[{"publication_status":"published","language":[{"iso":"eng"}],"ec_funded":1,"related_material":{"record":[{"relation":"dissertation_contains","id":"1400","status":"public"}]},"issue":"7404","volume":486,"abstract":[{"text":"Colorectal tumours that are wild type for KRAS are often sensitive to EGFR blockade, but almost always develop resistance within several months of initiating therapy. The mechanisms underlying this acquired resistance to anti-EGFR antibodies are largely unknown. This situation is in marked contrast to that of small-molecule targeted agents, such as inhibitors of ABL, EGFR, BRAF and MEK, in which mutations in the genes encoding the protein targets render the tumours resistant to the effects of the drugs. The simplest hypothesis to account for the development of resistance to EGFR blockade is that rare cells with KRAS mutations pre-exist at low levels in tumours with ostensibly wild-type KRAS genes. Although this hypothesis would seem readily testable, there is no evidence in pre-clinical models to support it, nor is there data from patients. To test this hypothesis, we determined whether mutant KRAS DNA could be detected in the circulation of 28 patients receiving monotherapy with panitumumab, a therapeutic anti-EGFR antibody. We found that 9 out of 24 (38%) patients whose tumours were initially KRAS wild type developed detectable mutations in KRAS in their sera, three of which developed multiple different KRAS mutations. The appearance of these mutations was very consistent, generally occurring between 5 and 6months following treatment. Mathematical modelling indicated that the mutations were present in expanded subclones before the initiation of panitumumab treatment. These results suggest that the emergence of KRAS mutations is a mediator of acquired resistance to EGFR blockade and that these mutations can be detected in a non-invasive manner. They explain why solid tumours develop resistance to targeted therapies in a highly reproducible fashion.","lang":"eng"}],"oa_version":"Submitted Version","pmid":1,"main_file_link":[{"url":"http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3436069/","open_access":"1"}],"scopus_import":1,"intvolume":" 486","month":"06","date_updated":"2023-09-07T11:40:43Z","department":[{"_id":"KrCh"}],"_id":"3157","type":"journal_article","status":"public","year":"2012","publication":"Nature","day":"28","page":"537 - 540","date_created":"2018-12-11T12:01:43Z","date_published":"2012-06-28T00:00:00Z","doi":"10.1038/nature11219","oa":1,"quality_controlled":"1","publisher":"Nature Publishing Group","citation":{"mla":"Diaz Jr, Luis, et al. “The Molecular Evolution of Acquired Resistance to Targeted EGFR Blockade in Colorectal Cancers.” Nature, vol. 486, no. 7404, Nature Publishing Group, 2012, pp. 537–40, doi:10.1038/nature11219.","apa":"Diaz Jr, L., Williams, R., Wu, J., Kinde, I., Hecht, J., Berlin, J., … Vogelstein, B. (2012). The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature. Nature Publishing Group. https://doi.org/10.1038/nature11219","ama":"Diaz Jr L, Williams R, Wu J, et al. The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature. 2012;486(7404):537-540. doi:10.1038/nature11219","short":"L. Diaz Jr, R. Williams, J. Wu, I. Kinde, J. Hecht, J. Berlin, B. Allen, I. Božić, J. Reiter, M. Nowak, K. Kinzler, K. Oliner, B. Vogelstein, Nature 486 (2012) 537–540.","ieee":"L. Diaz Jr et al., “The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers,” Nature, vol. 486, no. 7404. Nature Publishing Group, pp. 537–540, 2012.","chicago":"Diaz Jr, Luis, Richard Williams, Jian Wu, Isaac Kinde, Joel Hecht, Jordan Berlin, Benjamin Allen, et al. “The Molecular Evolution of Acquired Resistance to Targeted EGFR Blockade in Colorectal Cancers.” Nature. Nature Publishing Group, 2012. https://doi.org/10.1038/nature11219.","ista":"Diaz Jr L, Williams R, Wu J, Kinde I, Hecht J, Berlin J, Allen B, Božić I, Reiter J, Nowak M, Kinzler K, Oliner K, Vogelstein B. 2012. The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature. 486(7404), 537–540."},"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","external_id":{"pmid":["22722843"]},"author":[{"first_name":"Luis","last_name":"Diaz Jr","full_name":"Diaz Jr, Luis"},{"last_name":"Williams","full_name":"Williams, Richard","first_name":"Richard"},{"first_name":"Jian","last_name":"Wu","full_name":"Wu, Jian"},{"full_name":"Kinde, Isaac","last_name":"Kinde","first_name":"Isaac"},{"full_name":"Hecht, Joel","last_name":"Hecht","first_name":"Joel"},{"last_name":"Berlin","full_name":"Berlin, Jordan","first_name":"Jordan"},{"last_name":"Allen","full_name":"Allen, Benjamin","first_name":"Benjamin"},{"first_name":"Ivana","last_name":"Božić","full_name":"Božić, Ivana"},{"first_name":"Johannes","id":"4A918E98-F248-11E8-B48F-1D18A9856A87","last_name":"Reiter","orcid":"0000-0002-0170-7353","full_name":"Reiter, Johannes"},{"first_name":"Martin","last_name":"Nowak","full_name":"Nowak, Martin"},{"first_name":"Kenneth","last_name":"Kinzler","full_name":"Kinzler, Kenneth"},{"first_name":"Kelly","full_name":"Oliner, Kelly","last_name":"Oliner"},{"first_name":"Bert","last_name":"Vogelstein","full_name":"Vogelstein, Bert"}],"publist_id":"3537","title":"The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers","project":[{"grant_number":"279307","name":"Quantitative Graph Games: Theory and Applications","call_identifier":"FP7","_id":"2581B60A-B435-11E9-9278-68D0E5697425"},{"grant_number":"S 11407_N23","name":"Rigorous Systems Engineering","_id":"25832EC2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}]},{"_id":"3260","status":"public","type":"journal_article","date_updated":"2023-09-07T11:40:43Z","department":[{"_id":"KrCh"}],"oa_version":"Submitted Version","pmid":1,"abstract":[{"text":"Many scenarios in the living world, where individual organisms compete for winning positions (or resources), have properties of auctions. Here we study the evolution of bids in biological auctions. For each auction, n individuals are drawn at random from a population of size N. Each individual makes a bid which entails a cost. The winner obtains a benefit of a certain value. Costs and benefits are translated into reproductive success (fitness). Therefore, successful bidding strategies spread in the population. We compare two types of auctions. In “biological all-pay auctions”, the costs are the bid for every participating individual. In “biological second price all-pay auctions”, the cost for everyone other than the winner is the bid, but the cost for the winner is the second highest bid. Second price all-pay auctions are generalizations of the “war of attrition” introduced by Maynard Smith. We study evolutionary dynamics in both types of auctions. We calculate pairwise invasion plots and evolutionarily stable distributions over the continuous strategy space. We find that the average bid in second price all-pay auctions is higher than in all-pay auctions, but the average cost for the winner is similar in both auctions. In both cases, the average bid is a declining function of the number of participants, n. The more individuals participate in an auction the smaller is the chance of winning, and thus expensive bids must be avoided.\r\n","lang":"eng"}],"intvolume":" 81","month":"02","main_file_link":[{"url":"http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279759/ ","open_access":"1"}],"scopus_import":1,"language":[{"iso":"eng"}],"publication_status":"published","ec_funded":1,"related_material":{"record":[{"status":"public","id":"1400","relation":"dissertation_contains"}]},"volume":81,"issue":"1","project":[{"_id":"2581B60A-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"279307","name":"Quantitative Graph Games: Theory and Applications"},{"_id":"25832EC2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"S 11407_N23","name":"Rigorous Systems Engineering"},{"_id":"2584A770-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Modern Graph Algorithmic Techniques in Formal Verification","grant_number":"P 23499-N23"},{"name":"Microsoft Research Faculty Fellowship","_id":"2587B514-B435-11E9-9278-68D0E5697425"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"chicago":"Chatterjee, Krishnendu, Johannes Reiter, and Martin Nowak. “Evolutionary Dynamics of Biological Auctions.” Theoretical Population Biology. Academic Press, 2012. https://doi.org/10.1016/j.tpb.2011.11.003.","ista":"Chatterjee K, Reiter J, Nowak M. 2012. Evolutionary dynamics of biological auctions. Theoretical Population Biology. 81(1), 69–80.","mla":"Chatterjee, Krishnendu, et al. “Evolutionary Dynamics of Biological Auctions.” Theoretical Population Biology, vol. 81, no. 1, Academic Press, 2012, pp. 69–80, doi:10.1016/j.tpb.2011.11.003.","short":"K. Chatterjee, J. Reiter, M. Nowak, Theoretical Population Biology 81 (2012) 69–80.","ieee":"K. Chatterjee, J. Reiter, and M. Nowak, “Evolutionary dynamics of biological auctions,” Theoretical Population Biology, vol. 81, no. 1. Academic Press, pp. 69–80, 2012.","apa":"Chatterjee, K., Reiter, J., & Nowak, M. (2012). Evolutionary dynamics of biological auctions. Theoretical Population Biology. Academic Press. https://doi.org/10.1016/j.tpb.2011.11.003","ama":"Chatterjee K, Reiter J, Nowak M. Evolutionary dynamics of biological auctions. Theoretical Population Biology. 2012;81(1):69-80. doi:10.1016/j.tpb.2011.11.003"},"title":"Evolutionary dynamics of biological auctions","external_id":{"pmid":["22120126"]},"publist_id":"3388","author":[{"id":"2E5DCA20-F248-11E8-B48F-1D18A9856A87","first_name":"Krishnendu","orcid":"0000-0002-4561-241X","full_name":"Chatterjee, Krishnendu","last_name":"Chatterjee"},{"last_name":"Reiter","orcid":"0000-0002-0170-7353","full_name":"Reiter, Johannes","id":"4A918E98-F248-11E8-B48F-1D18A9856A87","first_name":"Johannes"},{"first_name":"Martin","last_name":"Nowak","full_name":"Nowak, Martin"}],"oa":1,"publisher":"Academic Press","quality_controlled":"1","publication":"Theoretical Population Biology","day":"01","year":"2012","date_created":"2018-12-11T12:02:19Z","doi":"10.1016/j.tpb.2011.11.003","date_published":"2012-02-01T00:00:00Z","page":"69 - 80"},{"date_updated":"2023-09-07T11:43:52Z","department":[{"_id":"PeJo"}],"_id":"3258","status":"public","type":"journal_article","article_type":"original","language":[{"iso":"eng"}],"publication_identifier":{"issn":["1546-1726"]},"publication_status":"published","volume":15,"issue":"4","related_material":{"record":[{"status":"public","id":"2964","relation":"dissertation_contains"}]},"oa_version":"Published Version","pmid":1,"abstract":[{"lang":"eng","text":"CA3 pyramidal neurons are important for memory formation and pattern completion in the hippocampal network. It is generally thought that proximal synapses from the mossy fibers activate these neurons most efficiently, whereas distal inputs from the perforant path have a weaker modulatory influence. We used confocally targeted patch-clamp recording from dendrites and axons to map the activation of rat CA3 pyramidal neurons at the subcellular level. Our results reveal two distinct dendritic domains. In the proximal domain, action potentials initiated in the axon backpropagate actively with large amplitude and fast time course. In the distal domain, Na+ channel–mediated dendritic spikes are efficiently initiated by waveforms mimicking synaptic events. CA3 pyramidal neuron dendrites showed a high Na+-to-K+ conductance density ratio, providing ideal conditions for active backpropagation and dendritic spike initiation. Dendritic spikes may enhance the computational power of CA3 pyramidal neurons in the hippocampal network."}],"month":"04","intvolume":" 15","scopus_import":"1","main_file_link":[{"url":"http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3617474/","open_access":"1"}],"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","citation":{"ista":"Kim S, Guzmán J, Hu H, Jonas PM. 2012. Active dendrites support efficient initiation of dendritic spikes in hippocampal CA3 pyramidal neurons. Nature Neuroscience. 15(4), 600–606.","chicago":"Kim, Sooyun, José Guzmán, Hua Hu, and Peter M Jonas. “Active Dendrites Support Efficient Initiation of Dendritic Spikes in Hippocampal CA3 Pyramidal Neurons.” Nature Neuroscience. Nature Publishing Group, 2012. https://doi.org/10.1038/nn.3060.","ama":"Kim S, Guzmán J, Hu H, Jonas PM. Active dendrites support efficient initiation of dendritic spikes in hippocampal CA3 pyramidal neurons. Nature Neuroscience. 2012;15(4):600-606. doi:10.1038/nn.3060","apa":"Kim, S., Guzmán, J., Hu, H., & Jonas, P. M. (2012). Active dendrites support efficient initiation of dendritic spikes in hippocampal CA3 pyramidal neurons. Nature Neuroscience. Nature Publishing Group. https://doi.org/10.1038/nn.3060","ieee":"S. Kim, J. Guzmán, H. Hu, and P. M. Jonas, “Active dendrites support efficient initiation of dendritic spikes in hippocampal CA3 pyramidal neurons,” Nature Neuroscience, vol. 15, no. 4. Nature Publishing Group, pp. 600–606, 2012.","short":"S. Kim, J. Guzmán, H. Hu, P.M. Jonas, Nature Neuroscience 15 (2012) 600–606.","mla":"Kim, Sooyun, et al. “Active Dendrites Support Efficient Initiation of Dendritic Spikes in Hippocampal CA3 Pyramidal Neurons.” Nature Neuroscience, vol. 15, no. 4, Nature Publishing Group, 2012, pp. 600–06, doi:10.1038/nn.3060."},"title":"Active dendrites support efficient initiation of dendritic spikes in hippocampal CA3 pyramidal neurons","author":[{"last_name":"Kim","full_name":"Kim, Sooyun","first_name":"Sooyun","id":"394AB1C8-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0003-2209-5242","full_name":"Guzmán, José","last_name":"Guzmán","id":"30CC5506-F248-11E8-B48F-1D18A9856A87","first_name":"José"},{"id":"4AC0145C-F248-11E8-B48F-1D18A9856A87","first_name":"Hua","full_name":"Hu, Hua","last_name":"Hu"},{"first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas"}],"publist_id":"3390","article_processing_charge":"No","external_id":{"pmid":["22388958"]},"project":[{"_id":"25BDE9A4-B435-11E9-9278-68D0E5697425","grant_number":"SFB-TR3-TP10B","name":"Glutamaterge synaptische Übertragung und Plastizität in hippocampalen Mikroschaltkreisen"}],"day":"01","publication":"Nature Neuroscience","year":"2012","doi":"10.1038/nn.3060","date_published":"2012-04-01T00:00:00Z","date_created":"2018-12-11T12:02:18Z","page":"600 - 606","acknowledgement":"This work was supported by the Deutsche Forschungsgemeinschaft (TR 3/B10) and the European Union (European Research Council Advanced grant to P.J.).","quality_controlled":"1","publisher":"Nature Publishing Group","oa":1},{"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","date_updated":"2023-09-07T11:43:51Z","citation":{"ista":"Kim S. 2012. Active properties of hippocampal CA3 pyramidal neuron dendrites. Institute of Science and Technology Austria.","chicago":"Kim, Sooyun. “Active Properties of Hippocampal CA3 Pyramidal Neuron Dendrites.” Institute of Science and Technology Austria, 2012.","ieee":"S. Kim, “Active properties of hippocampal CA3 pyramidal neuron dendrites,” Institute of Science and Technology Austria, 2012.","short":"S. Kim, Active Properties of Hippocampal CA3 Pyramidal Neuron Dendrites, Institute of Science and Technology Austria, 2012.","apa":"Kim, S. (2012). Active properties of hippocampal CA3 pyramidal neuron dendrites. Institute of Science and Technology Austria.","ama":"Kim S. Active properties of hippocampal CA3 pyramidal neuron dendrites. 2012.","mla":"Kim, Sooyun. Active Properties of Hippocampal CA3 Pyramidal Neuron Dendrites. Institute of Science and Technology Austria, 2012."},"supervisor":[{"last_name":"Jonas","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"}],"department":[{"_id":"PeJo"},{"_id":"GradSch"}],"title":"Active properties of hippocampal CA3 pyramidal neuron dendrites","article_processing_charge":"No","publist_id":"3755","author":[{"last_name":"Kim","full_name":"Kim, Sooyun","first_name":"Sooyun","id":"394AB1C8-F248-11E8-B48F-1D18A9856A87"}],"_id":"2964","status":"public","type":"dissertation","language":[{"iso":"eng"}],"day":"01","degree_awarded":"PhD","year":"2012","publication_status":"published","publication_identifier":{"issn":["2663-337X"]},"date_created":"2018-12-11T12:00:35Z","related_material":{"record":[{"status":"public","id":"3258","relation":"part_of_dissertation"}]},"date_published":"2012-06-01T00:00:00Z","page":"65","oa_version":"None","abstract":[{"lang":"eng","text":"CA3 pyramidal neurons are important for memory formation and pattern completion in the hippocampal network. These neurons receive multiple excitatory inputs from numerous sources. Therefore, the rules of spatiotemporal integration of multiple synaptic inputs and propagation of action potentials are important to understand how CA3 neurons contribute to higher brain functions at cellular level. By using confocally targeted patch-clamp recording techniques, we investigated the biophysical properties of rat CA3 pyramidal neuron dendrites. We found two distinct dendritic domains critical for action potential initiation and propagation: In the proximal domain, action potentials initiated in the axon backpropagate actively with large amplitude and fast time course. In the distal domain, Na+-channel mediated dendritic spikes are efficiently evoked by local dendritic depolarization or waveforms mimicking synaptic events. These findings can be explained by a high Na+-to-K+ conductance density ratio of CA3 pyramidal neuron dendrites. The results challenge the prevailing view that proximal mossy fiber inputs activate CA3 pyramidal neurons more efficiently than distal perforant inputs by showing that the distal synapses trigger a different form of activity represented by dendritic spikes. The high probability of dendritic spike initiation in the distal area may enhance the computational power of CA3 pyramidal neurons in the hippocampal network. "}],"month":"06","publisher":"Institute of Science and Technology Austria","alternative_title":["ISTA Thesis"]},{"acknowledgement":"This review comes from a themed issue on Cell structure and dynamics Edited by Jason Swedlow and Gaudenz Danuser","oa_version":"None","abstract":[{"lang":"eng","text":"Visualizing and analyzing shape changes at various scales, ranging from single molecules to whole organisms, are essential for understanding complex morphogenetic processes, such as early embryonic development. Embryo morphogenesis relies on the interplay between different tissues, the properties of which are again determined by the interaction between their constituent cells. Cell interactions, on the other hand, are controlled by various molecules, such as signaling and adhesion molecules, which in order to exert their functions need to be spatiotemporally organized within and between the interacting cells. In this review, we will focus on the role of cell adhesion functioning at different scales to organize cell, tissue and embryo morphogenesis. We will specifically ask how the subcellular distribution of adhesion molecules controls the formation of cell-cell contacts, how cell-cell contacts determine tissue shape, and how tissue interactions regulate embryo morphogenesis."}],"intvolume":" 24","month":"02","scopus_import":1,"publisher":"Elsevier","quality_controlled":"1","publication":"Current Opinion in Cell Biology","language":[{"iso":"eng"}],"day":"01","year":"2012","publication_status":"published","date_created":"2018-12-11T12:02:14Z","volume":24,"doi":"10.1016/j.ceb.2011.11.006","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"961"}]},"issue":"1","date_published":"2012-02-01T00:00:00Z","page":"148 - 153","_id":"3246","status":"public","type":"journal_article","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_updated":"2023-09-07T12:05:08Z","citation":{"ieee":"V. Barone and C.-P. J. Heisenberg, “Cell adhesion in embryo morphogenesis,” Current Opinion in Cell Biology, vol. 24, no. 1. Elsevier, pp. 148–153, 2012.","short":"V. Barone, C.-P.J. Heisenberg, Current Opinion in Cell Biology 24 (2012) 148–153.","apa":"Barone, V., & Heisenberg, C.-P. J. (2012). Cell adhesion in embryo morphogenesis. Current Opinion in Cell Biology. Elsevier. https://doi.org/10.1016/j.ceb.2011.11.006","ama":"Barone V, Heisenberg C-PJ. Cell adhesion in embryo morphogenesis. Current Opinion in Cell Biology. 2012;24(1):148-153. doi:10.1016/j.ceb.2011.11.006","mla":"Barone, Vanessa, and Carl-Philipp J. Heisenberg. “Cell Adhesion in Embryo Morphogenesis.” Current Opinion in Cell Biology, vol. 24, no. 1, Elsevier, 2012, pp. 148–53, doi:10.1016/j.ceb.2011.11.006.","ista":"Barone V, Heisenberg C-PJ. 2012. Cell adhesion in embryo morphogenesis. Current Opinion in Cell Biology. 24(1), 148–153.","chicago":"Barone, Vanessa, and Carl-Philipp J Heisenberg. “Cell Adhesion in Embryo Morphogenesis.” Current Opinion in Cell Biology. Elsevier, 2012. https://doi.org/10.1016/j.ceb.2011.11.006."},"title":"Cell adhesion in embryo morphogenesis","department":[{"_id":"CaHe"}],"publist_id":"3423","author":[{"id":"419EECCC-F248-11E8-B48F-1D18A9856A87","first_name":"Vanessa","last_name":"Barone","orcid":"0000-0003-2676-3367","full_name":"Barone, Vanessa"},{"id":"39427864-F248-11E8-B48F-1D18A9856A87","first_name":"Carl-Philipp J","last_name":"Heisenberg","full_name":"Heisenberg, Carl-Philipp J","orcid":"0000-0002-0912-4566"}]}]