Elektrochemisch gesteuerte zeitaufgelöste Infrarotspektroskopie an Redox-Membranproteinen in einer biomimetischen Membran-Architektur

Das Protein Cytochrom c Oxidase (CcO) ist ein Enzym der mitochondrialen Atmungskette. Als letzter Komplex (Komplex IV) einer Elektronentransportkette katalysiert sie die Reduktion von molekularem Sauerstoff zu Wasser. Hierbei werden Elektronen von Cytochrom c (Cc) in das Enzym geleitet. Die durch den Redoxprozess freiwerdende freie Enthalpie wird dazu genutzt, einen Protonengradienten über die innere Mitochondrien-Membran aufzubauen. Die zurückwandernden Protonen treiben in der ATP-Synthase die Produktion von Adenosintriphosphat (ATP) an, dem universellen Energieträger in lebenden Organismen. Gegenstand dieser Dissertation sind zeitaufgelöste ATR-FTIR-Messungen des direkten Elektronentransfers in die CcO. Das Protein wird hierzu orientiert auf einer Goldelektrode immobilisiert und in eine künstliche Membran rekonstituiert (Protein-tethered Bilayer Lipid Membrane, ptBLM). Das ptBLM-System wird hinsichtlich einer möglichst hohen Protein-Aktivität optimiert. Elektronen werden durch elektrochemische Anregung von der Elektrode in die CcO injiziert. Die Goldoberfläche wird auf die reflektierende Oberfläche eines Silizium-ATR-Kristalls aufgebracht. Durch die Präparation einer rauen Oberfläche (RMS-Rauigkeit ca. 5 nm) wird eine Verstärkung der IR-Absorption erreicht. Die mit den Ladungstransferprozessen einhergehenden Konformationsänderungen der die Redoxzentren umgebenden Gruppen (CONH-Gerüst und Aminosäure-Seitenketten) können durch Infrarot-Spektroskopie nachgewiesen werden. Phasensensitive Detektion (PSD) wird zur Rauschminderung eingesetzt, um Geschwindigkeitskonstanten für die Redox-Übergänge zu bestimmen. Im Bereich der Amid-I-Bande werden etliche Peaks identifiziert, die sich mit dem Redoxzustand des Proteins ändern. Für das CuA-Zentrum, welches als erstes der vier Redoxzentren der CcO reduziert wird, wird die schnellste Geschwindigkeitskonstante ks=4870/s ermittelt. Für das Häm a3-Zentrum wird eine Geschwindigkeitskonstante von ks=13,8/s ermittelt. Die Ergebnisse sind konsistent zu elektrochemischen und Raman-Spektroskopie-Experimenten, welche ebenfalls in unserer Gruppe durchgeführt wurden. Weitere Themen dieser Dissertation sind der Nachweis der Anwendbarkeit des ptBLM-Systems für andere Membranproteine (Beispiel: bakterielles photosynthetisches Reaktionszentrum) und der Einsatz des ATR-FTIR-Setups für verschiedene künstliche Membransysteme (Aktivitätsnachweis des OR5-Geruchsrezeptors in einer peptidgestützten Membran, Eigenschaften eines Oligoethylenglycol-Spacers).

Quadri di sintomi. Teoria della immagini, storia dell'arte e scienze umane in medicina

Lo studio analizza il modo in cui la storia dell’arte e la visual culture vengono utilizzate all’interno delle medical humanities, e cerca di suggerire un metodo più utile rispetto a quelli fin qui proposti. Lo scritto è organizzato in due parti. Nella prima parte sono analizzate alcune teorie e pratiche delle scienze umane in medicina. In particolare, ci concentriamo sulla medicina narrativa e sugli approcci con cui la storia dell’arte viene inclusa nella maggioranza dei programmi di medical humanities. Dopodiché, proponiamo di riconsiderare questi metodi e di implementare il ruolo di un pensiero storico e visivo all’interno di tali insegnamenti. Nella seconda parte, alla luce di quanto emerso nella prima, ci dedichiamo a uno studio di caso: la rappresentazione della melanconia amorosa, o mal d’amore, in una serie di dipinti olandesi del Secolo d’Oro. Colleghiamo queste opere a trattati medico-filosofici dell’epoca che permettano di inquadrare il mal d’amore in un contesto storico; in seguito, analizziamo alcune interpretazioni fornite da studiosi e storici dell’arte a noi contemporanei. In particolare, esaminiamo lo studio pionieristico di Henry Meige, pubblicato sulla “Nouvelle iconographie de la Salpêtrière” nel 1899, da cui emerge la possibilità di un confronto critico sia con le posizioni iconodiagnostiche di Charcot e Richer sia con quelle della prima psicoanalisi.

Expériences du sacré et (dé)figurations du Christ. Artaud, Beckett, Pasolini

« Dieu est mort » proclame à l’envi le fou nietzschéen. C’est sous l’égide inquiète de cette assertion paroxystique, traduisant ce «malaise de la culture» qu’évoquait Freud, que la pensée, la littérature et l’art du XXe siècle européen évoluent. Cependant, le christianisme dont ce cri signe l’extrême décadence, n’est pas seul à imprégner les productions artistiques de ce siècle, même les plus prétendument athées, mais avant tout la figure du Christ - autour de laquelle sont structurés tant cette religion que son système de croyance – semble, littéralement et paradoxalement, infester l’imaginaire du XXe siècle, sous des formes plus ou moins fantasmatiques. Ce travail se propose ainsi précisément d’étudier, dans une optique interdisciplinaire entre littérature, art et cinéma, cette dynamique controversée, ses causes, les processus qui la sous-tendent ainsi que ses effets, à partir des œuvres de trois auteurs : Artaud, Beckett et Pasolini. L’objectif est de fournir une clé de lecture de cette problématique qui mette en exergue comment « la conversion de la croyance », comme la définit Deleuze, à laquelle ces auteurs participent, n’engendre pas un rejet purement profanatoire du christianisme mais, à l’inverse, la mise en œuvre d’un mouvement aussi violent que libératoire qualifié par Nancy de « déconstruction du christianisme ». Ce travail entend donc étudier tout d’abord à la lumière de l’expérience intérieure de Bataille, l’imaginaire christique qui sous-tend leurs productions ; puis, d’en analyser les mouvements et les effets en les questionnant sur la base de cette dynamique ambivalente que Grossman nomme la « défiguration de la forme christique ». Les excès délirants d’Artaud, l’ironie tranchante de Beckett et la passion ambiguë de Pasolini s’avèrent ainsi participer à un mouvement commun qui, oscillant entre reprise et rejet, débouche sur une attitude tout aussi destructive que revitalisante des fondements du christianisme.

La violenza sull'anziano: Aspetti medico-legali di una problematica sommersa

L’abuso dell’anziano è una condizione estremamente diffusa e ha un grande costo umano e finanziario. La dimensione reale del problema del maltrattamento dell’anziano non è stata correttamente definita, in particolare i casi segnalati ufficialmente di abuso sono solo la "punta dell'iceberg". In questi anni il problema è stato riconosciuto a livello internazionale come un fenomeno comune, che viene sottostimato e degno di attenzione da parte della comunità scientifica. In Italia non ci sono molti dati, la prevalenza degli abusi e maltrattamenti può essere circa il 5% e il problema è ampiamente sottovalutato, perché sono scarse le segnalazioni di abusi. Le evidenze disponibili dimostrano che l'abuso sugli anziani in Italia costituisce una questione pubblica, tuttavia, la legislazione e le politiche per affrontare il fenomeno sono scarse, riflettendo la mancanza di una strategia nazionale coerente e globale. Il codice civile italiano non contiene alcun riferimento esplicito a persone anziane, e pochi sono anche gli articoli del codice penale che riguardano le persone anziane. Gli articoli più rilevanti interessate sono le seguenti: art. 572: "Maltrattamenti contro familiari e conviventi" e art. 643: "circonvenzione di persone incapaci". Il presente studio ha lo scopo di analizzare la situazione attuale del fenomeno nel nostro Paese, al fine di valutare la dimensione del problema e le relazioni di abuso e maltrattamenti tra vittime, caregiver e operatori sanitari alle autorità.

Still/moving images. Il rapporto dialettico tra cinema e fotografia nelle pratiche artistiche contemporanee.

Tra le plurime conseguenze dell’avvento del digitale, la riarticolazione dei rapporti tra immagine statica e immagine in movimento è certamente una delle più profonde. Sintomatica dei cambiamenti in atto sia nei film studies sia nella storia dell’arte, tale riarticolazione richiede un ripensamento dei confini disciplinari tradizionali entro cui il cinema e la fotografia sono stati affrontati come oggetti di studio separati e distinti. Nell’adottare un approccio molteplice, volto a comprendere prospettive provenienti dalla New Film History e dalla media archaeology, dalla teoria dell’arte e dagli studi visuali, questo lavoro esplora l’esistenza di una relazione dialettica tra il cinema e la fotografia intesa in modo duplice: come tensione costitutiva tra due media indissolubilmente connessi – non tanto in considerazione di un medesimo principio realistico di rappresentazione quanto, piuttosto, in virtù di uno scambio incessante nella modellizzazione di categorie quali il tempo, il movimento, l’immobilità, l’istante, la durata; come istanza peculiare della pratica artistica contemporanea, paradigma di riferimento nella produzione estetica di immagini. La tesi si suddivide in tre capitoli. Il primo si concentra sul rapporto tra l’immobilità e il movimento dell’immagine come cifra in grado di connettere l’estetica delle attrazioni e la cronofotografia a una serie di esperienze filmiche e artistiche prodotte nei territori delle avanguardie. Il secondo capitolo considera l’emergenza, dagli anni Novanta, di pratiche artistiche in cui l’incontro intermediale tra film e fotografia fornisce modelli di analisi volti all’indagine dell’attuale condizione estetica e tecnologica. Il terzo offre una panoramica critica su un caso di studio, la GIF art. La GIF è un formato digitale obsoleto che consente di produrre immagini che appaiono, simultaneamente, come fisse e animate; nel presente lavoro, la GIF è discussa come un medium capace di contraddire i confini attraverso cui concepiamo l’immagine fissa e in movimento, suggerendo, inoltre, un possibile modello di pensiero storico-cronologico anti-lineare.

A mesoscopic simulation method for electrolyte solutions

This thesis deals with the development of a novel simulation technique for macromolecules in electrolyte solutions, with the aim of a performance improvement over current molecular-dynamics based simulation methods. In solutions containing charged macromolecules and salt ions, it is the complex interplay of electrostatic interactions and hydrodynamics that determines the equilibrium and non-equilibrium behavior. However, the treatment of the solvent and dissolved ions makes up the major part of the computational effort. Thus an efficient modeling of both components is essential for the performance of a method. With the novel method we approach the solvent in a coarse-grained fashion and replace the explicit-ion description by a dynamic mean-field treatment. Hence we combine particle- and field-based descriptions in a hybrid method and thereby effectively solve the electrokinetic equations. The developed algorithm is tested extensively in terms of accuracy and performance, and suitable parameter sets are determined. As a first application we study charged polymer solutions (polyelectrolytes) in shear flow with focus on their viscoelastic properties. Here we also include semidilute solutions, which are computationally demanding. Secondly we study the electro-osmotic flow on superhydrophobic surfaces, where we perform a detailed comparison to theoretical predictions.

Chapter II: Diagnostic methods

Non-invasive vascular studies can provide crucial information on the presence, location, and severity of critical limb ischaemia (CLI), as well as the initial assessment or treatment planning. Ankle-brachial index with Doppler ultrasound, despite limitations in diabetic and end-stage renal failure patients, is the first-line evaluation of CLI. In this group of patients, toe-brachial index measurement may better establish the diagnosis. Other non-invasive measurements, such as segmental limb pressure, continuous-wave Doppler analysis and pulse volume recording, are of limited accuracy. Transcutaneous oxygen pressure (TcPO(2)) measurement may be of value when rest pain and ulcerations of the foot are present. Duplex ultrasound is the most important non-invasive tool in CLI patients combining haemodynamic evaluation with imaging modality. Computed tomography angiography (CTA) and magnetic resonance angiography (MRA) are the next imaging studies in the algorithm for CLI. Both CTA and MRA have been proven effective in aiding the decision-making of clinicians and accurate planning of intervention. The data acquired with CTA and MRA can be manipulated in a multiplanar and 3D fashion and can offer exquisite detail. CTA results are generally equivalent to MRA, and both compare favourably with contrast angiography. The individual use of different imaging modalities depends on local availability, experience, and costs. Contrast angiography represents the gold standard, provides detailed information about arterial anatomy, and is recommended when revascularisation is needed.

The effects of isoflurane minimum alveolar concentration on withdrawal reflex activity evoked by repeated transcutaneous electrical stimulation in ponies

The aim of this study was to quantify the effects of isoflurane at approximately the minimum alveolar concentration (peri-MAC) on the temporal summation (TS) of reflex activity in ponies. TS was evoked by repeated electrical stimulations applied at 5 Hz for 2 s on the digital nerve of the left forelimb of seven ponies. Surface electromyographic activity was recorded from the deltoid and common digital extensor muscles. TS thresholds and amplitude of response to stimulations of increasing intensities were assessed during anaesthesia at 0.85, 0.95 and 1.05 times the individual MAC, and after anaesthesia in standing animals. Under isoflurane anaesthesia, TS thresholds increased significantly in a concentration-dependent fashion and at each isoflurane MAC, the responses increased significantly for increasing stimulation intensities. A concentration-dependent depression of evoked reflexes with a reduction in the slopes of the stimulus-response function was observed for both muscles. The results demonstrated that with this model it is possible to describe and quantify the effects of anaesthetics on spinal sensory-motor processing in ponies.

Women's Dress as an Expression of Social Development in Bohemia in the Years 1850-1950"

The nature of Czech fashion was shaped both by the social environment - not particularly wealthy, modest, influenced by the Protestant tradition - and by efforts towards women's emancipation. This resulted in a rejection of unnecessarily quirky elements in fashion as early as the 1870s. As far as style was concerned, Czech fashion followed the Viennese, German and French, and from the 1890s also the English models, and also found inspiration in contemporary aesthetic principles. National political ambitions appeared in inspiration drawn from folk costume. Feminist struggles and sports paved the way for the acceptance of reformist and practical dress, in which Czech designers took an active part. These trends reached a peak around 1929, with the design of a complete "civilised" women's apparel, based on trouser suits. The peak periods in the development of Czech fashion were the 1920s and 1930s, when a number of top fashion houses were established and both fashion and society magazines with original fashion designs, photographs and articles were published. These produced a specifically Czech fashion, showing French inspiration but opting rather for an English style, which was artistically advanced, practical, luxurious and democratic. After 1948, fashion too fell under the centralised control of the communist regime.

Retention in care of HIV-infected children from HIV test to start of antiretroviral therapy: systematic review

BACKGROUND In adults it is well documented that there are substantial losses to the programme between HIV testing and start of antiretroviral therapy (ART). The magnitude and reasons for loss to follow-up and death between HIV diagnosis and start of ART in children are not well defined. METHODS We searched the PubMed and EMBASE databases for studies on children followed between HIV diagnosis and start of ART in low-income settings. We examined the proportion of children with a CD4 cell count/percentage after after being diagnosed with HIV infection, the number of treatment-eligible children starting ART and predictors of loss to programme. Data were extracted in duplicate. RESULTS Eight studies from sub-Saharan Africa and two studies from Asia with a total of 10,741 children were included. Median age ranged from 2.2 to 6.5 years. Between 78.0 and 97.0% of HIV-infected children subsequently had a CD4 cell count/percentage measured, 63.2 to 90.7% of children with an eligibility assessment met the eligibility criteria for the particular setting and time and 39.5 to 99.4% of the eligible children started ART. Three studies reported an association between low CD4 count/percentage and ART initiation while no association was reported for gender. Only two studies reported on pre-ART mortality and found rates of 13 and 6 per 100 person-years. CONCLUSION Most children who presented for HIV care met eligibility criteria for ART. There is an urgent need for strategies to improve the access to and retention to care of HIV-infected children in resource-limited settings.

Temporal trends in the characteristics of children at antiretroviral therapy initiation in southern Africa: the IeDEA-SA Collaboration

BACKGROUND Since 2005, increasing numbers of children have started antiretroviral therapy (ART) in sub-Saharan Africa and, in recent years, WHO and country treatment guidelines have recommended ART initiation for all infants and very young children, and at higher CD4 thresholds for older children. We examined temporal changes in patient and regimen characteristics at ART start using data from 12 cohorts in 4 countries participating in the IeDEA-SA collaboration. METHODOLOGY/PRINCIPAL FINDINGS Data from 30,300 ART-naïve children aged <16 years at ART initiation who started therapy between 2005 and 2010 were analysed. We examined changes in median values for continuous variables using the Cuzick's test for trend over time. We also examined changes in the proportions of patients with particular disease severity characteristics (expressed as a binary variable e.g. WHO Stage III/IV vs I/II) using logistic regression. Between 2005 and 2010 the number of children starting ART each year increased and median age declined from 63 months (2006) to 56 months (2010). Both the proportion of children <1 year and ≥10 years of age increased from 12 to 19% and 18 to 22% respectively. Children had less severe disease at ART initiation in later years with significant declines in the percentage with severe immunosuppression (81 to 63%), WHO Stage III/IV disease (75 to 62%), severe anemia (12 to 7%) and weight-for-age z-score<-3 (31 to 28%). Similar results were seen when restricting to infants with significant declines in the proportion with severe immunodeficiency (98 to 82%) and Stage III/IV disease (81 to 63%). First-line regimen use followed country guidelines. CONCLUSIONS/SIGNIFICANCE Between 2005 and 2010 increasing numbers of children have initiated ART with a decline in disease severity at start of therapy. However, even in 2010, a substantial number of infants and children started ART with advanced disease. These results highlight the importance of efforts to improve access to HIV diagnostic testing and ART in children.

When to start antiretroviral therapy in children aged 2-5 years: a collaborative causal modelling analysis of cohort studies from southern Africa

BACKGROUND There is limited evidence on the optimal timing of antiretroviral therapy (ART) initiation in children 2-5 y of age. We conducted a causal modelling analysis using the International Epidemiologic Databases to Evaluate AIDS-Southern Africa (IeDEA-SA) collaborative dataset to determine the difference in mortality when starting ART in children aged 2-5 y immediately (irrespective of CD4 criteria), as recommended in the World Health Organization (WHO) 2013 guidelines, compared to deferring to lower CD4 thresholds, for example, the WHO 2010 recommended threshold of CD4 count <750 cells/mm(3) or CD4 percentage (CD4%) <25%. METHODS AND FINDINGS ART-naïve children enrolling in HIV care at IeDEA-SA sites who were between 24 and 59 mo of age at first visit and with ≥1 visit prior to ART initiation and ≥1 follow-up visit were included. We estimated mortality for ART initiation at different CD4 thresholds for up to 3 y using g-computation, adjusting for measured time-dependent confounding of CD4 percent, CD4 count, and weight-for-age z-score. Confidence intervals were constructed using bootstrapping. The median (first; third quartile) age at first visit of 2,934 children (51% male) included in the analysis was 3.3 y (2.6; 4.1), with a median (first; third quartile) CD4 count of 592 cells/mm(3) (356; 895) and median (first; third quartile) CD4% of 16% (10%; 23%). The estimated cumulative mortality after 3 y for ART initiation at different CD4 thresholds ranged from 3.4% (95% CI: 2.1-6.5) (no ART) to 2.1% (95% CI: 1.3%-3.5%) (ART irrespective of CD4 value). Estimated mortality was overall higher when initiating ART at lower CD4 values or not at all. There was no mortality difference between starting ART immediately, irrespective of CD4 value, and ART initiation at the WHO 2010 recommended threshold of CD4 count <750 cells/mm(3) or CD4% <25%, with mortality estimates of 2.1% (95% CI: 1.3%-3.5%) and 2.2% (95% CI: 1.4%-3.5%) after 3 y, respectively. The analysis was limited by loss to follow-up and the unavailability of WHO staging data. CONCLUSIONS The results indicate no mortality difference for up to 3 y between ART initiation irrespective of CD4 value and ART initiation at a threshold of CD4 count <750 cells/mm(3) or CD4% <25%, but there are overall higher point estimates for mortality when ART is initiated at lower CD4 values. Please see later in the article for the Editors' Summary.

Rechtsmittel gegen Entscheide des juge d'appui bei der internationalen Schiedsgerichtsbarkeit der Schweiz

The author examines whether and by which means the decisions handed down by the State judge giving his support to the arbitral proceeding (juge d'appui) may be appealed. Every relevant Article in the PILA (Private International Law Act) is addressed and analyzed in this regard (Art. 179(2) and (3), Art. 180(3), Art. 183(2), Art. 184(3) and Art. 185) by reference to the present legal doctrine and case law. Concerning the stages of appeal, the view is held that by direct or analogous application of Art. 356(2) CPC (Civil Procedure Code) the juge d'appui has jurisdiction as the sole instance of the Canton to render decisions in support of the arbitral tribunal. On the federal level however, the parties shall have the right to appeal against these decisions by filing a civil law appeal before the Swiss Federal Supreme Court, with the exception of most decisions given by juge d'appui within the meaning of Art. 180(3) PILA. As to this federal appeal, it is established that the case law of the Swiss Federal Supreme Court under the FTA (Act on the Federal Tribunal) indicates the Court's inclination to qualify both negative and positive decisions issued by the juge d'appui as final decisions in terms of Art. 90 FTA. In reference to the upcoming revision of the PILA's 12th Chapter the author concludes that the legislator might implement some clarifications in the current legal framework. It seems particularly advisable to ensure that all relevant Articles in the PILA regarding decisions of the juge d'appui explicitly reference to Art. 356(2) CPC. Moreover, the author is of the opinion that it would also be expedient to specify the