Superficial shoulder muscle synergy analysis in Facioscapulohumeral Dystrophy during humeral elevation tasks

Facioscapulohumeral Dystrophy (FSHD) is a progressive muscle-wasting disease which leads to a decline in upper extremity functionality. Although the scapulohumeral joint's stability and functionality are affected, evidence on the synergetic control of the shoulder muscles in FSHD individuals is still lacking. The aim of this study is to understand the neuromuscular changes in shoulder muscle control in people with FSHD. Upper arm kinematics and electromyograms (EMG) of eight upper extremity muscles were recorded during shoulder abduction-adduction and flexion-extension tasks in eleven participants with FSHD and eleven healthy participants. Normalized muscle activities were extracted from EMG signals. Non-negative matrix factorization was used to compute muscle synergies. Maximum muscle activities were compared using non-parametric analysis of variance. Similarities between synergies were also calculated using correlation. The Biceps Brachii was significantly more active in the FSHD group (25±2%) while Trapezius Ascendens and Serratus Anterior were less active (32±7% and 39±4% respectively). Muscle synergy weights were altered in FSHD individuals and showed greater diversity while controls mostly used one synergy for both tasks. The decreased activity by selected scapula rotator muscles and muscle synergy weight alterations show that neuromuscular control of the scapulohumeral joint is less consistent in people with FSHD compared to healthy participants. Assessments of muscle coordination strategies can be used to evaluate motor output variability and assist in management of the disease

Paradigm of biased PAR1 (protease-activated receptor-1) activation and inhibition in endothelial cells dissected by phosphoproteomics

Thrombin is the key serine protease of the coagulation cascade and mediates cellular responses by activation of PARs (protease-activated receptors). The predominant thrombin receptor is PAR1, and in endothelial cells (ECs), thrombin dynamically regulates a plethora of phosphorylation events. However, it has remained unclear whether thrombin signaling is exclusively mediated through PAR1. Furthermore, mechanistic insight into activation and inhibition of PAR1-mediated EC signaling is lacking. In addition, signaling networks of biased PAR1 activation after differential cleavage of the PAR1 N terminus have remained an unresolved issue. Here, we used a quantitative phosphoproteomics approach to show that classical and peptide activation of PAR1 induce highly similar signaling, that low thrombin concentrations initiate only limited phosphoregulation, and that the PAR1 inhibitors vorapaxar and parmodulin-2 demonstrate distinct antagonistic properties. Subsequent analysis of the thrombin-regulated phosphosites in the presence of PAR1 inhibitors revealed that biased activation of PAR1 is not solely linked to a specific G-protein downstream of PAR1. In addition, we showed that only the canonical thrombin PAR1 tethered ligand induces extensive early phosphoregulation in ECs. Our study provides detailed insight in the signaling mechanisms downstream of PAR1. Our data demonstrate that thrombin-induced EC phosphoregulation is mediated exclusively through PAR1, that thrombin and thrombin-tethered ligand peptide induce similar phosphoregulation, and that only canonical PAR1 cleavage by thrombin generates a tethered ligand that potently induces early signaling. Furthermore, platelet PAR1 inhibitors directly affect EC signaling, indicating that it will be a challenge to design a PAR1 antagonist that will target only those pathways responsible for tissue pathology

Devolatilisation characteristics of coal and biomass with respect to temperature and heating rate for HIsarna alternative ironmaking process

HIsarna process offers a novel low CO2 emission alternative to the blast furnace for primary iron production. This new smelting ironmaking technology is flexible in raw material usage such as the substitution of biomass for coal as a reductant. Reduction is conducted through multiple mechanisms within the smelting vessel including gaseous reaction products from thermal decomposition of volatile matters reacting directly with iron oxide containing slags and injected iron ore. In this study, four coals with notable differences in volatile matter content along with two biomass samples sourced from wood and grass origins were investigated for the selection of suitable fuel mix. Thermogravimetric analysis (TGA) was used to measure the weight loss of the carbonaceous materials and a vertical tube furnace coupled with a quadrupole mass spectrometer (VTF-QMS) was employed for off-gas analysis during the devolatilisation. During TGA tests the samples were heated under a 99.9999 % argon atmosphere to 1500 °C at three different heating rates to investigate the kinetics of thermal decomposition for these materials. Through use of the Kissinger– Akahira–Sonuse model an average activation energy was determined as a function of the conversion degree. The furnace experiments were carried out under a 99.999% Ar atmosphere to a peak temperature of 1500 °C, at a heating rate of 10 °C/min. The wt% of reducing gases e.g. H2, CO, and hydrocarbons, and the temperature required for these gases to evolve was notably different for each materials, but the respective maximum peaks of evolution of these gases corresponded well to the maximum rate of mass loss. Furthermore, the off-gas analysis reveals torrefied grass contains large amount of water and carbon dioxide which will be released at very low temperature, therefore pre-treatment to the temperature of ~400 °C is necessary to produce chars with similar properties to coal injected in HIsarna

Evaluation of devolatilization behaviour of different carbonaceous materials under rapid heating for the novel HIsarna ironmaking process

A drop-tube furnace coupled with quadrupole mass spectrometer (DTF-QMS) was employed to simulate rapid heating conditions that carbonaceous materials experience during HIsarna injection with the measurement of gas composition change as a result. A devolatilization study for thermal coal (TC) and charcoal (CC) samples was carried out at three temperatures of 1000, 1250 and 1500 °C under an initial high purity Ar gas environment. The volatiles released were measured online by QMS, while the char yield was determined directly by the weight of particles collected and the deficit was calculated by subtracting the gas yielded from the total weight loss. The study reveals that working temperature has a strong impact on the devolatilization rate, the maximum weight loss and the variation in gas species produced. Due to intensification in the carbon oxidation and secondary reactions at higher temperatures, there was an increase in the weight loss, which led to a greater yield of H2 and CO but less yield of hydrocarbons, CO2 and H2O. Despite lower volatile matter content in charcoal, the weight loss for charcoal (29%) was higher than that for thermal coal (23%) at 1500 °C. Although the amount of H2 produced for both materials is similar, the amount of CO produced by charcoal is twice of that by thermal coal, and accounts for 79% of the total gas weight formed by charcoal. This suggests that a higher rate of carbon oxidation takes place through O2 containing groups within the charcoal, which results in lower char efficiency. It was found that thermal coal produces a significant amount of tar, while a large number of particles in the form of soot/dust escaped from the bulk material during charcoal injection but no tar formation was observed

Fundamental understanding on the use of different carbon sources in the alternative ironmaking HIsarna process

HIsarna process offers a low CO2 emission alternative to the blast furnace for hot metal production. This new smelting ironmaking technology is flexible in raw materials such as substitution of coal with biomass. The reduction process is conducted through multiple mechanisms within the smelting reduction vessel (SRV) including reactions of the gaseous products from thermal decomposition of carbonaceous materials with iron oxide in slags. Since the construction of the HIsarna pilot plant (at the capacity of 8t hot metal/hour) in Tata Steel site in the Netherlands in 2010, several successful trial campaigns have been completed using thermal coals. Campaigns to partially replace coal with biomass and charge steel scraps in the SRV were also successfully conducted since 2018 demonstrating further significant CO2 emission reduction, however, the change in process performance due to biomass injection was noticed. To advance the fundamental understanding of the use of different carbonaceous materials in the HIsarna process and help optimise the carbonaceous material selection, a systematic research has been carried out for different carbon sources under simulated HIsarna thermal conditions. The thermodynamic and kinetic behaviours of the carbon-gas-slag-metal systems have been studied for coal and biomass injection in laboratory experiments. This talk will introduce some research findings from this systematic research, including slow/rapid devolatilisation of the carbon sources injected, structural characteristics of the resultant chars, and slag-carbon reactions for coals and biomass

Gasification and physical-chemical characteristics of carbonaceous materials in relation to HIsarna ironmaking process

HIsarna ironmaking process is one of the emerging technologies being developed to mitigate the increasing carbon footprint from the steel making industry. This innovative process offers flexibility with the type of reductants used in the smelting reduction vessel for the conversion of iron ore to liquid hot metal. Natural gas is well known for being a relatively clean fossil fuel producing carbon black and hydrogen when it undergoes thermal decomposition. The gasification reactivity of carbon black compared to the carbonaceous materials used in HIsarna process is investigated in this work using isothermal gravimetric analysis (TGA) method at 1250˚C, 1350˚C and 1450˚C under atmospheric pressure. Furthermore, physical-chemical characteristics of the individual carbonaceous materials, which may influence the reactivity, are evaluated systematically. The experimental results show that carbon black is the least reactive followed by thermal coal and charcoal. It was found that the effect of the morphology of the carbonaceous materials on the reactivity is dominant compared to the surface area of the materials. In addition, the reactivity increases with the alkali index (AI) and the level of the amorphousness of the material’s structure. Three well-known kinetic models, i.e. the volumetric model (VM), the grain model (GM) and the random pore model (RPM) were applied to predict the gasification behaviour of the three carbonaceous materials. The random pore model best describes the gasification reaction of the selected samples due to the influence of the pore diffusion on the reaction. It is observed that the activation energy of the samples are not following the order of reactivity, this can be explained by the kinetic compensation effect

Prolonged dual hypothermic oxygenated machine preservation (DHOPE-PRO) in liver transplantation:study protocol for a stage 2, prospective, dual-arm, safety and feasibility clinical trial

INTRODUCTION: End-ischaemic preservation of a donor liver by dual hypothermic oxygenated machine perfusion (DHOPE) for 2 hours prior to transplantation is sufficient to mitigate ischaemia-reperfusion damage and fully restore cellular energy levels. Clinical studies have shown beneficial outcomes after transplantation of liver grafts preserved by DHOPE compared with static cold storage. In addition to graft reconditioning, DHOPE may also be used to prolong preservation time, which could facilitate logistics for allocation and transplantation globally. METHODS AND ANALYSIS: This is a prospective, pseudo-randomised, dual-arm, IDEAL-D (Idea, Development, Exploration, Assessment, Long term study-Framework for Devices) stage 2 clinical device trial designed to determine safety and feasibility of prolonged DHOPE (DHOPE-PRO). The end-time of the donor hepatectomy will determine whether the graft will be assigned to the intervention (16:00–3:59 hour) or to the control arm (4:00–15:59 hour). In total, 36 livers will be included in the study. Livers in the intervention group (n=18) will undergo DHOPE-PRO (≥4 hours) until implantation the following morning, whereas livers in the control group (n=18) will undergo regular DHOPE (2 hours) prior to implantation. The primary endpoint of this study is a composite of the occurrence of all (serious) adverse events during DHOPE and up to 30 days after liver transplantation. ETHICS AND DISSEMINATION: The protocol was approved by the Medical Ethical Committee of Groningen, METc2020.126 in June 2020, and the study was registered in the Netherlands National Trial Registry (https://www.trialregister.nl/) prior to initiation. TRIAL REGISTRATION NUMBER: NL8740

До питання фольклоризму та фольклоризації творчості трудових мігрантів

The topicality of the research is caused by the lack of study of creative activities of the Ukrainians who are hunting for a job abroad. Prose, poetry, small genres are not the object of the thorough research yet. At the same time folkloristic processes flow lively among this group of people. This thought is proved by author’s own fieldwork. Dramatic peculiarities of migrants’ creativity (homesickness, loneliness, nostalgia) help laborers to bear their lives. Some of the bright examples of migrant folklore (poems, jokes, and a vocabulary) are given in the article as well

Evidence for a rebalanced hemostatic system in pediatric liver transplantation:A prospective cohort study

In adults with end-stage liver disease concurrent changes in pro- and antihemostatic pathways result in a rebalanced hemostasis. Children though, have a developing hemostatic system, different disease etiologies, and increased risk of thrombosis. This study aimed to assess the hemostatic state of children during and after liver transplantation. Serial blood samples were obtained from 20 children (≤16 years) undergoing primary liver transplantation (September 2017-October 2018). Routine hemostasis tests, thrombomodulin-modified thrombin generation, clot lysis times, and hemostatic proteins were measured. Reference values were established using an age-matched control group of 30 children. Thrombocytopenia was present in study patients. Von Willebrand factors were doubled and ADAMTS13 levels decreased during and after transplantation up until day 30, when platelet count had normalized. Whereas prothrombin time and activated partial thromboplastin time were prolonged during transplantation, thrombin generation was within normal ranges, except during perioperative heparin administration. Fibrinogen, factor VIII levels, and clot lysis time were elevated up until day 30. In conclusion, children with end-stage liver disease are in tight hemostatic balance. During transplantation a temporary heparin-dependent hypocoagulable state is present, which rapidly converts to a hemostatic balance with distinct hypercoagulable features that persist until at least day 30. This hypercoagulable state may contribute to the risk of posttransplant thrombosis