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Die Suche nach dem Selbst und nach der Wahrheit – ein solcher Titel weckt zweifellos hohe Erwartungen, spricht doch diese Frage in jüngster Zeit nicht nur esoterisch ausgerichtete Geister an. Vielmehr spielt sie im Rahmen aktueller Arbeiten zur Konstruktion und Wahrnehmung von Individualität sowie zur "Produktion von Wahrheit" durch Praktiken der Befragung oder der Verschriftlichung des Rechts eine zentrale Rolle. So ist den Herausgebern des vorl. Bandes zuzustimmen, wenn sie das Prozessverfahren der Inquisition oder die Aufnahme von Aussagen zu Besitz- und Lehnsverhältnissen nicht nur mit Blick auf die hierbei produzierten Informationen selbst analysieren möchten. Vielmehr unterstreichen sie die Fruchtbarkeit der Prozesssituation und ihres Umfelds für die Untersuchung der sich hier manifestierenden Machtverhältnisse, aber auch der sozialen Verflechtungen. Beide Aspekte spiegeln sich in den Techniken der Befragung, in der Zuweisung von (oder Forderung nach) Rederaum und in der schriftlichen Aufzeichnung der mündlich und performativ produzierten Äußerungen. Alleine, und soviel sei vorweggenommen, die in den bilanzierenden Einleitungen von Verdon (S. 9–16, 77–82) und Faggion (S. 17–26, 83–97) angedeuteten möglichen Wege der Forschung werden von den Beiträgen des Bandes leider nur auf Teilstücken begangen. ...
Since Inhibitor of Apoptosis (IAP) proteins have been implicated in cellular adaptation to endoplasmic reticulum (ER) stress, we investigated the regulation of ER stress-induced apoptosis by small-molecule second mitochondria-derived activator of caspase (Smac) mimetics that antagonize IAP proteins. Here, we discover that Smac mimetic suppresses tunicamycin (TM)-induced apoptosis via resolution of the unfolded protein response (UPR) and ER stress. Smac mimetics such as BV6 selectively inhibit apoptosis triggered by pharmacological or genetic inhibition of protein N-glycosylation using TM or knockdown of DPAGT1, the enzyme that catalyzes the first step of protein N-glycosylation. In contrast, BV6 does not rescue cell death induced by other typical ER stressors (i.e., thapsigargin (TG), dithiothreitol, brefeldin A, bortezomib, or 2-deoxyglucose). The protection from TM-triggered apoptosis is found for structurally different Smac mimetics and for genetic knockdown of cellular IAP (cIAP) proteins in several cancer types, underlining the broader relevance. Interestingly, lectin microarray profiling reveals that BV6 counteracts TM-imposed inhibition of protein glycosylation. BV6 consistently abolishes TM-stimulated accumulation of ER stress markers such as glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) and reduces protein kinase RNA-like ER kinase (PERK) phosphorylation and X box-binding protein 1 (XBP1) splicing upon TM treatment. BV6-stimulated activation of nuclear factor-κB (NF-κB) contributes to the resolution of ER stress, since NF-κB inhibition by overexpression of dominant-negative IκBα superrepressor counteracts the suppression of TM-stimulated transcriptional activation of CHOP and GRP78 by BV6. Thus, our study is the first to show that Smac mimetic protects from TM-triggered apoptosis by resolving the UPR and ER stress. This provides new insights into the regulation of cellular stress responses by Smac mimetics.
L’ouvrage à présenter réunit les contributions de la dernière d’une série de conférences organisées par le Max-Planck-Institut für Geschichte en collaboration avec la Mission historique en Allemagne, le British Council et la Polska Misja Historyczna. Il conclut un tour d’horizon sur la question de »La mémoire culturelle des sciences [historiques] à l’époque moderne« qui restera, malheureusement, à jamais incomplet sous forme de livre, les actes de la deuxième conférence »Justice, pouvoir et violence au Moyen Âge« n’ayant pas été publiés. Mais on ne regrettera pas seulement l’absence du deuxième volet dans ce triptyque: avec la fermeture en 2006 du seul Max-Planck-Institut consacré à l’histoire générale, une coopération fertile entre les instituts historiques de plusieurs nations touche désormais à sa fin. Ceci est d’autant plus regrettable que la communauté internationale des historiens, et en particulier des médiévistes, à Göttingen avait su créer un lieu de contacts et d’échanges fertiles. ...
Purpose: To analyze leg pain severity data from a randomized controlled trial (RCT) of lumbar disc surgery using integrated approaches that adjust pain scores collected at scheduled follow-up visits for confounding clinical events occurring between visits. Methods. Data were derived from an RCT of a bone-anchored annular closure device (ACD) following lumbar discectomy versus lumbar discectomy alone (Control) in patients with large postsurgical annular defects. Leg pain was recorded on a 0 to 100 scale at 6 weeks, 3 months, 6 months, 1 year, and 2 years of follow-up. Patients with pain reduction ≥20 points relative to baseline were considered responders. Unadjusted analyses utilized pain scores reported at follow-up visits. Since symptomatic reherniation signifies clinical failure of lumbar discectomy, integrated analyses adjusted pain scores following a symptomatic reherniation by baseline observation carried forward for continuous data or classification as nonresponders for categorical data.
Results: Among 550 patients (272 ACD, 278 Control), symptomatic reherniation occurred in 10.3% of ACD patients and in 21.9% of controls (p < 0.001) through 2 years. There was no difference in leg pain scores at the 2-year visit between ACD and controls (12 versus 14; p = 0.33) in unadjusted analyses, but statistically significant differences favoring ACD (19 versus 29; p < 0.001) in integrated analyses. Unadjusted nonresponder rates were 6.0% with ACD and 6.7% with controls (p = 0.89), but 15.7% and 27.8% (p = 0.001) in integrated analyses. The probability of nonresponse was 16.4% with ACD and 18.3% with controls (p = 0.51) in unadjusted analysis, and 23.7% and 31.2% (p = 0.04) in integrated analyses.
Conclusion: In an RCT of lumbar disc surgery, an integrated analysis of pain severity that adjusted for the confounding effects of clinical failures occurring between follow-up visits resulted in different conclusions compared to an unadjusted analysis of pain scores reported at follow-up visits only.
Das Leben und Wirken des Burgunderherzogs Karls des Kühnen ist zwar gut erforscht. Dennoch bot es sich an, im Rahmen der unter anderem in Bern gezeigten Ausstellung im Frühjahr 2008 eine begleitende wissenschaftliche Tagung zu organisieren. Der hier zu besprechende Band vereinigt nun die Tagungsbeiträge ausgewiesener Spezialistinnen und Spezialisten auf gelungene Art und Weise und in ansprechender Form. ...
Music is an effective means of stress-reduction. However, to date there has been no systematic comparison between musical and language-based means of stress reduction in an ambulatory setting. Furthermore, although the aim for listening to music appears to play a role in its effect, this has not yet been investigated thoroughly. We compared musical means, language-based means like guided relaxation or self-enhancement exercises, and a combination of both with respect to their potential to reduce perceived stress. Furthermore, we investigated whether the aim one wants to achieve by listening to these means had an impact on their effect. We tested 64 participants (age: M = 40.09 years; 18 female) for 3–10 days during their everyday life using an app containing three means: musical means, language-based means, and a combination of both. For the music and the combination conditions participants were asked to select an aim: relaxation or activation. We measured perceived stress, relaxation, activation, and electrical skin resistance (ESR) as a marker of sympathetic nervous system (SNS) activity before and after using the app. Participants were instructed to use the app as often as desired. Overall, perceived stress was reduced after using the app, while perceived relaxation and activation were increased. There were no differences between the three means regarding their effect on perceived stress and relaxation, but music led to a greater increase in ESR and perceived activation compared to the other means. There was a decrease in ESR only for music. Moreover, perceived stress was reduced and perceived relaxation was increased to greater extent if the aim “relaxation” had been selected. Perceived activation, however, showed a larger increase if the aim had been “activation,” which was even more marked in the case of music listening. Our results indicate that all three means reduced perceived stress and promoted feelings of relaxation and activation. For enhancing feelings of activation music seems to be more effective than the other means, which was reflected in increased SNS activity as well. Furthermore, the choice of an aim plays an important role for the reduction of stress, and promotion of relaxation and activation.
L’introduction de cet ouvrage rappelle que l’un des critères plus ou moins explicites de différenciation entre la modernité et ce qui la précède et entre la démocratie et les formes traditionnelles d’exercice du pouvoir est précisément la place tenue par les rites, cérémonies et autres gestes significatifs par eux-mêmes. La cérémonie serait par essence plutôt surannée, vue d’une manière péjorative. Le Centre d’études médiévales de Berne (Berner Mittelalter Zentrum/BMZ) a rassemblé plusieurs chercheurs, dans les années 2005–2006, autour de ce thème. Les organisateurs présentent en introduction une riche problématique dans laquelle ils rappellent tout ce qu’ils doivent spécialement à Gerd Althoff et à Jean-Claude Schmitt. On signalera en particulier l’attention portée à l’histoire de l’art et à l’histoire religieuse dans un souci de cohérence globale. Les contributions viennent de spécialistes de différents domaines et sont regroupées sous différentes sections: »Méthodologie«, »Liturgie«, »Droit«, »Politique« et, enfin, une réflexion conclusive à partir de données linguistiques. ...
Extinction of fear responses is critical for adaptive behavior and deficits in this form of safety learning are hallmark of anxiety disorders. However, the neuronal mechanisms that initiate extinction learning are largely unknown. Here we show, using single-unit electrophysiology and cell-type specific fiber photometry, that dopamine neurons in the ventral tegmental area (VTA) are activated by the omission of the aversive unconditioned stimulus (US) during fear extinction. This dopamine signal occurred specifically during the beginning of extinction when the US omission is unexpected, and correlated strongly with extinction learning. Furthermore, temporally-specific optogenetic inhibition or excitation of dopamine neurons at the time of the US omission revealed that this dopamine signal is both necessary for, and sufficient to accelerate, normal fear extinction learning. These results identify a prediction error-like neuronal signal that is necessary to initiate fear extinction and reveal a crucial role of DA neurons in this form of safety learning.
Avec le présent fascicule, le Mittelalterzentrum (Centre d’études médiévales) de la Berlin-Brandenburgische Akademie der Wissenschaften (BBAW) inaugure une nouvelle série: une fois par an, le centre organisera une conférence publique qui sera ensuite publiée sous ce format. Dans la préface, Michael Borgolte, porte-parole du Mittelalterzentrum, indique que le centre a choisi ce format afin de mettre en relief la contribution des disciplines médiévistes au travail de la BBAW, mais aussi afin de promouvoir la réflexion des disciplines concernées sur leur propre position et d’animer le dialogue et les contacts interdisciplinaires. Bref, il s’agit de montrer, entre autres, l’actualité des recherches médiévistes – et le choix du premier conférencier n’aurait pu être meilleur: Otto Gerhard Oexle, ancien directeur du Max-Planck-Institut für Geschichte à Göttingen, réfléchit et écrit depuis longtemps sur le travail des historiens et ses implications théoriques, mais aussi sur le rôle social de l’histoire en général dans les sociétés contemporaines. Il met tout particulièrement l’accent sur le rôle constitutif que jouent le Moyen Âge et les images que nous nous en faisons pour la mise en place de la »modernité«.
Background: Transcatheter aortic valve replacement (TAVR) is a therapeutic option for patients with aortic valve stenosis at increased surgical risk. Telomeres are an established marker for cellular senescence and have served to evaluate cardiovascular diseases including severe aortic valve stenosis. In our study, we hypothesized that telomere length may be a predictor for outcome and associated with comorbidities in patients with TAVR.
Methods and results: We analyzed leucocyte telomere length from 155 patients who underwent TAVR and correlated the results with 1-year mortality and severe comorbidities. The cohort was subdivided into 3 groups according to telomere length. Although a trend for a positive correlation of telomere length with a lower EuroSCORE could be found, telomere length was not associated with survival, aortic valve opening area or cardiovascular comorbidities (peripheral, coronary or cerebrovascular disease). Interestingly, long telomeres were significantly correlated to a reduced left ventricular ejection fraction (LVEF).
Conclusion: In elderly patients with severe aortic valve stenosis, leucocyte telomere length did not predict post-procedural survival. The correlation between long telomere length and reduced LVEF in these patients deserves further attention.