On the use of phosphor thermometry for temperature monitoring in manufacturing processes

In the metalworking industry, continuous monitoring and control of temperature is vital to enhance process efficiency, reduce wastage, and attain product reliability in high-value manufacturing processes. The capabilities of conventional techniques such as the use of thermocouples and infrared thermometry for measuring temperature in these processes are limited. For example, in forging processes, there may be a need for mechanical alteration of the die to accommodate thermocouples for die surface temperature measurements, and with infrared thermometry, knowledge of the emissivity of the surfaces of process components is required for accurate temperature measurements. Given that phosphor thermometry has not previously been used in manufacturing processes, here, we report its potential implementation using the phosphor Mg4FGeO6:Mn for measurements of die surface temperature in a forging press. First, with this phosphor, laboratory trials were conducted to describe the cyclic heating of a die by pre-heated billets, which is a process leading to thermal fatigue that requires monitoring in practical applications. Then, the phosphor thermometry technique was demonstrated for die temperature measurements on a 2100 tonne screw press at the Advanced Forming and Research Centre (AFRC). The results show that phosphor thermometry is a candidate technique that would potentially enable more accurate measurements not possible by other techniques in this manufacturing process

Low survival rate and muscle fiber-dependent aging effects in the McArdle disease mouse model

Altres ajuts: The present study was funded by grants received from the Fondo de Investigaciones Sanitarias (FIS, grant PI16/01492 and PI15/00558) and cofunded by 'Fondos FEDER'. Gisela Nogales-Gadea is supported by a Trampoline Grant #21108 from AMF Telethon.McArdle disease is an autosomal recessive disorder caused by the absence of the muscle glycogen phosphorylase, which leads to impairment of glycogen breakdown. The McArdle mouse, a model heavily affected by glycogen accumulation and exercise intolerance, was used to characterize disease progression at three different ages. The molecular and histopathological consequences of the disease were analyzed in five different hind-limb muscles (soleus, extensor digitorum longus, tibialis anterior, gastrocnemius and quadriceps) of young (8-week-old), adult (35-week-old) and old (70-week-old) mice. We found that McArdle mice have a high perinatal and post-weaning mortality. We also observed a progressive muscle degeneration, fibrosis and inflammation process that was not associated with an increase in muscle glycogen content during aging. Additionally, this progressive degeneration varied among muscle and fiber types. Finally, the lack of glycogen content increase was associated with the inactivation of glycogen synthase and not with compensatory expression of the Pygl and/or Pygb genes in mature muscle

RUNX/AML and C/EBP factors regulate CD11a integrin expression in myeloid cells through overlapping regulatory elements

The CD11a/CD18 (leukocyte functionassociated antigen 1 [LFA-1]) integrin mediates critical leukocyte adhesive interactions during immune and inflammatory responses. The CD11a promoter directs CD11a/CD18 integrin expression, and its activity in lymphoid cells depends on a functional RUNX1/AML-1–binding site (AML-110) within the MS7 sequence. We now report that MS7 contains a C/EBPbinding site (C/EBP-100), which overlaps with AML-110 and is bound by C/EBP factors in myeloid cells. C/EBP and RUNX/ AML factors compete for binding to their respective cognate elements and bind to the CD11a promoter MS7 sequence in a cell lineage- and differentiation-dependent manner. In myeloid cells MS7 is primarily recognized by C/EBP factors in proliferating cells whereas RUNX/AMLfactors (especially RUNX3/AML-2) bind to MS7 in differentiated cells. RUNX3/AML-2 binding to the CD11a promoter correlates with increased RUNX3/AML-2 protein levels and enhanced CD11a/CD18 cell surface expression. The relevance of the AML-110 element is underscored by the ability of AML-1/ETO to inhibit CD11a promoter activity, thus explaining the low CD11a/CD18 expression in t(8;21)–containing myeloid leukemia cells. Therefore, the expression of the CD11a/CD18 integrin in myeloid cells is determined through the differential occupancy of the CD11a proximal promoter by transcription factors implicated in the pathogenesis of myeloid leukemia

Evolution of the use of corticosteroids for the treatment of hospitalised COVID-19 patients in Spain between March and November 2020: SEMI-COVID national registry

Objectives: Since the results of the RECOVERY trial, WHO recommendations about the use of corticosteroids (CTs) in COVID-19 have changed. The aim of the study is to analyse the evolutive use of CTs in Spain during the pandemic to assess the potential influence of new recommendations. Material and methods: A retrospective, descriptive, and observational study was conducted on adults hospitalised due to COVID-19 in Spain who were included in the SEMI-COVID- 19 Registry from March to November 2020. Results: CTs were used in 6053 (36.21%) of the included patients. The patients were older (mean (SD)) (69.6 (14.6) vs. 66.0 (16.8) years; p < 0.001), with hypertension (57.0% vs. 47.7%; p < 0.001), obesity (26.4% vs. 19.3%; p < 0.0001), and multimorbidity prevalence (20.6% vs. 16.1%; p < 0.001). These patients had higher values (mean (95% CI)) of C-reactive protein (CRP) (86 (32.7-160) vs. 49.3 (16-109) mg/dL; p < 0.001), ferritin (791 (393-1534) vs. 470 (236- 996) µg/dL; p < 0.001), D dimer (750 (430-1400) vs. 617 (345-1180) µg/dL; p < 0.001), and lower Sp02/Fi02 (266 (91.1) vs. 301 (101); p < 0.001). Since June 2020, there was an increment in the use of CTs (March vs. September; p < 0.001). Overall, 20% did not receive steroids, and 40% received less than 200 mg accumulated prednisone equivalent dose (APED). Severe patients are treated with higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%. Conclusions: Patients with greater comorbidity, severity, and inflammatory markers were those treated with CTs. In severe patients, there is a trend towards the use of higher doses. The mortality benefit was observed in patients with oxygen saturation </=90%

GWAS for Systemic Sclerosis Identifies Multiple Risk Loci and Highlights Fibrotic and Vasculopathy Pathways

Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments.Funding: This work was supported by Spanish Ministry of Economy and Competitiveness (grant ref. SAF2015-66761-P), Consejeria de Innovacion, Ciencia y Tecnologia, Junta de Andalucía (P12-BIO-1395), Ministerio de Educación, Cultura y Deporte through the program FPU, Juan de la Cierva fellowship (FJCI-2015-24028), Red de Investigación en Inflamación y Enfermadades Reumaticas (RIER) from Instituto de Salud Carlos III (RD16/0012/0013), and Scleroderma Research Foundation and NIH P50-HG007735 (to H.Y.C.). H.Y.C. is an Investigator of the Howard Hughes Medical Institute. PopGen 2.0 is supported by a grant from the German Ministry for Education and Research (01EY1103). M.D.M and S.A. are supported by grant DoD W81XWH-18-1-0423 and DoD W81XWH-16-1-0296, respectively

A stop-codon mutation in the human mtDNA cytochrome c oxidase I gene disrupt functional structure of complex IV

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Infusion of platelets transiently reduces nucleoside overload in MNGIE

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is caused by thymidine phosphorylase (TP) deficiency, which leads to toxic accumulations of thymidine (dThd) and deoxyuridine (dUrd). In this work, we report that infusion of platelets from healthy donors to patients with MNGIE restored transiently circulating TP and reduced plasma dThd and dUrd levels, suggesting that treatments to achieve permanent restoration of circulating TP such as allogeneic stem cell transplantation or gene transfer might be therapeutic