311 research outputs found
A laboratory device for mesuring the method of eddy currents the diffusion coefficient of hydrogen in metals hydrogenation
A method is proposed for measuring the diffusion coefficient of hydrogen in a membrane made of a titanium alloy VT1-0 based on the use of eddy currents and an installation for its implementation is described. An eddy current sensor is located on the membrane, which is the wall of the electrolytic cell. The diffusion process is measured under the conditions of formation of titanium hydrides. The formation of titanium hydrides during hydrogenation is monitored over time by measuring the diffraction spectra. The results of the measurement of the diffusion coefficient of hydrogen by the proposed method are given in the conditions of formation of titanium hydrides in the membrane. The results can be used to determine the diffusion coefficients of hydrogen in various structural materials, in space technology, nuclear power engineering, in products subjected to hydrogenation during operation
Mitogenomics and the genetic differentiation of contemporary <i>Balaena mysticetus</i> (Cetacea) from Svalbard
Full mitochondrial genomes were assembled for 12 recently sampled animals from the Svalbard bowhead whale (Balaena mysticetus) stock via high-throughput sequencing data, facilitating analysis of the demographic history of the population for the first time. The Svalbard population has retained noticeable amounts of mitochondrial genome diversity despite extreme historical harvest levels. Haplotype and nucleotide diversities were similar to those estimated earlier for other bowhead whale populations. The reconstructed demographic history was in accordance with a boom–bust scenario, combining a slight Pleistocene population growth 25 000–35 000 years ago and a Holocene decline. Employing a mutation rate of 3.418 × 10–8 substitutions per site per year, the time to the most recent common ancestor for the mitochondrial genomes of the contemporary Svalbard bowhead whales was estimated to be 68 782 (54 353–83 216) years before the present. Based on 370 bp fragments of the D-loop region, significant genetic differentiation was detected between all extant bowhead whale populations across the circumpolar Arctic. Thus, the Svalbard bowhead whales can be regarded as a population with its own genetic legacy
Regenerative potential of human muscle stem cells in chronic inflammation
International audienceABSTRACT: INTRODUCTION: Chronic inflammation is a profound systemic modification of the cellular microenvironment which could affect survival, repair and maintenance of muscle stem cells. The aim of this study was to define the role of chronic inflammation on the regenerative potential of satellite cells in human muscle. METHODS: As a model for chronic inflammation, 11 patients suffering from rheumatoid arthritis (RA) were included together with 16 patients with osteoarthritis (OA) as controls. The mean age of both groups was 64 years, with more females in the RA group compared to the OA group. During elective knee replacement surgery, a muscle biopsy was taken from the distal musculus vastus medialis. Cell populations from four RA and eight OA patients were used for extensive phenotyping because these cell populations showed no spontaneous differentiation and myogenic purity greater than 75% after explantation. RESULTS: After mononuclear cell explantation, myogenic purity, viability, proliferation index, number of colonies, myogenic colonies, growth speed, maximum number of population doublings and fusion index were not different between RA and OA patients. Furthermore, the expression of proteins involved in replicative and stress-induced premature senescence and apoptosis, including p16, p21, p53, hTERT and cleaved caspase-3, was not different between RA and OA patients. Mean telomere length was shorter in the RA group compared to the OA group. CONCLUSIONS: In the present study we found evidence that chronic inflammation in RA does not affect the in vitro regenerative potential of human satellite cells. Identification of mechanisms influencing muscle regeneration by modulation of its microenvironment may, therefore, be more appropriate
Tumor evolution metrics predict recurrence beyond 10 years in locally advanced prostate cancer
Cancer evolution lays the groundwork for predictive oncology. Testing evolutionary metrics requires quantitative measurements in controlled clinical trials. We mapped genomic intratumor heterogeneity in locally advanced prostate cancer using 642 samples from 114 individuals enrolled in clinical trials with a 12-year median follow-up. We concomitantly assessed morphological heterogeneity using deep learning in 1,923 histological sections from 250 individuals. Genetic and morphological (Gleason) diversity were independent predictors of recurrence (hazard ratio (HR) = 3.12 and 95% confidence interval (95% CI) = 1.34–7.3; HR = 2.24 and 95% CI = 1.28–3.92). Combined, they identified a group with half the median time to recurrence. Spatial segregation of clones was also an independent marker of recurrence (HR = 2.3 and 95% CI = 1.11–4.8). We identified copy number changes associated with Gleason grade and found that chromosome 6p loss correlated with reduced immune infiltration. Matched profiling of relapse, decades after diagnosis, confirmed that genomic instability is a driving force in prostate cancer progression. This study shows that combining genomics with artificial intelligence-aided histopathology leads to the identification of clinical biomarkers of evolution
Krebsberatung: „Gut gegen Kopfkino“ : Maßnahmen, die Männern den Weg in Krebsberatungsstellen ebnen : Ideen und Empfehlungen aus der Praxis
Einleitung
Männer nutzen seltener psychosoziale Unterstützung als Frauen, auch wenn sie psychisch belastet sind. Ziel war, verschiedene Maßnahmen zu entwickeln, die Männern die Inanspruchnahme der Angebote von Krebsberatungsstellen erleichtern sollen. Dieser Beitrag gibt die Erfahrungen aus der Praxis wieder, die wir im Rahmen der Studie WAG-ES! gewinnen konnten.
Methode
Ein Maßnahmenpaket wurde in vier Schritten entwickelt, dabei auf Praxistauglichkeit und Umsetzbarkeit geprüft und zu einem Katalog zusammengefasst. Anschließend wurde es in einer mehrmonatigen Pilotierungs- und Interventionsphase in sieben Krebsberatungsstellen umgesetzt und an die jeweiligen Gegebenheiten adaptiert.
Ergebnisse
Das Maßnahmenpaket besteht aus vier Säulen: Öffentlichkeitsarbeit, Schnittstellen & Zuweisende, strukturelle Veränderungen und männerspezifische Aktivitäten. Ziel der Öffentlichkeitsarbeit ist, Zuweisende über das Beratungsangebot und männerspezifische Angebote zu informieren und mögliche Fehlvorstellungen über psychosoziale Beratung zu korrigieren. Die Zuweisenden wurden gezielt angesprochen und hatten eine Schlüsselfunktion. Strukturelle Veränderungen, zum Beispiel eine Abendsprechstunde, konnten leicht umgesetzt werden. Besonders wichtig waren männerspezifische Angebote. Dabei wurde die körperliche Aktivität oder Informationsvermittlung an erste Stelle gesetzt. Später, wenn sich eine Vertrautheit entwickelt hatte, konnten auch emotional oder schambesetzte Themen angesprochen und bearbeitet werden.
Schlussfolgerung
Das erarbeitete Maßnahmenpaket ist praxistauglich und kann in der Breite eingesetzt werden
Evaluation of DNA Methylation Episignatures for Diagnosis and Phenotype Correlations in 42 Mendelian Neurodevelopmental Disorders.
Genetic syndromes frequently present with overlapping clinical features and inconclusive or ambiguous genetic findings which can confound accurate diagnosis and clinical management. An expanding number of genetic syndromes have been shown to have unique genomic DNA methylation patterns (called episignatures ). Peripheral blood episignatures can be used for diagnostic testing as well as for the interpretation of ambiguous genetic test results. We present here an approach to episignature mapping in 42 genetic syndromes, which has allowed the identification of 34 robust disease-specific episignatures. We examine emerging patterns of overlap, as well as similarities and hierarchical relationships across these episignatures, to highlight their key features as they are related to genetic heterogeneity, dosage effect, unaffected carrier status, and incomplete penetrance. We demonstrate the necessity of multiclass modeling for accurate genetic variant classification and show how disease classification using a single episignature at a time can sometimes lead to classification errors in closely related episignatures. We demonstrate the utility of this tool in resolving ambiguous clinical cases and identification of previously undiagnosed cases through mass screening of a large cohort of subjects with developmental delays and congenital anomalies. This study more than doubles the number of published syndromes with DNA methylation episignatures and, most significantly, opens new avenues for accurate diagnosis and clinical assessment in individuals affected by these disorders
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