Evaluation of Metal Plasticity and Research on the Mechanics of Pressure Treatment Processes Under Complex Loading

A calculating apparatus has been developed to help evaluate the stress-strain state in the plastic forming processes accompanied by a complex loading in which the Bauschinger effect can be manifested. The developed methods are based on the phenomenological approach in which a material map is devised in the form of flow curves, Bauschinger curves, a function j characterizing the hereditary influence of the loading history, plasticity diagrams, and limiting strain surfaces. To evaluate the plasticity resource used, taking into account the non-monotonicity of loading, the relations for determining the main components of the guiding strain-rate tensor were obtained, which made it possible to simplify the calculation of the components of the damage tensor. With the help of the developed calculating apparatus, the applied plasticity resource was evaluated in the process of radial extrusion with the contour sag, which allowed setting the limiting parameters of the shaping. Also, as a result of the research, an increase in the plasticity of the metal was established by selecting rational loading paths in the space of the dimensionless coordinates h, ms, and eu. For example, in the process of radial extrusion with the contour sag due to a change in the nature of the deformation, it was possible to obtain a flange diameter of 44 mm, with the initial diameter of the cylindrical workpiece being 20 mm. The results obtained are important because in most cases the processes of metal pressure treatment are accompanied by non-monotonic deformatio

Modeling of the Process of the Shot Based on the Numerical Solution of the Equations of Internal Ballistics

The study of the process of firing a firearm, taking into account the degree of wear of the barrel, requires an assessment of the losses of powder gases due to their breakthrough between the barrel walls and the projectile. Currently, the known methods for solving the equations of internal ballistics do not provide for obtaining results wich take into account the loss of part of the powder gases. As a result, there was a need to overcome the contradiction between the needs of applied ballistics and the capabilities of the existing scientific and methodological apparatus for solving the equations of internal ballistics.The principles of construction of the difference scheme for the numerical solution of the equations of internal ballistics on the condition of the influence of typical defects of the barrel channels and ammunition are stated. Recurrent expressions for step-by-step calculation of ballistic elements of the shot are given, initial conditions for the first and second periods of the shot are defined. The practical testing of the difference scheme by the numerical solution of the equations of internal ballistics for characteristic combinations of initial data is carried out and its adequacy is confirmed. The expediency of creating a database of ballistic shot elements for typical defects of the barrel channels and powder charges is substantiated.As a result of researches, the difference scheme for the numerical solution of the equations of internal ballistics wich provide the possibility of taking into account the influence of typical defects of the barrel channels and ammunition on ballistic elements of the shot is obtained. This opens the way to improving the operational control of the technical condition of weapons and ammunition by advancing its reliability and efficiency.Based on the numerical solution of the equations of internal ballistics, it is possible to simulate the influence of the deviation of the geometrical parameters of the barrel channel and the degradation of the powder charge on the course of the shot process. This explains the importance and usefulness of the work for applied ballistic

Retinal ganglion cell repopulation for vision restoration in optic neuropathy: a roadmap from the RReSTORe Consortium

Abstract Retinal ganglion cell (RGC) death in glaucoma and other optic neuropathies results in irreversible vision loss due to the mammalian central nervous system’s limited regenerative capacity. RGC repopulation is a promising therapeutic approach to reverse vision loss from optic neuropathies if the newly introduced neurons can reestablish functional retinal and thalamic circuits. In theory, RGCs might be repopulated through the transplantation of stem cell-derived neurons or via the induction of endogenous transdifferentiation. The RGC Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration (RReSTORe) Consortium was established to address the challenges associated with the therapeutic repair of the visual pathway in optic neuropathy. In 2022, the RReSTORe Consortium initiated ongoing international collaborative discussions to advance the RGC repopulation field and has identified five critical areas of focus: (1) RGC development and differentiation, (2) Transplantation methods and models, (3) RGC survival, maturation, and host interactions, (4) Inner retinal wiring, and (5) Eye-to-brain connectivity. Here, we discuss the most pertinent questions and challenges that exist on the path to clinical translation and suggest experimental directions to propel this work going forward. Using these five subtopic discussion groups (SDGs) as a framework, we suggest multidisciplinary approaches to restore the diseased visual pathway by leveraging groundbreaking insights from developmental neuroscience, stem cell biology, molecular biology, optical imaging, animal models of optic neuropathy, immunology & immunotolerance, neuropathology & neuroprotection, materials science & biomedical engineering, and regenerative neuroscience. While significant hurdles remain, the RReSTORe Consortium’s efforts provide a comprehensive roadmap for advancing the RGC repopulation field and hold potential for transformative progress in restoring vision in patients suffering from optic neuropathies

Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI) : a phase 3, placebo-controlled, randomised trial

Background: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. Methods: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). Findings: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8–3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74–0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, p interaction=0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo; HR 0·96 [95% CI 0·78–1·18], p=0·68), as well as all-cause death (282 [5·1%] vs 323 [5·8%]; 0·88 [0·75–1·03], p=0·11). TIMI major bleeding occurred in 111 (2·0%) of 5536 patients receiving ticagrelor and 62 (1·1%) of 5564 patients receiving placebo (HR 2·03 [95% CI 1·48–2·76], p<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36–3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74–1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75–0·95, p=0·005, in contrast to patients without PCI where it did not, p interaction=0·012. Benefit was present irrespective of time from most recent PCI. Interpretation: In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk