FDZ Annual Report 2008

"Following the exceedingly positive response to our Annual Report 2007, you now have the Annual Report 2008 of the Research Data Centre (FDZ) of the Federal Employment Agency at the Institute for Employment Research in this FDZ Methodenreport. Like last year, the FDZ Annual Report 2008 is not a glossy brochure full of photos but summarises the main events of the past 12 months in a few pages. The Annual Report 2008 is mainly based on key figures which the FDZ made available to the German Council for Social and Economic Data for their evaluation in 2009. The Annual Report also serves to provide transparency for our users, who after all justify the existence of the FDZ. The Report is divided into the following chapters: 'General function', 'Basic information', 'The service-oriented FDZ', 'The international FDZ' and, as an apt conclusion, 'Research at the FDZ'." (Author's abstract, IAB-Doku) ((en)) Additional Information Here you can find the German version of the report.Forschungsdatenzentrum - Bericht, Bundesagentur für Arbeit, IAB, amtliche Statistik, Datenzugang, Datenschutz, Arbeitsmarkt- und Berufsforschung, IAB-Beschäftigtenstichprobe, IAB-Betriebspanel, IAB-Betriebs-Historik-Panel, IAB-Linked-Employer-Employee-Datensatz, Integrierte Erwerbsbiografien, Datenaufbereitung, Datenausgabe, BA-Beschäftigtenpanel, Befragung, IAB-Querschnittsbefragung, IAB-Haushaltspanel, IAB-kombinierte Firmendaten, IAB-Weiterbildungspanel

Understanding the differential consequences of checkpoint adaptation following DNA damage in repair-proficient and repair-deficient cells

When cells experience DNA damage, they halt the cell cycle before sister chromatid separation has begun in response to the activation of the DNA damage checkpoint. This surveillance mechanism provides time to repair the damage and only when repair has been successful the cell cycle is resumed. Therefore, cell cycle arrest and damage repair are important processes to ensure the stability of the genome and the faithful transfer of genetic information to daughter cells. However, if repair is not possible, cells can override the DNA damage checkpoint and terminate the cell cycle arrest by a mechanism called (checkpoint) adaptation. Although many proteins have been shown to be involved in the adaptation process, its molecular mechanisms still remain elusive. Especially the critical determinants initiating checkpoint adaptation have not been fully identified. Understanding this pathway is of particular interest since checkpoint adaptation is a driving force of genome instability and has detrimental consequences including cell death and various genomic aberrations. Interestingly, the concept of checkpoint adaptation is not only found in unicellular eukaryotes like yeast but also in multicellular organisms. Especially during cancerogenesis, checkpoint adaptation is thought to contribute to genome instability. We could previously show that inhibition of the highly conserved TOR nutrient signalling pathway either by genetic or pharmacologic means prevents checkpoint adaptation in Saccharomyces cerevisiae. These observations suggests that nutrient signalling pathways involving TOR signalling node play an important role in response to DNA damage. We set out to further investigate the link between nutrient signalling, checkpoint adaptation and genome stability. We show that prevention of adaptation can be achieved by modulating the Tap42-PP2A axis downstream of TOR signalling. We found that pharmacological inhibition of TOR by rapamycin affects protein levels of Cdc5, a major factor promoting adaptation. Using RAD52-deficient yeast cells to mimic the DNA repair defect observed in many human cancers, we confirmed previous results showing that preventing adaptation sensitizes these cells to genotoxins. However, if adaptation is allowed to occur, repair-deficient cells acquire genotoxin resistance and display an aneuploid karyotype. Gene expression profiling revealed that resistant repair-defective yeast cells exhibit common aneuploidy-associated phenotypes. Although resistant aneuploid cells are still checkpoint-competent, they can proliferate in the presence of persistent DNA damage. This underlines the role of checkpoint adaptation in the acquisition of genotoxin resistance. Taken together, our results highlight an intriguing relationship between the DNA damage response and genome stability, which appears to be associated with checkpoint adaptation and nutrient signalling pathways. Furthermore, using an easily tractable model organism such as budding yeast, we provide insights into the relationship between fundamental and highly conserved cellular processes that could be useful for drug development and disease treatment in humans as well

A disruption management system for automotive inbound networks: concepts and challenges

Production processes in the automotive industry are highly dependent on reliable inbound logistics processes, because in lean production systems delays or mistakes often result in expensive interruptions of production processes. However, transport processes are always subject to unavoidable disturbances, delays, or mistakes. The goal of the research project ProveIT is to provide an IT system improving the transparency by monitoring transport processes in real-time: deviations from the transport plans are identified predictively, and classified dynamically as disruptions if they have negative impacts on the subsequent processes. If a disruption occurs, the operations managers are provided with mitigation actions automatically generated by escalation-based online optimization algorithms. In this contribution, we introduce the use cases, the architecture and main concepts of the ProveIT disruption management system, and report on challenges faced during field experiments with our application partners, Bosch, ZF, and Geis

A Genetically Encoded Tool Kit for Manipulating and Monitoring Membrane Phosphatidylinositol 4,5-Bisphosphate in Intact Cells

BACKGROUND: Most ion channels are regulated by phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)) in the cell membrane by diverse mechanisms. Important molecular tools to study ion channel regulation by PtdIns(4,5)P(2) in living cells have been developed in the past. These include fluorescent PH-domains as sensors for Förster resonance energy transfer (FRET), to monitor changes in plasma membrane(.) For controlled and reversible depletion of PtdIns(4,5)P(2), voltage-sensing phosphoinositide phosphatases (VSD) have been demonstrated as a superior tool, since they are independent of cellular signaling pathways. Combining these methods in intact cells requires multiple transfections. We used self-cleaving viral 2A-peptide sequences for adenovirus driven expression of the PH-domain of phospholipase-Cδ1 (PLCδ1) fused to ECFP and EYFP respectively and Ciona intestinalis VSP (Ci-VSP), from a single open reading frame (ORF) in adult rat cardiac myocytes. METHODS AND RESULTS: Expression and correct targeting of ECFP-PH-PLCδ1(,) EYFP-PH-PLCδ1, and Ci-VSP from a single tricistronic vector containing 2A-peptide sequences first was demonstrated in HEK293 cells by voltage-controlled FRET measurements and Western blotting. Adult rat cardiac myocytes expressed Ci-VSP and the two fluorescent PH-domains within 4 days after gene transfer using the vector integrated into an adenoviral construct. Activation of Ci-VSP by depolarization resulted in rapid changes in FRET ratio indicating depletion of PtdIns(4,5)P(2) in the plasma membrane. This was paralleled by inhibition of endogenous G protein activated K(+) (GIRK) current. By comparing changes in FRET and current, a component of GIRK inhibition by adrenergic receptors unrelated to depletion of PtdIns(4,5)P(2) was identified. CONCLUSIONS: Expression of a FRET sensor pair and Ci-VSP from a single ORF provides a useful approach to study regulation of ion channels by phosphoinositides in cell lines and transfection-resistant postmitotic cells. Generally, adenoviral constructs containing self-cleaving 2A-peptide sequences are highly suited for simultaneous transfer of multiple genes in adult cardiac myocytes

Urban Climate Under Change [UC]2 – A National Research Programme for Developing a Building-Resolving Atmospheric Model for Entire City Regions

Large cities and urban regions are confronted with rising pressure by environmental pollution, impacts of climate change, as well as natural and health hazards. They are characterised by heterogeneous mosaics of urban structures, causing modifications of atmospheric processes on different temporal and spatial scales. Planning authorities need reliable, locally relevant information on urban atmospheric processes, providing fine spatial resolutions in city quarters or street canyons, as well as projections of future climates, specifically downscaled to individual cities. Therefore, building-resolving urban climate models for entire city regions are required as tool for urban development and planning, air quality control, as well as for design of actions for climate change mitigation and adaptation. To date, building-resolving atmospheric models covering entire large cities are mostly missing. The German research programme “Urban Climate Under Change” ([UC]2) aims at developing a new urban climate model, to acquire three-dimensional observational data for model testing and validation, and to test its practicability and usability in collaboration with relevant stakeholders to provide a scientifically sound and practicable instrument to address the above mentioned challenges. This article provides an outline of the collaborative activities of the [UC]2 research programme

Arbeitsqualität und wirtschaftlicher Erfolg: Längsschnittstudie in deutschen Betrieben ; erster Zwischenbericht

Instrumente des Personalmanagements prägen in wesentlichen Bereichen die Qualität der Arbeit in Unternehmen und haben somit einen zentralen Einfluss auf die Motivation, die Bindung, die Effizienz und letztendlich auf die Produktivität der Mitarbeiterinnen und Mitarbeiter. Aus diesem Grund sind die Wirksamkeit von Instrumenten des Personalmanagements und deren Auswirkungen auf die Arbeitsqualität zunehmend in den Fokus von Wissenschaft, Wirtschaft und Öffentlichkeit gerückt. Während zahlreiche Unternehmensberatungen die Einführung vermeintlich wirksamer Instrumente des Personalmanagements bei Unternehmen anstoßen oder begleiten, arbeiten Wissenschaftler daran, die Verbreitung und die Wirksamkeit dieser Instrumente unter Berücksichtigung der Heterogenität der Unternehmen zu analysieren

Non-invasive measurement of steroids in fish-holding water 1327

Summary Fish behaviourists are increasingly turning to non-invasive measurement of steroid hormones in holding water, as opposed to blood plasma. When some of us met at a workshop in Faro, Portugal, in September, 2007, we realised that there were still many issues concerning the application of this procedure that needed resolution, including: Why do we measure release rates rather than just concentrations of steroids in the water? How does one interpret steroid release rates when dealing with fish of different sizes? What are the merits of measuring conjugated as well as free steroids in water? In the 'static' sampling procedure, where fish are placed in a separate container for a short period of time, does this affect steroid releaseand, if so, how can it be minimised? After exposing a fish to a behavioural stimulus, when is the optimal time to sample? What is the minimum amount of validation when applying the procedure to a new species? The purpose of this review is to attempt to answer these questions and, in doing so, to emphasize that application of the non-invasive procedure requires more planning and validation than conventional plasma sampling. However, we consider that the rewards justify the extra effort

HEPPA-II model-measurement intercomparison project : EPP indirect effects during the dynamically perturbed NH winter 2008-2009

We compare simulations from three high-top (with upper lid above 120 km) and five medium-top (with upper lid around 80 km) atmospheric models with observations of odd nitrogen (NOx D NO+NO2), temperature, and carbon monoxide from seven satellite instruments (ACE-FTS on SciSat, GOMOS, MIPAS, and SCIAMACHY on Envisat, MLS on Aura, SABER on TIMED, and SMR on Odin) during the Northern Hemisphere (NH) polar winter 2008/2009. The models included in the comparison are the 3-D chemistry transport model 3dCTM, the ECHAM5/MESSy Atmospheric Chemistry (EMAC) model, FinROSE, the Hamburg Model of the Neutral and Ionized Atmosphere (HAMMO-NIA), the Karlsruhe Simulation Model of the Middle Atmosphere (KASIMA), the modelling tools for SOlar Climate Ozone Links studies (SOCOL and CAO-SOCOL), and the Whole Atmosphere Community Climate Model (WACCM4). The comparison focuses on the energetic particle precipitation (EPP) indirect effect, that is, the polar winter descent of NOx largely produced by EPP in the mesosphere and lower thermosphere. A particular emphasis is given to the impact of the sudden stratospheric warming (SSW) in January 2009 and the subsequent elevated stratopause (ES) event associated with enhanced descent of mesospheric air. The chemistry climate model simulations have been nudged toward reanalysis data in the troposphere and stratosphere while being unconstrained above. An odd nitrogen upper boundary condition obtained from MIPAS observations has further been applied to medium-top models. Most models provide a good representation of the mesospheric tracer descent in general, and the EPP indirect effect in particular, during the unperturbed (pre-SSW) period of the NH winter 2008/2009. The observed NOx descent into the lower mesosphere and stratosphere is generally reproduced within 20 %. Larger discrepancies of a few model simulations could be traced back either to the impact of the models' gravity wave drag scheme on the polar wintertime meridional circulation or to a combination of prescribed NOx mixing ratio at the uppermost model layer and low vertical resolution. In March-April, after the ES event, however, modelled mesospheric and stratospheric NOx distributions deviate significantly from the observations. The too-fast and early downward propagation of the NO x tongue, encountered in most simulations, coincides with a temperature high bias in the lower mesosphere (0.2-0.05 hPa), likely caused by an overestimation of descent velocities. In contrast, upper-mesospheric temperatures (at 0.05-0.001 hPa) are generally underestimated by the high-top models after the onset of the ES event, being indicative for too-slow descent and hence too-low NOx fluxes. As a consequence, the magnitude of the simulated NOx tongue is generally underestimated by these models. Descending NOx amounts simulated with mediumtop models are on average closer to the observations but show a large spread of up to several hundred percent. This is primarily attributed to the different vertical model domains in which the NOx upper boundary condition is applied. In general, the intercomparison demonstrates the ability of state-of- the-art atmospheric models to reproduce the EPP indirect effect in dynamically and geomagnetically quiescent NH winter conditions. The encountered differences between observed and simulated NOx, CO, and temperature distributions during the perturbed phase of the 2009 NH winter, however, emphasize the need for model improvements in the dynamical representation of elevated stratopause events in order to allow for a better description of the EPP indirect effect under these particular conditions.Peer reviewe

Fronto-striatal alterations correlate with apathy severity in behavioral variant frontotemporal dementia

Structural and functional changes in cortical and subcortical regions have been reported in behavioral variant frontotemporal dementia (bvFTD), however, a multimodal approach may provide deeper insights into the neural correlates of neuropsychiatric symptoms. In this multicenter study, we measured cortical thickness (CTh) and subcortical volumes to identify structural abnormalities in 37 bvFTD patients, and 37 age- and sex-matched healthy controls. For seed regions with significant structural changes, whole-brain functional connectivity (FC) was examined in a sub-cohort of N = 22 bvFTD and N = 22 matched control subjects to detect complementary alterations in brain network organization. To explore the functional significance of the observed structural and functional deviations, correlations with clinical and neuropsychological outcomes were tested where available. Significantly decreased CTh was observed in the bvFTD group in caudal middle frontal gyrus, left pars opercularis, bilateral superior frontal and bilateral middle temporal gyrus along with subcortical volume reductions in bilateral basal ganglia, thalamus, hippocampus, and amygdala. Resting-state functional magnetic resonance imaging showed decreased FC in bvFTD between: dorsal striatum and left caudal middle frontal gyrus;putamen and fronto-parietal regions;pallidum and cerebellum. Conversely, bvFTD showed increased FC between: left middle temporal gyrus and paracingulate gyrus;caudate nucleus and insula;amygdala and parahippocampal gyrus. Additionally, cortical thickness in caudal, lateral and superior frontal regions as well as caudate nucleus volume correlated negatively with apathy severity scores of the Neuropsychiatry Inventory Questionnaire. In conclusion, multimodal structural and functional imaging indicates that fronto-striatal regions have a considerable influence on the severity of apathy in bvFTD

HEPPA-II model–measurement intercomparison project: EPP indirect effects during the dynamically perturbed NH winter 2008-2009

We compare simulations from three high-top (with upper lid above 120 km) and five medium-top (with upper lid around 80 km) atmospheric models with observations of odd nitrogen (NOx  =  NO + NO2), temperature, and carbon monoxide from seven satellite instruments (ACE-FTS on SciSat, GOMOS, MIPAS, and SCIAMACHY on Envisat, MLS on Aura, SABER on TIMED, and SMR on Odin) during the Northern Hemisphere (NH) polar winter 2008/2009. The models included in the comparison are the 3-D chemistry transport model 3dCTM, the ECHAM5/MESSy Atmospheric Chemistry (EMAC) model, FinROSE, the Hamburg Model of the Neutral and Ionized Atmosphere (HAMMONIA), the Karlsruhe Simulation Model of the Middle Atmosphere (KASIMA), the modelling tools for SOlar Climate Ozone Links studies (SOCOL and CAO-SOCOL), and the Whole Atmosphere Community Climate Model (WACCM4). The comparison focuses on the energetic particle precipitation (EPP) indirect effect, that is, the polar winter descent of NOx largely produced by EPP in the mesosphere and lower thermosphere. A particular emphasis is given to the impact of the sudden stratospheric warming (SSW) in January 2009 and the subsequent elevated stratopause (ES) event associated with enhanced descent of mesospheric air. The chemistry climate model simulations have been nudged toward reanalysis data in the troposphere and stratosphere while being unconstrained above. An odd nitrogen upper boundary condition obtained from MIPAS observations has further been applied to medium-top models. Most models provide a good representation of the mesospheric tracer descent in general, and the EPP indirect effect in particular, during the unperturbed (pre-SSW) period of the NH winter 2008/2009. The observed NOx descent into the lower mesosphere and stratosphere is generally reproduced within 20 %. Larger discrepancies of a few model simulations could be traced back either to the impact of the models\u27 gravity wave drag scheme on the polar wintertime meridional circulation or to a combination of prescribed NOx mixing ratio at the uppermost model layer and low vertical resolution. In March–April, after the ES event, however, modelled mesospheric and stratospheric NOx distributions deviate significantly from the observations. The too-fast and early downward propagation of the NOx tongue, encountered in most simulations, coincides with a temperature high bias in the lower mesosphere (0.2–0.05 hPa), likely caused by an overestimation of descent velocities. In contrast, upper-mesospheric temperatures (at 0.05–0.001 hPa) are generally underestimated by the high-top models after the onset of the ES event, being indicative for too-slow descent and hence too-low NOx fluxes. As a consequence, the magnitude of the simulated NOx tongue is generally underestimated by these models. Descending NOx amounts simulated with medium-top models are on average closer to the observations but show a large spread of up to several hundred percent. This is primarily attributed to the different vertical model domains in which the NOx upper boundary condition is applied. In general, the intercomparison demonstrates the ability of state-of-the-art atmospheric models to reproduce the EPP indirect effect in dynamically and geomagnetically quiescent NH winter conditions. The encountered differences between observed and simulated NOx, CO, and temperature distributions during the perturbed phase of the 2009 NH winter, however, emphasize the need for model improvements in the dynamical representation of elevated stratopause events in order to allow for a better description of the EPP indirect effect under these particular conditions