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CONTENTS: Keynote Address and Invited Plenary Lectures Symposia Debates and Panels Oral Presentations and Specific Topics Poster Presentations Workshop Presentations Case Study Presentations and Media Presentations Symposien Workshops
Over the past two decades the “one drug – one target – one disease” concept became the prevalent paradigm in drug discovery. The main idea of this approach is the identification of a single protein target whose inhibition leads to a successful treatment of the examined disease. The predominant assumption is that highly selective ligands would avoid unwanted side effects caused by binding to secondary non-therapeutic targets. In recent years the results of post-genomic and network biology showed that proteins rarely act in isolated systems but rather as a part of a highly connected network [1]. In addition this connectivity leads to more robust systems that cannot be interfered by the inhibition of a single target of that network and consequently might not lead to the desired therapeutic effect [2]. Furthermore studies prove that robust systems are rather affected by weak inhibitions of several parts than by a complete inhibition of a single selected element of that system [3]. Therefore there is an increasing interest in developing drugs that take effect on multiple targets simultaneously but is concurrently a great challenge for medicinal chemists. There has to be a sufficient activity on each target as well as an adequate pharmacokinetic profile [4]. Early design strategies tried to link the pharmacophors of known inhibitors, however these methods often lead to high molecular weight and low ligand efficacy. We present a new rational approach based on a retrosynthetic combinatorial analysis procedure [5] on approved ligands of multiple targets. These RECAP fragments are used to design a large combinatorial library containing molecules featuring chemical properties of each ligand class. The molecules are further validated by machine learning models, like random forests and self-organizing maps, regarding their activity on the targets of interest.
The LANSCE linear accelerator at Los Alamos National Laboratory provides H− and H+ beams to several user facilities that support Isotope Production, NNSA Stockpile Stewardship, and Basic Energy Science programs. These beams are initially accelerated to 750 keV using Cockcroft-Walton (CW) based injectors that have been in operation for over 37 years. They have failure modes which can result in prolonged operational downtime due to the unavailability of replacement parts. To reduce long-term operational risks and to realize future beam performance goals in support of the Materials Test Station (MTS) and the Matter-Radiation Interactions in Extremes (MaRIE) Facility, plans are underway to develop a Radio-Frequency Quadrupole (RFQ) based front end as a modern injector replacement for the existing CW injectors. Our progress to date will be discussed.
Beam test of the direct plasma injection scheme (DPIS) is carried out successfully for the first time in China, by setting up a comprehensive test and research platform of RFQ and laser ion source. The C6+ beam is accelerated successfully, and the peak beam current reaches more than 6mA which is measured by a Faraday cup of unique structure. The RF power coupled into the RFQ cavity is also examined, and results reveal that it is the RF power of about 195kW that can produce the peak beam current.
Beam measurements with the new RFQ beam matching section at the Frankfurt Funneling Experiment
(2011)
Funneling is a method to increase low energy beam currents in multiple stages. The Frankfurt Funneling Experiment is a model of such a stage. The experiment is built up of two ion sources with electrostatic lens systems, a Two-Beam-RFQ accelerator, a funneling deflector and a beam diagnostic system. The two beams are bunched and accelerated in a Two-Beam RFQ. A funneling deflector combines the bunches to a common beam axis. A new beam transport system between RFQ accelerator and deflector has been constructed and mounted. With these extended RFQ-electrodes the drift between the Two-Beam-RFQ and the rf-deflector will be minimized and therefore unwanted emittance growth reduced. After first rf measurements current work are beam tests with the improved Two-Beam-RFQ. First results will be presented.
A CW RFQ prototype
(2011)
A short RFQ prototype was built for RF-tests of high power RFQ structures. We will study thermal effects and determine critical points of the design. HF-simulations with CST Microwave Studio and measurements were done. The cw-tests with 20 kW/m RF-power and simulations of thermal effects with ALGOR were finished successfully. The optimization of some details of the HF design is on focus now. First results and the status of the project will be presented.
"Finnegans Wake" has struck many of its exegetes as the epitome of the postmodern text. The oddity of James Joyce's last work has been and still is a provocation not only for literary criticism and theory but for every reader of the work. It provokes us to reflect on our preconceptions concerning such fundamental issues as reading, meaning and understanding. Due to this very quality, the work has been a fertile intellectual stimulus for an illustrious band of thinkers of the ―post-projects. Its singularity has provoked and facilitated the further development of theoretical frameworks beyond the confines of literary theory proper. This essay will trace the elaborate theoretical responses of Umberto Eco and Jacques Lacan to Joyce's grand literary arcanum. Eco's concept of the openness of modern works of art and Lacan's elaboration of his psychoanalytic concepts of the symptom and of the Borromean knot were inspired by their study of Joyce. As an extreme instance of literariness, Finnegans Wake thus constitutes an ideal opportunity to consider the scope and boundaries of the scholarly study of literary texts more generally.
Die Grenzen und Möglichkeiten der Philologie im Holocaust-Diskurs : das Beispiel Theresienstadt
(2011)
Philology seems to have come to a crossroads. One path leads back to the save haven of established core strengths and competences, the other path promises new perspectives through further expansion into the vastness of cultural studies. If philology is to continue as a discipline relevant to society as a whole, retreat into pure philology — concentrating only on the text itself, adhering to national boundaries — is no viable option. Instead, by opening itself up for the questions and methods of truly interdisciplinary inquiry, philology can emerge in new shape, powerful enough to adequately address issues of interdisciplinary, intercultural and intergenerational importance. This essay will argue for such an extension of philology into cultural studies through an examination of texts, songs and plays written in and about the Terezín ghetto. The songs of Leo Strauß and Manfred Greiffenhagen, the ghetto opera "Der Kaiser von Atlantis" (The Emperor of Atlantis), as well as Roy Kift's play "Camp Comedy" and Frido Mann's parable "Terezín" will exemplify the potential of philology’s conjunction with history, sociology and cultural studies.