3,795 research outputs found

    The Christian Perception of Islam in the Late Middle Ages and in the Reformation

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    Das 15. und 16. Jahrhundert waren durch die äußere Bedrohung durch das Osmanische Reich in mentalitätsgeschichtlicher Hinsicht mannigfach verbunden. Dies kam auch darin zum Ausdruck, dass sich die Reformatoren einige mittelalterliche Texte zur Wahrnehmung des Islam (Georg von Ungarn, Robert v. Kettons Übersetzung des Koran u.a.) aneigneten, sie erneut oder erstmals publizierten, aber auch zum Zweck der binnenchristlichen Polemik aktualisierten. Die Muster in der Wahrnehmung der „türkischen Religion“ pluralisierten sich; neben traditionell häresiologischen spielten Wahrnehmungsweisen eine verstärkte Rolle, die die „Unwahrheit“ des Islam anhand des Koran selbst zu erweisen versuchten. Die Turkisierung der innerchristlichen Gegner trug dazu bei, religionskulturelle Wissensbestände über die fremde Religion präsent zu halten und zu popularisieren

    Improving the acute and perioperative hemodynamic assessment

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    First, this thesis aimed to extend the evidence on the applicability of hemodynamic monitoring during the perioperative period and after admission to the ICU. Second, we aimed to gain knowledge on how to improve the conduct of studies in perioperative and critical care medicine.We provided an overview of the current evidence for hemodynamic monitoring in perioperative goal-directed therapy. We showed that the studies on this subject showed clinical heterogeneity and risk of bias. Extension of all aspects of hemodynamic monitoring was considered in this thesis. A study was performed on the educated guess of physicians when estimating cardiac output using clinical examination to help improve the reliability of the clinical examination. We showed that physicians at the bed-side mainly consider mottling score and norepinephrine dose when estimating cardiac output. In another study, we demonstrated that blood pressure measurements differ when measured invasively or non-invasively and that these differences may have clinical consequences. We also showed that echocardiography could be performed by novices, but experts are needed to interpret obtained images. We demonstrated that cardiac output measurements vary in critically ill patients when measured with echocardiography or uncalibrated pulse wave analysis.For the second part of this thesis, we demonstrated that various mortality prediction models exist for critically ill patients. Quality of methodology often lacks for these models, and improvements have to be made to help patient care. To help improve the quality of studies, we finally propose that study protocols are prepublished and made available for peer-review before conduct

    American Voices. Remarks on the Earlier History of Art History in the United States and the Reception of Germanic Art Historians

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    This essay presents a critique of recent historiographic considerations of German art historians in the United States. It traces this history back to Johann Valentin Haidt in the eighteenth century. Using Princeton as a point of reference, it traces the innovations in the history of the discipline in the United States that were developed largely independent of the impact of German émigrés, and then turns to consider the possible impact of German speakers. Finally it takes issue with the idea of German Jewish identity in art history

    ‘Indifferent Things?’ Reflections on Reformation and Art in the Baltic Region

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    This chapter presents reflections on issues raised by IndifferentThings? Objects and Images in Post-Reformation Churches in the BalticSea Region. It discusses the recent historiography of interpretativeapproaches, periodisation, the canon, iconoclasm, theories ofresponse, comparative contexts, and issues of aesthetics

    Detergent-protein and detergent-lipid interactions : implications for two-dimensional crystallization of membrane proteins and development of tools for high throughput crystallography

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    2.1 Scope of this Thesis This thesis represents an attempt to enlighten the role of the detergent in reconstitution and more specifically in two-dimensional (2D) crystallogenesis of membrane proteins. The construction of a tool for precise and routine measurements of detergent concentrations provided a valuable tool for better understanding and controlling the detergent issue. Additionally, a novel approach for detergent removal in 2D crystallization, i.e. the use of cyclodextrins was explored and a nanoliter dispensing high throughput tool was developed allowing for profound and sophisticated screening of optimal conditions for protein reconstitution and crystallization. 2.2 Combining Electron Microscopy and Atomic Force Microscopy Although electron crystallography has proven to be a powerful approach to structure determination of membrane proteins (for a recent example see (Gonen et al., 2005)) successes are somehow restricted to certain classes of membrane proteins (e.g., outer membrane porins, aquaporins, naturally occurring crystalline proteins). This is mainly due to the stability of these proteins with respect to biochemical manipulation. One can not exclude however, that these are simply more amenable to crystallization due to the nature of their molecular surfaces. 2D crystallization exhibits several advantages compared to 3D crystallization of membrane proteins: The simple fact that the proteins are allowed to reside in a native-like environment, i.e., the membrane and that their function is not impaired by the lateral crystal contacts is of considerable interest. If structural investigations shall not be restricted to static snapshots of different conformations and moreover structure-function relationships shall be established, then electron microscopy (EM) in combination with atomic force microscopy (AFM) surely represent a valuable approach. In Chapter 2 the combination of such data has been successfully applied to the ammonium transporter AmtB from Escherichia coli. The aim was to determine the crystal packing of the double-layered 2D crystals of AmtB by AFM in order to process the cryo EM data. Additionally, the AFM images, due to their outstanding signal-to-noise ratio, enabled the direct visualization of trimers in the reconstituted membranes. The topographical data from the AFM allowed the assessment of a single layer within the double layered crystals. 2.3 Investigating the Role of the Detergent In Chapter 3 the development of a fast and precise method for detergent concentration determination is presented. The robustness and wide application range of this method has been demonstrated by comparing concentrations of radioactively labeled dodecyl-[beta],D-maltoside (DDM) with measured contact angles, by measuring the amount of DDM bound to the proton/galactose symporter GalP from E. coli, by measuring the effects of 100 mM NaCl on the cmc of dodecyl-N,Ndimethylamine- N-oxide, by characterizing the surface energy of Parafilm, and finally by revealing the stoichiometry of complex formation between methyl-[beta]-cyclodextrin (MBCD) and different de- tergents. The possibility of performing such measurements routinely in membrane biochemistry is unique compared to all other methods available to date. Chapter 4 addresses the major aspects of detergent use in membrane protein purification and crystallization. First, the stability of GalP in different detergents is assessed, unveiling profound differences in the capacity of detergents to keep the protein in solution. Second, it is demonstrated, that the amount of a detergent, i.e., dodecyl-�,Dmaltoside, bound to a protein can be controlled during purification. At last the amount of different detergents for solubilization of E. coli lipids is determined, showing differences in the mechanisms by which detergents promote solubilization. Banerjee et al. (Banerjee et al., 1995) examined the preferential affinity of detergents for different lipids in mixed membranes (such as biological membranes). They showed that different detergents extract the serotonin 5-HT1A receptor from native membranes along with different lipids. The effect is considerable and might explain why different detergents exhibit such a different ability to keep a protein in its native state, because some might simply not be able to co-solubilize native lipids essential for the stability (and function) of the protein. The amount of detergent bound to a protein is of special interest when using dialysis or dilution for detergent removal. Furthermore, in most cases the protein must not be exposed to excess detergent which anyway fails to satisfactorily mimic the native bilayer. As pointed out in the discussion of Chapter 4, protein reconstitution is facilitated when the detergent collar that is present around the hydrophobic region of membrane proteins in solution is near its solubility limit (Psol). The same is true for the lipid: Reconstitution is likely to happen when liposomes are forming, therefore an excess of detergent is not desirable either. Additionally, even detergents known to have adverse effects on protein stability can be used for lipid solubilization, given that they are present at a minimal concentration. The use of detergent mixtures in crystallization can also have the effect of reducing the size of the detergent collar around the protein. Moreover, the free detergent concentration in detergent mixtures is altered by the presence of the second species and can be crucial to the formation of crystals in some cases (Koning, 2003). When using minimal amounts of detergent in a crystallization mixture, special care should be taken with respect to the formation of ternary micelles. Ideally, equilibration of the ternary mixtures prior to detergent removal needs to be completed. 2.4 The Use of Cyclodextrins for High Thorughput 2D Crystallization of Membrane Proteins Chapter 5 demonstrates the feasibility of the cyclodextrin-based detergent removal for twodimensional crystallization. The possibility of choosing different kinetics, simply by adding different amounts of cyclodextrin at various time intervals is one of the major advantages of this method. By implementing optical spectroscopy, it would be possible to slow down the detergent removal rate at the onset of proteoliposome and 2D crystal formation. As pointed out by Lichtenberg et al. (Lichtenberg et al., 2000) the rate of detergent removal has to be slow enough to allow for detergent-induced vesicle size growth, a process which is usually quite slow. This aspect is important to keep in mind as one defines the rate of detergent neutralization (in contrast to dialysis). At a first glance one might think that in this respect the cyclodextrin approach bears no advantage compared to dialysis. However, the rate of low-cmc detergent removal using dialysis can be too slow, thereby keeping the protein out from its native environment for too long, ultimately promoting its precipitation. In Chapter 6 we present an apparatus for parallel quantitative reconstitution and 2D crystallization of membrane proteins. Cyclodextrin provides a unique opportunity for high throughput implementation compared to other methods available today. Protein concentrating through controlled evaporation with concomitant detergent neutralization (to prevent detergent concentrating) is advantageous compared to commercially available protein concentrating devices which very often concentrate detergent micelles too. Moreover, the possibility of using one protein preparation for wide screening ensures that inconsistencies in results arising from preparative differences are excluded. Often, the detergent and lipid concentration of the purified protein are ill characterized, and this variability may be a cause for much of the irreproducibility and failure in crystallization (Wiener, 2004). So far the use of wide screening matrices (sparse matrix design) in 2D crystallography was restricted by the enormous number of experiments and amount of protein needed for a rigorous screening. The presented machine makes it possible to partially compensate for the first bottleneck in protein structure elucidation, which is the over-expression of membrane proteins. Fig. 2.1 summarizes the screening strategy based on the criteria discussed in Chapter 6 and above. Screening efficiency is provided by the subdivision of the problem into multiple subproblems and by their sequential screening. With the high throughput approach however, a new bottleneck arises as one will produce a large number of crystallization trials, which have to be screened for their outcome. Therefore –in analogy to the x-ray community– the development of automated sample preparation and automated electron microscopic analysis would provide substantial support to the 2D crystallographer. Combining step-by-step identification of key values necessary for crystallization (and/or efficient reconstitution) together with high throughput screening matrices opens up new prospects in the en deavor to membrane protein structure and function determination. Now it is possible to apply a semi-rational screening strategy and this might contribute to transform 2D crystallization from art to science (Jap et al., 1992)

    Inglehart's world value survey and Q methodology

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    The study of human behavior has become central concern for social scientific studies, in particular to better understand and frame complex reality in different fields. This article aims to compare two methods to analyze, how people think, believe, and act in regards to a certain topic: Inglehart's World Value Survey (WVS) and Q Methodology (Q). Whilst WVS displays behavior proportions of a representative sample, Q looks for the differences in field of choice. Both attempt to reveal contemporary discourses, and both are using quantitative measures to do so, large n scale factor analysis in case of the WVS and the inverted bell curve in Q Methodology. We want to show Pros and Cons of these two methods, which have become so useful for social scientific research

    Hybrid waveguide-bulk multi-path interferometer with switchable amplitude and phase

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    We design and realise a hybrid interferometer consisting of three paths based on integrated as well as on bulk optical components. This hybrid construction offers a good compromise between stability and footprint on one side and means of intervention on the other. As experimentally verified by the absence of higher-order interferences, amplitude and phase can be manipulated in all paths independently. In conjunction with single photons, the setup can, therefore, be applied for fundamental investigations on quantum mechanics.Comment: accepted in APL Photonic
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