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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.
Chromatic, geometric and space charge effects on laser accelerated protons focused by a solenoid
(2011)
We studied numerically emittance and transmission effects by chromatic and geometric aberrations, with and without space charge, for a proton beam behind a solenoid in the laser proton experiment LIGHT at GSI. The TraceWin code was employed using a field map for the solenoid and an initial distribution with exponential energy dependence close to the experiment. The results show a strong effect of chromatic, and a relatively weak one of geometric aberrations as well as dependence of proton transmission on distance from the solenoid. The chromatic effect has an energy filtering property due to the finite radius beam pipe. Furthermore, a relatively modest dependence of transmission on space charge is found for p production intensity below 1011.
Experimental results and theoretical predictions in laser acceleration of protons achieved energies of ten to several tens of MeV. The LIGHT project (Laser Ion Generation, Handling and Transport) is proposed to use the PHELIX laser accelerated protons and to provide transport, focusing and injection into a conventional accelerator. This study demonstrates transport and focusing of laser-accelerated 10 MeV protons by a pulsed 18 T magnetic solenoid. The effect of co-moving electrons on the beam dynamics is investigated. The unique features of the proton distribution like small emittances and high yield of the order of 1013 protons per shot open new research area. The possibility of creating laser based injectors for ion accelerators is addressed. With respect to transit energies, direct matching into DTL's seems adequate. The bunch injection into a proposed CH− structure is under investigation at IAP Frankfurt. Options and simulation tools are presented.
The superconducting CH-structure (Crossbar-H-mode) is a multi-cell drift tube cavity for the low and medium energy range operated in the H21-mode, which has been developed at the Institute for Applied Physics (IAP) of Frankfurt University. With respect to different high power applications two types of superconducting CH-structures (f = 325 MHz, β = 0.16, seven cells and f = 217 MHz, β = 0.059, 15 cells) are presently under construction and accordingly under development. The structural mechanical simulation is a very important aspect of the cavity design. Furthermore, several simulations with ANSYS Workbench have been performed to predict the deformation of the cavity walls due to the cavity cool-down, pressure effects and mechanical vibrations. To readjust the fast frequency changes in consequence of the cavity shape deformation, a new concept for the dynamic frequency tuning has been investigated, including a novel type of bellow-tuner.
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.
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.
We review our knowledge of the phase diagram of QCD as a function of temperature, chemical potential and quark masses. The presence of tricritical lines at imaginary chemical potential m = i p 3 T, with known scaling behaviour in their vicinity, puts constraints on this phase diagram, especially in the case of two light flavors. We show first results in our project to determine the finite-temperature behaviour in the Nf = 2 chiral limit.
For the research program with cooled antiprotons at FAIR a dedicated 70 MeV, 70 mA proton injector is required. The main acceleration of this room temperature linac will be provided by six CH cavities operated at 325 MHz. Each cavity will be powered by a 2.5 MW Klystron. For the second acceleration unit from 11.5 MeV to 24.2 MeV a 1:2 scaled model has been built. Low level RF measurements have been performed to determine the main parameters and to prove the concept of coupled CH cavities. For this second tank technical and mechanical investigations have been performed in 2010 to develop a complete technical concept for the manufacturing. In Spring 2011, the construction of the first power prototype has started. The main components of this cavity will be ready for measurements in summer 2011. At that time, the cavity will be tested with a preliminary aluminum drift tube structure, which will allow precise frequency and field tuning. This paper will report on the recent technical development and achievements. It will outline the main fabrication steps towards that novel type of proton DTL. Also first low level RF measurements are expected.
At the Institute for Applied Physics (IAP), University of Frankfurt, a s.c. 325 MHz CH-Cavity is under development for future beam tests at GSI UNILAC, Darmstadt. The cavity with 7 accelerating cells has a geometrical beta of 0.15 corresponding to 11.4 AMeV. The design gradient is 5 MV/m. The geometry of this resonator was optimized with respect to a compact design, low peak fields, surface processing, power coupling and tuning. Furthermore a new tuning system based on bellow tuners inside the resonator will control the frequency during operation. After rf tests in Frankfurt the cavity will be tested with a 10 mA, 11.4 AMeV beam delivered by the GSI UNILAC. In this paper rf simulations, multipacting analysis as well as thermal calculations will be presented.
Vom 17. bis 19. Februar 2011 luden Jens Eder, Joseph Imorde und Maike Sarah Reinerth für die Filmwissenschaft / Mediendramaturgie der Universität Mainz und die Kunstgeschichte der Universität Siegen Forscher und Forscherinnen unterschiedlicher Disziplinen zu einem Workshop mit dem Thema "Medium Menschenbild" ein. Förderer waren der Forschungsschwerpunkt "Medienkonvergenz" der Johannes Gutenberg-Universität Mainz und das Labor Neue Kunst Siegen. Ziel der Tagung war, das grundsätzliche Verhältnis von Medialität und Menschenbild zu analysieren, die Spezifik medial vermittelter Menschenbilder im interdisziplinären Austausch zu diskutieren sowie auf die in ihnen implizit enthaltenen konzeptuellen Vorstellungen hinzuweisen. ...
Schließlich untersuchte die Kunsthistorikerin HELEN BARR (Frankfurt am Main) den "neuen Menschen" in Werbeanzeigen illustrierter Zeitschriften der 1920er-Jahre. Das breite Spektrum der Werbung für Pflegeprodukte und Genussmittel suggeriere Orientierungshilfe in der urbanisierten Welt und propagiere ideale Menschenbilder der Moderne. ...
This article presents a multiscale approach for detecting and monitoring soil erosion phenomena (i.e. gully erosion) in the agro-industrial area around the city of Taroudannt, Souss basin, Morocco. The study area is characterized as semi-arid with an annual average precipitation of 200 mm. Water scarcity, high population dynamics and changing land use towards huge areas of irrigation farming present numerous threats to sustainability. The agro-industry produces citrus fruits and vegetables in monocropping, mainly for the European market. Badland areas strongly affected by gully erosion border the agricultural areas as well as residential areas. To counteract the significant loss of land, land-leveling measures are attempted to create space for plantations and greenhouses. In order to develop sustainable approaches to limit gully growth the detection and monitoring of gully systems is fundamental. Specific gully sites are monitored with unmanned aerial vehicle (UAV) taking small-format aerial photographs (SFAP). This enables extremely high-resolution analysis (SFAP resolution: 2-10 cm) of the actual size of the gully channels as well as a detailed continued surveillance of their growth. Transferring the methodology on a larger scale using Quickbird satellite data (resolution: 60 cm) leads to the possibility of a large-scale analysis of the whole area around the city of Taroudannt (Area extent: ca. 350 km²). The results will then reveal possible relationships of gully growth and agro-industrial management and may even illustrate further interdependencies. The main objective is the identification of areas with high gully-erosion risk due to non-sustainable land use and the development of mitigation strategies for the study area.
Es ist eine alte Debatte. Auf der einen Seite steht die althergebrachte Maxime, alles, was wert ist, gesagt zu werden, müsse in jeder Sprache gesagt werden können - umso mehr dann, wenn es sich um die Wissenschaft handelt, die den Anspruch erhebt, universelle Wahrheiten zu erfassen. Demgegenüber steht ein immer wieder anzutreffender Gedanke, dessen wohl inspirierteste Formulierung von Wilhelm von Humboldt stammt, nämlich, dass die Verschiedenheit der Sprachen nicht nur eine von „Schällen und Zeichen“, sondern eine der „Weltansichten selbst“ sei. Thema dieses Vortrags ist die Frage, wo die Wahrheit zwischen diesen scheinbaren Gegensätzen liegt.
Chopper systems are used to pulse charged particle beams. In most cases, electric deflection systems are used to generate beam pulses of defined lengths and appropriate repetition rates. At high beam intensities, the field distribution of the chopper system needs to be adapted precisely to the beam dynamics in order to avoid aberrations. An additional challenge is a robust design which guarantees reliable operation. For the Frankfurt Neutron Source FRANZ, an E×B chopper system is being developed which combines static magnetic deflection with a pulsed electric field in a Wien filter configuration. It will generate proton pulses with a flat top of 50 ns at a repetition rate of 250 kHz for 120 keV, 200 mA beams. For the electric deflection, pre-experiments with static and pulsed fields were performed using a helium ion beam. In pulsed mode operation, ion beams of different energies were deflected with voltages of up to ±6 kV and the resulting response was measured using a beam current transformer. A comparison between experiments and theoretical calculations as well as numerical simulations are presented.
An optimized design of a stellarator-type storage ring for low energy ion beams was numerically investigated. The magnetic field variation along the circumference and therefore magnetic heating is suppressed by using simple circular correction coils. Particle-in-Cell (PIC) simulations in a magnetic flux coordinate system show the ability of high current ion beam accumulation in such a configuration with unique features for clockwise and anticlockwise moving beams. Additionally scaled down experiments with two 30 degree room temperature toroidal segments were performed to demonstrate toroidal transport and to develop optical beam diagnostics. Properties of multi-component beams, redistribution of transversal momenta in the non-adiabatic part of the experimental configuration and investigation of strongly confined beam induced electron clouds will be addressed.
At GSI a new, superconducting (sc) continuous wave (cw) LINAC is under design in cooperation with the Institute for Applied Physics (IAP) of Frankfurt University and the Helmholtz Institut Mainz (HIM). This proposed LINAC is highly requested by a broad community of future users to fulfill the requirements of nuclear chemistry, nuclear physics, and especially in the research field of Super Heavy Elements (SHE). In this context the preliminary layout of the LINAC has been carried out by IAP. The main acceleration of up to 7.3 AMeV will be provided by nine sc Crossbar-H-mode (CH) cavities operated at 217 MHz. Currently, a prototype of the cw LINAC as a demonstrator is under development. The demonstrator comprises a sc CH-cavity embedded between two sc solenoids mounted in a horizontal cryomodule. A full performance test of the demonstrator in 2013/14 by injecting and accelerating a beam from the GSI High Charge Injector (HLI) is one important milestone of the project. The status of the demonstrator is presented.
Development of fragmented low-Z ion beams for the NA61 fixed-target experiment at the CERN SPS
(2011)
The NA61 experiment, aims to study the properties of the onset of deconfinement at low SPS energies and to find signatures of the critical point of strongly interacting matter. A broad range in T-μB phase diagram will be covered by performing an energy (13A-158A GeV/c) and system size (p+p, Be+Be, Ar+Ca, Xe+La) scan. In a first phase, fragmented ion beams of 7Be or 11C produced as secondaries with the same momentum per nucleon when the incident primary Pb-ion beam hits a thin Be target will be used. The H2 beam line that transports the beam to the experiment acts as a double spectrometer which combined with a new thin target (degrader) where fragments loose energy proportional to the square of their charge allows the separation of the wanted A/Z fragments. Thin scintillators and TOF measurement for the low energy points are used as particle identification devices. In this paper results from the first test of the fragmented ion beam done in 2010 will be presented showing that a pure Be beam can be obtained satisfying the needs of the experiment.
Es war eine in jeder Hinsicht außergewöhnliche Tagung, die Ende Oktober 2010 in Marbach stattfand. 20 renommierte Historiker/innen kamen zusammen, um an ihren akademischen Lehrer und Mentor Wolfgang J. Mommsen zu erinnern. Jeder sollte, so die Vorgabe der beiden Organisatoren Christoph Cornelißen und Gerhard Hirschfeld, aus seinem Forschungsfeld berichten und den Einfluss Mommsens auf diesen Themengebieten einschätzen und beschreiben. Der entsprechende Tagungsband mit den Beiträge konnte bereits auf der Konferenz vorgestellt werden. Zugegen war auch die Familie Mommsen und ebenso der Zwillingsbruder Hans Mommsen. ...
QCD at finite temperature and denisty remains intractable by Monte Carlo simulations for quark
chemical potentials m >∼T. It has been a long standing problem to derive effective theories from
QCD which describe the phase structure of the former with controlled errors. We propose a
solution to this problem by a combination of analytical and numerical methods. Starting from
lattice QCD with in Wilson’s formulation, we derive an effective action in terms of Polyakov
loops by means of combined strong coupling and hopping expansions. The theory correctly
reflects the centre-symmetry in the pure gauge limit and its breaking through quarks. It is valid
for heavy quarks and lattices up to Nt ∼ 6. Its sign problem can be solved and we are able to
calculate the deconfinement transition of QCD with heavy quarks for all chemical potentials.
We report on the first steps of an ongoing project to add gauge observables and gauge corrections
to the well-studied strong coupling limit of staggered lattice QCD, which has been shown earlier
to be amenable to numerical simulations by the worm algorithm in the chiral limit and at finite
density. Here we show how to evaluate the expectation value of the Polyakov loop in the framework
of the strong coupling limit at finite temperature, allowing to study confinement properties
along with those of chiral symmetry breaking. We find the Polyakov loop to rise smoothly, thus
signalling deconfinement. The non-analytic nature of the chiral phase transition is reflected in the
derivative of the Polyakov loop. We also discuss how to construct an effective theory for non-zero
lattice coupling, which is valid to O(b).
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.