@article{FerreiraGamazonAlEjehetal.2019, author = {Ferreira, Manuel A. and Gamazon, Eric R. and Al-Ejeh, Fares and Aittom{\"a}ki, Kristiina and Andrulis, Irene L. and Anton-Culver, Hoda and Arason, Adalgeir and Arndt, Volker and Aronson, Kristan J. and Arun, Banu K. and Asseryanis, Ella and Azzollini, Jacopo and Balma{\~n}a, Judith and Barnes, Daniel R. and Barrowdale, Daniel and Beckmann, Matthias W. and Behrens, Sabine and Benitez, Javier and Bermisheva, Marina and Bialkowska, Katarzyna and Blomqvist, Carl and Bogdanova, Natalia V. and Bojesen, Stig E. and Bolla, Manjeet K. and Borg, Ake and Brauch, Hiltrud and Brenner, Hermann and Broeks, Annegien and Burwinkel, Barbara and Cald{\´e}s, Trinidad and Caligo, Maria A. and Campa, Daniele and Campbell, Ian and Canzian, Federico and Carter, Jonathan and Carter, Brian D. and Castelao, Jose E. and Chang-Claude, Jenny and Chanock, Stephen J. and Christiansen, Hans and Chung, Wendy K. and Claes, Kathleen B. M. and Clarke, Christine L. and Couch, Fergus J. and Cox, Angela and Cross, Simon S. and Czene, Kamila and Daly, Mary B. and de la Hoya, Miguel and Dennis, Joe and Devilee, Peter and Diez, Orland and D{\"o}rk, Thilo and Dunning, Alison M. and Dwek, Miriam and Eccles, Diana M. and Ejlertsen, Bent and Ellberg, Carolina and Engel, Christoph and Eriksson, Mikael and Fasching, Peter A. and Fletcher, Olivia and Flyger, Henrik and Friedman, Eitan and Frost, Debra and Gabrielson, Marike and Gago-Dominguez, Manuela and Ganz, Patricia A. and Gapstur, Susan M. and Garber, Judy and Garc{\´i}a-Closas, Montserrat and Garc{\´i}a-S{\´a}enz, Jos{\´e} A. and Gaudet, Mia M. and Giles, Graham G. and Glendon, Gord and Godwin, Andrew K. and Goldberg, Mark S. and Goldgar, David E. and Gonz{\´a}lez-Neira, Anna and Greene, Mark H. and Gronwald, Jacek and Guen{\´e}l, Pascal and Haimann, Christopher A. and Hall, Per and Hamann, Ute and He, Wei and Heyworth, Jane and Hogervorst, Frans B. L. and Hollestelle, Antoinette and Hoover, Robert N. and Hopper, John L. and Hulick, Peter J. and Humphreys, Keith and Imyanitov, Evgeny N. and Isaacs, Claudine and Jakimovska, Milena and Jakubowska, Anna and James, Paul A. and Janavicius, Ramunas and Jankowitz, Rachel C. and John, Esther M. and Johnson, Nichola and Joseph, Vijai and Karlan, Beth Y. and Khusnutdinova, Elza and Kiiski, Johanna I. and Ko, Yon-Dschun and Jones, Michael E. and Konstantopoulou, Irene and Kristensen, Vessela N. and Laitman, Yael and Lambrechts, Diether and Lazaro, Conxi and Leslie, Goska and Lester, Jenny and Lesueur, Fabienne and Lindstr{\"o}m, Sara and Long, Jirong and Loud, Jennifer T. and Lubiński, Jan and Makalic, Enes and Mannermaa, Arto and Manoochehri, Mehdi and Margolin, Sara and Maurer, Tabea and Mavroudis, Dimitrios and McGuffog, Lesley and Meindl, Alfons and Menon, Usha and Michailidou, Kyriaki and Miller, Austin and Montagna, Marco and Moreno, Fernando and Moserle, Lidia and Mulligan, Anna Marie and Nathanson, Katherine L. and Neuhausen, Susan L. and Nevanlinna, Heli and Nevelsteen, Ines and Nielsen, Finn C. and Nikitina-Zake, Liene and Nussbaum, Robert L. and Offit, Kenneth and Olah, Edith and Olopade, Olufunmilayo I. and Olsson, H{\aa}kan and Osorio, Ana and Papp, Janos and Park-Simon, Tjoung-Won and Parsons, Michael T. and Pedersen, Inge Sokilde and Peixoto, Ana and Peterlongo, Paolo and Pharaoh, Paul D. P. and Plaseska-Karanfilska, Dijana and Poppe, Bruce and Presneau, Nadege and Radice, Paolo and Rantala, Johanna and Rennert, Gad and Risch, Harvey A. and Saloustros, Emmanouil and Sanden, Kristin and Sawyer, Elinor J. and Schmidt, Marjanka K. and Schmutzler, Rita K. and Sharma, Priyanka and Shu, Xiao-Ou and Simard, Jaques and Singer, Christian F. and Soucy, Penny and Southey, Melissa C. and Spinelli, John J. and Spurdle, Amanda B. and Stone, Jennifer and Swerdlow, Anthony J. and Tapper, William J. and Taylor, Jack A. and Teixeira, Manuel R. and Terry, Mary Beth and Teul{\´e}, Alex and Thomassen, Mads and Th{\"o}ne, Kathrin and Thull, Darcy L. and Tischkowitz, Marc and Toland, Amanda E. and Torres, Diana and Truong, Th{\´e}r{\`e}se and Tung, Nadine and Vachon, Celine M. and van Asperen, Christi J. and van den Ouweland, Ans M. W. and van Rensburg, Elizabeth J. and Vega, Ana and Viel, Alexandra and Wang, Qin and Wappenschmidt, Barbara and Weitzel, Jeffrey N. and Wendt, Camilla and Winqvist, Robert and Yang, Xiaohong R. and Yannoukakos, Drakoulis and Ziogas, Argyrios and Kraft, Peter and Antoniou, Antonis C. and Zheng, Wei and Easton, Douglas F. and Milne, Roger L. and Beesley, Jonathan and Chenevix-Trench, Georgia}, title = {Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer}, series = {Nature Communications}, volume = {10}, journal = {Nature Communications}, organization = {EMBRACE Collaborators, GC-HBOC Study Collaborators, GEMO Study Collaborators, ABCTB Investigators, HEBON Investigators, BCFR Investigators}, doi = {10.1038/s41467-018-08053-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228024}, year = {2019}, abstract = {Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.}, language = {en} } @article{HohenauerBerkingSchmidtetal.2013, author = {Hohenauer, Tobias and Berking, Carola and Schmidt, Andreas and Haferkamp, Sebastian and Senft, Daniela and Kammerbauer, Claudia and Fraschka, Sabine and Graf, Saskia Anna and Irmler, Martin and Beckers, Johannes and Flaig, Michael and Aigner, Achim and H{\"o}bel, Sabrina and Hoffmann, Franziska and Hermeking, Heiko and Rothenfusser, Simon and Endres, Stefan and Ruzicka, Thomas and Besch, Robert}, title = {The neural crest transcription factor Brn3a is expressed in melanoma and required for cell cycle progression and survival}, series = {EMBO Molecular Medicine}, volume = {5}, journal = {EMBO Molecular Medicine}, issn = {1757-4676}, doi = {10.1002/emmm.201201862}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-122193}, pages = {919-934}, year = {2013}, abstract = {Pigment cells and neuronal cells both are derived from the neural crest. Here, we describe the Pit-Oct-Unc (POU) domain transcription factor Brn3a, normally involved in neuronal development, to be frequently expressed in melanoma, but not in melanocytes and nevi. RNAi-mediated silencing of Brn3a strongly reduced the viability of melanoma cell lines and decreased tumour growth in vivo. In melanoma cell lines, inhibition of Brn3a caused DNA double-strand breaks as evidenced by Mre11/Rad50-containing nuclear foci. Activated DNA damage signalling caused stabilization of the tumour suppressor p53, which resulted in cell cycle arrest and apoptosis. When Brn3a was ectopically expressed in primary melanocytes and fibroblasts, anchorage-independent growth was increased. In tumourigenic melanocytes and fibroblasts, Brn3a accelerated tumour growth in vivo. Furthermore, Brn3a cooperated with proliferation pathways such as oncogenic BRAF, by reducing oncogene-induced senescence in non-malignant melanocytes. Together, these results identify Brn3a as a new factor in melanoma that is essential for melanoma cell survival and that promotes melanocytic transformation and tumourigenesis.}, language = {en} } @phdthesis{Schmidt2004, author = {Schmidt, Robert}, title = {The behavioral economics of foreign exchange markets - a psychological view on human expectation formation in foreign exchange markets}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-14921}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2004}, abstract = {The development of free floating exchange rates can hardly be explained by macroeconomic fundamentals as supposed by traditional economic theories. Therefore, prominent economists yet conclude that there exists an 'exchange rate disconnect puzzle' (see Obstfeld and Rogoff [2000]). The observable exchange rate trends are often attributed to an excessive speculative trading behavior of foreign exchange market participants. In this study we deal with psychological factors, which may be important for understanding the observable exchange rate movements. Thus, our study belongs to the new research field of behavioral economics, which considers the relevance of psychological factors in economic contexts. The main objective of behavioral economists is to develop a more realistic view of the actual human behavior in the context of economics. Therefore, behavioral economists often refer to the work of behavioral decision theorists, who introduced new concepts under the general heading of bounded rationality. Central to the concept of bounded rationality is the assumption that humans' actual behavior deviates from the ideal of economic rationality due to at least two reasons: first, decisions are usually based on an incomplete information basis (limited information) and, second, the information processing of human beings is limited by their computational capacities (limited cognitive resources). Due to these limitations people are forced to apply simplification mechanisms in information processing. Important simplification mechanisms, which play a decisive role in the process judgment and decision making, are simple heuristics. Simple heuristics can principally be characterized as simple rules of thumb, which allow quick and efficient decisions even under a high degree of uncertainty. In this study, our aim is to analyze the relevance of simple heuristics in the context of foreign exchange markets. In our view, the decision situation in foreign exchange markets can serve as a prime example for decision situations in which simple heuristics are especially relevant as the complexity of the decision situation is very high. The study is organized as follows. In Chapter II, we deal with the exchange rate disconnect puzzle. In particular, we discuss and check the main implications of the traditional economic approach for explaining exchange rate movements. The asset market theory of exchange rate determination implies that exchange rates are mainly driven by the development of macroeconomic fundamentals. Furthermore the asset market theory assumes that foreign exchange market participants form rational expectations concerning future exchange rate developments and that exchange rates are determined in efficient markets. Overall the empirical evidence suggests that the traditional approach for explaining exchange rate changes is at odds with the data. Chapter III addresses the existence of long and persistent trends in exchange rate time series. Overall, our empirical analysis reveals that exchange rates show a clear tendency to move in long and persistent trends. Furthermore, we discuss the relevance of speculation in foreign exchange markets. With regard to the impact of speculation, economic theory states that speculation can have either a stabilizing effect or a destabilizing effect on exchange rates. At the end of Chapter III, we examine the Keynesian view on the functioning of asset markets. In Chapter IV we explore the main insights from the new research field of behavioral economics. A main building block of behavioral economics is the concept of bounded rationality first introduced by Herbert Simon [1955]. In the centre of the concept of bounded rationality is a psychological analysis of the actual human judgment and decision behavior. In Chapter IV, we discuss the concept of bounded rationality in detail and illustrate important insights of behavioral decision theories. In particular, we deal with the relevance of simple heuristics in the context of foreign exchange markets. Chapter V provides experimental and empirical evidence for the suggested relevance of simple heuristics in foreign exchange markets. In the first experiment, we deal with the human expectation formation. We compare point forecasts of the EUR/USD exchange rate surveyed from professional analysts and experimentally generated point forecasts of students for a simulated exchange rate time series. The results show that the forecasting performance of both groups differs substantially. Afterwards we analyze the nature of expectation formation of both groups in detail to reveal similarities and differences, which allow us to draw reasonable explanations for the differences in the forecasting performances. In the second experiment, we analyze the expectation formation in an experimental foreign exchange market. This approach allows us to consider the relevance of expectation feedback as individuals' expectations directly influence the actual realization of the time series. Thus, Keynes' predictions on the importance of conventions in asset markets can be analyzed. Overall, both experiments reveal that the human beings tend to apply simple trend heuristics, when forming their expectations about future exchange rates. In the empirical part of Chapter V we deal with the usefulness of such simple trend heuristics in real world. Only if simple trend heuristics lead to profits in the specific environment of foreign exchange markets, their application can be recommended. Thus, we analyze the profitability of simple technical analysis tools in foreign exchange markets. Finally, Chapter VI provides concluding remarks.}, subject = {Devisenmarkt}, language = {en} } @article{JakubietzJakubietzMeffertetal.2017, author = {Jakubietz, Michael G. and Jakubietz, Rafael G. and Meffert, Rainer H. and Schmidt, Karsten and Zahn, Robert K.}, title = {Biomechanical properties of first dorsal extensor compartment regarding adequacy as a bone-ligament-bone graft}, series = {Plastic and Reconstructive Surgery Global Open}, volume = {5}, journal = {Plastic and Reconstructive Surgery Global Open}, number = {7}, doi = {10.1097/GOX.0000000000001397}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158851}, pages = {e1397}, year = {2017}, abstract = {Background: Bone-ligament-bone grafts for reconstruction of the scapholunate ligament are a valuable tool to prevent disease progression to carpal collapse. Locally available grafts do not require an additional donor site. The first extensor compartment was evaluated biomechanically regarding its possible use as an autograft. Methods: Twelve native fresh-frozen, human cadaver specimens were tested by applying axial tension in a Zwick Roell machine. Load to failure, transplant elongation, and bony avulsion were recorded. The load to failure was quantitated in newtons (N) and the displacement in length (millimeters). Parameters were set at distinct points as start of tension, 1 mm stretch and 1.5 mm dissociation, failure and complete tear, and were evaluated under magnified visual control. Although actual failure occurred at higher tension, functional failure was defined at a stretch of 1.5 mm. Results: Mean load at 1 mm elongation was 44.1 ± 28 N and at 1.5 mm elongation 57.5 ± 42 N. Failure occurred at 111 ± 83.1 N. No avulsion of the bony insertion was observed. Half the transplants failed in the central part of the ligament, while the rest failed near the insertion but not at the insertion itself. Analysis of tension strength displayed a wide range from 3.8 to 83.7 N/mm at a mean of 33.4 ± 28.4 N/mm. Conclusions: The biomechanical tensile properties of the first dorsal extensor compartment are similar to those of the dorsal part of the scapholunate ligament. A transplant with a larger bone stock and a longer ligament may display an advantage, as insertion is possible in the dorsal, easily accessible part of the carpal bones rather than in the ar{\^e}te-like region adjacent to the insertion of the scapholunate ligament. In this study, 1.5 mm lengthening of the bone-ligament-bone transplant was defined as clinical failure, as such elongation will cause severe gapping and is considered as failure of the transplant.}, language = {en} } @article{CoelhoKultimaCosteaetal.2018, author = {Coelho, Luis Pedro and Kultima, Jens Roat and Costea, Paul Igor and Fournier, Coralie and Pan, Yuanlong and Czarnecki-Maulden, Gail and Hayward, Matthew Robert and Forslund, Sofia K. and Schmidt, Thomas Sebastian Benedikt and Descombes, Patrick and Jackson, Janet R. and Li, Qinghong and Bork, Peer}, title = {Similarity of the dog and human gut microbiomes in gene content and response to diet}, series = {Microbiome}, volume = {6}, journal = {Microbiome}, doi = {10.1186/s40168-018-0450-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223177}, year = {2018}, abstract = {Background Gut microbes influence their hosts in many ways, in particular by modulating the impact of diet. These effects have been studied most extensively in humans and mice. In this work, we used whole genome metagenomics to investigate the relationship between the gut metagenomes of dogs, humans, mice, and pigs. Results We present a dog gut microbiome gene catalog containing 1,247,405 genes (based on 129 metagenomes and a total of 1.9 terabasepairs of sequencing data). Based on this catalog and taxonomic abundance profiling, we show that the dog microbiome is closer to the human microbiome than the microbiome of either pigs or mice. To investigate this similarity in terms of response to dietary changes, we report on a randomized intervention with two diets (high-protein/low-carbohydrate vs. lower protein/higher carbohydrate). We show that diet has a large and reproducible effect on the dog microbiome, independent of breed or sex. Moreover, the responses were in agreement with those observed in previous human studies. Conclusions We conclude that findings in dogs may be predictive of human microbiome results. In particular, a novel finding is that overweight or obese dogs experience larger compositional shifts than lean dogs in response to a high-protein diet.}, language = {en} }