Skin Cornification Proteins Provide Global Link between ROS Detoxification and Cell Migration during Wound Healing

Wound healing is a complex dynamic process characterised by a uniform flow of events in nearly all types of tissue damage, from a small skin scratch to myocardial infarction. Reactive oxygen species (ROS) are essential during the healing process at multiple stages, ranging from the initial signal that instigates the immune response, to the triggering of intracellular redox-dependent signalling pathways and the defence against invading bacteria. Excessive ROS in the wound milieu nevertheless impedes new tissue formation. Here we identify small proline-rich (SPRR) proteins as essential players in this latter process, as they directly link ROS detoxification with cell migration. A literature-based meta-analysis revealed their up-regulation in various forms of tissue injury, ranging from heart infarction and commensal-induced gut responses to nerve regeneration and burn injury. Apparently, SPRR proteins have a far more widespread role in wound healing and tissue remodelling than their established function in skin cornification. It is inferred that SPRR proteins provide injured tissue with an efficient, finely tuneable antioxidant barrier specifically adapted to the tissue involved and the damage inflicted. Their recognition as novel cell protective proteins combining ROS detoxification with cell migration will provide new venues to study and manage tissue repair and wound healing at a molecular level

Activin enhances skin tumourigenesis and malignant progression by inducing a pro-tumourigenic immune cell response

Activin is an important orchestrator of wound repair, but its potential role in skin carcinogenesis has not been addressed. Here we show using different types of genetically modified mice that enhanced levels of activin in the skin promote skin tumour formation and their malignant progression through induction of a pro-tumourigenic microenvironment. This includes accumulation of tumour-promoting Langerhans cells and regulatory T cells in the epidermis. Furthermore, activin inhibits proliferation of tumour-suppressive epidermal γδ T cells, resulting in their progressive loss during tumour promotion. An increase in activin expression was also found in human cutaneous basal and squamous cell carcinomas when compared with control tissue. These findings highlight the parallels between wound healing and cancer, and suggest inhibition of activin action as a promising strategy for the treatment of cancers overexpressing this factor

Review of Intrinsic Motivation in Simulation-based Game Testing

This paper presents a review of intrinsic motivation in player modeling, with a focus on simulation-based game testing. Modern AI agents can learn to win many games; from a game testing perspective, a remaining research problem is how to model the aspects of human player behavior not explained by purely rational and goal-driven decision making. A major piece of this puzzle is constituted by intrinsic motivations, i.e., psychological needs that drive behavior without extrinsic reinforcement such as game score. We first review the common intrinsic motivations discussed in player psychology research and artificial intelligence, and then proceed to systematically review how the various motivations have been implemented in simulated player agents. Our work reveals that although motivations such as competence and curiosity have been studied in AI, work on utilizing them in simulation-based game testing is sparse, and other motivations such as social relatedness, immersion, and domination appear particularly underexplored

ATF2 Variable βIP\beta_{IP} Parameters

Optical configurations with variable $\beta_{IP}$ parameters can be useful during the commissioning of the ATF2 beam line and for the performance optimisation, to limit the beam sensitivity to displacements and energy errors. Such configurations are calculated, and the resulting tolerances studies

The clinical outcome of the Metha short hip stem: a systematic scoping review

Introduction: Short femoral stems were designed to bridge the gap between conventional straight design stems and hip resurfacing prostheses in total hip arthroplasty (THA). A number of clinical trials have been recently conducted to assess the clinical and safety profile of the cementless, colarless, tapered Metha short hip stem in young or active middle-aged individuals. Methods: A systematic scoping review was conducted according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. 4 reviewers independently conducted the search using the MEDLINE/PubMed database and the Cochrane Database of Systematic Reviews. These databases were queried with the terms “short” AND “hip” AND “stem”. Results: From the initial 773 studies we finally chose 12 studies after applying our inclusion-exclusion criteria. The number of operated hips that were included in these studies was 5048 (mean BMI range: 22.7–35.2, mean age range: 44.4–60.4 years, mean follow-up range: 2–9 years). The mean modified Coleman methodology score was 52.3/100, while it ranged from 31/100 to 63/100. All mean clinical outcome scores that were used in the studies illustrated significant postoperative improvement when compared with the respective initial values. The revision rate of the Metha stem for component-related reasons was 2.5%, while the rate of major complications not requiring revision of the Metha stem was 2.8%. Conclusions: The Metha stem performs well in young or active middle-aged THA patients. Further studies are required for the assessment of the long-term results. © The Author(s) 2020