TY - GEN A1 - Morris, Penelope J. A1 - Salt, Carina A1 - Raila, Jens A1 - Brenten, Thomas A1 - Kohn, Barbara A1 - Schweigert, Florian J. A1 - Zentek, Jürgen T1 - Safety evaluation of vitamin A in growing dogs T2 - Potsprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - 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. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 686 KW - puppies KW - dogs KW - Retinol KW - Retinyl esters KW - vitamin A Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-414929 IS - 686 ER - TY - GEN A1 - Caliendo, Marco A1 - Hogenacker, Jens T1 - The German labor market after the Great Recession BT - successful reforms and future challenges T2 - Postprints der Universität Potsdam : Wirtschafts- und Sozialwissenschaftliche Reihe N2 - 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. T3 - Zweitveröffentlichungen der Universität Potsdam : Wirtschafts- und Sozialwissenschaftliche Reihe - 129 KW - unemployment KW - labor force participation KW - Labor supply KW - benefit systems KW - public policy Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-435195 SN - 1867-5808 IS - 129 ER - TY - GEN A1 - Krippendorff, Ben-Fillippo A1 - Oyarzún, Diego A. A1 - Huisinga, Wilhelm T1 - Predicting the F(ab)-mediated effect of monoclonal antibodies in vivo by combining cell-level kinetic and pharmacokinetic modelling T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - 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. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 958 KW - cell-level kinetics KW - pharmacokinetic models KW - therapeutic proteins KW - EGFR Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-431051 SN - 1866-8372 IS - 958 SP - 125 EP - 139 ER - TY - GEN A1 - Adam, Jos J. A1 - Bovend'Eerdt, Thamar J. H. A1 - Dooren, Fleur E. P. van A1 - Fischer, Martin H. A1 - Pratt, Jay T1 - The closer the better BT - hand proximity dynamically affects letter recognition accuracy T2 - Postprints der Universität Potsdam : Humanwissenschaftliche Reihe N2 - 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. T3 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe - 607 KW - perception and action Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-432963 SN - 1866-8364 IS - 607 SP - 1533 EP - 1538 ER - TY - GEN A1 - Wojcinski, Sebastian A1 - Dupont, Jennifer A1 - Schmidt, Werner A1 - Cassel, Michael A1 - Hillemanns, Peter T1 - Real-time ultrasound elastography in 180 axillary lymph nodes BT - elasticity distribution in healthy lymph nodes and prediction of breast cancer metastases T2 - Postprints der Universität Potsdam : Humanwissenschaftliche Reihe N2 - 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. T3 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe - 626 KW - breast ultrasound KW - axillary lymph nodes KW - sonoelastography KW - real-time tissue elastography KW - cancer detection KW - elasticity imaging KW - HI-RTE KW - lymph node metastases Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-431584 SN - 1866-8364 IS - 626 ER - TY - GEN A1 - Ebert, Birgitta E. A1 - Lamprecht, Anna-Lena A1 - Steffen, Bernhard A1 - Blank, Lars M. T1 - Flux-P BT - automating metabolic flux analysis T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - 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. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1054 KW - 13C metabolic flux analysis KW - MFA KW - high-throughput analysis KW - scientific workflows KW - workflow management KW - Bio-jETI Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-476696 SN - 1866-8372 IS - 1054 SP - 872 EP - 890 ER - TY - GEN A1 - Jing, Runchun A1 - Ambrose, Michael A. A1 - Knox, Maggie R. A1 - Smykal, Petr A1 - Hybl, Miroslav A1 - Ramos, Á. A1 - Caminero, Constantino A1 - Burstin, Judith A1 - Duc, Gerard A1 - van Soest, L. J. M. A1 - Święcicki, W. K. A1 - Pereira, M. Graca A1 - Vishnyakova, Margarita A1 - Davenport, Guy F. A1 - Flavell, Andrew J. A1 - Ellis, T. H. Noel T1 - Genetic diversity in European Pisum germplasm collections T2 - Postprints der Universität Potsdam : Mathematisch Naturwissenschaftliche Reihe N2 - 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. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 871 KW - germplasm collection KW - insertion polymorphism KW - retrotransposon insertion KW - broad continuum KW - SSAP marker Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-434743 SN - 1866-8372 IS - 871 SP - 367 EP - 380 ER - TY - GEN A1 - Cheng, Lisa Lai-Shen A1 - Vicente, Luis T1 - Verb doubling in Mandarin Chinese T2 - Postprints der Universität Potsdam : Humanwissenschaftliche Reihe N2 - 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. T3 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe - 629 KW - Mandarin Chinese KW - verb doubling KW - verb movement KW - cleft KW - lian…dou Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-436880 SN - 1866-8364 IS - 629 SP - 1 EP - 37 ER - TY - GEN A1 - Hische, Manuela A1 - Larhlimi, Abdelhalim A1 - Schwarz, Franziska A1 - Fischer-Rosinský, Antje A1 - Bobbert, Thomas A1 - Assmann, Anke A1 - Catchpole, Gareth S. A1 - Pfeiffer, Andreas F. H. A1 - Willmitzer, Lothar A1 - Selbig, Joachim A1 - Spranger, Joachim T1 - A distinct metabolic signature predictsdevelopment of fasting plasma glucose T2 - Postprints der Universität Potsdam : Mathematisch Naturwissenschaftliche Reihe N2 - Background High blood glucose and diabetes are amongst the conditions causing the greatest losses in years of healthy life worldwide. Therefore, numerous studies aim to identify reliable risk markers for development of impaired glucose metabolism and type 2 diabetes. However, the molecular basis of impaired glucose metabolism is so far insufficiently understood. The development of so called 'omics' approaches in the recent years promises to identify molecular markers and to further understand the molecular basis of impaired glucose metabolism and type 2 diabetes. Although univariate statistical approaches are often applied, we demonstrate here that the application of multivariate statistical approaches is highly recommended to fully capture the complexity of data gained using high-throughput methods. Methods We took blood plasma samples from 172 subjects who participated in the prospective Metabolic Syndrome Berlin Potsdam follow-up study (MESY-BEPO Follow-up). We analysed these samples using Gas Chromatography coupled with Mass Spectrometry (GC-MS), and measured 286 metabolites. Furthermore, fasting glucose levels were measured using standard methods at baseline, and after an average of six years. We did correlation analysis and built linear regression models as well as Random Forest regression models to identify metabolites that predict the development of fasting glucose in our cohort. Results We found a metabolic pattern consisting of nine metabolites that predicted fasting glucose development with an accuracy of 0.47 in tenfold cross-validation using Random Forest regression. We also showed that adding established risk markers did not improve the model accuracy. However, external validation is eventually desirable. Although not all metabolites belonging to the final pattern are identified yet, the pattern directs attention to amino acid metabolism, energy metabolism and redox homeostasis. Conclusions We demonstrate that metabolites identified using a high-throughput method (GC-MS) perform well in predicting the development of fasting plasma glucose over several years. Notably, not single, but a complex pattern of metabolites propels the prediction and therefore reflects the complexity of the underlying molecular mechanisms. This result could only be captured by application of multivariate statistical approaches. Therefore, we highly recommend the usage of statistical methods that seize the complexity of the information given by high-throughput methods. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 850 KW - prediction KW - fasting glucose KW - type 2 diabetes KW - metabolomics KW - plasma KW - random forest KW - metabolite KW - regression KW - biomarker Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-427400 SN - 1866-8372 IS - 850 ER - TY - GEN A1 - Lin, Chiao-I A1 - Khajooei, Mina A1 - Engel, Tilman A1 - Nair, Alexandra A1 - Heikkila, Mika A1 - Kaplick, Hannes A1 - Mayer, Frank T1 - The effect of chronic ankle instability on muscle activations in lower extremities T2 - Postprints der Universität Potsdam : Humanwissenschaftliche Reihe N2 - Background/Purpose Muscular reflex responses of the lower extremities to sudden gait disturbances are related to postural stability and injury risk. Chronic ankle instability (CAI) has shown to affect activities related to the distal leg muscles while walking. Its effects on proximal muscle activities of the leg, both for the injured- (IN) and uninjured-side (NON), remain unclear. Therefore, the aim was to compare the difference of the motor control strategy in ipsilateral and contralateral proximal joints while unperturbed walking and perturbed walking between individuals with CAI and matched controls. Materials and methods In a cross-sectional study, 13 participants with unilateral CAI and 13 controls (CON) walked on a split-belt treadmill with and without random left- and right-sided perturbations. EMG amplitudes of muscles at lower extremities were analyzed 200 ms after perturbations, 200 ms before, and 100 ms after (Post100) heel contact while walking. Onset latencies were analyzed at heel contacts and after perturbations. Statistical significance was set at alpha≤0.05 and 95% confidence intervals were applied to determine group differences. Cohen’s d effect sizes were calculated to evaluate the extent of differences. Results Participants with CAI showed increased EMG amplitudes for NON-rectus abdominus at Post100 and shorter latencies for IN-gluteus maximus after heel contact compared to CON (p<0.05). Overall, leg muscles (rectus femoris, biceps femoris, and gluteus medius) activated earlier and less bilaterally (d = 0.30–0.88) and trunk muscles (bilateral rectus abdominus and NON-erector spinae) activated earlier and more for the CAI group than CON group (d = 0.33–1.09). Conclusion Unilateral CAI alters the pattern of the motor control strategy around proximal joints bilaterally. Neuromuscular training for the muscles, which alters motor control strategy because of CAI, could be taken into consideration when planning rehabilitation for CAI. T3 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe - 712 KW - Electromyography KW - Hip KW - Skeletal joints KW - Knees KW - Legs KW - Musculoskeletal injury KW - Walking KW - Ankles Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-515632 SN - 1866-8364 ER -