Versagenssimulation dynamisch belasteter Proben mit unterschiedlichen Mehrachsigkeitszuständen unter Verwendung des Johnson-Cook-Versagensmodells für eine Nickelbasislegierung

Das Versagensverhalten verschiedener prismatischer Scherproben wurde in einer Split-Hopkinson-Pressure-Bar-Anlage und das verschiedener gekerbter Rundzugproben in einer Schnellzerreißmaschine bei hohen Dehnraten untersucht. In Finite-Elemente-Simulationen mit ausschließlich einem viskoplastischen Deformationsmodell (Johnson-Cook), das thermische Entfestigung berücksichtigt, werden die experimentellen Kraft-Zeit-Verläufe weder bezüglich des Zeitpunktes des Einsetzens des Versagens noch bezüglich des dann auftretenden starken Kraftabfalls richtig wiedergegeben. Erst bei zusätzlicher Verwendung eines Schädigungs- bzw. Versagensmodells ist eine zufriedenstellende Übereinstimmung von Experiment und Simulation zu erzielen. Bei den vorgestellten Untersuchungen wurde das Johnson-Cook -Versagensmodell verwendet, das auch den Einfluss der Mehrachsigkeit berücksichtigt. Das Materialverhalten kann in Versuchen, die einen breiten Bereich von Mehrachsigkeiten aufweisen, mit nur einem Satz von Materialparametern simuliert werden

Immunotherapeutic targeting of membrane Hsp70-expressing tumors using recombinant human granzyme B

Background: We have previously reported that human recombinant granzyme B (grB) mediates apoptosis in membrane heat shock protein 70 (Hsp70)-positive tumor cells in a perforin-independent manner

Contrasting the Percutaneous Nerve Evaluation Versus Staged Implantation in Sacral Neuromodulation

Sacral neuromodulation is increasingly used for the treatment of voiding dysfunction, pelvic pain syndromes, and gastrointestinal disorders. While increased use of this technology has led to a greater understanding of its potential as well as its limitations, difficulty persists in identifying the patients that will benefit most. Either of two trial stimulation techniques is performed before placement of a permanent neuromodulator: the monopolar percutaneous nerve evaluation and the tined quadripolar staged trial. The preponderance of recent literature asserts the superior sensitivity of the staged trial over percutaneous nerve evaluation. However, the techniques offer disparate advantages, and other issues, such as cost-effectiveness, remain largely unexplored. The role of sacral neuromodulation will continue to expand as physicians and patients become increasingly aware of its therapeutic potential. Widespread adoption of this clinically superior technique will most rapidly help the greatest number of patients

Simulation der Spansegmentierung beim Hochgeschwindigkeits- Zerspanen unter Berücksichtigung duktiler Schädigung

Die für das Hochgeschwindigkeitsspanen charakteristische Segmentierung der Späne wird durch eine starke Lokalisierung der Deformation in der primären Scherzone verursacht. Für die untersuchte Nickelbasislegierung IN718 wurden lokal in den Scherbändern eines segmentierten Spans ausgeprägte Gefügeänderungen in Form sehr starker Kornstreckungen sowie teilweise Trennungen der Abgleitufer festgestellt. Ein viskoplastisches Modell, welches nur Dehnungsverfestigung und thermische Entfestigung berücksichtigt, ist nicht ausreichend, um das Versagen durch Scherbandbildung und die in einem Scherband bei seiner Entstehung gemessenen Temperaturen zutreffend wiederzugeben.Im Rahmen einer makroskopischen Betrachtung des Werkstoffverhaltens wird ein einfaches Modell für duktile Schädigung bei hohen Verformungsgeschwindigkeiten und großen Deformationen untersucht. Der Einfluss der Spannungs-Mehrachsigkeit auf die duktile Schädigung wird anhand von Hochgeschwindigkeits-Zugversuchen an gekerbten Proben sowie anhand von Doppel-Scherversuchen im Split-Hopkinson-Pressure-Bar-Aufbau simuliert. Durch die Berücksichtigung duktiler Schädigung gelingt sowohl die Darstellung der segmentierten Spanform bei gleichzeitiger Wiedergabe der in einem entstehenden Scherband gemessenen Temperaturen bei einer FESimulation des Orthogonal-Spanprozesses als auch die Simulation der Geschwindigkeitsabhängigkeit der Spansegmentierung

Anatomical considerations and emerging strategies for reducing new onset conduction disturbances in percutaneous structural heart disease interventions

Transcatheter procedures offer an alternative to cardiac surgery in select patients with structural heart disease (SHD). Unfortunately, inadvertent disruption of electrical pathways and subsequent development of new onset conduction disturbances can occur in up to 5–70% of percutaneous interventions, result in pacemaker implantation, and confer a worse prognosis. The physical proximity between the conduction system (atrioventricular node, bundle of His, and bundle branches) and the site of percutaneous repair is increasingly recognized as a key factor influencing new onset conduction disturbance development in procedures located near the conduction system. This review covers the incidence, clinical significance, and mechanisms of new onset conduction disturbances and discusses current and emerging strategies to address this complication in these populations

Metatranscriptomics reveal differences in in situ energy and nitrogen metabolism among hydrothermal vent snail symbionts

Despite the ubiquity of chemoautotrophic symbioses at hydrothermal vents, our understanding of the influence of environmental chemistry on symbiont metabolism is limited. Transcriptomic analyses are useful for linking physiological poise to environmental conditions, but recovering samples from the deep sea is challenging, as the long recovery times can change expression profiles before preservation. Here, we present a novel, in situ RNA sampling and preservation device, which we used to compare the symbiont metatranscriptomes associated with Alviniconcha, a genus of vent snail, in which specific host–symbiont combinations are predictably distributed across a regional geochemical gradient. Metatranscriptomes of these symbionts reveal key differences in energy and nitrogen metabolism relating to both environmental chemistry (that is, the relative expression of genes) and symbiont phylogeny (that is, the specific pathways employed). Unexpectedly, dramatic differences in expression of transposases and flagellar genes suggest that different symbiont types may also have distinct life histories. These data further our understanding of these symbionts' metabolic capabilities and their expression in situ, and suggest an important role for symbionts in mediating their hosts' interaction with regional-scale differences in geochemistry

Human Amniotic Epithelial Cell Transplantation Induces Markers of Alternative Macrophage Activation and Reduces Established Hepatic Fibrosis

Chronic hepatic inflammation from multiple etiologies leads to a fibrogenic response that can progress to cirrhosis and liver failure. Transplantation of human amniotic epithelial cells (hAEC) from term delivered placenta has been shown to decrease mild to moderate hepatic fibrosis in a murine model. To model advanced human liver disease and assess the efficacy of hAEC therapy, we transplanted hAEC in mice with advanced hepatic fibrosis. Immunocompetent C57BL/6 mice were administered carbon tetrachloride (CCl4) twice weekly resulting in bridging fibrosis by 12 weeks. hAEC (2×106) were infused via the tail vein at week 8 or weeks 8 and 10 (single and double dose, respectively). Human cells were detected in mouse liver four weeks after transplantation showing hAEC engraftment. CCl4 treated mice receiving single or double hAEC doses showed a significant but similar decrease in liver fibrosis area associated with decreased activation of collagen-producing hepatic stellate cells and decreased hepatic protein levels of the pro-fibrogenic cytokine, transforming growth factor-beta1. CCl4 administration caused hepatic T cell infiltration that decreased significantly following hAEC transplantation. Hepatic macrophages play a crucial role in both fibrogenesis and fibrosis resolution. Mice exposed to CCl4 demonstrated increased numbers of hepatic macrophages compared to normal mice; the number of macrophages decreased significantly in CCl4 treated mice given hAEC. These mice had significantly lower hepatic protein levels of the chemokine monocyte chemoattractant protein-1 than mice given CCl4 alone. Alternatively activated M2 macrophages are associated with fibrosis resolution. CCl4 treated mice given hAEC showed increased expression of genes associated with M2 macrophages including YM-1, IL-10 and CD206. We provide novel data showing that hAEC transplantation induces a wound healing M2 macrophage phenotype associated with reduction of established hepatic fibrosis that justifies further investigation of this potential cell-based therapy for advanced hepatic fibrosis

European position paper on the management of patients with patent foramen ovale. General approach and left circulation thromboembolism

The presence of a patent foramen ovale (PFO) is implicated in the pathogenesis of a number of medical conditions; however, the subject remains controversial and no official statements have been published. This interdisciplinary paper, prepared with involvement of eight European scientific societies, aims to review the available trial evidence and to define the principles needed to guide decision making in patients with PFO. In order to guarantee a strict process, position statements were developed with the use of a modified grading of recommendations assessment, development, and evaluation (GRADE) methodology. A critical qualitative and quantitative evaluation of diagnostic and therapeutic procedures was performed, including assessment of the risk/benefit ratio. The level of evidence and the strength of the position statements of particular management options were weighed and graded according to predefined scales. Despite being based often on limited and non-randomised data, while waiting for more conclusive evidence, it was possible to conclude on a number of position statements regarding a rational general approach to PFO management and to specific considerations regarding left circulation thromboembolism. For some therapeutic aspects, it was possible to express stricter position statements based on randomised trials. This position paper provides the first largely shared, interdisciplinary approach for a rational PFO management based on the best available evidence