Susceptor-assisted fast microwave sintering of TiN reinforced SiAlON composites in a single mode cavity

In the present study, 17 wt % TiN reinforced α-β SiAlON composites were sintered at low temperature by susceptor-assisted microwave heating. The effect of TiN addition on dielectrical properties of starting powders, as well as the influence of sintering temperature on phase evolution, microstructure development and mechanical properties of α/β-SiAlON-TiN composites were investigated. The obtained results showed that TiN addition increased the microwave absorbing properties which is reflected in the peak sintering temperature. Thus, the α:β ratio decreased and mechanical properties were improved, especially the fracture toughness of the composites. Furthermore, an estimate of energy consumption during microwave assisted sintering at the laboratory scale is presented. As a result, the highest values for relative density (97.1%), Vickers hardness (13.35 ± 0.47 GPa), and fracture toughness (7.52 ± 0.54 MPa m^1/2) were obtained by microwave sintering for 30 min at 1300 °C.     

Skeletal Muscle Health and Cognitive Function: A Narrative Review

Sarcopenia is the loss of skeletal muscle mass and function with advancing age. It involves both complex genetic and modifiable risk factors, such as lack of exercise, malnutrition and reduced neurological drive. Cognitive decline refers to diminished or impaired mental and/or intellectual functioning. Contracting skeletal muscle is a major source of neurotrophic factors, including brain-derived neurotrophic factor, which regulate synapses in the brain. Furthermore, skeletal muscle activity has important immune and redox effects that modify brain function and reduce muscle catabolism. The identification of common risk factors and underlying mechanisms for sarcopenia and cognition may allow the development of targeted interventions that slow or reverse sarcopenia and also certain forms of cognitive decline. However, the links between cognition and skeletal muscle have not been elucidated fully. This review provides a critical appraisal of the literature on the relationship between skeletal muscle health and cognition. The literature suggests that sarcopenia and cognitive decline share pathophysiological pathways. Ageing plays a role in both skeletal muscle deterioration and cognitive decline. Furthermore, lifestyle risk factors, such as physical inactivity, poor diet and smoking, are common to both disorders, so their potential role in the muscle–brain relationship warrants investigation.     

Design and Characterization of a New pVII Combinatorial Phage Display Peptide Library for Protease Substrate Mining Using Factor VII Activating Protease (FSAP) as Model

We describe a novel, easy and efficient combinatorial phage display peptide substrate-mining method to map the substrate specificity of proteases. The peptide library is displayed on the pVII capsid of the M13 bacteriophage, which renders pIII necessary for infectivity and efficient retrieval, in an unmodified state. As capture module, the 3XFLAG was chosen due to its very high binding efficiency to anti-FLAG mAbs and its independency of any post-translational modification. This library was tested with Factor-VII activating protease (WT-FSAP) and its single-nucleotide polymorphism variant Marburg-I (MI)-FSAP. The WT-FSAP results confirmed the previously reported Arg/Lys centered FSAP cleavage site consensus as dominant, as well as reinforcing MI-FSAP as a loss-of-function mutant. Surprisingly, rare substrate clones devoid of basic amino acids were also identified. Indeed one of these peptides was cleaved as free peptide, thus suggesting a broader range of WT-FSAP substrates than previously anticipated.     

Modeling Alcohol Dehydrogenase Catalysis in Deep Eutectic Solvent/Water Mixtures

The use of oxidoreductases (EC1) in non-conventional reaction media has been increasingly explored. In particular, deep eutectic solvents (DESs) have emerged as a novel class of solvents. Herein, an in-depth study of bioreduction with an alcohol dehydrogenase (ADH) in the DES glyceline is presented. The activity and stability of ADH in mixtures of glyceline/water with varying water contents were measured. Furthermore, the thermodynamic water activity and viscosity of mixtures of glyceline/water have been determined. For a better understanding of the observations, molecular dynamics simulations were performed to quantify the molecular flexibility, hydration layer, and intraprotein hydrogen bonds of ADH. The behavior of the enzyme in DESs follows the classic dependence of water activity (a_W) in non-conventional media. At low a_W values (<0.2), ADH does not show any activity; at higher a_W values, the activity was still lower than that in pure water due to the high viscosities of the DES. These findings could be further explained by increased enzyme flexibility with increasing water content.     

The Gut Microbiota: A Potential Gateway to Improved Health Outcomes in Breast Cancer Treatment and Survivorship

Breast cancer is the most frequently diagnosed cancer in women worldwide. The disease and its treatments exert profound effects on an individual’s physical and mental health. There are many factors that impact an individual’s risk of developing breast cancer, their response to treatments, and their risk of recurrence. The community of microorganisms inhabiting the gastrointestinal tract, the gut microbiota, affects human health through metabolic, neural, and endocrine signaling, and immune activity. It is through these mechanisms that the gut microbiota appears to influence breast cancer risk, response to treatment, and recurrence. A disrupted gut microbiota or state of ‘dysbiosis’ can contribute to a biological environment associated with higher risk for cancer development as well as contribute to negative treatment side-effects. Many cancer treatments have been shown to shift the gut microbiota toward dysbiosis; however, the microbiota can also be positively manipulated through diet, prebiotic and probiotic supplementation, and exercise. The objective of this review is to provide an overview of the current understanding of the relationship between the gut microbiota and breast cancer and to highlight potential strategies for modulation of the gut microbiota that could lead to improved clinical outcomes and overall health in this population.     

A modelling framework to support design of complex engineering systems in early design stages

Production, assembly or logistic systems exist in widespread domains. It is agreed that more than 50% of life-cycle performance, costs and environmental impacts of such systems are due to those decisions that are made in their early design stages (Reich, Res Eng Design 28(4):411–419, https://doi.org/10.1007/s00163-017-0270-7, 2017). However, the large scale and multi-disciplinary essence of such systems make their design considerably challenging. Most of the design approaches follow a sequential approach such that the design in each lower level is finalized/frozen before proceeding to the next level. However, such approaches do not properly address the interaction between different design disciplines which may later lead to design inconsistencies. Therefore, this paper aimed to propose a modelling framework that allows having an integrated approach in the early design stages of such systems. To this end, first the framework prescribed developing an executable meta-architecture that can embody all the design requirements. Second, the framework describes the interconnections between the meta-architecture with certain supporting algorithms and optimization models. This allows generating and simulating different design alternatives and observing the impact of different design decisions on system integrated performance. Therefore, the proposed framework with its providing outcomes can be used to support the decision making in early design stages of such systems. The framework is applied in a real case study from the warehousing domain, which serves to show the practical application of the proposed framework.     

Use of Eddy Current Conductivity and Hardness Testing to Evaluate Heat Damage in Aluminum Alloys

Aluminum alloys are heat treated to provide optimal material properties for use in a variety of applications. However, when exposed to abnormally high temperatures, an evaluation must be performed to determine if the aluminum component has been compromised. Nondestructive evaluation of aluminum alloys, by means of electrical conductivity and hardness tests, can assist in determining the condition of the part. These techniques require experience and engineering judgment to properly interpret the data produced in order to determine whether a part needs to be replaced. This article will elaborate on issues with these nondestructive techniques to help diagnose the condition of aluminum alloys exposed to high temperatures.     

Transport phenomena in electrolyte solutions: Nonequilibrium thermodynamics and statistical mechanics

The theory of transport phenomena in multicomponent electrolyte solutions is presented here through the integration of continuum mechanics, electromagnetism, and nonequilibrium thermodynamics. The governing equations of irreversible thermodynamics, including balance laws, Maxwell's equations, internal entropy production, and linear laws relating the thermodynamic forces and fluxes, are derived. Green–Kubo relations for the transport coefficients connecting electrochemical potential gradients and diffusive fluxes are obtained in terms of the flux–flux time correlations. The relationship between the derived transport coefficients and those of the Stefan–Maxwell and infinitely dilute frameworks are presented, and the connection between the transport matrix and experimentally measurable quantities is described. To exemplify the application of the derived Green–Kubo relations in molecular simulations, the matrix of transport coefficients for lithium and chloride ions in dimethyl sulfoxide is computed using classical molecular dynamics and compared with experimental measurements.     

Silicene Nanoribbons on an Insulating Thin Film

Silicene, a new 2D material has attracted intense research because of the ubiquitous use of silicon in modern technology. However, producing free-standing silicene has proved to be a huge challenge. Until now, silicene could be synthesized only on metal surfaces where it naturally forms strong interactions with the metal substrate that modify its electronic properties. Here, the authors report the first experimental evidence of silicene nanoribbons on an insulating NaCl thin film. This work represents a major breakthrough, for the study of the intrinsic properties of silicene, and by extension to other 2D materials that have so far only been grown on metal surfaces.     

E7766, a Macrocycle-Bridged Stimulator of Interferon Genes (STING) Agonist with Potent Pan-Genotypic Activity

A strategy for creating potent and pan-genotypic stimulator of interferon genes (STING) agonists is described. Locking a bioactive U-shaped conformation of cyclic dinucleotides by introducing a transannular macrocyclic bridge between the nucleic acid bases leads to a topologically novel macrocycle-bridged STING agonist (MBSA). In addition to substantially enhanced potency, the newly designed MBSAs, exemplified by clinical candidate E7766 , exhibit broad pan-genotypic activity in all major human STING variants. E7766 is shown to have potent antitumor activity with long lasting immune memory response in a mouse liver metastatic tumor model. Two complementary stereoselective synthetic routes to E7766 are also described.