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  • NARCIS (Royal Netherlands Academy of Arts and Sciences)  (15)
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  • 1
    Language: English
    In: Science translational medicine, 15 December 2010, Vol.2(62), pp.62ra93
    Description: Lung cancer remains one of the leading causes of cancer-related death in developed countries. Although lung adenocarcinomas with EGFR mutations or EML4-ALK fusions respond to treatment by epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibition, respectively, squamous cell lung cancer currently lacks therapeutically exploitable genetic alterations. We conducted a systematic search in a set of 232 lung cancer specimens for genetic alterations that were therapeutically amenable and then performed high-resolution gene copy number analyses. We identified frequent and focal fibroblast growth factor receptor 1 (FGFR1) amplification in squamous cell lung cancer (n = 155), but not in other lung cancer subtypes, and, by fluorescence in situ hybridization, confirmed the presence of FGFR1 amplifications in an independent cohort of squamous cell lung cancer samples (22% of cases). Using cell-based screening with the FGFR inhibitor PD173074 in a large (n = 83) panel of lung cancer cell lines, we demonstrated that this compound inhibited growth and induced apoptosis specifically in those lung cancer cells carrying amplified FGFR1. We validated the FGFR1 dependence of FGFR1-amplified cell lines by FGFR1 knockdown and by ectopic expression of an FGFR1-resistant allele (FGFR1(V561M)), which rescued FGFR1-amplified cells from PD173074-mediated cytotoxicity. Finally, we showed that inhibition of FGFR1 with a small molecule led to significant tumor shrinkage in vivo. Thus, focal FGFR1 amplification is common in squamous cell lung cancer and associated with tumor growth and survival, suggesting that FGFR inhibitors may be a viable therapeutic option in this cohort of patients.
    Keywords: Lung Neoplasms -- Genetics ; Receptor, Fibroblast Growth Factor, Type 1 -- Metabolism
    ISSN: 19466234
    E-ISSN: 1946-6242
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  • 2
    In: Nature, 2018
    Description: Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology.
    Keywords: DNA Methylation ; Central Nervous System Neoplasms -- Diagnosis;
    ISSN: 0028-0836
    E-ISSN: 1476-4687
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  • 3
    In: Nature Genetics, 2015, Vol.47(2), p.164
    Description: Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1 p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P 〈 5 x [10.sup.-8]. Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.
    Keywords: Ovarian Cancer – Genetic Aspects ; Quantitative Trait Loci – Identification and Classification ; Quantitative Trait Loci – Health Aspects;
    ISSN: 1061-4036
    E-ISSN: 15461718
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  • 4
    Language: English
    In: Science (New York, N.Y.), 18 October 2013, Vol.342(6156), pp.1243092
    Description: The vast extent of the Amazon Basin has historically restricted the study of its tree communities to the local and regional scales. Here, we provide empirical data on the commonness, rarity, and richness of lowland tree species across the entire Amazon Basin and Guiana Shield (Amazonia), collected in 1170 tree plots in all major forest types. Extrapolations suggest that Amazonia harbors roughly 16,000 tree species, of which just 227 (1.4%) account for half of all trees. Most of these are habitat specialists and only dominant in one or two regions of the basin. We discuss some implications of the finding that a small group of species--less diverse than the North American tree flora--accounts for half of the world's most diverse tree community.
    Keywords: Biodiversity ; Rivers ; Trees -- Classification
    ISSN: 00368075
    E-ISSN: 1095-9203
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  • 5
    In: Nature Genetics, 2013, Vol.45(4), p.371
    Description: Journal article. TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOGs, we analyzed ~480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants. Most associations cluster into three independent peaks. The minor allele at the peak 1 SNP rs2736108 associates with longer telomeres (P = 5.8 × 10!-7), lower risks for estrogen receptor (ER)-negative (P = 1.0 × 10!-8) and BRCA1 mutation carrier (P = 1.1 × 10!-5) breast cancers and altered promoter assay signal. The minor allele at the peak 2 SNP rs7705526 associates with longer telomeres (P = 2.3 × 10!-14), higher risk of low-malignant-potential ovarian cancer (P = 1.3 × 10!-15) and greater promoter activity. The minor alleles at the peak 3 SNPs rs10069690 and rs2242652 increase ER-negative (P = 1.2 × 10!-12) and BRCA1 mutation carrier (P = 1.6 × 10!-14) breast and invasive ovarian (P = 1.3 × 10!-11) cancer risks but not via altered telomere length. The cancer risk alleles of rs2242652 and rs10069690, respectively, increase silencing and generate a truncated TERT splice variant.. European Commission Seventh Framework Programme (agreement 223175-HEALTH-F2-2009-223175); Cancer Research UK (C1287/A10118 and C1287/A12014)
    Keywords: Genetics ; Breast Cancer Susceptibility;
    ISSN: 1061-4036
    E-ISSN: 15461718
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  • 6
    Language: English
    In: Sci Rep, 2018, Vol.8(1), pp.1003-1003
    Description: Species distribution models (SDMs) are widely used in ecology and conservation. Presence-only SDMs such as MaxEnt frequently use natural history collections (NHCs) as occurrence data, given their huge numbers and accessibility. NHCs are often spatially biased which may generate inaccuracies in SDMs. Here, we test how the distribution of NHCs and MaxEnt predictions relates to a spatial abundance model, based on a large plot dataset for Amazonian tree species, using inverse distance weighting (IDW). We also propose a new pipeline to deal with inconsistencies in NHCs and to limit the area of occupancy of the species. We found a significant but weak positive relationship between the distribution of NHCs and IDW for 66% of the species. The relationship between SDMs and IDW was also significant but weakly positive for 95% of the species, and sensitivity for both analyses was high. Furthermore, the pipeline removed half of the NHCs records. Presence-only SDM applications should consider this limitation, especially for large biodiversity assessments projects, when they are automatically generated without subsequent checking. Our pipeline provides a conservative estimate of a species’ area of occupancy, within an area slightly larger than its extent of occurrence, compatible to e.g. IUCN red list assessments.
    Keywords: Article;
    ISSN: 2045-2322
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  • 7
    Language: English
    In: Science advances, November 2015, Vol.1(10), pp.e1500936
    Description: Estimates of extinction risk for Amazonian plant and animal species are rare and not often incorporated into land-use policy and conservation planning. We overlay spatial distribution models with historical and projected deforestation to show that at least 36% and up to 57% of all Amazonian tree species are likely to qualify as globally threatened under International Union for Conservation of Nature (IUCN) Red List criteria. If confirmed, these results would increase the number of threatened plant species on Earth by 22%. We show that the trends observed in Amazonia apply to trees throughout the tropics, and we predict that most of the world's 〉40,000 tropical tree species now qualify as globally threatened. A gap analysis suggests that existing Amazonian protected areas and indigenous territories will protect viable populations of most threatened species if these areas suffer no further degradation, highlighting the key roles that protected areas, indigenous peoples, and improved governance can play in preventing large-scale extinctions in the tropics in this century.
    Keywords: Amazonia ; Conservation ; Deforestation ; Indigenous Areas ; Protected Areas ; Tree Species
    ISSN: 2375-2548
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  • 8
    Language: English
    In: Nature Communications, 2016, Vol.7, pp.urn:issn:2041-1723
    Description: A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P〈2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
    Keywords: Chemistry(All) ; Biochemistry, Genetics And Molecular Biology(All) ; Physics And Astronomy(All)
    ISSN: 2041-1723
    Source: NARCIS (National Academic Research and Collaborations Information System)
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  • 9
    In: Hollestelle, Antoinette; van der Baan, Frederieke H. Berchuck, Andrew; Johnatty, Sharon E.; Aben, Katja K.; Agnarsson, Bjarni A.; Aittomäki, Kristiina; Alducci, Elisa; Andrulis, Irene L.; Anton-Culver, Hoda; Antonenkova, Natalia N.; Antoniou, Antonis C.; Apicella, Carmel; Arndt, Volker; Arnold, Norbert; Arun, Banu K.; Arver, Brita; Ashworth, Alan; Baglietto, Laura; Balleine, Rosemary; Bandera, Elisa V.; Barrowdale, Daniel; Bean, Yukie T.; Beckmann, Lars; Beckmann, Matthias W.; Benitez, Javier; Berger, Andreas; Berger, Raanan; Beuselinck, Benoit; Bisogna, Maria; Bjorge, Line; Blomqvist, Carl; Bogdanova, Natalia V.; Bojesen, Anders; Bojesen, Stig E.; Bolla, Manjeet K.; Bonanni, Bernardo; Brand, Judith S.; Brauch, Hiltrud; Brenner, Hermann; Brinton, Louise; Brooks-Wilson, Angela; Bruinsma, Fiona; Brunet, Joan; Brüning, Thomas; Budzilowska, Agnieszka; Bunker, Clareann H.; Burwinkel, Barbara; Butzow, Ralf; Buys, Saundra S.; Caligo, Maria A.; Campbell, Ian; Carter, Jonathan; Chang-Claude, Jenny; Chanock, Stephen J.; Claes, Kathleen B.M.; Collée, J. Margriet; Cook, Linda S.; Couch, Fergus J.; Cox, Angela; Cramer, Daniel; Cross, Simon S.; Cunningham, Julie M.; Cybulski, Cezary; Czene, Kamila; Damiola, Francesca; Dansonka-Mieszkowska, Agnieszka; Darabi, Hatef; de la Hoya, Miguel; deFazio, Anna; Dennis, Joseph; Devilee, Peter; Dicks, Ed M.; Diez, Orland; Doherty, Jennifer A.; Domchek, Susan M.; Dorfling, Cecilia M.; Dörk, Thilo; Silva, Isabel Dos Santos; du Bois, Andreas; Dumont, Martine; Dunning, Alison M.; Duran, Mercedes; Easton, Douglas F.; Eccles, Diana; Edwards, Robert P.; Ehrencrona, Hans; Ejlertsen, Bent; Ekici, Arif B.; Ellis, Steve D.; Engel, Christoph; Eriksson, Mikael; Fasching, Peter A.; Feliubadalo, Lidia; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Fontaine, Annette; Fortuzzi, Stefano; Fostira, Florentia; Fridley, Brooke L.; Friebel, Tara; Friedman, Eitan; Friel, Grace; Frost, Debra; Garber, Judy; García-Closas, Montserrat; Gayther, Simon A.; Gentry-Maharaj, Aleksandra; Gerdes, Anne-Marie; Giles, Graham G.; Glasspool, Rosalind; Glendon, Gord; Godwin, Andrew K.; Goodman, Marc T.; Gore, Martin; Greene, Mark H.; Grip, Mervi; Gronwald, Jacek; Gschwantler Kaulich, Daphne; Guénel, Pascal; Guzman, Starr R.; Haeberle, Lothar; Haiman, Christopher A.; Hall, Per; Halverson, Sandra L.; Hamann, Ute; Hansen, Thomas V.O.; Harter, Philipp; Hartikainen, Jaana M.; Healey, Sue; Hein, Alexander; Heitz, Florian; Henderson, Brian E.; Herzog, Josef; T Hildebrandt, Michelle A.; Høgdall, Claus K.; Høgdall, Estrid; Hogervorst, Frans B.L.; Hopper, John L.; Humphreys, Keith; Huzarski, Tomasz; Imyanitov, Evgeny N.; Isaacs, Claudine; Jakubowska, Anna; Janavicius, Ramunas; Jaworska, Katarzyna; Jensen, Allan; Jensen, Uffe Birk; Johnson, Nichola; Jukkola-Vuorinen, Arja; Kabisch, Maria; Karlan, Beth Y.; Kataja, Vesa; Kauff, Noah; Kelemen, Linda E.; Kerin, Michael J.; Kiemeney, Lambertus A.; Kjaer, Susanne K.; Knight, Julia A.; Knol-Bout, Jacoba P.; Konstantopoulou, Irene; Kosma, Veli-Matti; Krakstad, Camilla; Kristensen, Vessela; Kuchenbaecker, Karoline B.; Kupryjanczyk, Jolanta; Laitman, Yael; Lambrechts, Diether; Lambrechts, Sandrina; Larson, Melissa C.; Lasa, Adriana; Laurent-Puig, Pierre; Lazaro, Conxi; Le, Nhu D.; Le Marchand, Loic; Leminen, Arto; Lester, Jenny; Levine, Douglas A.; Li, Jingmei; Liang, Dong; Lindblom, Annika; Lindor, Noralane; Lissowska, Jolanta; Long, Jirong; Lu, Karen H.; Lubinski, Jan; Lundvall, Lene; Lurie, Galina; Mai, Phuong L.; Mannermaa, Arto; Margolin, Sara; Mariette, Frederique; Marme, Frederik; Martens, John W.M.; Massuger, Leon F.A.G.; Maugard, Christine; Mazoyer, Sylvie; McGuffog, Lesley; McGuire, Valerie; McLean, Catriona; McNeish, Iain; Meindl, Alfons; Menegaux, Florence; Menéndez, Primitiva; Menkiszak, Janusz; Menon, Usha; Mensenkamp, Arjen R.; Miller, Nicola; Milne, Roger L.; Modugno, Francesmary; Montagna, Marco; Moysich, Kirsten B.; Müller, Heiko; Mulligan, Anna Marie; Muranen, Taru A.; Narod, Steven A.; Nathanson, Katherine L.; Ness, Roberta B.; Neuhausen, Susan L.; Nevanlinna, Heli; Neven, Patrick; Nielsen, Finn C.; Nielsen, Sune F.; Nordestgaard, Børge G.; Nussbaum, Robert L.; Odunsi, Kunle; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I.; Olson, Janet E.; Olson, Sara H.; Oosterwijk, Jan C.; Orlow, Irene; Orr, Nick; Orsulic, Sandra; Osorio, Ana; Ottini, Laura; Paul, James; Pearce, Celeste L.; Pedersen, Inge Sokilde; Peissel, Bernard; Pejovic, Tanja; Pelttari, Liisa M.; Perkins, Jo; Permuth-Wey, Jenny; Peterlongo, Paolo; Peto, Julian; Phelan, Catherine M.; Phillips, Kelly-Anne; Piedmonte, Marion; Pike, Malcolm C.; Platte, Radka; Plisiecka-Halasa, Joanna; Poole, Elizabeth M.; Poppe, Bruce; Pylkäs, Katri; Radice, Paolo; Ramus, Susan J.; Rebbeck, Timothy R.; Reed, Malcolm W.R.; Rennert, Gad; Risch, Harvey A.; Robson, Mark; Rodriguez, Gustavo C.; Romero, Atocha; Rossing, Mary Anne; Rothstein, Joseph H.; Rudolph, Anja; Runnebaum, Ingo; Salani, Ritu; Salvesen, Helga B.; Sawyer, Elinor J.; Schildkraut, Joellen M.; Schmidt, Marjanka K.; Schmutzler, Rita K.; Schneeweiss, Andreas; Schoemaker, Minouk J.; Schrauder, Michael G.; Schumacher, Fredrick; Schwaab, Ira; Scuvera, Giulietta; Sellers, Thomas A.; Severi, Gianluca; Seynaeve, Caroline M.; Shah, Mitul; Shrubsole, Martha; Siddiqui, Nadeem; Sieh, Weiva; Simard, Jacques; Singer, Christian F.; Sinilnikova, Olga M.; Smeets, Dominiek; Sohn, Christof; Soller, Maria; Song, Honglin; Soucy, Penny; Southey, Melissa C.; Stegmaier, Christa; Stoppa-Lyonnet, Dominique; Sucheston, Lara; Swerdlow, Anthony; Tangen, Ingvild L.; Tea, Muy-Kheng; Teixeira, Manuel R.; Terry, Kathryn L.; Terry, Mary Beth; Thomassen, Mads; Thompson, Pamela J.; Tihomirova, Laima; Tischkowitz, Marc; Toland, Amanda Ewart; Tollenaar, Rob A.E.M.; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Tsimiklis, Helen; Tung, Nadine; Tworoger, Shelley S.; Tyrer, Jonathan P.; Vachon, Celine M.; Van 't Veer, Laura J.; van Altena, Anne M.; Van Asperen, C.J.; van den Berg, David; van den Ouweland, Ans M.W.; van Doorn, Helena C.; Van Nieuwenhuysen, Els; van Rensburg, Elizabeth J.; Vergote, Ignace; Verhoef, Senno; Vierkant, Robert A.; Vijai, Joseph; Vitonis, Allison F.; von Wachenfeldt, Anna; Walsh, Christine; Wang, Qin; Wang-Gohrke, Shan; Wappenschmidt, Barbara; Weischer, Maren; Weitzel, Jeffrey N.; Weltens, Caroline; Wentzensen, Nicolas; Whittemore, Alice S.; Wilkens, Lynne R.; Winqvist, Robert; Wu, Anna H.; Wu, Xifeng; Yang, Hannah P.; Zaffaroni, Daniela; Pilar Zamora, M.; Zheng, Wei; Ziogas, Argyrios; Chenevix-Trench, Georgia; Pharoah, Paul D.P.; Rookus, Matti A.; Hooning, Maartje J.; Goode, Ellen L. (2016). No clinical utility of kras variant rs61764370 for ovarian or breast cancer. Gynecologic Oncology 141 (2), 386-401
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ygyno.2015.04.034 Byline: Antoinette Hollestelle, Frederieke H. van der Baan, Andrew Berchuck, Sharon E. Johnatty, Katja K. Aben, Bjarni A. Agnarsson, Kristiina Aittomaki, Elisa Alducci, Irene L. Andrulis, Hoda Anton-Culver, Natalia N. Antonenkova, Antonis C. Antoniou, Carmel Apicella, Volker Arndt, Norbert Arnold, Banu K. Arun, Brita Arver, Alan Ashworth, Laura Baglietto, Rosemary Balleine, Elisa V. Bandera, Daniel Barrowdale, Yukie T. Bean, Lars Beckmann, Matthias W. Beckmann, Javier Benitez, Andreas Berger, Raanan Berger, Benoit Beuselinck, Maria Bisogna, Line Bjorge, Carl Blomqvist, Natalia V. Bogdanova, Anders Bojesen, Stig E. Bojesen, Manjeet K. Bolla, Bernardo Bonanni, Judith S. Brand, Hiltrud Brauch, Hermann Brenner, Louise Brinton, Angela Brooks-Wilson, Fiona Bruinsma, Joan Brunet, Thomas Bruning, Agnieszka Budzilowska, Clareann H. Bunker, Barbara Burwinkel, Ralf Butzow, Saundra S. Buys, Maria A. Caligo, Ian Campbell, Jonathan Carter, Jenny Chang-Claude, Stephen J. Chanock, Kathleen B.M. Claes, J. Margriet Collee, Linda S. Cook, Fergus J. Couch, Angela Cox, Daniel Cramer, Simon S. Cross, Julie M. Cunningham, Cezary Cybulski, Kamila Czene, Francesca Damiola, Agnieszka Dansonka-Mieszkowska, Hatef Darabi, Miguel de la Hoya, Anna deFazio, Joseph Dennis, Peter Devilee, Ed M. Dicks, Orland Diez, Jennifer A. Doherty, Susan M. Domchek, Cecilia M. Dorfling, Thilo Dork, Isabel Dos Santos Silva, Andreas du Bois, Martine Dumont, Alison M. Dunning, Mercedes Duran, Douglas F. Easton, Diana Eccles, Robert P. Edwards, Hans Ehrencrona, Bent Ejlertsen, Arif B. Ekici, Steve D. Ellis, Christoph Engel, Mikael Eriksson, Peter A. Fasching, Lidia Feliubadalo, Jonine Figueroa, Dieter Flesch-Janys, Olivia Fletcher, Annette Fontaine, Stefano Fortuzzi, Florentia Fostira, Brooke L. Fridley, Tara Friebel, Eitan Friedman, Grace Friel, Debra Frost, Judy Garber, Montserrat Garcia-Closas, Simon A. Gayther, Aleksandra Gentry-Maharaj, Anne-Marie Gerdes, Graham G. Giles, Rosalind Glasspool, Gord Glendon, Andrew K. Godwin, Marc T. Goodman, Martin Gore, Mark H. Greene, Mervi Grip, Jacek Gronwald, Daphne Gschwantler Kaulich, Pascal Guenel, Starr R. Guzman, Lothar Haeberle, Christopher A. Haiman, Per Hall, Sandra L. Halverson, Ute Hamann, Thomas V.O. Hansen, Philipp Harter, Jaana M. Hartikainen, Sue Healey, Alexander Hein, Florian Heitz, Brian E. Henderson, Josef Herzog, Michelle A. T Hildebrandt, Claus K. Hogdall, Estrid Hogdall, Frans B.L. Hogervorst, John L. Hopper, Keith Humphreys, Tomasz Huzarski, Evgeny N. Imyanitov, Claudine Isaacs, Anna Jakubowska, Ramunas Janavicius, Katarzyna Jaworska, Allan Jensen, Uffe Birk Jensen, Nichola Johnson, Arja Jukkola-Vuorinen, Maria Kabisch, Beth Y. Karlan, Vesa Kataja, Noah Kauff, Linda E. Kelemen, Michael J. Kerin, Lambertus A. Kiemeney, Susanne K. Kjaer, Julia A. Knight, Jacoba P. Knol-Bout, Irene Konstantopoulou, Veli-Matti Kosma, Camilla Krakstad, Vessela Kristensen, Karoline B. Kuchenbaecker, Jolanta Kupryjanczyk, Yael Laitman, Diether Lambrechts, Sandrina Lambrechts, Melissa C. Larson, Adriana Lasa, Pierre Laurent-Puig, Conxi Lazaro, Nhu D. Le, Loic Le Marchand, Arto Leminen, Jenny Lester, Douglas A. Levine, Jingmei Li, Dong Liang, Annika Lindblom, Noralane Lindor, Jolanta Lissowska, Jirong Long, Karen H. Lu, Jan Lubinski, Lene Lundvall, Galina Lurie, Phuong L. Mai, Arto Mannermaa, Sara Margolin, Frederique Mariette, Frederik Marme, John W.M. Martens, Leon F.A.G. Massuger, Christine Maugard, Sylvie Mazoyer, Lesley McGuffog, Valerie McGuire, Catriona McLean, Iain McNeish, Alfons Meindl, Florence Menegaux, Primitiva Menendez, Janusz Menkiszak, Usha Menon, Arjen R. Mensenkamp, Nicola Miller, Roger L. Milne, Francesmary Modugno, Marco Montagna, Kirsten B. Moysich, Heiko Muller, Anna Marie Mulligan, Taru A. Muranen, Steven A. Narod, Katherine L. Nathanson, Roberta B. Ness, Susan L. Neuhausen, Heli Nevanlinna, Patrick Neven, Finn C. Nielsen, Sune F. Nielsen, Borge G. Nordestgaard, Robert L. Nussbaum, Kunle Odunsi, Kenneth Offit, Edith Olah, Olufunmilayo I. Olopade, Janet E. Olson, Sara H. Olson, Jan C. Oosterwijk, Irene Orlow, Nick Orr, Sandra Orsulic, Ana Osorio, Laura Ottini, James Paul, Celeste L. Pearce, Inge Sokilde Pedersen, Bernard Peissel, Tanja Pejovic, Liisa M. Pelttari, Jo Perkins, Jenny Permuth-Wey, Paolo Peterlongo, Julian Peto, Catherine M. Phelan, Kelly-Anne Phillips, Marion Piedmonte, Malcolm C. Pike, Radka Platte, Joanna Plisiecka-Halasa, Elizabeth M. Poole, Bruce Poppe, Katri Pylkas, Paolo Radice, Susan J. Ramus, Timothy R. Rebbeck, Malcolm W.R. Reed, Gad Rennert, Harvey A. Risch, Mark Robson, Gustavo C. Rodriguez, Atocha Romero, Mary Anne Rossing, Joseph H. Rothstein, Anja Rudolph, Ingo Runnebaum, Ritu Salani, Helga B. Salvesen, Elinor J. Sawyer, Joellen M. Schildkraut, Marjanka K. Schmidt, Rita K. Schmutzler, Andreas Schneeweiss, Minouk J. Schoemaker, Michael G. Schrauder, Fredrick Schumacher, Ira Schwaab, Giulietta Scuvera, Thomas A. Sellers, Gianluca Severi, Caroline M. Seynaeve, Mitul Shah, Martha Shrubsole, Nadeem Siddiqui, Weiva Sieh, Jacques Simard, Christian F. Singer, Olga M. Sinilnikova, Dominiek Smeets, Christof Sohn, Maria Soller, Honglin Song, Penny Soucy, Melissa C. Southey, Christa Stegmaier, Dominique Stoppa-Lyonnet, Lara Sucheston, Anthony Swerdlow, Ingvild L. Tangen, Muy-Kheng Tea, Manuel R. Teixeira, Kathryn L. Terry, Mary Beth Terry, Mads Thomassen, Pamela J. Thompson, Laima Tihomirova, Marc Tischkowitz, Amanda Ewart Toland, Rob A.E.M. Tollenaar, Ian Tomlinson, Diana Torres, Therese Truong, Helen Tsimiklis, Nadine Tung, Shelley S. Tworoger, Jonathan P. Tyrer, Celine M. Vachon, Laura J. Van 't Veer, Anne M. van Altena, C.J. Van Asperen, David van den Berg, Ans M.W. van den Ouweland, Helena C. van Doorn, Els Van Nieuwenhuysen, Elizabeth J. van Rensburg, Ignace Vergote, Senno Verhoef, Robert A. Vierkant, Joseph Vijai, Allison F. Vitonis, Anna von Wachenfeldt, Christine Walsh, Qin Wang, Shan Wang-Gohrke, Barbara Wappenschmidt, Maren Weischer, Jeffrey N. Weitzel, Caroline Weltens, Nicolas Wentzensen, Alice S. Whittemore, Lynne R. Wilkens, Robert Winqvist, Anna H. Wu, Xifeng Wu, Hannah P. Yang, Daniela Zaffaroni, M. Pilar Zamora, Wei Zheng, Argyrios Ziogas, Georgia Chenevix-Trench, Paul D.P. Pharoah, Matti A. Rookus, Maartje J. Hooning, Ellen L. Goode Abstract: Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3' UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Article History: Received 9 March 2015; Accepted 19 April 2015
    Keywords: Kras Variant ; Breast Cancer ; Ovarian Cancer ; Genetic Association ; Clinical Outcome ; Genome-Wide Association ; Microrna-Binding-Site ; Susceptibility Loci ; Risk ; Prostate ; Identification ; Polymorphisms ; Endometriosis ; Women
    ISSN: 0090-8258
    E-ISSN: 10956859
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  • 10
    In: Phys. Rev. D 93, 122005 (2016)
    Description: The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal. Comment: Replaced with published version. Added journal reference and DOI
    Keywords: Astrophysics - High Energy Astrophysical Phenomena ; Astrophysics - Instrumentation And Methods For Astrophysics
    ISSN: 24700010
    E-ISSN: 24700029
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