Nanomechanical behavior of individual phases and size effect in WC-Co by means of high temperature nanoindentation and electron microscopy: A study from ambient to high temperature

The dependence of the hardness and deformation mechanism of individual phases in WC-Co on microstructural parameters such as grain size and orientation was investigated by nanoindentation and electron microscopy from ambient to high temperature. At room temperature, the binder phase only exhibits a hardness of about 10 GPa, whilst the hardness of WC grains were measured about 29-30 and 37 GPa for the prismatic and basal orientation, respectively. All WC orientations exhibited a similar decrease in hardness as the temperature increased. A broad range of WC prismatic grain areas (AWC-prismatic), from about 2 to 1000 µm2, were selected and subsequently indented to investigate any size effect. A slight decrease in the hardness of WC prismatic grains (HWC-prismatic) as a function of AWC-prismatic was observed. Damage mechanisms occurring in WC-Co during nanoindentation were investigated for the different grain orientation at various temperature. The damage was visualised using electron microscopy near the residual indent as well as focused ion beam sectioning across the indent. The three dimensional distribution of plastic deformation across multiple grains in the vicinity of an indent was examined using Electron Back Scattered Diffraction (EBSD) and Electron Channelling Contrast Imaging (ECCI). The ECCI enabled the observation of crystal defects, especially dislocations, in th plastic zone. The dislocation density and spatial distribution in the deformed WC-Co were compared to that of an untested WC-Co to relate the quantity of defects as well as their origin to the state of stress in the material. The collected data represent useful guidance for manufacturer of hardmetals, provides important information underpinning an understanding of the relationship between WC-Co microstructure and mechanical properties, and also highlight the performance of WC-Co at operating temperatures. Please click Additional Files below to see the full abstract

Estimation of fatigue strength of TiN coatings using cyclic micro-impact testing

This study delves into the behaviour of a thin TiN coating on a tool steel substrate material under dynamic and cyclic impacts through a comprehensive approach combining experimental testing and computational modelling. In dynamic impact tests, a pendulumbased setup investigates material responses under varying acceleration loads, revealing a distinctive "ringing effect" as the indenter bounces off the specimen's surface, with all plastic deformation concentrated during the initial impact. The study also quantifies dynamic hardness values, highlighting load-dependent behaviour and assessing the coating system's energy dissipation capabilities. In cyclic impact tests, materials experience permanent plastic deformation with each cycle, ultimately leading to coating failure. Chemical analysis identifies an interlayer between the coating and substrate, while cross-sectional analysis reveals the extent of coating damage due to cycling and load. A three-dimensional map is constructed, connecting acceleration load, sensed depth, and cycles to coating failure, and an empirical equation characterizes the relationship between depth and cycles before failure. The computational model scrutinizes traction component distribution during loading and unloading, with a focus on normal and shear tractions. The findings suggest the potential significance of normal traction in interface fatigue failure. Overall, offering implications for understanding and mitigating fatigue-related failures across various applications

Foregrounding the perspectives of mental health service users during the COVID-19 pandemic

This viewpoint highlights the critical importance of the perspectives of mental health service-users during the COVID-19 pandemic. This viewpoint is based on a review of recent research and literature and draws on consultations with experts by experience, including the lead author. We argue that expertise-by-experience is critical to policy, service development and research; but there is a risk it will be neglected at a time of rapid and reactive clinical development. Understanding and responding to the nuances of individual need can only be achieved through coproducing service strategy design, delivery and research with mental health service users. The consultation outlined in this viewpoint gives some indication of the type of valuable insights that can be gained through seeking and listening to the perspectives of experts by experience. Our discussions revealed that experience of managing severe and complex mental health conditions can actually be advantageous when facing a crisis such as COVID-19

Hepatitis E in England and Wales

In 2005, 329 cases of hepatitis E virus infection were confirmed in England and Wales; 33 were confirmed indigenous infections, and a further 67 were estimated to be indigenous infections. Hepatitis E should be considered in the investigation of patients with hepatitis even if they have no history of travel

Randomised nano-/micro- impact testing – A novel experimental test method to simulate erosive damage caused by solid particle impacts

A novel randomised nano-/micro-scale impact test method has been developed to experimentally simulate particulate erosion where statistically distributed impacts with defined energy occur sequentially within the test area. Tests have been performed on two brittle glasses (fused silica and BK7) to easily highlight the interaction between impacts, as well as on two ceramic thermal barrier coating systems (TBCs, yttria stabilised zirconia, 7YSZ, and gadolinium zirconate, GZO) that experience erosion in service. Differences in erosion resistance were reproduced in the randomised impact tests, with GZO less impact resistant than 7YSZ, and BK7 significantly worse than fused silica. The impact data show that erosion resistance is influenced by different factors for the glasses (crack morphology, longer-length interaction of radial-lateral cracks in BK7 vs cone-cracking in fused silica) and TBCs (fracture toughness).Support from Innovate UK under Smart Award project #10020751, High temperature tools for designing sustainable erosion resistant coatings, is gratefully acknowledged

Sulfatase-2 from Cancer Associated Fibroblasts: An Environmental Target for Hepatocellular Carcinoma?

Introduction: Heparin sulphate proteoglycans in the liver tumour microenvironment (TME) are key regulators of cell signalling, modulated by sulfatase-2 (SULF2). SULF2 overexpression occurs in hepatocellular carcinoma (HCC). Our aims were to define the nature and impact of SULF2 in the HCC TME. Methods: In liver biopsies from 60 patients with HCC, expression and localization of SULF2 were analysed associated with clinical parameters and outcome. Functional and mechanistic impacts were assessed with immunohistochemistry (IHC), in silico using The Cancer Genome Atlas (TGCA), in primary isolated cancer activated fibroblasts, in monocultures, in 3D spheroids, and in an independent cohort of 20 patients referred for sorafenib. IHC targets included αSMA, glypican-3, β-catenin, RelA-P-ser536, CD4, CD8, CD66b, CD45, CD68, and CD163. SULF2 impact of peripheral blood mononuclear cells was assessed by migration assays, with characterization of immune cell phenotype using fluorescent activated cell sorting. Results: We report that while SULF2 was expressed in tumour cells in 15% (9/60) of cases, associated with advanced tumour stage and type 2 diabetes, SULF2 was more commonly expressed in cancer-associated fibroblasts (CAFs) (52%) and independently associated with shorter survival (7.2 vs. 29.2 months, p = 0.003). Stromal SULF2 modulated glypican-3/β-catenin signalling in vitro, although in vivo associations suggested additional mechanisms underlying the CAF-SULF2 impact on prognosis. Stromal SULF2 was released by CAFS isolated from human HCC. It was induced by TGFβ1, promoted HCC proliferation and sorafenib resistance, with CAF-SULF2 linked to TGFβ1 and immune exhaustion in TGCA HCC patients. Autocrine activation of PDGFRβ/STAT3 signalling was evident in stromal cells, with the release of the potent monocyte/macrophage chemoattractant CCL2 in vitro. In human PBMCs, SULF2 preferentially induced the migration of macrophage precursors (monocytes), inducing a phenotypic change consistent with immune exhaustion. In human HCC tissues, CAF-SULF2 was associated with increased macrophage recruitment, with tumouroid studies showing stromal-derived SULF2-induced paracrine activation of the IKKβ/NF-κB pathway, tumour cell proliferation, invasion, and sorafenib resistance. Conclusion: SULF2 derived from CAFs modulates glypican-3/β-catenin signalling but also the HCC immune TME, associated with tumour progression and therapy resistance via activation of the TAK1/IKKβ/NF-κB pathway. It is an attractive target for combination therapies for patients with HCC

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist