@misc{MorrisSaltRailaetal.2012, author = {Morris, Penelope J. and Salt, Carina and Raila, Jens and Brenten, Thomas and Kohn, Barbara and Schweigert, Florian J. and Zentek, J{\"u}rgen}, title = {Safety evaluation of vitamin A in growing dogs}, series = {Potsprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Potsprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {686}, doi = {10.25932/publishup-41492}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-414929}, pages = {10}, year = {2012}, abstract = {The safe upper limit for inclusion of vitamin A in complete diets for growing dogs is uncertain, with the result that current recommendations range from 5.24 to 104.80 mu mol retinol (5000 to 100 000 IU vitamin A)/4184 kJ (1000 kcal) metabolisable energy (ME). The aim of the present study was to determine the effect of feeding four concentrations of vitamin A to puppies from weaning until 1 year of age. A total of forty-nine puppies, of two breeds, Labrador Retriever and Miniature Schnauzer, were randomly assigned to one of four treatment groups. Following weaning at 8 weeks of age, puppies were fed a complete food supplemented with retinyl acetate diluted in vegetable oil and fed at 1ml oil/100 g diet to achieve an intake of 5.24, 13.10, 78.60 and 104.80 mu mol retinol (5000, 12 500, 75 000 and 100 000 IU vitamin A)/4184 kJ (1000 kcal) ME. Fasted blood and urine samples were collected at 8, 10, 12, 14, 16, 20, 26, 36 and 52 weeks of age and analysed for markers of vitamin A metabolism and markers of safety including haematological and biochemical variables, bone-specific alkaline phosphatase, cross-linked carboxyterminal telopeptides of type I collagen and dual-energy X-ray absorptiometry. Clinical examinations were conducted every 4 weeks. Data were analysed by means of a mixed model analysis with Bonferroni corrections for multiple endpoints. There was no effect of vitamin A concentration on any of the parameters, with the exception of total serum retinyl esters, and no effect of dose on the number, type and duration of adverse events. We therefore propose that 104.80 mu mol retinol (100 000 IU vitamin A)/4184 kJ (1000 kcal) is a suitable safe upper limit for use in the formulation of diets designed for puppy growth.}, language = {en} } @misc{CaliendoHogenacker2012, author = {Caliendo, Marco and Hogenacker, Jens}, title = {The German labor market after the Great Recession}, series = {Postprints der Universit{\"a}t Potsdam : Wirtschafts- und Sozialwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Wirtschafts- und Sozialwissenschaftliche Reihe}, number = {129}, issn = {1867-5808}, doi = {10.25932/publishup-43519}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-435195}, pages = {26}, year = {2012}, abstract = {The reaction of the German labor market to the Great Recession 2008/09 was relatively mild - especially compared to other countries. The reason lies not only in the specific type of the recession - which was favorable for the German economy structure - but also in a series of labor market reforms initiated between 2002 and 2005 altering, inter alia, labor supply incentives. However, irrespective of the mild response to the Great Recession, there are a number of substantial future challenges the German labor market will soon have to face. Female labor supply still lies well below that of other countries and a massive demographic change over the next 50 years will have substantial effects on labor supply as well as the pension system. In addition, due to a skill-biased technological change over the next decades, firms will face problems of finding employees with adequate skills. The aim of this paper is threefold. First, we outline why the German labor market reacted in such a mild fashion, describe current economic trends of the labor market in light of general trends in the European Union, and reveal some of the main associated challenges. Thereafter, the paper analyzes recent reforms of the main institutional settings of the labor market which influence labor supply. Finally, based on the status quo of these institutional settings, the paper gives a brief overview of strategies to combat adequately the challenges in terms of labor supply and to ensure economic growth in the future.}, language = {en} } @misc{KleessenNikoloski2012, author = {Kleessen, Sabrina and Nikoloski, Zoran}, title = {Dynamic regulatory on/off minimization for biological systems under internal temporal perturbations}, series = {Postprints der Universit{\"a}t Potsdam : Mathematisch Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch Naturwissenschaftliche Reihe}, number = {852}, issn = {1866-8372}, doi = {10.25932/publishup-43112}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-431128}, pages = {15}, year = {2012}, abstract = {Background: Flux balance analysis (FBA) together with its extension, dynamic FBA, have proven instrumental for analyzing the robustness and dynamics of metabolic networks by employing only the stoichiometry of the included reactions coupled with adequately chosen objective function. In addition, under the assumption of minimization of metabolic adjustment, dynamic FBA has recently been employed to analyze the transition between metabolic states. Results: Here, we propose a suite of novel methods for analyzing the dynamics of (internally perturbed) metabolic networks and for quantifying their robustness with limited knowledge of kinetic parameters. Following the biochemically meaningful premise that metabolite concentrations exhibit smooth temporal changes, the proposed methods rely on minimizing the significant fluctuations of metabolic profiles to predict the time-resolved metabolic state, characterized by both fluxes and concentrations. By conducting a comparative analysis with a kinetic model of the Calvin-Benson cycle and a model of plant carbohydrate metabolism, we demonstrate that the principle of regulatory on/off minimization coupled with dynamic FBA can accurately predict the changes in metabolic states. Conclusions: Our methods outperform the existing dynamic FBA-based modeling alternatives, and could help in revealing the mechanisms for maintaining robustness of dynamic processes in metabolic networks over time.}, language = {en} } @misc{KrippendorffOyarzunHuisinga2012, author = {Krippendorff, Ben-Fillippo and Oyarz{\´u}n, Diego A. and Huisinga, Wilhelm}, title = {Predicting the F(ab)-mediated effect of monoclonal antibodies in vivo by combining cell-level kinetic and pharmacokinetic modelling}, series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {958}, issn = {1866-8372}, doi = {10.25932/publishup-43105}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-431051}, pages = {125 -- 139}, year = {2012}, abstract = {Cell-level kinetic models for therapeutically relevant processes increasingly benefit the early stages of drug development. Later stages of the drug development processes, however, rely on pharmacokinetic compartment models while cell-level dynamics are typically neglected. We here present a systematic approach to integrate cell-level kinetic models and pharmacokinetic compartment models. Incorporating target dynamics into pharmacokinetic models is especially useful for the development of therapeutic antibodies because their effect and pharmacokinetics are inherently interdependent. The approach is illustrated by analysing the F(ab)-mediated inhibitory effect of therapeutic antibodies targeting the epidermal growth factor receptor. We build a multi-level model for anti-EGFR antibodies by combining a systems biology model with in vitro determined parameters and a pharmacokinetic model based on in vivo pharmacokinetic data. Using this model, we investigated in silico the impact of biochemical properties of anti-EGFR antibodies on their F(ab)-mediated inhibitory effect. The multi-level model suggests that the F(ab)-mediated inhibitory effect saturates with increasing drug-receptor affinity, thereby limiting the impact of increasing antibody affinity on improving the effect. This indicates that observed differences in the therapeutic effects of high affinity antibodies in the market and in clinical development may result mainly from Fc-mediated indirect mechanisms such as antibody-dependent cell cytotoxicity.}, language = {en} } @misc{DallmeyerClaussenWangetal.2012, author = {Dallmeyer, Anne and Claussen, Martin and Wang, Yongbo and Herzschuh, Ulrike}, title = {Spatial variability of Holocene changes in the annual precipitation pattern}, series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {905}, issn = {1866-8372}, doi = {10.25932/publishup-43277}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-432771}, pages = {20}, year = {2012}, abstract = {This study provides a detailed analysis of the mid-Holocene to present-day precipitation change in the Asian monsoon region. We compare for the first time results of high resolution climate model simulations with a standardised set of mid-Holocene moisture reconstructions. Changes in the simulated summer monsoon characteristics (onset, withdrawal, length and associated rainfall) and the mechanisms causing the Holocene precipitation changes are investigated. According to the model, most parts of the Indian subcontinent received more precipitation (up to 5 mm/day) at mid-Holocene than at present-day. This is related to a stronger Indian summer monsoon accompanied by an intensified vertically integrated moisture flux convergence. The East Asian monsoon region exhibits local inhomogeneities in the simulated annual precipitation signal. The sign of this signal depends on the balance of decreased pre-monsoon and increased monsoon precipitation at mid-Holocene compared to present-day. Hence, rainfall changes in the East Asian monsoon domain are not solely associated with modifications in the summer monsoon circulation but also depend on changes in the mid-latitudinal westerly wind system that dominates the circulation during the pre-monsoon season. The proxy-based climate reconstructions confirm the regional dissimilarities in the annual precipitation signal and agree well with the model results. Our results highlight the importance of including the pre-monsoon season in climate studies of the Asian monsoon system and point out the complex response of this system to the Holocene insolation forcing. The comparison with a coarse climate model simulation reveals that this complex response can only be resolved in high resolution simulations.}, language = {en} } @misc{AdamBovend'EerdtDoorenetal.2012, author = {Adam, Jos J. and Bovend'Eerdt, Thamar J. H. and Dooren, Fleur E. P. van and Fischer, Martin H. and Pratt, Jay}, title = {The closer the better}, series = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, number = {607}, issn = {1866-8364}, doi = {10.25932/publishup-43296}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-432963}, pages = {1533 -- 1538}, year = {2012}, abstract = {A growing literature has suggested that processing of visual information presented near the hands is facilitated. In this study, we investigated whether the near-hands superiority effect also occurs with the hands moving. In two experiments, participants performed a cyclical bimanual movement task requiring concurrent visual identification of briefly presented letters. For both the static and dynamic hand conditions, the results showed improved letter recognition performance with the hands closer to the stimuli. The finding that the encoding advantage for near-hand stimuli also occurred with the hands moving suggests that the effect is regulated in real time, in accordance with the concept of a bimodal neural system that dynamically updates hand position in external space.}, language = {en} } @misc{WojcinskiDupontSchmidtetal.2012, author = {Wojcinski, Sebastian and Dupont, Jennifer and Schmidt, Werner and Cassel, Michael and Hillemanns, Peter}, title = {Real-time ultrasound elastography in 180 axillary lymph nodes}, series = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, number = {626}, issn = {1866-8364}, doi = {10.25932/publishup-43158}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-431584}, pages = {12}, year = {2012}, abstract = {Background To determine the general appearance of normal axillary lymph nodes (LNs) in real-time tissue sonoelastography and to explore the method′s potential value in the prediction of LN metastases. Methods Axillary LNs in healthy probands (n=165) and metastatic LNs in breast cancer patients (n=15) were examined with palpation, B-mode ultrasound, Doppler and sonoelastography (assessment of the elasticity of the cortex and the medulla). The elasticity distributions were compared and sensitivity (SE) and specificity (SP) were calculated. In an exploratory analysis, positive and negative predictive values (PPV, NPV) were calculated based upon the estimated prevalence of LN metastases in different risk groups. Results In the elastogram, the LN cortex was significantly harder than the medulla in both healthy (p=0.004) and metastatic LNs (p=0.005). Comparing healthy and metastatic LNs, there was no difference in the elasticity distribution of the medulla (p=0.281), but we found a significantly harder cortex in metastatic LNs (p=0.006). The SE of clinical examination, B-mode ultrasound, Doppler ultrasound and sonoelastography was revealed to be 13.3\%, 40.0\%, 14.3\% and 60.0\%, respectively, and SP was 88.4\%, 96.8\%, 95.6\% and 79.6\%, respectively. The highest SE was achieved by the disjunctive combination of B-mode and elastographic features (cortex >3mm in B-mode or blue cortex in the elastogram, SE=73.3\%). The highest SP was achieved by the conjunctive combination of B-mode ultrasound and elastography (cortex >3mm in B-mode and blue cortex in the elastogram, SP=99.3\%). Conclusions Sonoelastography is a feasible method to visualize the elasticity distribution of LNs. Moreover, sonoelastography is capable of detecting elasticity differences between the cortex and medulla, and between metastatic and healthy LNs. Therefore, sonoelastography yields additional information about axillary LN status and can improve the PPV, although this method is still experimental.}, language = {en} } @misc{EbertLamprechtSteffenetal.2012, author = {Ebert, Birgitta E. and Lamprecht, Anna-Lena and Steffen, Bernhard and Blank, Lars M.}, title = {Flux-P}, series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {1054}, issn = {1866-8372}, doi = {10.25932/publishup-47669}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-476696}, pages = {872 -- 890}, year = {2012}, abstract = {Quantitative knowledge of intracellular fluxes in metabolic networks is invaluable for inferring metabolic system behavior and the design principles of biological systems. However, intracellular reaction rates can not often be calculated directly but have to be estimated; for instance, via 13C-based metabolic flux analysis, a model-based interpretation of stable carbon isotope patterns in intermediates of metabolism. Existing software such as FiatFlux, OpenFLUX or 13CFLUX supports experts in this complex analysis, but requires several steps that have to be carried out manually, hence restricting the use of this software for data interpretation to a rather small number of experiments. In this paper, we present Flux-P as an approach to automate and standardize 13C-based metabolic flux analysis, using the Bio-jETI workflow framework. Exemplarily based on the FiatFlux software, it demonstrates how services can be created that carry out the different analysis steps autonomously and how these can subsequently be assembled into software workflows that perform automated, high-throughput intracellular flux analysis of high quality and reproducibility. Besides significant acceleration and standardization of the data analysis, the agile workflow-based realization supports flexible changes of the analysis workflows on the user level, making it easy to perform custom analyses.}, language = {en} } @misc{JingAmbroseKnoxetal.2012, author = {Jing, Runchun and Ambrose, Michael A. and Knox, Maggie R. and Smykal, Petr and Hybl, Miroslav and Ramos, {\´A}. and Caminero, Constantino and Burstin, Judith and Duc, Gerard and van Soest, L. J. M. and Święcicki, W. K. and Pereira, M. Graca and Vishnyakova, Margarita and Davenport, Guy F. and Flavell, Andrew J. and Ellis, T. H. Noel}, title = {Genetic diversity in European Pisum germplasm collections}, series = {Postprints der Universit{\"a}t Potsdam : Mathematisch Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch Naturwissenschaftliche Reihe}, number = {871}, issn = {1866-8372}, doi = {10.25932/publishup-43474}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-434743}, pages = {367 -- 380}, year = {2012}, abstract = {The distinctness of, and overlap between, pea genotypes held in several Pisum germplasm collections has been used to determine their relatedness and to test previous ideas about the genetic diversity of Pisum. Our characterisation of genetic diversity among 4,538 Pisum accessions held in 7 European Genebanks has identified sources of novel genetic variation, and both reinforces and refines previous interpretations of the overall structure of genetic diversity in Pisum. Molecular marker analysis was based upon the presence/absence of polymorphism of retrotransposon insertions scored by a high-throughput microarray and SSAP approaches. We conclude that the diversity of Pisum constitutes a broad continuum, with graded differentiation into sub-populations which display various degrees of distinctness. The most distinct genetic groups correspond to the named taxa while the cultivars and landraces of Pisum sativum can be divided into two broad types, one of which is strongly enriched for modern cultivars. The addition of germplasm sets from six European Genebanks, chosen to represent high diversity, to a single collection previously studied with these markers resulted in modest additions to the overall diversity observed, suggesting that the great majority of the total genetic diversity collected for the Pisum genus has now been described. Two interesting sources of novel genetic variation have been identified. Finally, we have proposed reference sets of core accessions with a range of sample sizes to represent Pisum diversity for the future study and exploitation by researchers and breeders.}, language = {en} } @misc{ChengVicente2012, author = {Cheng, Lisa Lai-Shen and Vicente, Luis}, title = {Verb doubling in Mandarin Chinese}, series = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, number = {629}, issn = {1866-8364}, doi = {10.25932/publishup-43688}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-436880}, pages = {1 -- 37}, year = {2012}, abstract = {This article examines two so-far-understudied verb doubling constructions in Mandarin Chinese, viz., verb doubling clefts and verb doubling lian…dou. We show that these constructions have the same internal syntax as regular clefts and lian…dou sentences, the doubling effect being epiphenomenal; therefore, we classify them as subtypes of the general cleft and lian…dou constructions, respectively, rather than as independent constructions. Additionally, we also show that, as in many other languages with comparable constructions, the two instances of the verb are part of a single movement chain, which has the peculiarity of allowing Spell-Out of more than one link.}, language = {en} }