Flow effects on the dendritic microstructure of AlSi-base alloys

Fluid flow changes heat and mass transport during solidification, thereby affecting the evolution of the microstructure. In order to quantify effects of convection, it is important that fluid flow can be modified experimentally. We performed directional solidification experiments with binary AlSi alloys of different compositions, using a microgravity environment for diffusive solidification and adding rotating magnetic fields to generate flow. Flow velocities up to 10 mm/s and various solidification velocities were realized while maintaining a constant temperature gradient at the solid-liquid interface. The microstructure observed in samples processed on earth and in space is characterized by primary and secondary dendrite arm spacing and the fractal dimension of the dendrites. It is found that fluid flow usually accelerates growth and coarsening of the dendritic structures and leads to new kinetic laws. The branching of dendritic networks, however, is hardly affected by flow

Enzymatic logic of ubiquitin chain assembly

Protein ubiquitination impacts virtually every biochemical pathway in eukaryotic cells. The fate of a ubiquitinated protein is largely dictated by the type of ubiquitin modification with which it is decorated, including a large variety of polymeric chains. As a result, there have been intense efforts over the last two decades to dissect the molecular details underlying the synthesis of ubiquitin chains by ubiquitin-conjugating (E2) enzymes and ubiquitin ligases (E3s). In this review, we highlight these advances. We discuss the evidence in support of the alternative models of transferring one ubiquitin at a time to a growing substrate-linked chain (sequential addition model) versus transferring a pre-assembled ubiquitin chain (en bloc model) to a substrate. Against this backdrop, we outline emerging principles of chain assembly: multisite interactions, distinct mechanisms of chain initiation and elongation, optimal positioning of ubiquitin molecules that are ultimately conjugated to each other, and substrate-assisted catalysis. Understanding the enzymatic logic of ubiquitin chain assembly has important biomedical implications, as the misregulation of many E2s and E3s and associated perturbations in ubiquitin chain formation contribute to human disease. The resurgent interest in bifunctional small molecules targeting pathogenic proteins to specific E3s for polyubiquitination and subsequent degradation provides an additional incentive to define the mechanisms responsible for efficient and specific chain synthesis and harness them for therapeutic benefit

Improved Postoperative Kneeling Ability in Posterior Stabilized Total Knee Arthroplasty with Medialised Dome-Patella Resurfacing: A Retrospective Comparative Outcome Analysis.

OBJECTIVES This investigation aimed to evaluate if the modifications to prosthesis designs improve patients' clinical and functional outcomes after total knee arthroplasty (TKA), with a special focus on pain and kneeling ability. METHODS Retrospective and comparative analysis of consecutive patients who were treated with posterior stabilized TKA using two different prostheses designs (single surgeon, single vendor). Group 1 received a traditional design TKA (PFC Sigma; DePuy, Inc., Warsaw, IN) with conventional dome-patella resurfacing and group 2 received a modern design implant (Attune; DePuy, Inc., Warsaw, IN), with medialised dome-patella resurfacing. Functional outcome (range of motion: ROM) and the Oxford Knee Score (OKS) were collected preoperatively, at 4-6 weeks and 12 months following surgery. RESULTS Ninety-nine participants were included. Of these, 30 received traditional design implants, and 69 the modern design knee implants. The comparison between the two implants showed a statistically significant increased total OKS and kneeling ability in the modern design cohort at 1-year follow-up compared to the traditional design cohort (p < 0.01). In the modern design group, 53% (N=37) could kneel easily or with little difficulty, compared to 30% (N=9) in the traditional design group. No statistically significant differences in ROM or the OKS pain component were seen. CONCLUSION The incorporation of a medialized dome-patella in modern knee implant design may offer advantages over traditional designs, as seen in improved total OKS and kneeling ability at one-year follow-up. Further research with larger cohorts is needed to confirm these findings and explore the broader impact of implant design changes on patient outcomes. LEVEL OF EVIDENCE Clinical Study, Level III

Furnace Technology for Experiments on Sounding Rockets: Directional Solidification of Al-cast Alloys in ARTEX

Abstract The effect of controlled fluid flow on the microstructure formation in Al-cast alloys is studied experimentally: During three sounding rocket missions (TEXUS 39, TEXUS 41 and MAXUS 7) four samples of the composition Al-6wt.% Si were directionally solidified upwards under a medium temperature gradient (4K/mm) at constant solidification velocities (0.06 and 0.12mm/s). The application of rotating magnetic fields (RMF) during solidification offers the possibility to create defined flow conditions in solidification processing in microgravity to compare diffusive solidification conditions with convective ones. The paper shows that experiments under microgravity conditions yield other microstructures as experiments under earth conditions (with and without fluid flow): The secondary dendrite arm spacing was found to decrease, as the convection effects were reduced in microgravity. The forced fluid flow conditions result in pronounced macrosegregation effects. For high fluid flow velocity a change to pure eutectic solidification at the axis of the samples is observed

Protein disulfide isomerase acts as an injury response signal that enhances fibrin generation via tissue factor activation

The activation of initiator protein tissue factor (TF) is likely to be a crucial step in the blood coagulation process, which leads to fibrin formation. The stimuli responsible for inducing TF activation are largely undefined. Here we show that the oxidoreductase protein disulfide isomerase (PDI) directly promotes TF-dependent fibrin production during thrombus formation in vivo. After endothelial denudation of mouse carotid arteries, PDI was released at the injury site from adherent platelets and disrupted vessel wall cells. Inhibition of PDI decreased TF-triggered fibrin formation in different in vivo murine models of thrombus formation, as determined by intravital fluorescence microscopy. PDI infusion increased — and, under conditions of decreased platelet adhesion, PDI inhibition reduced — fibrin generation at the injury site, indicating that PDI can directly initiate blood coagulation. In vitro, human platelet–secreted PDI contributed to the activation of cryptic TF on microvesicles (microparticles). Mass spectrometry analyses indicated that part of the extracellular cysteine 209 of TF was constitutively glutathionylated. Mixed disulfide formation contributed to maintaining TF in a state of low functionality. We propose that reduced PDI activates TF by isomerization of a mixed disulfide and a free thiol to an intramolecular disulfide. Our findings suggest that disulfide isomerases can act as injury response signals that trigger the activation of fibrin formation following vessel injury

(INVITED)Tm:YAG crystal-derived double-clad fibers – A hybrid approach towards high gain and high efficiency Tm lasers

The hybrid approach of combining a Tm:YAG laser crystal with an amorphous fused silica tube is investigated to evaluate the suitability of the resulting crystal-derived fibers for efficient double-clad fiber lasers. The fabrication process and fiber properties of these Tm fibers are investigated, focusing on the dependence of the active fiber properties on the incorporated Tm3+ concentration. Crystal rods with different doping concentrations (TmxY1-x)3Al5O12 (x = 0.02, 0.05 and 0.08) were used as starting core material for fiber drawing. The investigated fibers are mechanically stable and result in a fairly homogenous and amorphous core glass with optical absorption and emission spectra that are similar to conventional Tm:Al doped silica fibers. Regarding laser properties with 790 nm cladding pumping, we could achieve a maximum slope efficiency of 47% with an output power of 4 W. The fiber laser results are compared to a conventionally fabricated double-clad Tm fiber prepared by Modified Chemical Vapor Deposition and solution doping. To the best of our knowledge, we demonstrate the highest laser output and the highest efficiency obtained from a Tm:YAG crystal-derived fiber

Late Quaternary evolution of rivers, lakes and peatlands in northeast Germany reflecting past climatic and human impact – an overview

Die Kenntnis der regionalen Paläohydrologie ist eine wesentliche Grundlage für das Verständnis aktueller Umweltfragen, wie zum Beispiel nach den Gründen von hydrologischen Veränderungen, dem Einfluss von Landnutzungsstrategien und der Wirksamkeit von Renaturierungsvorhaben in Feuchtgebieten. Auch die Interpretation von Modellierungsergebnissen zu den künftigen Einflüssen des Klima- und Landnutzungswandels auf das Gewässersystem kann durch die Einbeziehung (prä-) historischer Analogien verbessert werden. Für das glazial geprägte nordostdeutsche Tiefland wurde eine Übersicht der vorliegenden paläohydrologischen Befunde für den Zeitraum der letzten etwa 20.000 Jahre erarbeitet. Die Entwicklung der Flüsse wurde mit Blick auf die Tal-/Auengenese und das Ablagerungsmilieu, die Veränderung des Tal- und Gerinneverlaufs sowie den Paläoabfluss bzw. das Paläohochwasser betrachtet. Wesentliche genetische Unterschiede bestehen zwischen Alt- (Elster- und Saalekaltzeit) und Jungmoränengebieten (Weichselkaltzeit) sowie zwischen hoch und tief gelegenen Tälern. Letztere sind stark durch Wasserspiegelveränderungen in der Nord- und Ostsee beeinflusst worden. Die Entwicklung der Seen wurde hinsichtlich der Seebildung, die überwiegend eine Folge der spätpleistozänen bis frühholozänen Toteistieftau-Dynamik ist, und der Veränderungen im Ablagerungsmilieu analysiert. Weiterhin standen Seespiegelveränderungen im Fokus, wobei sich hoch variable lokale Befunde mit einigen Übereinstimmungen zeigten. Der Überblick zur Moorentwicklung konzentrierte sich auf hydrogenetische Moorentwicklungsphasen und auf die langfristige Entwicklung des Grundwasserspiegels. Enge Beziehungen zwischen der Entwicklung der Flüsse, Seen und Moore bestanden insbesondere im Spätholozän durch komplexe Vermoorungsprozesse in den großen Flusstälern. Bis in das Spätholozän wurde die regionale Hydrologie überwiegend durch klimatische, geomorphologische und nicht-anthropogene biologische Faktoren gesteuert. Seit dem Spätmittelalter wurde in der Region das Gewässernetz und der Wasserkreislauf im starken Maß durch anthropogene Interventionen beeinflusst (z.B. Aufstau von Flüssen und Seen, Bau von Kanälen und Deichen, Moorkultivierung). In den letzten etwa 50 Jahren haben dann sogar die kurzfristigen anthropogenen Eingriffe, z.B. in Form von Abflussregulierung, Hydromelioration und künstlicher Seebildung, die Wirksamkeit langfristiger klimatischer und geomorphologischer Prozesse übertroffen.researc

Individualized web-based exercise for the treatment of depression : randomized controlled trial

Background: Due to the high prevalence of depressive disorders, it is mandatory to develop therapeutic strategies that provide universal access and require limited financial and human resources. Web-based therapeutic approaches fulfill these conditions. Objective: The objective of our study was to assess the feasibility, acceptability, and efficacy of a supervised, individualized 8-week Web-based exercise intervention conducted for patients with moderate to severe depression. Methods: We recruited 20 patients with unipolar depression and randomly assigned them into 2 groups (intervention, exercise program group, n=14, and control, treatment-as-usual group, n=6). At baseline, depressive symptoms were rated via the Quick Inventory of Depressive Symptomatology (QIDS) by patients themselves (QIDS–self-report, QIDS-SR) and by a blinded psychiatrist (QIDS–clinician rating, QIDS-C). In addition, performance diagnostics (lactate analysis, spiroergometry during a treadmill walking test) were conducted. Quality of life was assessed via the Short Form-36 questionnaire (SF-36) and self-efficacy via the General Self Efficacy scale (GSE). In addition, habitual physical activity (HPA) was determined via the Baecke questionnaire. Participants of the intervention group received exercise schedules once weekly with endurance and strength training instructions. Rating of depressive symptoms was repeated after 6-12 days and 8 weeks; performance diagnostics and the completion of all the questionnaires were repeated after 8 weeks only. Results: The severity of depression subsided significantly in the intervention group after 8 weeks (median change in QIDS-SR: −5; interquartile range, IQR: −2 to −10), although it was already evident within the first 6-12 days (median change in QIDS-SR: −6; IQR: −2 to −8). During the intervention, participants undertook a median of 75 (IQR: 63 to 98) minutes of endurance training per week or 84% (16 [IQR: 9 to 19] of 19 [IQR: 15 to 21]) recommended endurance units in total. In addition, 9 (IQR: 4 to 12) of 10 (IQR: 8 to 13) recommended strength training exercise units were conducted during the 8 weeks. Performance diagnostics revealed a substantial increase in the maximum output in Watt for the intervention group after 8 weeks. Moreover, the intervention showed a favorable effect on SF-36 items “emotional well-being” and “social functioning” as well as on GSE and HPA scores. Conclusions: Our individualized Web based exercise intervention for moderate to severe depression was highly accepted by the patients and led to a significant and clinically relevant improvement of depressive symptoms

Literatur-Rundschau

Herbert Riehl-Heyse: Das tägliche Gegengift. Reportagen und Essays 1972–2003 / Hans Ulrich Kempski berichtet. Große Reportagen eines legendären Journalisten (Walter Hömberg)Anna-Katharina Linau: Gebete im Internet. Eine praktisch-theologische Untersuchung (Manfred Riegger)Benjamin Ziemann: Sozialgeschichte der Religion. Von der Reformation bis zur Gegenwart (Regina Polak)Peter Szyszka / Dagmar Schütte / Katharina Urbahn: Public Relations in Deutschland. Eine empirische Studie zum Berufsfeld Öffentlichkeitsarbeit (Sonja B. Lorenz)Franziska Weder: Organisationskommunikation und PR (Romy Fröhlich)Thomas Roessing: Öffentliche Meinung – die Erforschung der Schweigespirale (Anna-Maria Deisenberg)

An alternative CYB5A transcript is expressed in aneuploid ALL and enriched in relapse

Background: B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a genetically heterogenous malignancy with poor prognosis in relapsed adult patients. The genetic basis for relapse in aneuploid subtypes such as near haploid (NH) and high hyperdiploid (HeH) BCP-ALL is only poorly understood. Pathogenic genetic alterations remain to be identified. To this end, we investigated the dynamics of genetic alterations in a matched initial diagnosis-relapse (ID-REL) BCP-ALL cohort. Here, we firstly report the identification of the novel genetic alteration CYB5Aalt, an alternative transcript of CYB5A, in two independent cohorts. Methods: We identified CYB5alt in the RNAseq-analysis of a matched ID-REL BCP-ALL cohort with 50 patients and quantified its expression in various molecular BCP-ALL subtypes. Findings were validated in an independent cohort of 140 first diagnosis samples from adult BCP-ALL patients. Derived from patient material, the alternative open reading frame of CYB5Aalt was cloned (pCYB5Aalt) and pCYB5Aalt or the empty vector were stably overexpressed in NALM-6 cells. RNA sequencing was performed of pCYB5Aalt clones and empty vector controls followed by differential expression analysis, gene set enrichment analysis and complementing cell death and viability assays to determine functional implications of CYB5Aalt. Results: RNAseq data analysis revealed non-canonical exon usage of CYB5Aalt starting from a previously undescribed transcription start site. CYB5Aalt expression was increased in relapsed BCP-ALL and its occurrence was specific towards the shared gene expression cluster of NH and HeH BCP-ALL in independent cohorts. Overexpression of pCYB5Aalt in NALM-6 cells induced a distinct transcriptional program compared to empty vector controls with downregulation of pathways related to reported functions of CYB5A wildtype. Interestingly, CYB5A wildtype expression was decreased in CYB5Aalt samples in silico and in vitro. Additionally, pCYB5Aalt NALM-6 elicited a more resistant drug response. Conclusions: Across all age groups, CYB5Aalt was the most frequent secondary genetic event in relapsed NH and HeH BCP-ALL. In addition to its high subgroup specificity, CYB5Aalt is a novel candidate to be potentially implicated in therapy resistance in NH and HeH BCP-ALL. This is underlined by overexpressing CYB5Aalt providing first evidence for a functional role in BCL2-mediated apoptosis