61 research outputs found

    Математическое моделирование системы отслеживания шва в сварке электронным пучком

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    В ходе исследований разработана математическая модель системы отслеживания шва в сварке электронным пучком. Экспериментально доказана эффективность применения данной модели к любой электронно-сварочной установке. Для простейшего детектора излучения (пластины-детектора) без использования физических фильтров были получены электронные изображения сварных швов, отличающиеся высокой четкостью. Эмпирически доказана независимость сканирования от механических характеристик электронно-сварочной установки. Доказано, что отсутствие источников электронов с необходимой мощностью пучка не является препятствием для получения достаточного качества измерений.In the course of research, a mathematical model of the tracking system of a weld in electron beam welding was developed. The effectiveness of applying this model to any electronic welding installation has been experimentally proven. For the simplest radiation detector (detector plate) without the use of physical filters, electronic images of welds, which are distinguished by high definition, were obtained. Empirically proven independence of the scan from the mechanical characteristics of the electronic welding installation. It is proved that the absence of electron sources with the necessary beam power is not an obstacle to obtaining a sufficient measurement quality

    Experimental investigation of the elasticity of the human diaphragm

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    <p>Abstract</p> <p>Background</p> <p>Traumatic diaphragmatic ruptures affect mainly the left side. In an experimental study in human corpses we examined the stretch behaviour of the left and right diaphragmatic halves.</p> <p>Methods</p> <p>In a total of 8 male and 8 female corpses each diaphragmatic half was divided into 4 different segments. Each segments stretch behaviour was investigated. In steps of 2 N the stretch was increased up to 24 N.</p> <p>Results</p> <p>In the female the left diaphragm showed a stronger elasticity compared to the right. Additionally the left diaphragm in females showed a higher elasticity in comparison to the left in males. Traumatic diaphragmatic ruptures affect mostly the central tendineous part or the junction between tendineous and muscular part of the diaphragmatic muscle. Accordingly we found a lower elasticity in these parts compared with the other diaphragmatic segments.</p> <p>Conclusion</p> <p>In summary it can be said that albeit some restrictions we were able to determine the elasticity of different diaphragmatic segments quantitatively and reproduceably with our presented method. Thereby a comparison of results of different diaphragmatic segments as well as of both diaphragmatic halves and of both genders was possible</p

    Elevated circulating Hsp70 levels are correlative for malignancies in different mammalian species

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    Circulating Hsp70 levels were determined in feline and porcine cohorts using two different ELISA systems. These comparative animal models of larger organisms often reflect diseases, and especially malignant tumors, better than conventional rodent models. It is therefore essential to investigate the biology and utility of tumor biomarkers in animals such as cats and pigs. In this study, levels of free Hsp70 in the blood of cats with spontaneously occurring tumors were detected using a commercial Hsp70 ELISA (R&D Systems). Sub-analysis of different tumor groups revealed that animals with tumors of epithelial origin presented with significantly elevated circulating Hsp70 concentrations. In addition to free Hsp70 levels measured with the R&D Systems Hsp70 ELISA, levels of exosomal Hsp70 were determined using the compHsp70 ELISA in pigs. Both ELISA systems detected significantly elevated Hsp70 levels (R&D Systems: median 24.9 ng/mL; compHsp70: median 44.2 ng/mL) in the blood of a cohort of APC1311/+^{1311/+} pigs diagnosed with high-grade adenoma polyps, and the R&D Systems Hsp70 ELISA detected also elevated Hsp70 levels in animals with low-grade polyps. In contrast, in flTP53R167H^{R167H} pigs, suffering from malignant osteosarcoma, the compHsp70 ELISA (median 674.32 ng/mL), but not the R&D Systems Hsp70 ELISA (median 4.78 ng/mL), determined significantly elevated Hsp70 concentrations, indicating that in tumor-bearing animals, the dominant form of Hsp70 is of exosomal origin. Our data suggest that both ELISA systems are suitable for detecting free circulating Hsp70 levels in pigs with high-grade adenoma, but only the compHsp70 ELISA can measure elevated, tumor-derived exosomal Hsp70 levels in tumor-bearing animals

    Crying and feeding problems in infancy and cognitive outcome in preschool children born at risk : a prospective population study

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    Objective: To investigate whether regulatory problems, i.e., crying and feeding problems in infants > 3 months of age, predict cognitive outcome in preschool children born at risk even when controlled for confounding factors. Methods: A prospective longitudinal study of children born in a geographically defined area in Germany. N = 4427 children of 6705 eligible survivors (66%) participated at all four assessment points (neonatal, 5, 20, and 56 months of age). Excessive crying and feeding problems were measured at 5 months. Mental development was assessed with the Griffiths Scale at 20 months, and cognitive assessments were conducted at 56 months. Neonatal complications, neurological, and psychosocial factors were controlled as confounders in structural equation modeling and analyses of variance. Results: One in five infants suffered from single crying or feeding problems, and 2% had multiple regulatory problems, i.e., combined crying and feeding problems at 5 months. In girls, regulatory problems were directly predictive of lower cognition at 56 months, even when controlled for confounders, whereas in boys, the influence on cognition at 56 months was mediated by low mental development at 20 months. Both in boys and girls, shortened gestational age, neonatal neurological complications, and poor parent-infant relationship were predictive of regulatory problems at 5 months and lower cognition at 56 months. Conclusion: Regulatory problems in infancy have a small but significant adverse effect on cognitive development

    mRNA trans-splicing dual AAV vectors for (epi)genome editing and gene therapy

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    Large genes including several CRISPR-Cas modules like gene activators (CRISPRa) require dual adeno-associated viral (AAV) vectors for an efficient in vivo delivery and expression. Current dual AAV vector approaches have important limitations, e.g., low reconstitution efficiency, production of alien proteins, or low flexibility in split site selection. Here, we present a dual AAV vector technology based on reconstitution via mRNA trans-splicing (REVeRT). REVeRT is flexible in split site selection and can efficiently reconstitute different split genes in numerous in vitro models, in human organoids, and in vivo. Furthermore, REVeRT can functionally reconstitute a CRISPRa module targeting genes in various mouse tissues and organs in single or multiplexed approaches upon different routes of administration. Finally, REVeRT enabled the reconstitution of full-length ABCA4 after intravitreal injection in a mouse model of Stargardt disease. Due to its flexibility and efficiency REVeRT harbors great potential for basic research and clinical applications

    Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

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    Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation
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