and experimentally investigated and are shown to be enhanced with increasing quantum confinement. This is in contrast to our previous results for CdSe and CdTe QDs where the reduced density of states dominated and resulted in a decrease in 2PA with a decrease in QD size. Qualitatively this trend can be understood by the highly symmetric distribution of conduction and valence band states in PbS that results in an accumulation of allowed 2PA transitions in certain spectral regions. We also measure the frequency nondegenerate 2PA cross sections that are up to five times larger than for the degenerate case. We use a k·p four-band envelope function formalism to model the increasing trend of the two-photon cross sections due to quantum confinement and also due to resonance enhancement in the nondegenerate case.     

UVM-based verification methodology for RFID-enabled smart-sensor systems

Universal verification methodology (UVM) is a standardized methodology for verifying integrated circuit designs. In this contribution, we present a UVM-based verification methodology for verifying mixed-signal smart-sensor systems. Our approach permits the validation of system functionality before implementation and also to verify the implementation on various levels of abstraction. The model-based verification approach enables to build a scalable and reusable framework, in which assertions and constrained-random stimuli are used to monitor and also to verify mixed-signal-system behavior automatically. A comprehensive example of an radio-frequency identification-based smart-sensor mixed-signal system used for bioanalytical applications is presented. Along with the designed UVM test bench architecture, we describe a novel solution for estimating the power consumption of the digital sub-system using application-specific random-activity patterns generated during UVM test bench runs (Neumann et al., Synthesis Modelling Analysis and Simulation Methods and Application to Circuit Design, SMACD, 2012).     

Synthesis of solid epoxy resins base on BPC II and bisphenol A using conventional heating equipment and microwave

New solid state epoxy resins based on diglycidyl ether of 1,1‐dichloro‐2,2 bis (4‐hydroxyphenyl), ethylene (BPC) and BPA epoxy resins in the reaction with BPC and BPA were developed. Solid epoxy resins were synthesised by the use of two different heating methods: conventional and microwave reactor. The use of microwave radiation as novel heating medium as an alternative to the conventional methods, which provide a quicker and more effective synthesis. The solid epoxies have high melting points higher than 100°C and the polycondensation degree remains between n = 4–12. Epoxy value stays low and occurs around 0,02–0,1. BPA epoxy resins and diglycidylether of BPC II were compared in terms of reaction speed. It can be seen that the reaction of BPC diglycidylether occurs approximately 20% quicker given the same reaction conditions of temperature, and balance of catalyst. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 3850–3854, 2006     

Mechanical Properties and the Microstructure of Al2O3/Al/Al2O3 Joints with the Surface Modification of Alumina by a Thin Layer of Ti + Nb

Al₂O₃/Al/Al₂O₃ joints were formed by liquid-state bonding of alumina substrates covered with a thin Ti + Nb coating of 900 nm thickness with the use of an Al interlayer of 30 μm at 973 K under a vacuum of 0.2 mPa for 5 min. The bond strength of the joints was examined by a four-point bending test at 295, 373, and 473 K. Optical, scanning, and transmission electron microscopies were applied for detailed characterization of the interface structure and failure characteristics of fractured joint surfaces. The analysis of the results has shown that (i) bonding occurred due to the formation of a reactive interface on the metal side of the joint in the presence of Al₃Nb(Ti) precipitates and (ii) modification of Al₂O₃ by a thin layer of Ti + Nb increases the hardness at the interface and makes it possible to achieve reliable joints working at elevated temperatures.     

Discovery and biological activity of 6BrCaQ as an inhibitor of the Hsp90 protein folding machinery

Heat shock protein 90 (Hsp90) is a significant target in the development of rational cancer therapy, due to its role at the crossroads of multiple signaling pathways associated with cell proliferation and viability. Here, a novel series of Hsp90 inhibitors containing a quinolein‐2‐one scaffold was synthesized and evaluated in cell proliferation assays. Results from these structure–activity relationships studies enabled identification of the simplified 3‐aminoquinolein‐2‐one analogue 2 b (6BrCaQ), which manifests micromolar activity against a panel of cancer cell lines. The molecular signature of Hsp90 inhibition was assessed by depletion of standard known Hsp90 client proteins. Finally, processing and activation of caspases 7, 8, and 9, and the subsequent cleavage of PARP by 6BrCaQ, suggest stimulation of apoptosis through both extrinsic and intrinsic pathways.