Nanomechanical testing of Ti/Ni multilayer thin films

The main aim of the present work was to study the dependence of mechanical properties of Ti/Ni multilayer thin films on the thicknesses of constituent Ti and Ni layers. The multilayer thin films were made by depositing Ti and Ni layers alternately on single crystalline silicon substrates using magnetron sputtering method. Thickness of individual Ti and Ni layers varied from 1.7 nm to 100 nm, the total multilayer thickness was around 1 µm. The mechanical properties were characterized by means of nanoindentation experiments using a Hysitron dual head TI950 triboindenter equipped with diamond Berkovich tip in both static and dynamic loading regime in the load range from 50 µN to 11 mN. Moreover, nanoindentation tests were performed at elevated temperatures up to 500 oC using a Hysitron xSol heating stage. The nanoindentation data were evaluated using the recently developed home-made Nanoindentation General Evaluation Tool (NIGET) [1] software for independent analysis of loading and unloading curves which includes among others a basic treatment of uncertainties and systematic errors that are missing in commercial software provided together with instrumented indentation testing devices. The NIGET software has a graphical interface which uses libraries of the open source software Gwyddion [2]. The nanoindentation results were correlated with microstructure studies using XRD (X-ray diffraction technique), a Tescan LYRA 3XMU FEG/SEM×FIB scanning electron microscope (SEM), a Philips CM12 STEM transmission electron microscope (TEM) and a JEOL JEM-2100Fhigh resolution TEM. Thin lamellar cross sections for TEM observations were prepared using a focused ion beam (FIB) in SEM from two locations in each sample: an undisturbed layer and a central region of indentation print made with Berkovich tip with a relatively high load from the range of 0.5 to 1N. Please click Additional Files below to see the full abstract

Preclinical scenario of targeting myocardial fibrosis with chimeric antigen receptor (CAR) immunotherapy

Fibrosis is present in an important proportion of myocardial disorders. Injury activates cardiac fibroblasts, which deposit excess extracellular matrix, increasing tissue stiffness, impairing cardiac function, and leading to heart failure. Clinical therapies that directly target excessive fibrosis are limited, and more effective treatments are needed. Immunotherapy based on chimeric antigen receptor (CAR) T cells is a novel technique that redirects T lymphocytes toward specific antigens to eliminate the target cells. It is currently used in haematological cancers but has demonstrated efficacy in mouse models of hypertensive cardiac fibrosis, with activated fibroblasts as the target cells. CAR T cell therapy is associated with significant toxicities, but CAR natural killer cells can overcome efficacy and safety limitations. The use of CAR immunotherapy offers a potential alternative to current therapies for fibrosis reduction and restoration of cardiac function in patients with myocardial fibrosis

General conclusions regarding the planetary–solar–terrestrial interaction

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Using hydroxyl radical footprinting to explore the free energy landscape of protein folding.

Characterisation of the conformational states adopted during protein folding, including globally unfolded/disordered structures and partially folded intermediate species, is vital to gain fundamental insights into how a protein folds. In this work we employ fast photochemical oxidation of proteins (FPOP) to map the structural changes that occur in the folding of the four-helical bacterial immunity protein, Im7. Oxidative footprinting coupled with mass spectrometry (MS) is used to probe changes in the solvent accessibility of amino acid side-chains concurrent with the folding process, by quantifying the degree of oxidation experienced by the wild-type protein relative to a kinetically trapped, three-helical folding intermediate and an unfolded variant that lacks secondary structure. Analysis of the unfolded variant by FPOP-MS shows oxidative modifications consistent with the species adopting a solution conformation with a high degree of solvent accessibility. The folding intermediate, by contrast, experiences increased levels of oxidation relative to the wild-type, native protein only in regions destabilised by the amino acid substitutions introduced. The results demonstrate the utility of FPOP-MS to characterise protein variants in different conformational states and to provide insights into protein folding mechanisms that are complementary to measurements such as hydrogen/deuterium exchange labelling and Φ-value analysis

An analytical dynamic model of heat transfer from the heating body to the heated room

On the base of mathematical description of thermal balance the dynamic model of the hot-water heating body (radiator) was designed. The radiator is mathematically described as a heat transfer system between heating water and warmed-up air layer. Similarly, the dynamic model of heat transfer through the wall from the heated space to the outdoor environment was design. Both models were interconnected into dynamic model of heat transfer from the heating body to the heated room and they will be implemented into simulation model of the heating system in Matlab/Simulink environment