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  • 1
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    Fasching, P. A., Pharoah, P. D. P., Cox, A., Nevanlinna, H., Bojesen, S. E., Karn, T., Broeks, A., van Leeuwen, F. E., van 't Veer, L. J., Udo, R., Dunning, A. M., Greco, D., Aittomaki, K., Blomqvist, C., Shah, M., Nordestgaard, B. G., Flyger, H., Hopper, J. L., Southey, M. C., Apicella, C., Garcia-Closas, M., Sherman, M., Lissowska, J., Seynaeve, C., Huijts, P. E. A., Tollenaar, R. A. E. M., Ziogas, A., Ekici, A. B., Rauh, C., Mannermaa, A., Kataja, V., Kosma, V.-M., Hartikainen, J. M., Andrulis, I. L., Ozcelik, H., Mulligan, A.-M., Glendon, G., Hall, P., Czene, K., Liu, J., Chang-Claude, J., Wang-Gohrke, S., Eilber, U., Nickels, S., Dork, T., Schiekel, M., Bremer, M., Park-Simon, T.-W., Giles, G. G., Severi, G., Baglietto, L., Hooning, M. J., Martens, J. W. M., Jager, A., Kriege, M., Lindblom, A., Margolin, S., Couch, F. J., Stevens, K. N., Olson, J. E., Kosel, M., Cross, S. S., Balasubramanian, S. P., Reed, M. W. R., Miron, A., John, E. M., Winqvist, R., Pylkas, K., Jukkola-Vuorinen, A., Kauppila, S., Burwinkel, B., Marme, F., Schneeweiss, A., Sohn, C., Chenevix-Trench, G., k; Con; Fab Investigators, Lambrechts, D., Dieudonne, A.-S., Hatse, S., van Limbergen, E., Benitez, J., Milne, R. L., Zamora, M. P., Perez, J. I. A., Bonanni, B., Peissel, B., Loris, B., Peterlongo, P., Rajaraman, P., Schonfeld, S. J., Anton-Culver, H., Devilee, P., Beckmann, M. W., Slamon, D. J., Phillips, K.-A., Figueroa, J. D., Humphreys, M. K., Easton, D. F., Schmidt, M. K.
    Oxford University Press
    Publication Date: 2012-08-07
    Description: Recent genome-wide association studies identified 11 single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk. We investigated these and 62 other SNPs for their prognostic relevance. Confirmed BC risk SNPs rs17468277 ( CASP8 ), rs1982073 ( TGFB1 ), rs2981582 ( FGFR2 ), rs13281615 (8q24), rs3817198 ( LSP1 ), rs889312 ( MAP3K1 ), rs3803662 ( TOX3 ), rs13387042 (2q35), rs4973768 ( SLC4A7 ), rs6504950 ( COX11 ) and rs10941679 (5p12) were genotyped for 25 853 BC patients with the available follow-up; 62 other SNPs, which have been suggested as BC risk SNPs by a GWAS or as candidate SNPs from individual studies, were genotyped for replication purposes in subsets of these patients. Cox proportional hazard models were used to test the association of these SNPs with overall survival (OS) and BC-specific survival (BCS). For the confirmed loci, we performed an accessory analysis of publicly available gene expression data and the prognosis in a different patient group. One of the 11 SNPs, rs3803662 ( TOX3 ) and none of the 62 candidate/GWAS SNPs were associated with OS and/or BCS at P 〈0.01. The genotypic-specific survival for rs3803662 suggested a recessive mode of action [hazard ratio (HR) of rare homozygous carriers=1.21; 95% CI: 1.09–1.35, P =0.0002 and HR=1.29; 95% CI: 1.12–1.47, P =0.0003 for OS and BCS, respectively]. This association was seen similarly in all analyzed tumor subgroups defined by nodal status, tumor size, grade and estrogen receptor. Breast tumor expression of these genes was not associated with prognosis. With the exception of rs3803662 (TOX3), there was no evidence that any of the SNPs associated with BC susceptibility were associated with the BC survival. Survival may be influenced by a distinct set of germline variants from those influencing susceptibility.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
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  • 2
    Publication Date: 2019
    Description: 〈p〉Using the most comprehensive fish occurrence database, we evaluated the importance of ecological and historical drivers in diversity patterns of subdrainage basins across the Amazon system. Linear models reveal the influence of climatic conditions, habitat size and sub-basin isolation on species diversity. Unexpectedly, the species richness model also highlighted a negative upriver-downriver gradient, contrary to predictions of increasing richness at more downriver locations along fluvial gradients. This reverse gradient may be linked to the history of the Amazon drainage network, which, after isolation as western and eastern basins throughout the Miocene, only began flowing eastward 1–9 million years (Ma) ago. Our results suggest that the main center of fish diversity was located westward, with fish dispersal progressing eastward after the basins were united and the Amazon River assumed its modern course toward the Atlantic. This dispersal process seems not yet achieved, suggesting a recent formation of the current Amazon system.〈/p〉
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 3
    Publication Date: 2015-02-13
    Description: We present a scanning helium microscope equipped to make use of the unique contrast mechanisms, surface sensitivity, and zero damage imaging the technique affords. The new design delivers an order of magnitude increase in the available helium signal, yielding a higher contrast and signal-to-noise ratio. These improvements allow the microscope to produce high quality, intuitive images of samples using topological contrast, while setting the stage for investigations into further contrast mechanisms.
    Print ISSN: 0034-6748
    Electronic ISSN: 1089-7623
    Topics: Electrical Engineering, Measurement and Control Technology , Physics
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  • 4
    Publication Date: 2012-02-17
    Description: Xie, Y., Michielsens, C. G. J., and Martens, F. J. 2012. Classification of fish and non-fish acoustic tracks using discriminant function analysis. – ICES Journal of Marine Science, 69: 313–322. Hydroacoustic data acquired for estimating fish populations contain information on both fish and non-fish targets, so sonar technicians traditionally rely on their knowledge of fish behaviour and experience with hydroacoustics to remove non-fish targets from the hydroacoustic data. This process is often labour-intensive and time-consuming, making real-time assessment of fish populations difficult. Simple solutions are not always available for all circumstances. However, the split-beam sonar data collected in the lower Fraser River, British Columbia, Canada, showed distinct signatures between actively swimming fish and non-fish objects such as drifting debris, surface bubbles, and stationary objects in the water column and off the river bottom. Acoustic tracks of fish and non-fish targets were characterized by differentiable statistical patterns that were amenable to discriminant function analysis (DFA). An application of DFA to segregate fish and non-fish targets detected by a split-beam sonar system in the lower Fraser River is presented, characteristics of user-identified fish and non-fish acoustic tracks being utilized as learning samples for the DFA. Also, a method to rank the discriminating power of individual variables is presented, providing guidance for constructing efficient and effective discriminant functions with variables that offer high discriminating power. The DFA yielded classification accuracies of 96% for fish and 91% for non-fish tracks and reduced the manual sorting time by 50–75%.
    Print ISSN: 1054-3139
    Electronic ISSN: 1095-9289
    Topics: Biology , Geosciences , Physics
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  • 5
    Publication Date: 2011-03-16
    Description: Frontotemporal lobar degeneration is a progressive neurodegenerative syndrome that is the second most common cause of early-onset dementia. Mutations in the progranulin gene are a major cause of familial frontotemporal lobar degeneration [Baker M, et al. (2006) Nature 442:916–919 and Cruts M, et al. (2006) Nature 442:920–924]. Although progranulin is involved in wound healing, inflammation, and tumor growth, its role in the nervous system and the mechanism by which insufficient levels result in neurodegeneration are poorly understood [Eriksen and Mackenzie (2008) J Neurochem 104:287–297]. We have characterized the normal function of progranulin in the nematode Caenorhabditis elegans. We found that mutants lacking pgrn-1 appear grossly normal, but exhibit fewer apoptotic cell corpses during development. This reduction in corpse number is not caused by reduced apoptosis, but instead by more rapid clearance of dying cells. Likewise, we found that macrophages cultured from progranulin KO mice displayed enhanced rates of apoptotic-cell phagocytosis. Although most neurodegenerative diseases are thought to be caused by the toxic effects of aggregated proteins, our findings suggest that susceptibility to neurodegeneration may be increased by a change in the kinetics of programmed cell death. We propose that cells that might otherwise recover from damage or injury are destroyed in progranulin mutants, which in turn facilitates disease progression.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 6
    Publication Date: 1998-01-31
    Description: The cerebral cortex of Alzheimer's and Down syndrome patients is characterized by the presence of protein deposits in neurofibrillary tangles, neuritic plaques, and neuropil threads. These structures were shown to contain forms of beta amyloid precursor protein and ubiquitin-B that are aberrant (+1 proteins) in the carboxyl terminus. The +1 proteins were not found in young control patients, whereas the presence of ubiquitin-B+1 in elderly control patients may indicate early stages of neurodegeneration. The two species of +1 proteins displayed cellular colocalization, suggesting a common origin, operating at the transcriptional level or by posttranscriptional editing of RNA. This type of transcript mutation is likely an important factor in the widely occurring nonfamilial early- and late-onset forms of Alzheimer's disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉van Leeuwen, F W -- de Kleijn, D P -- van den Hurk, H H -- Neubauer, A -- Sonnemans, M A -- Sluijs, J A -- Koycu, S -- Ramdjielal, R D -- Salehi, A -- Martens, G J -- Grosveld, F G -- Peter, J -- Burbach, H -- Hol, E M -- New York, N.Y. -- Science. 1998 Jan 9;279(5348):242-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Graduate School for Neurosciences Amsterdam, Netherlands Institute for Brain Research, 1105 AZ Amsterdam, The Netherlands. f.van.leeuwen@nih.knaw.nl〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9422699" target="_blank"〉PubMed〈/a〉
    Keywords: Aged ; Aging/genetics ; Alzheimer Disease/*genetics/metabolism/pathology ; Amino Acid Sequence ; Amyloid beta-Protein Precursor/analysis/chemistry/*genetics ; Base Sequence ; *Brain Chemistry ; Cerebral Cortex/chemistry/pathology ; Cloning, Molecular ; Down Syndrome/*genetics/metabolism/pathology ; Female ; *Frameshift Mutation ; Hippocampus/chemistry/pathology ; Humans ; Male ; Molecular Sequence Data ; Neurites/chemistry ; Neurofibrillary Tangles/chemistry ; Neuropil/chemistry ; Polymerase Chain Reaction ; RNA Editing ; Repetitive Sequences, Nucleic Acid ; Sequence Deletion ; Transcription, Genetic ; Ubiquitins/analysis/chemistry/*genetics/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2016-05-07
    Description: A simple design for an inexpensive, cooled, free-jet beam source is described. The source assembly features an integrated cooling system as supplied by a counter-flow of chilled nitrogen, and is composed primarily of off-the-shelf tube fittings. The design facilitates rapid implementation and eases subsequent alignment with respect to any downstream beamline aperture. The source assembly outlined cools the full length of the stagnation volume, offering temperature control down to 100 K and long-term temperature stability better than ±1 K.
    Print ISSN: 0034-6748
    Electronic ISSN: 1089-7623
    Topics: Electrical Engineering, Measurement and Control Technology , Physics
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  • 8
    Publication Date: 2014-04-30
    Description: Speciation generally involves a three-step process--range expansion, range fragmentation and the development of reproductive isolation between spatially separated populations. Speciation relies on cycling through these three steps and each may limit the rate at which new species form. We estimate phylogenetic relationships among all Himalayan songbirds to ask whether the development of reproductive isolation and ecological competition, both factors that limit range expansions, set an ultimate limit on speciation. Based on a phylogeny for all 358 species distributed along the eastern elevational gradient, here we show that body size and shape differences evolved early in the radiation, with the elevational band occupied by a species evolving later. These results are consistent with competition for niche space limiting species accumulation. Even the elevation dimension seems to be approaching ecological saturation, because the closest relatives both inside the assemblage and elsewhere in the Himalayas are on average separated by more than five million years, which is longer than it generally takes for reproductive isolation to be completed; also, elevational distributions are well explained by resource availability, notably the abundance of arthropods, and not by differences in diversification rates in different elevational zones. Our results imply that speciation rate is ultimately set by niche filling (that is, ecological competition for resources), rather than by the rate of acquisition of reproductive isolation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Price, Trevor D -- Hooper, Daniel M -- Buchanan, Caitlyn D -- Johansson, Ulf S -- Tietze, D Thomas -- Alstrom, Per -- Olsson, Urban -- Ghosh-Harihar, Mousumi -- Ishtiaq, Farah -- Gupta, Sandeep K -- Martens, Jochen -- Harr, Bettina -- Singh, Pratap -- Mohan, Dhananjai -- England -- Nature. 2014 May 8;509(7499):222-5. doi: 10.1038/nature13272. Epub 2014 Apr 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolution, University of Chicago, Chicago, Illinois 60637, USA. ; 1] Department of Ecology and Evolution, University of Chicago, Chicago, Illinois 60637, USA [2] Department of Zoology, Swedish Museum of Natural History, 10405 Stockholm, Sweden. ; 1] Department of Ecology and Evolution, University of Chicago, Chicago, Illinois 60637, USA [2] Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany. ; 1] Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, Beijing 100101, China [2] Swedish Species Information Centre, Swedish University of Agricultural Sciences, Box 7007, 75007 Uppsala, Sweden. ; Systematics and Biodiversity, Department of Biology and Environmental Sciences, University of Gothenburg, 40530 Gothenburg, Sweden. ; Wildlife Institute of India, PO Box 18, Chandrabani, Dehradun 248001, India. ; Institute of Zoology, Johannes Gutenberg University, Mainz 55099, Germany. ; Max Planck Institute for Evolutionary Biology, August Thienemannstrasse 2, 24306 Plon, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24776798" target="_blank"〉PubMed〈/a〉
    Keywords: *Altitude ; Animals ; Body Size ; China ; *Ecosystem ; *Genetic Speciation ; India ; Phylogeny ; Reproduction ; Songbirds/anatomy & histology/*classification/*physiology ; Tibet
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 9
    Publication Date: 2012-06-23
    Description: All cancers carry somatic mutations in their genomes. A subset, known as driver mutations, confer clonal selective advantage on cancer cells and are causally implicated in oncogenesis, and the remainder are passenger mutations. The driver mutations and mutational processes operative in breast cancer have not yet been comprehensively explored. Here we examine the genomes of 100 tumours for somatic copy number changes and mutations in the coding exons of protein-coding genes. The number of somatic mutations varied markedly between individual tumours. We found strong correlations between mutation number, age at which cancer was diagnosed and cancer histological grade, and observed multiple mutational signatures, including one present in about ten per cent of tumours characterized by numerous mutations of cytosine at TpC dinucleotides. Driver mutations were identified in several new cancer genes including AKT2, ARID1B, CASP8, CDKN1B, MAP3K1, MAP3K13, NCOR1, SMARCD1 and TBX3. Among the 100 tumours, we found driver mutations in at least 40 cancer genes and 73 different combinations of mutated cancer genes. The results highlight the substantial genetic diversity underlying this common disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3428862/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3428862/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stephens, Philip J -- Tarpey, Patrick S -- Davies, Helen -- Van Loo, Peter -- Greenman, Chris -- Wedge, David C -- Nik-Zainal, Serena -- Martin, Sancha -- Varela, Ignacio -- Bignell, Graham R -- Yates, Lucy R -- Papaemmanuil, Elli -- Beare, David -- Butler, Adam -- Cheverton, Angela -- Gamble, John -- Hinton, Jonathan -- Jia, Mingming -- Jayakumar, Alagu -- Jones, David -- Latimer, Calli -- Lau, King Wai -- McLaren, Stuart -- McBride, David J -- Menzies, Andrew -- Mudie, Laura -- Raine, Keiran -- Rad, Roland -- Chapman, Michael Spencer -- Teague, Jon -- Easton, Douglas -- Langerod, Anita -- Oslo Breast Cancer Consortium (OSBREAC) -- Lee, Ming Ta Michael -- Shen, Chen-Yang -- Tee, Benita Tan Kiat -- Huimin, Bernice Wong -- Broeks, Annegien -- Vargas, Ana Cristina -- Turashvili, Gulisa -- Martens, John -- Fatima, Aquila -- Miron, Penelope -- Chin, Suet-Feung -- Thomas, Gilles -- Boyault, Sandrine -- Mariani, Odette -- Lakhani, Sunil R -- van de Vijver, Marc -- van 't Veer, Laura -- Foekens, John -- Desmedt, Christine -- Sotiriou, Christos -- Tutt, Andrew -- Caldas, Carlos -- Reis-Filho, Jorge S -- Aparicio, Samuel A J R -- Salomon, Anne Vincent -- Borresen-Dale, Anne-Lise -- Richardson, Andrea L -- Campbell, Peter J -- Futreal, P Andrew -- Stratton, Michael R -- 077012/Z/05/Z/Wellcome Trust/United Kingdom -- 088340/Wellcome Trust/United Kingdom -- 093867/Wellcome Trust/United Kingdom -- 10118/Cancer Research UK/United Kingdom -- CA089393/CA/NCI NIH HHS/ -- P30 CA016672/CA/NCI NIH HHS/ -- WT088340MA/Wellcome Trust/United Kingdom -- Cancer Research UK/United Kingdom -- Chief Scientist Office/United Kingdom -- Department of Health/United Kingdom -- England -- Nature. 2012 May 16;486(7403):400-4. doi: 10.1038/nature11017.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22722201" target="_blank"〉PubMed〈/a〉
    Keywords: Age Factors ; Breast Neoplasms/classification/*genetics/pathology ; Cell Transformation, Neoplastic/*genetics ; Cytosine/metabolism ; DNA Mutational Analysis ; Female ; Humans ; JNK Mitogen-Activated Protein Kinases/metabolism ; Mutagenesis/*genetics ; Mutation/*genetics ; Neoplasm Grading ; Oncogenes/*genetics ; Reproducibility of Results ; Signal Transduction/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2015-07-24
    Description: Aims Intercropping legumes and non-legumes may affect the root growth of both components in the mixture, and the non-legume is known to be strongly favored by increasing nitrogen (N) supply. The knowledge of how root systems affect the growth of the individual species is useful for understanding the interactions in intercrops as well as for planning cover cropping strategies. The aim of this work was (i) to determine if different levels of N in the topsoil influence root depth (RD) and intensity of barley and vetch as sole crops or as an intercropped mixture and (ii) to test if the choice of a mixture or the N availability in the topsoil will influence the N uptake by deep roots. Methods In this study, we combined rhizotron studies with root extraction and species identification by microscopy with studies of growth, N uptake and 15 N uptake from deeper soil layers, for studying the root interactions of root growth and N foraging for barley ( Hordeum vulgare L.) and vetch ( Vicia sativa L.), frequently grown in mixtures as cover crops. N was added at 0 (N0), 50 (N1) and 150 (N2) kg N ha –1 . The roots discrimination relying on the anatomical and morphological differences observed between dicots and monocots proved to be a reliable method providing valuable data for the analysis. Important Findings The intercrop and the barley attained slightly higher root intensity (RI) and RD than the vetch, with values around 150 crosses m –1 and 1.4 m, respectively, compared to 50 crosses m –1 and 0.9 m for the vetch. At deep soil layers, intercropping showed slightly larger RI values compared to the sole-cropped barley. The barley and the intercropping had larger root length density (RLD) values (200–600 m m –3 ) than the vetch (25–130) at 0.8–1.2 m depth. The topsoil N supply did not show a clear effect on the RI, RD or RLD; however, increasing topsoil N favored the proliferation of vetch roots in the intercropping at deep soil layers, with the barley:vetch root ratio ranging from 25 at N0 to 5 at N2. The N uptake of the barley was enhanced in the intercropping at the expense of the vetch (from ~100mg plant –1 to 200). The intercropped barley roots took up more labeled nitrogen (0.6mg 15 N plant –1 ) than the sole-cropped barley roots (0.3mg 15 N plant –1 ) from deep layers.
    Print ISSN: 1752-993X
    Electronic ISSN: 1752-9921
    Topics: Biology
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