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Lauschangriff mit tödlichen Folgen : Signalmoleküle von Bakterien können fremden Arten schaden
(2016)
Eine der wichtigsten Fähigkeiten aller Lebewesen ist die Kommunikation. Ihre universelle Ausdrucksform findet sie im Austausch hoch spezifischer Signalmoleküle. Bei der Entschlüsselung der diversen »Sprachen« und »Dialekte« von Bakterien machen Forscher immer wieder neue und überraschende Entdeckungen, die auch eine Alternative zu Antibiotika versprechen.
Es war kein Aprilscherz, als das »Time Magazine« am 1. April 2013 auf der Titelseite ankündigte, wie man Krebs heilen kann. Anlass war die Gründung einer Initiative zur besseren Vernetzung von klinischen Forschern und Grundlagenwissenschaftlern, um so neue Therapieansätze wie »Checkpoint-Inhibitoren« bei malignem Melanom (schwarzem Hautkrebs), auch auf andere Krebserkrankungen übertragen zu können. Checkpoint-Inhibitoren sind der erste echte Durchbruch in der Therapie von fortgeschrittenen Krebserkrankungen.
Software evolves. Developers and programmers manifest the needs that arise due to evolving software by making changes to the source code. While developers make such changes, reusing old code and rewriting existing code are inevitable. There are many challenges that a developer faces when manually reusing old code or rewriting existing code. Software tools and program transformation systems aid such reuse or rewriting of program source code. But there are significantly occuring development tasks that are hard to accomplish manually, where the current state-of-the-art tools are still not able to adequately automate these tasks. In this thesis, we discuss some of these unexplored challenges that a developer faces while reusing and rewriting program source code, the significance of such challenges, the existing automation support for these challenges and how we can improve upon them.
Modern software development relies on code reuse, which software developers
typically realize through hand-written abstractions, such as functions,
methods, or classes. However, such abstractions can be challenging to
develop and maintain. An alternative form of reuse is \emph{copy-paste-modify}, in which developers explicitly duplicate source code to adapt the duplicate for a new purpose. Copy-pasted code results in code clones, i.e., groups of code fragments that are similar to each other. Past research strongly suggests that copy-paste-modify is a popular technique among software developers. In this paper, we perform a small user study that shows that copy-paste-modify can be substantially faster to use than manual abstraction.
One might propose that software developers should forego hand-written abstractions in favour of copying and pasting. However, empirical evidence also shows that copy-paste-modify complicates software maintenance and increases the frequency of bugs. Furthermore, the developers in an informal poll we conducted strongly preferred to read code written using abstractions. To address the concern around copy-paste-modify, we propose a tool that merges similar pieces of code and automatically creates suitable abstractions. Our tool allows developers to get the best of both worlds: easy reuse together with custom abstractions. Because different kinds of abstractions may be beneficial in different contexts, our tool provides multiple abstraction mechanisms, which we selected based on a study of popular open-source repositories.
To demonstrate the feasibility of our approach, we have designed and implemented a prototype merging tool for C++ and evaluated our tool on a number of clones exhibiting some variation, i.e near clones, in popular Open Source packages. We observed that maintainers find our algorithmically created abstractions to be largely preferable to existing duplicated code. Rewriting existing code can be considered as a form of program transformation, where a program in one form is transformed into a program in another form. One significant form of program transformation is data representation migration that involves changing the type of a particular data structure, and then updating all of the operations that has a control or data dependence on that data structure according to the new type. Changing the data representation can provide benefits such as improving efficiency and improving the quality of the computed results. Performing such a transformation is challenging, because it requires applying data-type specific changes to code fragments that may be widely scattered throughout the source code connected by dataflow dependencies. Refactoring systems are typically sensitive to dataflow dependencies, but are not programmable with respect to the features of particular data types. Existing program transformation languages provide the needed flexibility, but do not concisely support reasoning about dataflow dependencies.
To address the needs of data representation migration, we propose a new approach to program transformation that relies on a notion of semantic dependency: every transformation step propagates the transformation process onward to code that somehow depends on the transformed code. Our approach provides a declarative transformation specification language, for expressing type-specific transformation rules. We further provide scoped rules, a mechanism for guiding rule application, and tags, a device for simple program analysis within our framework, to enable more powerful program transformations.
We have implemented a prototype transformation system based on these ideas for C and C++ code and evaluate it against three example specifications, including vectorization, transformation of integers to big integers, and transformation of array-of-structs data types to struct-of-arrays format. Our evaluation shows that our approach can improve program performance and the precision of the computed results, and that it scales to programs of at least 3700 lines.
Vitamin-D-Mangel – ein Risikofaktor für Diabetes : wie Forscher das Immunsystem umprogrammieren
(2016)
Was tun, wenn das Immunsystem nicht mehr zwischen fremden und eigenen Zellen unterscheiden kann? Bei Diabetes Typ 1, einer der häufigsten Autoimmunerkrankungen, gibt es bisher keine Heilung. Besonders schwierig wird die Therapie, wenn parallel dazu weitere Autoimmunerkrankungen auftreten. Mit Vitamin D und anderen Immunmodulatoren soll sich die Situation der Patienten in Zukunft grundlegend verbessern.
Organspenden retten und verlängern Leben : Prof. Dr. Ingeborg Hauser im Interview mit Dr. Anne Hardy
(2016)
Der 21. Mai 2015 ist für Claudia und Timothy Pillar ein besonderer Tag. Seitdem verbindet das Paar mehr als die Erlebnisse einer fast vierzigjährigen Ehe und ein gemeinsamer Sohn. Tim Pillar hat seiner Frau eine Niere gespendet und ihr damit wieder ein (fast) normales Leben ermöglicht. Inzwischen spricht sie von ihrer Krankheit in der Vergangenheitsform.
Überraschende neue Antworten auf die althergebrachte Frage nach dem »Eigenen« und »Fremden« geben die Romane des indischstämmigen Schriftstellers Moyez G. Vassanji, der in Kenia geboren wurde, seit Jahrzehnten in Kanada lebt und heute zu den bedeutendsten Autoren der ostafrikanischen Gegenwartsliteratur zählt. Seine Protagonisten verkörpern eine transregionale Verflechtungsgeschichte, die aus europäischer Perspektive kaum wahrgenommen wird, aber durchaus Impulse für aktuelle Debatten geben kann.
Der Film als modernes mobiles Medium lebt von Erfahrungen des Eigenen und Fremden. Zeigten die Reisefilme zu Beginn des 20. Jahrhunderts bewusst die »wunderbare Differenz« zur eigenen Wirklichkeit, wurde in der heilen Welt der Heimatfilme nach Ende des Zweiten Weltkriegs das Eigene für den Konsum verfügbar gemacht. Erst die Hollywood-Blockbuster verfolgten die Strategie, das kulturell Fremde so zu minimieren, dass daraus der für alle verständliche »Dialekt der Moderne« wurde.
Einflüsse aus anderen Sprachen gehören zum Sprachwandel. Doch wie viele fremde Wörter und Wendungen verträgt eine Sprache? Wann sind sie das Salz in der Suppe? Wann und warum gelten sie als Störfaktor? Das Verhältnis zum Fremdwort kann viel aussagen über den allgemeinen Zustand einer Sprachgemeinschaft – vor allem der deutschen.
Auf nur 25 Seiten schuf Tacitus gegen Ende des 1. Jahrhunderts »Germania« und damit auch das Volk der Germanen, das so gar nicht existierte. In der Antike lebten auf diesem Territorium völlig unabhängig voneinander vielerlei Stämme. Warum zeichnete Tacitus das positive Bild eines unverdorbenen, kampfeslustigen Naturvolks? Wollte er damit den dekadenten Römern einen Spiegel vorhalten? Wollte er vor den starken Gegnern im fremden Norden warnen, gegen die die Römer nicht wieder zu Felde ziehen sollten?
Die Deutschen traten »sich selbst immer ein wenig fremd gegenüber «, schreibt der Frankfurter Mittelalter-Historiker Johannes Fried in seinem Buch »Die Anfänge der Deutschen«, das deren »ethnische Taufe« vom späten 8. bis zum 12. Jahrhundert in den Blick nimmt. Das viel beachtete Werk, das nach 20 Jahren in einer überarbeiteten Neuausgabe vorliegt, lässt sich mittlerweile auch als Kommentar zur aktuellen Diskussion um eine angebliche Bedrohung »eigener« Werte lesen. Bernd Frye sprach mit Prof. Dr. Johannes Fried über ein Volk, das seinerseits aus fremden Elementen und Einwanderungsprozessen erwachsen ist.
Sie hören Stimmen, vermuten Botschaften in bedeutungslosen Ereignissen oder fühlen sich ferngesteuert: Die Symptome von Menschen mit einer schizophrenen Störung galten bisher als »uneinfühlbar«, da für Außenstehende nicht nachvollziehbar. Aktuelle neurowissenschaftliche Modelle helfen, die Verwechslung von »eigen« und »fremd« aufzuklären.
Zu Beginn der industriellen Massenproduktion und vor dem Zeitalter des Klons stand Serialität nicht für identische Reproduktion, sie verschränkte vielmehr Ordnung und Variation. Durch diese begriffliche Fassung von Serie war es möglich, dass sie nicht allein Mittel der Standardisierung und Gesetzmäßigkeit war, sondern mit ihr auch Varianzen und Differenzen formuliert werden konnten. Kunstgeschichtlich manifestiert die Serie - exemplarisch kann hierfür Claude Monet stehen - grundlegende konzeptionelle Veränderungen in der Auffassung von Kunst: Auf der einen Seite macht die serielle Darstellung deutlich, dass die bildende Kunst sich von ihrer repräsentativen Aufgabe emanzipiert hatte. Das Bild war fortan keine "Form 'natürlicher Malerei'", sondern eine Übersetzung, eine Transformation, die sich einem Wechselspiel denkerischer, technischer und darstellender Prozesse verdankt. Bild und bildnerische Verfahren werden erkennbar als künstlerische Verfahrensweisen, die auf je spezifische gesellschaftliche, zeitliche und ästhetische Anforderungen reagieren und diese einbeziehen. Auf der anderen Seite sind mit der seriellen Darstellung aufgrund ihrer Reflexion der Relationen der Elemente zueinander eine Spannung zwischen Offenheit und Geschlossenheit, eine Verräumlichung von Zeit und ein Umschlag von Diachronie in Synchronie verknüpft. Die Serie in der bildenden Kunst kann als eine Figur charakterisiert werden, die Konzepten der Identität, der Sukzession und linearen Entwicklung konträr ist. Insofern verwundert es nicht, dass in den 1960er Jahren, in denen das Interesse an seriellen Verfahren, Ordnungen und Produktionen erstarkte, das Prinzip der Serie zu Reformulierungen und Verschiebungen des Kunstbegriffs beigetragen hat.
So wie der intermediale Dialog eine Polyphonie der Erzählerperspektiven zum Ausdruck bringt, die in 'Leben? Oder Theater?' narratologisches Programm ist, stellt die Serialität hier kein rein formales Experiment dar, sondern ist eng mit der Erzählung verbunden. Auch wenn es im Folgenden vorrangig um eine Serialität im Medium des Bildes geht, ist diese in eine Bilder'geschichte', mithin in einen narrativen Gesamtzusammenhang integriert und muss aus diesem und in Hinblick auf ihre Funktion für diesen untersucht werden. Es wird sich zeigen, dass Wiederholung und Serialität in 'Leben? Oder Theater?' thematisch immer an die Auseinandersetzung mit dem Tod bzw. das Spannungsverhältnis zwischen Leben und Tod gebunden ist.
Aerosolteilchen agieren als Kondensationskeime für Wolkentröpfchen (engl. Cloud Condensation Nuclei, CCN) oder Eiskristalle und sind deswegen für die Wolken- und Niederschlagsbildung entscheidend. Sowohl die Aerosolpartikel als auch die Wolken können Sonnenlicht effizient streuen, wodurch ein kühlender Effekt auf das Klima ausgeübt wird. Einige der Teilchen, wie z. B. aufgewirbelter Staub oder Seesalz, werden direkt in die Atmosphäre injiziert; der größte Anteil der Teilchen und etwa die Hälfte der CCN werden allerdings durch die Kondensation gasförmiger Substanzen gebildet. Dieser Prozess wird als Nukleation oder Partikelneubildung (engl. New Particle Formation, NPF) bezeichnet. Trotz intensiver Forschung ist die NPF noch nicht vollständig verstanden, was an der Komplexität der chemischen Abläufe in der Atmosphäre und an der Schwierigkeit liegt, die relevanten Substanzen bei extrem geringen Mischungsverhältnissen (etwa ein Molekül oder Cluster per 1012 bis 1015 Moleküle) zu identifizieren und zu quantifizieren. Neben der Frage nach den bei der Nukleation beteiligten Substanzen ist außerdem noch unklar, ob Ionen-induzierte Nukleation ein wichtiger Prozess für das Klima ist. Das CLOUD-Projekt (Cosmics Leaving OUtdoor Droplets) am CERN soll diesen Fragen nachgehen, indem dort die Partikelbildung in einem Kammer-Experiment unter extrem gut kontrollierten Bedingungen simuliert wird. Die chemischen Systeme, die in dieser Schrift diskutiert werden, umfassen das binäre (H2SO4-H2O), das ternäre Ammoniak (H2SO4-H2O-NH3) und das ternäre Dimethylamin (H2SO4-H2O-(CH3)2NH)-System.
Einige der wesentlichen Ergebnisse von Experimenten an der CLOUD-Kammer werden diskutiert. Diese zeigen, dass das binäre und das ternäre Ammoniak System die atmosphärische Nukleation bei niedrigen Temperaturen erklären können, wohingegen das ternäre Dimethylamin System prinzipiell in der Lage ist, die hohen bodennahen Nukleationsraten bei atmosphärisch relevanten Schwefelsäure-Konzentrationen zu beschreiben. Des Weiteren werden zwei für Nukleationsstudien wesentliche Messmethoden vorgestellt. Das Chemical Ionization Mass Spectrometer (CIMS) wird zur Messung von gasförmiger Schwefelsäure verwendet, da H2SO4 vermutlich die wichtigste Substanz bei der atmosphärischen Nukleation ist. Das Chemical Ionization-Atmospheric Pressure interface-Time Of Flight (CI-APi-TOF) Massenspektrometer misst Schwefelsäure und neutrale Cluster. Beide Geräte wurden für den Einsatz bei CLOUD optimiert und instrumentelle Entwicklungen wurden in Bezug auf die Ionenquelle vorgenommen, die eine Korona-Entladung verwendet. Außerdem wurden eine Kalibrationseinheit zur Bereitstellung definierter Schwefelsäure-Konzentrationen entwickelt und das CI-APi-TOF aufgebaut. In Bezug auf das ternäre Dimethylamin System werden Nukleationsraten und die ersten Messungen von gro en nukleierenden neutralen Clustern präsentiert. Monomer- und Dimer-Konzentrationen der Schwefelsäure, die mit dem CIMS bei tiefen Temperaturen gemessen wurden, dienten der Ableitung der thermodynamischen Eigenschaften bei der Dimer-Bildung im binären und ternären Ammoniak System. Um möglichst exakte Nukleationsraten zu bestimmen, wurde eine neue Methode entwickelt, die es erlaubt, den Effekt der Selbst-Koagulation bei der Nukleation miteinzubeziehen.
Die zusammengefassten Studien tragen signifikant zum Verständnis der Partikelneubildung bei.
Der musikalische Serialismus wird bis heute als ein mechanistisches Kompositionsverfahren abgetan, wie es typisch für die verunsicherte Nachkriegszeit der 1950er Jahre zu sein scheint. Dieser Ansatz übersieht die grundsätzlichen Impulse, die von diesen Ansätzen bis heute ausgehen. Festmachen kann man dies z. B. daran, wie stark seit den 90er Jahren ein formales strukturorientiertes Denken in der elektronischen Musik zum Durchbruch gelangte, wie es noch mit Sound- und Midiorientierten Verfahren in den 80er Jahren nicht absehbar war. Für einen qualitativ neuen Typus form- und strukturgenerierender Tools im Virtuellen digitaler Symbolverarbeitung stehen heute kollaborative Echtzeitprogramme bereit, die 'Komposition' als ein neues strukturelles Dispositiv erfahren lassen und in direkter Linie zum Serialismus gesehen werden können.
Nur die Einbeziehung des Fremden bewahre vor steriler Identität, meinte Adorno, aus dem Exil in den USA nach Frankfurt zurückgekehrt. Wie steht es heute um Fremdheit und Fremde und um das Verhältnis von Eigenem und Fremdem? Das erkundet der Philosoph und Publizist Rolf Wiggershaus im Gespräch mit fünf Frankfurter Professorinnen und Professoren.
Haben Vorurteile einen Sinn? In der Entwicklungsgeschichte des Menschen vermutlich schon, um Freund und Feind unterscheiden zu können. Aber in der heutigen globalen, wenn auch komplexeren Welt ist es wichtig zu wissen, warum Vorurteile entstehen und welche Gruppenprozesse dahinterstecken. Die Sozialpsychologie kann seit den 1950er Jahren auf eine Vielzahl von Experimenten verweisen – mit spannenden Ergebnissen. Eines lautet: Je mehr Kontakt Menschen aus unterschiedlichen Gruppen miteinander haben, desto geringer sind auch die Vorurteile.
Die Begegnung mit dem Nachbarn bleibt nahezu kommunikationsfrei, wenn man nur darauf achtet, dass die Zweige der Birke nicht über die Grenze zu ihm hinüberwachsen. Ist der Nachbar nicht mehr nur der Andere von nebenan und gegenüber, sondern tendenziell längst ein Fremder geworden? Haben Nachbarschaften wirklich ihren sozialen Verpflichtungscharakter weitgehend verloren? Der Kulturanthropologe begibt sich auf Spurensuche.
Die 16 Bücher, die Ed Ruscha zwischen 1963 und 1978 publizierte, teilen eine Reihe charakteristischer Eigenschaften. In ihrer unprätentiösen Erscheinung bestechen sie auf unverkennbare Art und Weise durch ein klares Layout und eine nüchterne Typografie, die scheinbar im Widerspruch zu den oft etwas absurd anmutenden Titeln wie 'Twentysix Gasoline Stations', 'Nine Swimming Pools', 'Some Los Angeles Apartments' oder 'Every Building on the Sunset Strip' stehen. Im Innern der Bücher ist jeweils eine Serie meist schwarz-weißer Fotografien zu sehen, welche abbildet, was im Titel angekündigt wird: Tankstellen, Swimmingpools, Parkplätze etc. Obschon einem beim Durchblättern auf den ersten Blick hauptsächlich die Fotografien ins Auge springen, wird rasch deutlich, dass diese immer in engem Zusammenhang mit ihrem Trägermedium, dem Buch, stehen. Zwei Aspekte von Ruschas Fotobüchern sind interessant im Hinblick auf das Prinzip der Reihung: einerseits das prototypische Vorgehen des Künstlers in der Produktion seiner Publikationen und andererseits der Zusammenhang zwischen der Präsentation einer fotografischen Serie in Buchform und der daraus resultierenden doppelten Zeitlichkeit.
Einer der berühmtesten Sätze Nietzsches lautet: "Was ist also Wahrheit? Ein bewegliches Heer von Metaphern, Metonymien, Anthropomorphismen kurz eine Summe von menschlichen Relationen, die, poetisch und rhetorisch gesteigert, übertragen, geschmückt wurden, und die nach langem Gebrauche einem Volke fest, canonisch und verbindlich dünken [...]". Der Satz wird immer wieder zitiert und aufgerufen, wenn es darum geht, Geltungsansprüche von Theorien in Frage zu stellen, Begriffe und normative Vorstellungen zu dekonstruieren oder den Anteil des Figurativen im Denken hervorzukehren. Dabei liegt der Akzent dann auf den dominanten Tropen Metapher und Metonymie, wenn nicht allein auf der Metapher. In jedem Fall aber ist es die Identifizierung von Wahrheit und Metapher, die in den Mittelpunkt der Aufmerksamkeit gerückt wird, von Wahrheit und Bild oder übertragener, 'uneigentlicher', verschobener Bedeutung, von Wahrheit und nicht fixierbarer, sondern in Bewegung befindlicher Bedeutung, und die Verschiebung kommt - dem Wortsinn entsprechend - durch Tropen zustande. Denn zumindest traditionelle Rhetorik definiert Tropen als diejenigen Figuren, bei denen sich die Bedeutung vom ursprünglichen Wortinhalt wegwendet (τρέπεσϑαι). Tropen sind Wendungen des Sinns. An Nietzsches berühmtem Satz soll hier das Augenmerk kurz auf zwei andere Aspekte gerichtet werden: zum einen auf die in dem Satz selbst enthaltene Metapher, die des Heeres, und zum anderen auf die Struktur des Satzes, d. h. darauf, dass die Prädizierung der Wahrheit als "Heer von Metaphern, Metonymien, Anthropomorphismen" ihrerseits eine rhetorische Figur darstellt, nämlich eine Aufzählung.
One of the main things that we as humans do in our lifetime is the recognition and/or classification of all kind of visual objects. It is known that about fifty percentage of the neocortex is responsible for visual processing. This fact tells us that object recognition (OR) is a complex task in our and in the animal brain, but we do it in a fraction of a second.
The main question is: How does the brain exactly do it? Does the brain use some feature extraction algorithm for OR tasks? The hierarchical structure of the visual cortex and studies on a part of the visual cortex called V1 tell us that our brain uses feature extraction for OR tasks by Gabor filters. We also use our previous knowledge in object recognition to detect and recognize the objects which we never saw before. Also, as we grow up we learn new objects faster than before.
These facts imply that the visual cortex of human and other animals uses some common (universal) features at least in the first stages to distinguish between different objects. In this context, we might ask: Do universal features in images exist, such that by using them we are able to efficiently recognize any unknown object? Is it necessary to extract new special features for any new object? How about using existing features from other tasks for this? Is it possible to efficiently use extracted feature of a specific task for other tasks? Are there some general features in natural and non-natural images which can also be used for specific object recognition? For example, can we use extracted features of natural images also for handwritten digit classification?
In this context, our work proposes a new information-based approach and tries to give some answers to the questions above. As a result, in our case we found that we could indeed extract unique features which are valid in all three different kinds of tasks. They give classification results that are about as good as the results reported by the corresponding literature for the specialized systems, or even better ones.
Another problem of the OR task is the recognition of objects, independently of any perception changes. We as humans or also animals can recognize objects in spite of many deformations (e.g. changes in illumination, rotation in any direction or angles, distortion and scaling up or down) in a fraction of a second. When observing an object which we never saw, we can imagine the rotated or scaled up objectin our mind. Here, also the question arises: How does the brain solve this problem? To do this, does the brain learn some mapping algorithm (transformation), independent of the objects or their features?
There are many approaches to model the mapping task. One of the most versatile ones is the idea of dynamically changing mappings, the dynamic link mapping (DLM). Although the dynamic link mapping systems show interesting results, the DLM system has the problem of a high computational complexity. In addition, because it uses the least mean squared error as risk function, the performance for classification is also not optimal. For random values where outliers are present, this system may not work well because outliers influence the mean squared error classification much more than probability-based systems. Therefore, we would like to complete the DLM system by a modified approach.
In our contribution, we will introduce a new system which employs the information criteria (i.e. probabilities) to overcome the outlier problem of the DLM systems and has a smaller computational complexity. The new information based selforganised system can solve the problem of invariant object recognition, especially in the task of rotation in depth, and does not have the disadvantage of current DLM systems and has a smaller computational complexity.
Il presente lavoro ha come oggetto d'esame lo scontro del filosofo neo-idealista Giovanni Gentile (1875-1944) col Modernismo cattolico. Obiettivo del lavoro è offrire per la prima volta un esame completo della controversa, durata sei anni, dal 1903 al 1909, attraverso una constestualizzazione storico ecclesiastica e storico filosofica di essa. Il tutto basandosi sulla pubblicazione di inediti fonti d'archivio.
Background aims: Immunomagnetic enrichment of CD34+ hematopoietic “stem” cells (HSCs) using paramagnetic nanobead coupled CD34 antibody and immunomagnetic extraction with the CliniMACS plus system is the standard approach to generating T-cell-depleted stem cell grafts. Their clinical beneficence in selected indications is established. Even though CD34+ selected grafts are typically given in the context of a severely immunosuppressive conditioning with anti-thymocyte globulin or similar, the degree of T-cell depletion appears to affect clinical outcomes and thus in addition to CD34 cell recovery, the degree of T-cell depletion critically describes process quality. An automatic immunomagnetic cell processing system, CliniMACS Prodigy, including a protocol for fully automatic CD34+ cell selection from apheresis products, was recently developed. We performed a formal process validation to support submission of the protocol for CE release, a prerequisite for clinical use of Prodigy CD34+ products.
Methods: Granulocyte-colony stimulating factor–mobilized healthy-donor apheresis products were subjected to CD34+ cell selection using Prodigy with clinical reagents and consumables and advanced beta versions of the CD34 selection software. Target and non-target cells were enumerated using sensitive flow cytometry platforms.
Results: Nine successful clinical-scale CD34+ cell selections were performed. Beyond setup, no operator intervention was required. Prodigy recovered 74 ± 13% of target cells with a viability of 99.9 ± 0.05%. Per 5 × 10E6 CD34+ cells, which we consider a per-kilogram dose of HSCs, products contained 17 ± 3 × 10E3 T cells and 78 ± 22 × 10E3 B cells.
Conclusions: The process for CD34 selection with Prodigy is robust and labor-saving but not time-saving. Compared with clinical CD34+ selected products concurrently generated with the predecessor technology, product properties, importantly including CD34+ cell recovery and T-cell contents, were not significantly different. The automatic system is suitable for routine clinical application.
Multi-scale entropy (MSE) has been recently established as a promising tool for the analysis of the moment-to-moment variability of neural signals. Appealingly, MSE provides a measure of the predictability of neural operations across the multiple time scales on which the brain operates. An important limitation in the application of the MSE to some classes of neural signals is MSE's apparent reliance on long time series. However, this sparse-data limitation in MSE computation could potentially be overcome via MSE estimation across shorter time series that are not necessarily acquired continuously (e.g., in fMRI block-designs). In the present study, using simulated, EEG, and fMRI data, we examined the dependence of the accuracy and precision of MSE estimates on the number of data points per segment and the total number of data segments. As hypothesized, MSE estimation across discontinuous segments was comparably accurate and precise, despite segment length. A key advance of our approach is that it allows the calculation of MSE scales not previously accessible from the native segment lengths. Consequently, our results may permit a far broader range of applications of MSE when gauging moment-to-moment dynamics in sparse and/or discontinuous neurophysiological data typical of many modern cognitive neuroscience study designs.
In diesem polemischen Aufsatz ist die Kunst des klassischen Stils als natürliches Produkt und Erziehungsmittel der freien Gesellschaft und in dieser Hinsicht als Gegensatz der sogenannten Avantgarde-Kunst betrachtet.
Background: One aspect of premating isolation between diverging, locally-adapted population pairs is female mate choice for resident over alien male phenotypes. Mating preferences often show considerable individual variation, and whether or not certain individuals are more likely to contribute to population interbreeding remains to be studied. In the Poecilia mexicana-species complex different ecotypes have adapted to hydrogen sulfide (H2S)-toxic springs, and females from adjacent non-sulfidic habitats prefer resident over sulfide-adapted males. We asked if consistent individual differences in behavioral tendencies (animal personality) predict the strength and direction of the mate choice component of premating isolation in this system.
Results: We characterized focal females for their personality and found behavioral measures of ‘novel object exploration’, ‘boldness’ and ‘activity in an unknown area’ to be highly repeatable. Furthermore, the interaction term between our measures of exploration and boldness affected focal females’ strength of preference (SOP) for the resident male phenotype in dichotomous association preference tests. High exploration tendencies were coupled with stronger SOPs for resident over alien mating partners in bold, but not shy, females. Shy and/or little explorative females had an increased likelihood of preferring the non-resident phenotype and thus, are more likely to contribute to rare population hybridization. When we offered large vs. small conspecific stimulus males instead, less explorative females showed stronger preferences for large male body size. However, this effect disappeared when the size difference between the stimulus males was small.
Conclusions: Our results suggest that personality affects female mate choice in a very nuanced fashion. Hence, population differences in the distribution of personality types could be facilitating or impeding reproductive isolation between diverging populations depending on the study system and the male trait(s) upon which females base their mating decisions, respectively.
This dissertation provides a comprehensive account of the grammar of relative clause extraposition in English. Based on a systematic review and evaluation of the empirical generalizations and theoretical approaches provided in the literature on generative grammar, it is shown that none of the previous theories is able to account for all the relevant facts. Among the most problematic data are the Principle C and scope effects of relative clause extraposition, cases with obligatory relative clauses, and relative clauses with elliptical NPs as antecedents.
I propose a new analysis of relative clause extraposition within the constraint-based, monostratal grammatical framework of Head-driven Phrase Structure Grammar (HPSG), enhanced with the semantic theory of Lexical Resource Semantics (LRS). Crucially, it is a general analysis of relative clause attachment, since both canonical and extraposed relative clauses are licensed by the same syntactic and semantic constraints. The basic assumption is that a relative clause can be adjoined to any phrase that contains a suitable antecedent of the relative pronoun. The semantic information that licenses the relative clause is introduced by the determiner of the antecedent NP. The techniques of underspecified semantics and the standard semantic representation language used by LRS make it possible to formulate constraints which yield the correct intersective interpretation of the relative clause (arbitrarily distant from its antecedent NP) and at the same time link the scope of the antecedent NP to the adjunction site of the relative clause.
In combination with the revised HPSG binding theory developed in this dissertation, the proposed analysis is able to capture the major properties of relative clause attachment within a unified and internally consistent monostratal constraint-based grammatical framework.
Previous studies suggest that the application of Controlled Language (CL) rules can significantly improve the readability, consistency, and machine-translatability of source text. One of the justifications for the application of CL rules is that they can have a similar impact on several target languages by reducing the post-editing effort required to bring Machine Translation (Ml’) output to acceptable quality. In certain situations, however, post-editing services may not always be a viable solution. Web-based information is often expected to be made available in real-time to ensure that its access is not restricted to certain users based on their locale. Uncertainties remain with regard to the actual usefulness of MT output for such users, as no empirical study has examined the impact of CL rules on the usefulness, comprehensibility, and acceptability of MT technical documents from a Web user's perspective. In this study, a two-phase approach is used to determine whether Controlled English rules can have a significant impact on these three variables. First, individual CL rules are evaluated within an experimental environment, which is loosely based on a test suite.Two documents are then published and subject to a randomised evaluation within the framework of an online experiment using a customer satisfaction questionnaire. The findings indicate that a limited number of CL rules have a similar impact on the comprehensibility of French and German output at the segment level. The results of the online experiment show that the application of certain CL rules has the potential to significantly improve the comprehensibility of German MT technical documentation. Our findings also show that the introduction of CL rules did not lead to any significant improvement of the comprehensibility, usefulness, and acceptability of French MT technical documentation.
The research reported in this thesis examines two main questions: firstly, which dictionary type, bilingual or monolingual, is most effective for intermediate learners of German for reading comprehension, and secondly, which features make monolingual dictionary definitions effective for these learners. These questions divide the thesis into two parts. The first part compares the effectiveness of the bilingual versus the monolingual dictionary, and the second part compares two different monolingual definition styles.
The research was originally motivated by the observation that Hong Kong Chinese intermediate learners of German prefer to use a German-English bilingual dictionary. Since the translations are presented in the learners' second language, the effectiveness of this bilingual dictionary is doubtful. On the other hand, the learners are reluctant to use the monolingual dictionary, recommended to them by their language teachers. Three investigations were conducted in order to gain more detailed knowledge about the learners' dictionary preference, and the effectiveness of the two dictionary types. The learners' dictionary preference was investigated by means of a survey of ninety-eight foreign language students. The effectiveness of the bilingual and monolingual dictionary for reading comprehension and incidental vocabulary learning was first measured experimentally. The think-aloud method was then used in order to discover factors which determine the effectiveness of the two dictionary types.
The results of the experiment revealed that the German-English bilingual dictionary was not significantly more effective for the learners than the monolingual dictionary. The only monolingual dictionary available for German at that time, however, is linguistically too difficult for this proficiency level. Because of these findings, the research turned to monolingual dictionary definitions with the aim of identifying features that make them accessible to intermediate learners. Based on findings from the first think-aloud study, and principles promoted as user-friendly in the lexicographic literature, new definitions were developed for the target words in the research. These new definitions were compared with those in the existing dictionary. A second think-aloud study was conducted in order to generate hypotheses about individual definition features. These hypotheses were then tested in the second experiment, which was conducted with eighty-six learners of German in Shanghai.
The investigations reveal several features that determine the effectiveness of monolingual definitions for intermediate learners. The findings have theoretical and pedagogical implications. In the theoretical field, some lexicographic principles were recommended that are, unlike previous principles, based on empirical insights into user needs. In the pedagogical field, the research findings provide an empirical basis for the evaluation and recommendation of suitable dictionaries to intermediate learners.
A model of dictionary effectiveness is proposed. This model could help to assess the effectiveness of different information categories in dictionaries for different proficiency levels and different activity contexts. It could also provide lexicographic principles for the design of dictionaries. This research contributes one component to the proposed model: criteria for the effectiveness of definition features for intermediate learners in the activity context of reading.
Towards a German grammar programme for post-leaving certificate students at Dublin City University
(1999)
With the introduction of the communicative method of language learning, overall standards of grammatical competence and performance among Irish second level students would appear to have been significantly reduced. As a consequence, learners who continue to study a given language at third level apparently no longer possess the knowledge which, under the grammar-translation methodology, further education institutions were able to build upon. This thesis examines the basis for the above perceptions, investigates the role of formal grammar instruction in the second language acquisition process and reports on a programme which was developed at Dublin City University (DCU) in order to ease, for Irish university students of German, the transition from a primarily memory-based approach to language acquisition to the analytical approach which is still being considered crucial to a university student's linguistic education. While the research was undertaken in response to locally existing difficulties, it may also be considered as a case study of more general interest, and as such serve as an exemplar to German departments in other universities as well as to other foreign language departments both within DCU or outside. The aim of the programme under investigation was to ease the transition on a socio-affective, cognitive and metacognitive level without lowering overall proficiency expectations and standards. Primary research was conducted among secondary school teachers, post-Leaving Certificate students on entry into DCU and among third level lecturers. The purpose of this research was to identify and define the programme’s content and progression. To this effect, the German junior and senior cycle syllabi at second level were also taken into consideration. The subsequent German grammar programme was implemented at DCU in the academic year 1996/7. While the programme would appear to have been judged favourably regarding some affective and cognitive-motivational aspects, results show mixed success rates for the other two factors under investigation, cognitive-analytical and metacognitive skills. Thus, some degree courses and some language combinations clearly benefited more from the programme than others. One of the conclusions drawn from this research suggests that unless certain changes are introduced prior to students’ entry into third level, university graduates are likely to remain well below the standards of accuracy and overall proficiency which were previously achieved.
Two decades after the predicted “end of ideology”, we are observing a re-emphasis on party ideology under Hu Jintao. The paper looks into the reasons for and the factors shaping the re-formulation of the Chinese Communist Party’s (CCP) ideology since 2002 and assesses the progress and limits of this process. Based on the analysis of recent elite debates, it is argued that the remaking of ideology has been the consequence of perceived challenges to the legitimacy of CCP rule. Contrary to many Western commentators, who see China’s successful economic performance as the most important if not the only source of regime legitimacy, Chinese party theorists and scholars have come to regard Deng Xiaoping’s formula of performance-based legitimacy as increasingly precarious. In order to tackle the perceived “performance dilemma” of party rule, the adaptation and innovation of party ideology is regarded as a crucial measure to relegitimize CCP rule.
For more than two decades, the National Planning Office for Philosophy and Social Sciences (NPOPSS) has been managing official funding of social science research in China under the orbit of the Communist Party of China’s (CPC) propaganda system. By focusing on “Major Projects”, the most prestigious and well-funded program initiated by the NPOPSS in 2004, this contribution outlines the political and institutional ramifications of this line of official funding and attempts to identify larger shifts during the past decade in the “ideologics” of official social science research funding – the changing ideological circumscriptions of research agendas in the more narrow sense of echoing party theory and rhetoric and – in the broader sense – of adapting to an increasingly dominant official discourse of cultural and national self-assertion. To conclude, this article offers reflections on the potential repercussions of these shifts for international academic collaboration.
Obesity is associated with an increased risk of heart failure. Little is known about the impact of dietary changes on the cardiac sequelae in obese patients. Twenty-one obese subjects underwent a 12-week low calorie fasting phase of a formula diet. Transthoracic two-dimensional speckle-tracking echocardiography was performed to obtain systolic left ventricular strain before and after weight loss. Body mass index decreased significantly from 38.6 ± 6.2 to 31.5 ± 5.3 kg/m(2), and the total percentage fat loss was 19%. Weight reduction was associated with a reduction in blood pressure and heart rate. Left ventricular longitudinal global peak systolic strain was in the lower normal range (-18.7 ± 3.2%) before weight loss and was unchanged (-18.8 ± 2.4%) after 12 weeks on diet with substantial weight loss. Also, no significant change in global radial strain after weight loss was noted (41.1 ± 22.0 versus 43.9 ± 23.3, p = 0.09). Left atrial and ventricular dimensions were in normal range before fasting and remained unchanged after weight loss. In our study obesity was associated with normal systolic left ventricular function. A 12-week low calorie diet with successful weight loss can reduce blood pressure and heart rate. Systolic left ventricular function and morphology were not affected by rapid weight reduction.
Most research on human fear conditioning and its generalization has focused on adults whereas only little is known about these processes in children. Direct comparisons between child and adult populations are needed to determine developmental risk markers of fear and anxiety. We compared 267 children and 285 adults in a differential fear conditioning paradigm and generalization test. Skin conductance responses (SCR) and ratings of valence and arousal were obtained to indicate fear learning. Both groups displayed robust and similar differential conditioning on subjective and physiological levels. However, children showed heightened fear generalization compared to adults as indexed by higher arousal ratings and SCR to the generalization stimuli. Results indicate overgeneralization of conditioned fear as a developmental correlate of fear learning. The developmental change from a shallow to a steeper generalization gradient is likely related to the maturation of brain structures that modulate efficient discrimination between danger and (ambiguous) safety cues.
This position paper is the second ESCMID Consensus Document on this subject and aims to provide intensivists, infectious disease specialists, and emergency physicians with a standardized approach to the management of serious travel-related infections in the intensive care unit (ICU) or the emergency department. This document is a cooperative effort between members of two European Society of Clinical Microbiology and Infectious Diseases (ESCMID) study groups and was coordinated by Hakan Leblebicioglu and Jordi Rello for ESGITM (ESCMID Study Group for Infections in Travellers and Migrants) and ESGCIP (ESCMID Study Group for Infections in Critically Ill Patients), respectively. A relevant expert on the subject of each section prepared the first draft which was then edited and approved by additional members from both ESCMID study groups. This article summarizes considerations regarding clinical syndromes requiring ICU admission in travellers, covering immunocompromised patients.
Der vorliegende Band dokumentiert die Erhebungsinstrumente, die im BilWiss-Forschungsprogramm in den Erhebungen der folgenden Projektphasen zum Einsatz kamen: BilWiss („Bildungswissenschaftliches Wissen und der Erwerb professioneller Kompetenz in der Lehramtsausbildung“; 2009–2013), gefördert vom Programm des Bundesministerium für Bildung und Forschung „Entwicklung von Professionalität des pädagogischen Personals in Bildungseinrichtungen (ProPäda)“ unter dem Förderkennzeichen 01 JH 0910, und BilWiss-Beruf („Die Bedeutung des bildungswissenschaftlichen Hochschulwissens für den Berufseinstieg von Lehrkräften“; 2013–2016), gefördert vom BMBF Förderprogramm „Kompetenzmodellierung und Kompetenzerfassung im Hochschulsektor (KoKoHs)“ unter dem Förderkennzeichen 01 PK1 1007. Das Forschungsprogramm ist ein Verbundprojekt der Goethe-Universität Frankfurt (M. Kunter), der Universität Duisburg-Essen (D. Leutner), der Westfälischen Wilhelms-Universität Münster (E. Terhart), des Max-Planck-Instituts für Bildungsforschung (J. Baumert, nur Projektphase BilWiss) und der Technischen Universität München (T. Seidel, nur Projektphase BilWiss-Beruf).
Das Forschungsprogramm zielt darauf ab, zu untersuchen, inwieweit angehende Lehrkräfte durch das Studium der Bildungswissenschaften unterstützt werden, mit den vielfältigen Herausforderungen ihres Berufs professionell umzugehen. Die zentrale Annahme dabei ist, dass konzeptuelles Wissen über bildungswissenschaftliche Inhalte die professionelle Entwicklung im Vorbereitungsdienst und im Berufseinstieg unterstützt. Die Grundhypothese des Projekts lautet:
Bildungswissenschaftliche Inhalte und Zusammenhänge stellen einen begrifflichen Rahmen dar, den Lehrkräfte benötigen, um Unterrichts- und Schulereignisse angemessen zu interpretieren, zu reflektieren und so für die eigene Kompetenzentwicklung zu nutzen.
Um dies zu prüfen wurde im Rahmen des Forschungsprogramms ein standardisiertes Testinstrument zur Erfassung des bildungswissenschaftlichen Wissens entwickelt und in einer Vollerhebung von angehenden Lehrkräften zu Beginn des Vorbereitungsdienstes (n = 3298) an allen Studienseminaren in Nordrhein-Westfalen (NRW) eingesetzt. Um die Annahme zur Bedeutsamkeit des bildungswissenschaftlichen Wissens für die professionelle Entwicklung empirisch zu prüfen, wurde ein Teil dieser Lehramtsanwärter(innen) im Laufe des Vorbereitungsdienstes längsschnittlich begleitet, dabei wurden mehrfach das bildungswissenschaftliche Wissen und weitere Aspekte der professionellen Kompetenz sowie verschiedene Indikatoren des professionellen Verhaltens und beruflichen Erlebens erfasst. Die Erhebungszeitpunkte im Längsschnitt fanden ein Jahr nach dem Beginn des Vorbereitungsdienstes (n = 362), am Ende des Vorbereitungsdienstes (n = 284) und ca. zwei Jahre nach Berufseinstieg (n = 101) statt.
Die zeitliche Überschneidung des BilWiss-Projekts mit der Einführung eines reformierten Vorbereitungsdienstes im Rahmen der 2009 beschlossenen Neuerungen in der Lehrerbildung im Land NRW eröffnete zudem die Möglichkeit, die differenzielle Entwicklung der angehenden Lehrkräfte aufgrund unterschiedlicher Lerngelegenheiten in einer quasi-experimentellen Feldstudie empirisch zu untersuchen. Hierfür wurde zusätzlich zur oben bereits beschriebenen Kohorte, die sich im 24-monatigen Vorbereitungsdienst befand (Kohorte 1), eine weitere Kohorte in die Befragung einbezogen, die den reformierten verkürzten, 18-monatigen Vorbereitungsdienst absolviert (Kohorte 2). Die beiden Kohorten angehender Lehrkräfte stiegen zu verschiedenen Zeitpunkten in den Vorbereitungsdienst ein (Kohorte 1 = Anfang 2011; Kohorte 2 = Ende 2011), beendeten diesen jedoch durch die Verkürzung des Vorbereitungs-dienstes zu einem ähnlichen Zeitpunkt (Anfang 2013). Auch die Daten der Kohorte 2 wurde zu Beginn (n = 511) und Ende des Vorbereitungsdienstes (n = 386), sowie ca. zwei Jahre nach dem Berufseinstieg (n = 104) erhoben.
Weiterführende Informationen zum theoretischen Ansatz der Studie und Ergebnissen der Studie können der Internetseite http://www.bilwiss.uni-frankfurt.de sowie den unten aufgeführten Publikationen entnommen werden.
The fungal genus Pestalotiopsis s.l. contains approximately 300 described species and is globally distributed. The monotypic genus Pestalotia is considered the closest relative of Pestalotiopsis s.l. This study aims to investigate the diversity and systematics within Pestalotiopsis s.l. and its relation to Pestalotia. Therefore, an integrative approach is used considering molecular phylogeny methods as well as examination of morphological characters.
Recently, Pestalotiopsis s.l. was split into three genera with the addition of the newly erected Neopestalotiopsis and Pseudopestalotiopsis. The species of these genera are usually saprotrophic, phytoparasitic, or endophytic, and have been isolated from soil, air, and many kinds of anorganic material. The asexual fruiting bodies appear on infected plant material as black acervuli that release conidia. The conidia are important to examine for morphological taxon recognition. The number of conidial cells is the feature that distinguishes Pestalotiopsis s.l. spp. with five celled conidia, from Pestalotia pezizoides with six celled conidia. However, the significance of morphological characters is controversially discussed among mycologists. In recent years, 55 new species were described based on minor genetic distances and marginal or no morphological differences. Thus, the value of certain morphological characters and genetic markers need to be reconsidered.
In this study, 102 herbarium specimens of 26 described species, with an emphasis on plant pathogenic species from North America, have been morphologically examined and documented through drawings and photographs. Morphological examination was complemented with a comprehensive molecular dataset obtained from 191 cultures representing the genera Neopestalotiopsis, Pestalotia, Pestalotiopsis, Pseudopestalotiopsis, and Truncatella. One novelty of this work is that, besides the well-established markers ITS, TEF1, and ß-tubulin, the protein-coding genes MCM7 and TSR1 were successfully sequenced and included in the analyses. Phylogenies using Maximum Likelihood and Bayesian inference methods of single loci and the combined dataset were calculated. By comparison of these phylogenies, MCM7 was identified as the most powerful one in terms of phylogenetic resolution and statistical support of nodes and is proposed as an additional barcoding marker in Pestalotiopsis s.l.
In Pestalotiopsis, species delimitation was tested using the Baysian Phylogenetics and Phylogeography (BP&P) program that tests an existing species scenario against Bayesian inference methods under a multispecies coalescent model. The program supported only ten species out of the predetermined 19 species scenario. Measurements of conidia for species detected by BP&P were explored using a TukeyHSD-Test in the program R to find means that are significantly different from each other. This test revealed that combinations of morphological characters are required to distinguish between the ten species found by BP&P.
Another purpose of this work was to clarify the status of Pestalotia with regard to Pestalotiopsis s.l. Therefore, fresh epitypic material of Pestalotia pezizoides, was collected, isolated, and cultivated. The molecular analysis of a combined dataset of the gene regions ITS and LSU for species of Amphisphaeriales nested P. pezizoides in the genus Seiridium. Thus, synonymy of Pestalotia with Seiridium is proposed here. This is supported by morphology of the conidia. Further, an epitype is proposed for the type species of Pestalotiopsis, P. maculans. On the other hand, the recently proposed epitype of P. adusta is rejected here as it conflicts with the taxonomic hypothesis obtained in this study and its introduction is inconsistent with the formal requirements for epitypification. A new topotypic specimen is proposed instead. Additionally, several nomenclatural changes become necessary in many species examined. These include three new combinations and six synonyms of species of Pestalotiopsis s.l.
The conclusion of this work is that morphological data have potential as a valuable, inexpensive and easy way to recognize species. However, it is not the best method for species discovery and delimitation bearing in mind that in microfungi and many other organisms, individual plasticity and analogous structures are inadequately investigated. By phylogenetic analyses of molecular sequence data, it is possible to compare a great amount of equivalent characters and to delimit species that are morphologically cryptic. This is especially important since species of Pestalotiopsis s.l. mostly lack sexual structures that are helpful for morphological species delimitation in other groups of fungi. Thus, the Genealogical Concordance Species Concept (GCSC) finds its application in many fungal taxa. Conflicts in the genealogy between phylogenetic trees of different markers are interpreted as recombination of the genetic material within a linage. Accordingly, the change from conflict to congruence in a set of different phylogenetic trees can be seen as the species limit. It can be expected that increased application of the GCSC will lead to further approximation of described species numbers to the real number of species, especially in complicated groups like asexual microfungi.
Mobilizations in defence of ‘companion animals’ have become major sites of contestation in Chinese society in recent years. They often reject the existing ambiguity between the use of these animals as pets and as meat, demanding unambiguous respect for and protection of dogs. However, in a society where inequalities are as significant as in China, where the level of poverty, sickness, and environmental and industrial tragedies appears overwhelming, one may ask how pets’ destinies have become such a symbolic focus and source of occasional fury – for both Chinese and foreign audiences. Taking this question seriously, this article aims to examine such mobilizations in China – demanding the protection of dogs – as a starting point to theoretically unwrap the more general problem of how the perception of certain beings as ‘weak’ and as deserving the protection of society is socially constructed, and what the related choices imply. I argue that to better understand these mobilizations to protect dogs, we should not separate the focus of the calls for protection from the social web of relationships and oppositions in which they are entrenched.
In my paper I take issue with proponents of ‘intersectionality’ which believe that a theoretical concept cannot/should not be detached from its original context of invention. Instead, I argue that the traveling of theory in a global context automatically involves appropriations, amendment and changes in response to the original meaning. However, I reject the idea that ‘intersectionality’ can be used as a freefloating signifier; on the contrary, it has to be embedded in the respective (historical, social, cultural) context in which it is used. I will start by mapping some of the current debates engaging with the pros and cons of the global implementation of the concept (the controversy about master categories, the dispute about the centrality of ‘race’, and the argument about the amendment of categories). I will then turn to my own use of ‘intersectionality’ as a methodological tool (elaborated in Lutz and Davis 2005). Here, we shifted attention from how structures of racism, class discrimination and sexism determine individuals’ identities and practices to how individuals ongoingly and flexibly negotiate their multiple and converging identities in the context of everyday life. Introducing the term doing intersectionality we explored how individuals creatively and often in surprising ways draw upon various aspects of their multiple identities as a resource to gain control over their lives.
In my paper I will show how ‘gender’ or ‘ethnicity’ are invariably linked to structures of domination, but can also mobilize or deconstruct disempowering discourses, even undermine and transform oppressive practices.
Obstetrical care as a matter of time: ultrasound screening in anticipatory regimes of pregnancy
(2014)
This article explores the ways in which ultrasound screening influences the temporal dimensions of prevention in the obstetrical management of pregnancy. Drawing on praxeographic perspectives and empirically based on participant observation of ultrasound examinations in obstetricians’ offices, it asks how ultrasound scanning facilitates anticipatory modes of pregnancy management, and investigates the entanglement of different notions of time and temporality in the highly risk-oriented modes of prenatal care in Germany. Arguing that the paradoxical temporality of prevention – acting now in the name of the future – is intensified by ultrasound screening, I show how the attribution of risk regarding foetal growth in prenatal check-ups is based on the fragmentation of procreative time and ask how time standards come into play, how pregnancy is located in calendrical time, and how notions of foetal time and the everyday life times of pregnant women clash during negotiations between obstetricians and pregnant women about the determination of the due date. By analysing temporality as a practical accomplishment via technological devices such as ultrasound, the paper contributes to debates in feminist STS studies on the role of time in reproduction technologies and the management of pregnancy and birth in contemporary societies.
In diesem Arbeitspapier1 soll die statistische Erfassungstechnologie – im Foucaultschen Sinne einer gouvernementalen Technologie – in zwei ihrer zentralen Bestandteile, die Teilpraxen Zählen und Ordnen zerlegt werden, die gerade in ihrer Kombination einen Reifizierungseffekt von statistischem Wissen bewirken, der, wie hier gezeigt werden soll, wenn es um die Produktion von Wissen über „Rasse“/Ethnizität geht, als solcher gleichzeitig ein rassistischer Effekt ist. Die Macht der Zahlen einerseits und die zumeist stillschweigend im Hintergrund erfolgende taxonomische Arbeit andererseits wirken dabei als Teilpraxen der statistischen Erfassungstechnologie zusammen und bewirken gemeinsam deren Blackboxing-Effekt. Im ersten Abschnitt über das Zählen soll der Unterschied zwischen Zahlen und Worten aufgespürt werden, und damit der Unterschied zwischen Zahlenwissen und anderen Formen des Wissens. Im zweiten Abschnitt über das Ordnen wird ausführlicher die taxonomische Arbeit im Zusammenhang von Regierungswissen einschließlich ihrer Subjektivierungseffekte betrachtet und im Fortgang zunehmend auf die Anlage von Taxonomien der „Rasse“/Ethnizität für amtliche Statistiken fokussiert.
Die folgenden konzeptuellen Überlegungen dienen im Rahmen meiner Studie über das Dilemma der Erhebung von Ethnizitätsdaten zur Diskriminierungsmessung dazu, statistische Taxonomien als Instrument des Regierens und der Wissensproduktion in einer machtanalytischen Perspektive zu fassen.
This contribution1 is framed within the field of cultural studies and migration and ethnic relations, trying to examine how the Italian American experience has been imaginatively (re)created and received. It will entail an interdisciplinary approach about the cultural and literary analysis of the Italian diaspora in the United States, from a gender perspective that recovers the voice and historical presence of women as has been transmitted in the arts and critical methods. Focusing on the media and literary representations that deal with Italian migration to the United States since the last decades of the 19th century, their welcome or later development until our days, I make particular reference to a community mainly conceived in the masculine, as major receptions and persistent stereotypes about family relations and ethnicity attest. I will analyse, at the same time, the existence of other works that either contest or balance that cultural and gender stereotyping of the Italian American experience or community.
This paper1 investigates changes in the domestic work sector when passing from the informal to the formal labor market. The issue is explored within the context of the housework voucher policy (titres-services), which allows households to officially purchase weekly housework services from an authorized agency, through vouchers. This contribution has therefore a twofold focus: observing changes in labor market dynamics and investigating workers’ perception of this change. In order to discuss these issues, I will firstly look at the step from informal to formal labor market through two aspects: ethnic niches and individual labor dynamics – two bedrocks of Brussels domestic work market. Then, I will analyze workers’ personal experiences when acquiring a declared job in the voucher system.
Analyzing objective and subjective changes, a entral question of this article is to which extent the switch to the housework voucher system can bring empowerment to domestic workers. The sector work quality, in objective and subjective terms, has improved mainly by the setting of rules and by allowing workers to enjoy labor rights and a work status. The formal market dynamics of the housework voucher system remain, however, profoundly ethicized and marked by women’s presence, as was/is the shadow market.
The article shows that workers’ understanding of the transition from an informal to a formal sector is largely a result of their previous experiences and social position, mainly regarding migration status. This change will be thus much more assertive for workers who had their migrant status regularization and work formalization processes concomitantly, demonstrating that the most empowering shift is the one of acquiring papers, and not of entering declared work.
In the ‘age of transnationalization’, spatial mobility is highly valued as a resource and accordingly ‘sedentariness’ is often symbolically devalued. Migration between Poland and Germany (mainly from Poland to Germany) has a century-long tradition. Not only has it yielded the emergence of a dense transnational social space, but is also considered as a re-enactor of cultural traits and symbolic meanings. Spatial mobility is tied to notions of social mobility and to projects of life-making. Since legal restrictions for Polish migrants seeking to work and settle in Germany have vanished, the quest for ‘normalcy’ has enhanced and pressures towards even more migration have increased. I argue that symbolic meanings of mobility are decisive for hierarchies in transnational social spaces. I have put main emphasize on families’ practices of caring for and caring about each other: the first being more a physical or material activity, while the latter is a more symbolic and emotional one. The interviews reveal that people draw multiple differentiations between migrant populations in terms of their migration reasons as well as between the mobile and the immobile. Those differentiations are embedded in the distinct feature of the transnational social space between Poland and Germany with assumed differences in terms of ‘modernity’. At the end the symbolic meanings of mobility also help explain the puzzle of why the emigration rates from Poland are constantly high, although Poland is a comparatively wealthy country.
Often adopting a feminist perspective, the sociological literature on migrant domestic services (MDS) does not make explicit which feminist paradigm it speaks from. This article situates this literature within ongoing debates in feminist theory, in particular the tension between materialist and poststructuralist approaches. Then, it discusses the empirical relevance of each of those two paradigms on the example of the results of original research into the personalization of employment relationships in MDS.
The contribution proposes a new way of making sense of the diversity of feminist theories, distinguishing between modern and postmodern approaches. Indeed, since the 1980s, feminist theory in the US and Western Europe has undergone a ‘postmodern turn’, which renders previous typologies much less up-to-speed with recent developments in the field. Then, the article examines which paradigms are implicit in the sociological literature on MDS. Initially, personalization in MDS was mainly seen in materialist terms, as a way to maximize the quantity and quality of labour (including emotional labour) extracted from domestic workers. The emergence of postmodern approaches in feminist theory set off a progressive shift in MDS literature. First, this literature showed that personalization also fulfils identity functions for employers and
workers, then it widened its focus to include the affective dimensions of domestic labour (not to be confused with emotional labour). The final section shows how modern and postmodern feminist approaches can be combined within a single research, on the example of original research on personalization in MDS in Belgium and Poland. In particular, the contribution shows that the distinction between material functions of personalization on the one hand, and its emotional/identity functions on the other is not empirically operative. Indeed, migrant domestic workers generally use emotional/identity categories to frame material questions, and vice versa. This final part shows that, rather than representing incompatible approaches, modern and postmodern feminisms complete each other, in this case showing a fuller image of personalization processes in MDS.
This working paper is based on a lecture given at the Summer School “Multiple Inequalities in the Age of Transnationalization”, June 23-27 2014 at Goethe University Frankfurt. In it, I explore the linkages between sexuality and migration and aim to show that instead of deeming them a narrow subfield of migration studies, thinking through these linkages has much wider implications for different fields, including post- and decolonial queer studies, the study of race and sexuality, the study of citizenship and state projects of inclusion/exclusion, and for work that attempts to ce-center the predominant knowledge production focused on the Global North.
Highly-skilled labour migration in Switzerland: household strategies and professional careers
(2016)
The article investigates household strategies in the context of highly-skilled labour migration. It focuses on the ways highly-skilled migrants are taking up residence in Switzerland. The analysis shows different household strategies based on the perception of a further professional move. The perceived likeliness of a further move implies household strategies characterized by a high motility: the household remains ready to move and mobilises dedicated organisations (like outplacement agencies or international schools). When a further move is neither perceived nor wanted, the household develops more anchored strategies which are often cheaper. In order to cope with frequent mobilities, the analysis shows that household strategies are deeply gendered.
Der Artikel untersucht Rassismus und Sexismus und ihre materiellen und diskursiven Artikulationen an dem spezifischen Artikulationsort Haar, bzw. Locken. Anhand von biographisch-narrativen Interviews mit Frauen of Color und mit Hilfe von Ansätzen der Grounded Theory werden Fragen danach aufgeworfen, welche symbolischen Bedeutungen von Locken es gibt; Welche Umgangsformen mit Haar es gibt; Wie Haar eingesetzt wird; Ob es Widersprüche gibt; Wie sich diese artikulieren und wie Subjekte trotz rassistischer, sexistischer Diskurse und der damit verbundenen materiellen Unterdrückung handlungsmächtige Akteurinnen ihrer eigenen Biographien werden. Parallel wird der Forschungsprozess aus dekolonialer, feministischer Perspektive entwickelt, beschrieben und reflektiert und damit eine dekolonial feministische Methodologie entworfen.
This paper studies the linkage between international male migration and changes on land inheritance patterns in rural Oaxaca (Mexico). Land inheritance is a long-term exchange between parents and male adult children in Oaxaca: sons are bequeathed with land as long as they provide for their parents (and their wives care for their in-laws) while daughters are excluded from the family patrimony. Drawing on theoretical sample and 37 in depth interviews, this paper argues that intergenerational solidarity based on the parent-son alliance through inheritance is breaking down due to the uncertainty of men´s migration project along with the increase in the fallback position of wives, who may refuse to take care of elderly in-laws. Other alliances emerge instead: parents try to build new alliances with their daughters, bequeathing them agricultural and building plots. However, these new alliances and inheritance shifts are neither a heterogeneous process nor an automatic change and several family and social dimensions must be included to understand the different outcomes.
People who delay claiming Social Security receive higher lifelong benefits upon retirement. We survey individuals on their willingness to delay claiming later, if they could receive a lump sum in lieu of a higher annuity payment. Using a moment-matching approach, we calibrate a lifecycle model tracking observed claiming patterns under current rules and predict optimal claiming outcomes under the lump sum approach. Our model correctly predicts that early claimers under current rules would delay claiming most when offered actuarially fair lump sums, and for lump sums worth 87% as much, claiming ages would still be higher than at present.
The international diffusion of technology plays a key role in stimulating global growth and explaining co-movements of international equity returns. Existing empirical evidence suggests that countries are heterogeneous in their attitude toward innovation: Some countries rely more on technology adoption while other countries rely more on internal technology production. European countries that rely more on adoption are also typically characterized by lower fiscal policy exibility and higher labor market rigidity. We develop a two-country model – where both countries rely on R&D and adoption – to study the short-run and long-run effects of aggregate technology and adoption probability shocks on economic growth in the presence of the aforementioned asymmetries. Our framework suggests that an increase in the ability to adopt technology from abroad stimulates economic growth in the country that benefits from higher adoption rates but the beneficial effects also spread to the foreign country. Moreover, it helps explaining the differences in macro quantities and equity returns observed in the international data.
Asymmetric social norms
(2017)
Studies of cooperation in infinitely repeated matching games focus on homogeneous economies, where full cooperation is efficient and any defection is collectively sanctioned. Here we study heterogeneous economies where occasional defections are part of efficient play, and show how to support those outcomes through contagious punishments.
This paper sets the background for the Special Issue of the Journal of Empirical Finance on the European Sovereign Debt Crisis. It identifies the channel through which risks in the financial industry leaked into the public sector. It discusses the role of the bank rescues in igniting the sovereign debt crisis and reviews approaches to detect early warning signals to anticipate the buildup of crises. It concludes with a discussion of potential implications of sovereign distress for financial markets.
This paper investigates whether the overpricing of out-of-the money single stock calls can be explained by Tversky and Kahneman’s (1992) cumulative prospect theory (CPT). We argue that these options are overpriced because investors overweight small probability events and overpay for such positively skewed securities, i.e., characteristics of lottery tickets. We match a set of subjective density functions derived from risk-neutral densities, including CPT with the empirical probability distribution of U.S. equity returns. We find that overweighting of small probabilities embedded in CPT explains on average the richness of out-of-the money single stock calls better than other utility functions. The degree that agents overweight small probability events is, however, strongly timevarying and has a horizon effect, which implies that it is less pronounced in options of longer maturity. We also find that time-variation in overweighting of small probabilities is strongly explained by market sentiment, as in Baker and Wurgler (2006).
Low probability events are overweighted in the pricing of out-of the-money index puts and single stock calls. We find that this behavioral bias is strongly time-varying, linked to equity market sentiment, and higher moments of the risk-neutral density. An implied volatility (IV) sentiment measure that is jointly derived from index and single stock options explains investors' overweight of tail events the best. Our findings also suggest that IV-sentiment predicts equity markets reversals better than overweight of small probabilities itself. When employed in a trading strategy, IV-sentiment delivers economically significant results, which are more consistent than the ones produced by the market sentiment factor. The joint use of information from the single stock and index option markets seems to explain the forecasting power of IV-sentiment. Out-of-sample tests on reversal prediction show that our IV-sentiment measure adds value over and above traditional factors in the equity risk premium literature, especially as an equity-buying signal. This reversals prediction seems to improve time-series and cross-sectional momentum strategies.
Objective: The aim of this study was to assess the potential risk of gadobutrol-enhanced magnetic resonance imaging (MRI) in patients with moderate to severe renal impairment for the development of nephrogenic systemic fibrosis (NSF).
Materials and Methods: We performed a prospective, international, multicenter, open-label study in 55 centers. Patients with moderate to severe renal impairment scheduled for any gadobutrol-enhanced MRI were included. All patients received a single intravenous bolus injection of gadobutrol at a dose of 0.1 mmol/kg body weight. The primary target variable was the number of patients who develop NSF within a 2-year follow-up period.
Results: A total of 908 patients were enrolled, including 586 with moderate and 284 with severe renal impairment who are at highest risk for developing NSF. The mean time since renal disease diagnosis was 1.83 and 5.49 years in the moderate and severe renal impairment cohort, respectively. Overall, 184 patients (20.3%) underwent further contrast-enhanced MRI with other gadolinium-based contrast agents within the 2-year follow-up. No patient developed symptoms conclusive of NSF.
Conclusions: No safety concerns with gadobutrol in patients with moderate to severe renal impairment were identified. There were no NSF cases.
BACKGROUND: The analysis of microarray time series promises a deeper insight into the dynamics of the cellular response following stimulation. A common observation in this type of data is that some genes respond with quick, transient dynamics, while other genes change their expression slowly over time. The existing methods for detecting significant expression dynamics often fail when the expression dynamics show a large heterogeneity. Moreover, these methods often cannot cope with irregular and sparse measurements.
RESULTS: The method proposed here is specifically designed for the analysis of perturbation responses. It combines different scores to capture fast and transient dynamics as well as slow expression changes, and performs well in the presence of low replicate numbers and irregular sampling times. The results are given in the form of tables including links to figures showing the expression dynamics of the respective transcript. These allow to quickly recognise the relevance of detection, to identify possible false positives and to discriminate early and late changes in gene expression. An extension of the method allows the analysis of the expression dynamics of functional groups of genes, providing a quick overview of the cellular response. The performance of this package was tested on microarray data derived from lung cancer cells stimulated with epidermal growth factor (EGF).
CONCLUSION: Here we describe a new, efficient method for the analysis of sparse and heterogeneous time course data with high detection sensitivity and transparency. It is implemented as R package TTCA (transcript time course analysis) and can be installed from the Comprehensive R Archive Network, CRAN. The source code is provided with the Additional file 1.
Donald Trump’s foreign policy agenda has been characterized as unpredictable, unprecedented and – after a telling neologism of the president himself – unpresidented. In this blog post I will argue that the constituent parts of Trump’s foreign policy are all but new. What is new is their combination. Moreover, while Trump’s Jeffersonianism-Jacksonianism stands in stark contrast to the Wilsonianism-Hamiltonianism that Hillary Clinton embraced during her election campaign, it is only a partial departure from Barack Obama’s Jeffersonianism-Hamiltonianism.
Das Yin und Yang des Terrors
(2017)
Man stelle sich folgendes Szenario vor: Björn Höcke und Abū Bakr al-Baġdādī diskutieren bei Sandra Maischberger darüber, welche Konsequenzen Deutschland aus dem islamistischen Terrorismus ziehen sollte – und sie sind sich dabei einig.
Die Fiktion mag hanebüchen klingen. Nicht nur, weil der Möchtegern-Kalif des „Islamischen Staats“ (IS) unter keinen Umständen als Gast einer deutschen Talkshow in Erscheinung treten könnte – oder auch nur wollte. Sondern auch, weil der Möchtegern-Goebbels aus Thüringen sich stets als ritterlicher Gegner der Islamisten präsentiert, deren Denken und Handeln völlig unvereinbar sei mit dem Willen des hiesigen Volkes, den die Rechtspopulisten zu repräsentieren meinen. Gleicht man allerdings die (migrations-)politischen Willensbekundungen, die AFD und Co. als Antwort auf den islamistischen Terror bieten, ab mit den politischen Reaktionen, die sich der IS von Anschlägen in Europa erhofft, fällt es schwer, hier einen Widerspruch zu sehen. Vielmehr lässt ein solcher Abgleich die deutschen – und auch europäischen – Rechtspopulisten, für die Höcke hier stellvertretend steht, fast schon als heimliche Partner des IS erscheinen, deren Absichten sich bestens mit den Vorstellungen der IS-Strategen ergänzen.
Damit ist ein dialektisches Problem angesprochen, das dem Umgang mit dem Terrorismus stets inhärent ist. Immerhin gehört es zu den Binsenweisheiten der Konfliktforschung, dass terroristische Akteure Reaktionen provozieren wollen, die ihnen neue Handlungsmöglichkeiten eröffnen. Und dies wiederum verweist darauf, dass Politiker und Sicherheitsbehörden, aber auch die Medien dabei (ungewollt) zu Erfüllungsgehilfen werden können, wenn deren Reflexe dem terroristischen Kalkül entsprechen. Die Dynamik des Terrors speist sich eben nicht nur aus den Aktionen der Terroristen, sondern auch aus dem Verhalten ihrer Antagonisten und der Öffentlichkeit. Um jene Dynamik zu verstehen, reicht daher der Blick auf terroristische Strategien keineswegs aus. Vielmehr ist deren Effekt von den Reaktionen relationaler Akteure abhängig. Wer also dem Terrorismus das Wasser abgraben will, der muss – so paradox das klingt – auch Vorsicht gegenüber denen walten lassen, die Anstoß an ihm nehmen.
Diese Prämisse eröffnet eine kritische Perspektive auf Formen des Anti-Terrorismus. Denn demnach können Versuche, dem Terror die Stirn zu bieten, unbeabsichtigte (Neben-)Folgen mit sich bringen, welche die Dynamik des Terrors verstärken. Derartige backfire mechanisms sind es, die in diesem Beitrag problematisiert werden. Jedoch widmet er sich nicht der staatlichen Antiterrorpolitik, sondern erörtert, inwiefern das Zusammenspiel von Medien und Rechtspopulismus zur aktuellen Dynamik des islamistischen Terrorismus beiträgt. Diese Frage stellt sich vor dem Hintergrund, dass die jüngsten Anschläge in Europa eine virtuelle Form des Terrorismus darstellen, wo häufig Einzelpersonen im Namen des IS agieren, aber kaum bis gar nicht im Kontakt mit der Organisation standen. Es scheint daher die Vermutung nicht abwegig, dass co-konstitutive Faktoren – wie die Berichterstattung über den Terror und anti-muslimische Diskurse – eine nicht unbedeutende Rolle bei deren Radikalisierung und Aktivierung spielen.
In this meeting report, particularly addressing the topic of protection of the cardiovascular system from ischemia/reperfusion injury, highlights are presented that relate to conditioning strategies of the heart with respect to molecular mechanisms and outcome in patients’ cohorts, the influence of co-morbidities and medications, as well as the contribution of innate immune reactions in cardioprotection. Moreover, developmental or systems biology approaches bear great potential in systematically uncovering unexpected components involved in ischemia–reperfusion injury or heart regeneration. Based on the characterization of particular platelet integrins, mitochondrial redox-linked proteins, or lipid-diol compounds in cardiovascular diseases, their targeting by newly developed theranostics and technologies opens new avenues for diagnosis and therapy of myocardial infarction to improve the patients’ outcome.
Gleichstellungs-Monitor 2013
(2014)
Der vorliegende Text ist ein Bericht über die Ergebnisse einer qualitativen empirischen Befragung, die im Herbst 2015 in Haushalten eines Quartiers der Stadt Qingdao in China im Rahmen des BMBF-Projekts SEMIZENTRAL durchgeführt wurde. Das Gesamtprojekt umfasst die erstmalige Realisierung eines Resource Recovery Centers (RRC) als flexibles System mit Wasserrückgewinnung und Wiederverwertung in einer schnell wachsenden Stadt. Das Fachgebiet Abwassertechnik am Institut IWAR der Technischen Universität Darmstadt leitet das Projekt. Das ISOE ist Partner im Forschungsverbund und führt eine Stoffstrom- und eine damit verbundene Vulnerabilitätsanalyse für das Gebiet der Implementierung durch. In diesem Zusammenhang ist es wichtig, Einflussfaktoren des Umgangs mit Wasser und Abwasser durch die Bewohner und Bewohnerinnen zu erfassen. Thematischer Schwerpunkt der Befragung war, welche Alltagspraxis in Bezug auf Wasser und Abwasser die Bewohnerinnen und Bewohner haben und wie sich diese durch den Umzug aus einer traditionellen Dorfstruktur in ein modernes Wohnquartier verändert hat. Gleichzeitig sollte die Bekanntheit und Akzeptanz des Konzepts des RRC empirisch untersucht werden.
Under physiological conditions, endothelial cells and the endothelial nitric oxide (NO) synthase (eNOS) are the main source of NO in the cardiovascular system. However, several other cell types have also been implicated in the NO-dependent regulation of cell function, including erythrocytes. NO derived from red blood cells has been proposed to regulate erythrocyte membrane fluidity, inhibit platelet activation and induce vasodilation in hypoxic areas, but these proposals are highly controversial. In the current issue of Cell Communication and Signaling, an elegant study by Gambaryan et al., assayed NO production by erythrocytes by monitoring the activation of the platelet intracellular NO receptor, soluble guanylyl cyclase, and its downstream kinase protein kinase G. After systematically testing different combinations of erythrocyte/platelet suspensions, the authors found no evidence for platelet soluble guanylyl cyclase/protein kinase G activation by erythrocytes and conclude that erythrocytes do not release biologically active NO to inhibit platelet activation.
Recent advances in basic cardiovascular research as well as their translation into the clinical situation were the focus at the last "New Frontiers in Cardiovascular Research meeting". Major topics included the characterization of new targets and procedures in cardioprotection, deciphering new players and inflammatory mechanisms in ischemic heart disease as well as uncovering microRNAs and other biomarkers as versatile and possibly causal factors in cardiovascular pathogenesis. Although a number of pathological situations such as ischemia-reperfusion injury or atherosclerosis can be simulated and manipulated in diverse animal models, also to challenge new drugs for intervention, patient studies are the ultimate litmus test to obtain unequivocal information about the validity of biomedical concepts and their application in the clinics. Thus, the open and bidirectional exchange between bench and bedside is crucial to advance the field of ischemic heart disease with a particular emphasis of understanding long-lasting approaches in cardioprotection.
BACKGROUND AND PURPOSE: We evaluated cerebral white and gray matter changes in patients with iRLS in order to shed light on the pathophysiology of this disease.
METHODS: Twelve patients with iRLS were compared to 12 age- and sex-matched controls using whole-head diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) techniques. Evaluation of the DTI scans included the voxelwise analysis of the fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD).
RESULTS: Diffusion tensor imaging revealed areas of altered FA in subcortical white matter bilaterally, mainly in temporal regions as well as in the right internal capsule, the pons, and the right cerebellum. These changes overlapped with changes in RD. Voxel-based morphometry did not reveal any gray matter alterations.
CONCLUSIONS: We showed altered diffusion properties in several white matter regions in patients with iRLS. White matter changes could mainly be attributed to changes in RD, a parameter thought to reflect altered myelination. Areas with altered white matter microstructure included areas in the internal capsule which include the corticospinal tract to the lower limbs, thereby supporting studies that suggest changes in sensorimotor pathways associated with RLS.
Molecular cause and functional impact of altered synaptic lipid signaling due to a prg‐1 gene SNP
(2015)
Loss of plasticity-related gene 1 (PRG-1), which regulates synaptic phospholipid signaling, leads to hyperexcitability via increased glutamate release altering excitation/inhibition (E/I) balance in cortical networks. A recently reported SNP in prg-1 (R345T/mutPRG-1) affects ~5 million European and US citizens in a monoallelic variant. Our studies show that this mutation leads to a loss-of-PRG-1 function at the synapse due to its inability to control lysophosphatidic acid (LPA) levels via a cellular uptake mechanism which appears to depend on proper glycosylation altered by this SNP. PRG-1(+/-) mice, which are animal correlates of human PRG-1(+/mut) carriers, showed an altered cortical network function and stress-related behavioral changes indicating altered resilience against psychiatric disorders. These could be reversed by modulation of phospholipid signaling via pharmacological inhibition of the LPA-synthesizing molecule autotaxin. In line, EEG recordings in a human population-based cohort revealed an E/I balance shift in monoallelic mutPRG-1 carriers and an impaired sensory gating, which is regarded as an endophenotype of stress-related mental disorders. Intervention into bioactive lipid signaling is thus a promising strategy to interfere with glutamate-dependent symptoms in psychiatric diseases.
Left ventricular non-compaction cardiomyopathy and left ventricular assist device: a word of caution
(2016)
BACKGROUND: In patients with left ventricular non-compaction (LVNC), implantation of a left ventricular assist device (LVAD) may be performed as a bridge to transplantation. In this respect, the particular characteristics of the left ventricular myocardium may represent a challenge.
CASE PRESENTATION: We report a patient with LVNC who required urgent heart transplantation for inflow cannula obstruction nine months after receiving a LVAD. LVAD parameters, echocardiography and examination of the explanted heart suggested changes of left ventricular configuration brought about by LVAD support as the most likely cause of inflow cannula obstruction.
CONCLUSIONS: We conclude that changes experienced by non-compacted myocardium during LVAD support may give rise to inflow cannula obstruction and flow reduction. Presence of LVNC mandates tight surveillance for changes in LV configuration and LVAD flow characteristics and may justify urgent transplantation listing status.
The aim of this clinical trial was to evaluate the impact of all-trans retinoic acid (ATRA) in combination with chemotherapy and to assess the NPM1 status as biomarker for ATRA therapy in younger adult patients (18-60 years) with acute myeloid leukemia (AML). Patients were randomized for intensive chemotherapy with or without open-label ATRA (45 mg/m2, days 6-8; 15 mg/m2, days 9-21). Two cycles of induction therapy were followed by risk-adapted consolidation with high-dose cytarabine or allogeneic hematopoietic cell transplantation. Due to the open label character of the study, analysis was performed on an intention-to-treat (ITT) and a per-protocol (PP) basis. One thousand one hundred patients were randomized (556, STANDARD; 544, ATRA) with 38 patients treated vice versa. Median follow-up for survival was 5.2 years. ITT analyses revealed no difference between ATRA and STANDARD for the total cohort and for the subset of NPM1-mutated AML with respect to event-free (EFS; p = 0.93, p = 0.17) and overall survival (OS; p = 0.24 and p = 0.32, respectively). Pre-specified PP analyses revealed better EFS in NPM1-mutated AML (p = 0.05) and better OS in the total cohort (p = 0.03). Explorative subgroup analyses on an ITT basis revealed better OS (p = 0.05) in ATRA for genetic low-risk patients according to ELN recommendations. The clinical trial is registered at clinicaltrialsregister.eu (EudraCT Number: 2004-004321-95).
Cl(-) plays a crucial role in neuronal function and synaptic inhibition. However, the impact of neuronal morphology on the diffusion and redistribution of intracellular Cl(-) is not well understood. The role of spines in Cl(-) diffusion along dendritic trees has not been addressed so far. Because measuring fast and spatially restricted Cl(-) changes within dendrites is not yet technically possible, we used computational approaches to predict the effects of spines on Cl(-) dynamics in morphologically complex dendrites. In all morphologies tested, including dendrites imaged by super-resolution STED microscopy in live brain tissue, spines slowed down longitudinal Cl(-) diffusion along dendrites. This effect was robust and could be observed in both deterministic as well as stochastic simulations. Cl(-) extrusion altered Cl(-) diffusion to a much lesser extent than the presence of spines. The spine-dependent slowing of Cl(-) diffusion affected the amount and spatial spread of changes in the GABA reversal potential thereby altering homosynaptic as well as heterosynaptic short-term ionic plasticity at GABAergic synapses in dendrites. Altogether, our results suggest a fundamental role of dendritic spines in shaping Cl(-) diffusion, which could be of relevance in the context of pathological conditions where spine densities and neural excitability are perturbed.