Performance improvement in pharmaceutical R&D through new outsourcing models

The stimulation of innovation in the pharmaceutical industry through outsourcing of research and development (R&D) activities within the drug discovery and development process is analysed. The empirical data were collected through interviews with experts of pharmaceutical companies and service providers between 2002 and 2005. Additionally, in 2008, the outsourcing behaviour of the already interviewed and additional companies was analysed through desk research. The results show that the outsourcing behaviour of traditional and emerging pharmaceutical companies is completely different. Whereas the make-or-buy decisions of traditional companies are mainly competency or know-how driven, that of emerging companies are primarily capacity or cost driven. Nevertheless, for both types of companies the cooperation model of “strategic partnership” offers access to high-level expertise while reducing fixed costs and complexity. Within this model, external providers are temporarily integrated into internal R&D teams and thus able to support R&D projects flexibly and more timely

Photoproduction at collider energies: from RHIC and HERA to the LHC

We present the mini-proceedings of the workshop on ``Photoproduction at collider energies: from RHIC and HERA to the LHC'' held at the European Centre for Theoretical Studies in Nuclear Physics and Related Areas (ECT*, Trento) from January 15 to 19, 2007. The workshop gathered both theorists and experimentalists to discuss the current status of investigations of high-energy photon-induced processes at different colliders (HERA, RHIC, and Tevatron) as well as preparations for extension of these studies at the LHC. The main physics topics covered were: (i) small-$x$ QCD in photoproduction studies with protons and in electromagnetic (aka. ultraperipheral) nucleus-nucleus collisions, (ii) hard diffraction physics at hadron colliders, and (iii) photon-photon collisions at very high energies: electroweak and beyond the Standard Model processes. These mini-proceedings consist of an introduction and short summaries of the talks presented at the meeting

Dopamine transporter trafficking and Rit2 GTPase: Mechanism of action and in vivo impact

Following its evoked release, DA signaling is rapidly terminated by presynaptic reuptake, mediated by the cocaine-sensitive DAT. DAT surface availability is dynamically regulated by endocytic trafficking, and direct PKC activation acutely diminishes DAT surface expression by accelerating DAT internalization. Previous cell line studies demonstrated that PKC-stimulated DAT endocytosis requires both Ack1 inactivation, which releases a DAT-specific endocytic brake, and the neuronal GTPase, Rit2, which binds DAT. However, it is unknown whether Rit2 is required for PKC-stimulated DAT endocytosis in DAergic terminals, or whether there are region- and/or sex-dependent differences in PKC-stimulated DAT trafficking. Moreover, the mechanisms by which Rit2 controls PKC-stimulated DAT endocytosis are unknown. Here, we directly examined these important questions. Ex vivo studies revealed that PKC activation acutely decreased DAT surface expression selectively in ventral, but not dorsal, striatum. AAV-mediated, conditional Rit2 knockdown in DAergic neurons impacted baseline DAT surface:intracellular distribution in DAergic terminals from female ventral, but not dorsal, striatum. Further, Rit2 was required for PKC-stimulated DAT internalization in both male and female ventral striatum. FRET and surface pulldown studies in cell lines revealed that PKC activation drives DAT-Rit2 surface dissociation, and that the DAT N-terminus is required for both PKC-mediated DAT-Rit2 dissociation and DAT internalization. Finally, we found that Rit2 and Ack1 independently converge on DAT to facilitate PKC-stimulated DAT endocytosis. Together, our data provide greater insight into mechanisms that mediate PKC-regulated DAT internalization, and reveal unexpected region-specific differences in PKC-stimulated DAT trafficking in bona fide DAergic terminals

ISSUES IN HIGH-RESOLUTION ATMOSPHERIC MODELING IN COMPLEX TOPOGRAPHY --THE HiRCoT WORKSHOP

During the past years the atmospheric modeling community, both from the application and pure research perspectives, has been facing the challenge of high resolution numerical modeling in places with complex topography. In February 2012, as a result of the collaborative efforts of the Institute of Meteorology of the University of Natural Resources and Life Sciences (BOKUMet), the Arctic Region Supercomputing Center (ARSC), the Institute of Meteorology and Geophysics of the University of Innsbruck (IMG) and the enthusiasm of the scientific community, the HiRCoT workshop was held in Vienna, Austria. HiRCoT objectives were to: 1) Identify the problems encountered with numerical modeling at grid spacing lower than 1 km over complex terrain, that is, understand the key areas that are troublesome and formulate the key questions about them; 2) Map out possibilities on how to address these issues; 3) Allow the researchers to discuss the issues on a shared platform (online through a wikipage and face-to-face). This manuscript presents an overview of the topics and research priorities discussed in the workshop

Heavy-flavour and quarkonium production in the LHC era: from proton-proton to heavy-ion collisions

This report reviews the study of open heavy-flavour and quarkonium production in high-energy hadronic collisions, as tools to investigate fundamental aspects of Quantum Chromodynamics, from the proton and nucleus structure at high energy to deconfinement and the properties of the Quark-Gluon Plasma. Emphasis is given to the lessons learnt from LHC Run 1 results, which are reviewed in a global picture with the results from SPS and RHIC at lower energies, as well as to the questions to be addressed in the future. The report covers heavy flavour and quarkonium production in proton-proton, proton-nucleus and nucleus-nucleus collisions. This includes discussion of the effects of hot and cold strongly interacting matter, quarkonium photo-production in nucleus-nucleus collisions and perspectives on the study of heavy flavour and quarkonium with upgrades of existing experiments and new experiments. The report results from the activity of the SaporeGravis network of the I3 Hadron Physics programme of the European Union 7th Framework Programme

Energy loss of pions and electrons of 1 to 6 GeV/c in drift chambers operated with Xe,CO2(15%)

We present measurements of the energy loss of pions and electrons in drift chambers operated with a Xe,CO2(15%) mixture. The measurements are carried out for particle momenta from 1 to 6 GeV/c using prototype drift chambers for the ALICE TRD. Microscopic calculations are performed using input parameters calculated with GEANT3. These calculations reproduce well the measured average and most probable values for pions, but a higher Fermi plateau is required in order to reproduce our electron data. The widths of the measured distributions are smaller for data compared to the calculations. The electron/pion identification performance using the energy loss is also presented.Comment: 15 pages, 10 figures, accepted for publication in Nucl.Instrum.Meth.

Space charge in drift chambers operated with the Xe,CO2(15%) mixture

Using prototype modules of the ALICE Transition Radiation Detector we investigate space charge effects and the dependence of the pion rejection performance on the incident angle of the ionizing particle. The average pulse height distributions in the drift chambers operated with the Xe,CO2(15%) mixture provide quantitative information on the gas gain reduction due to space charge accumulating during the drift of the primary ionization. Our results demonstrate that the pion rejection performance of a TRD is better for tracks which are not at normal incidence to the anode wires. We present detailed simulations of detector signals, which reproduce the measurements and lend strong support to our interpretation of the measurements in terms of space charge effects.Comment: 18 pages, 10 figures, accepted for publication in Nucl.Instrum.Meth. A. Data files available at http://www-alice.gsi.de/tr

Position Reconstruction in Drift Chambers operated with Xe, CO2 (15%)

We present measurements of position and angular resolution of drift chambers operated with a Xe,CO$_2$(15%) mixture. The results are compared to Monte Carlo simulations and important systematic effects, in particular the dispersive nature of the absorption of transition radiation and non-linearities, are discussed. The measurements were carried out with prototype drift chambers of the ALICE Transition Radiation Detector, but our findings can be generalized to other drift chambers with similar geometry, where the electron drift is perpendicular to the wire planes.Comment: 30 pages, 18 figure