ALBERT

Description: Amorphous metal-oxide semiconductors have emerged as potential replacements for organic and silicon materials in thin-film electronics. The high carrier mobility in the amorphous state, and excellent large-area uniformity, have extended their applications to active-matrix electronics, including displays, sensor arrays and X-ray detectors. Moreover, their solution processability and optical transparency have opened new horizons for low-cost printable and transparent electronics on plastic substrates. But metal-oxide formation by the sol-gel route requires an annealing step at relatively high temperature, which has prevented the incorporation of these materials with the polymer substrates used in high-performance flexible electronics. Here we report a general method for forming high-performance and operationally stable metal-oxide semiconductors at room temperature, by deep-ultraviolet photochemical activation of sol-gel films. Deep-ultraviolet irradiation induces efficient condensation and densification of oxide semiconducting films by photochemical activation at low temperature. This photochemical activation is applicable to numerous metal-oxide semiconductors, and the performance (in terms of transistor mobility and operational stability) of thin-film transistors fabricated by this route compares favourably with that of thin-film transistors based on thermally annealed materials. The field-effect mobilities of the photo-activated metal-oxide semiconductors are as high as 14 and 7 cm(2) V(-1) s(-1) (with an Al(2)O(3) gate insulator) on glass and polymer substrates, respectively; and seven-stage ring oscillators fabricated on polymer substrates operate with an oscillation frequency of more than 340 kHz, corresponding to a propagation delay of less than 210 nanoseconds per stage.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Yong-Hoon -- Heo, Jae-Sang -- Kim, Tae-Hyeong -- Park, Sungjun -- Yoon, Myung-Han -- Kim, Jiwan -- Oh, Min Suk -- Yi, Gi-Ra -- Noh, Yong-Young -- Park, Sung Kyu -- England -- Nature. 2012 Sep 6;489(7414):128-32. doi: 10.1038/nature11434.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Flexible Display Research Center, Korea Electronics Technology Institute, Seongnam 463-816, Korea.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22955624" target="_blank"〉PubMed〈/a〉

Description: Alzheimer's disease is the most common form of dementia, characterized by two pathological hallmarks: amyloid-beta plaques and neurofibrillary tangles. The amyloid hypothesis of Alzheimer's disease posits that the excessive accumulation of amyloid-beta peptide leads to neurofibrillary tangles composed of aggregated hyperphosphorylated tau. However, to date, no single disease model has serially linked these two pathological events using human neuronal cells. Mouse models with familial Alzheimer's disease (FAD) mutations exhibit amyloid-beta-induced synaptic and memory deficits but they do not fully recapitulate other key pathological events of Alzheimer's disease, including distinct neurofibrillary tangle pathology. Human neurons derived from Alzheimer's disease patients have shown elevated levels of toxic amyloid-beta species and phosphorylated tau but did not demonstrate amyloid-beta plaques or neurofibrillary tangles. Here we report that FAD mutations in beta-amyloid precursor protein and presenilin 1 are able to induce robust extracellular deposition of amyloid-beta, including amyloid-beta plaques, in a human neural stem-cell-derived three-dimensional (3D) culture system. More importantly, the 3D-differentiated neuronal cells expressing FAD mutations exhibited high levels of detergent-resistant, silver-positive aggregates of phosphorylated tau in the soma and neurites, as well as filamentous tau, as detected by immunoelectron microscopy. Inhibition of amyloid-beta generation with beta- or gamma-secretase inhibitors not only decreased amyloid-beta pathology, but also attenuated tauopathy. We also found that glycogen synthase kinase 3 (GSK3) regulated amyloid-beta-mediated tau phosphorylation. We have successfully recapitulated amyloid-beta and tau pathology in a single 3D human neural cell culture system. Our unique strategy for recapitulating Alzheimer's disease pathology in a 3D neural cell culture model should also serve to facilitate the development of more precise human neural cell models of other neurodegenerative disorders.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4366007/" 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/PMC4366007/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Choi, Se Hoon -- Kim, Young Hye -- Hebisch, Matthias -- Sliwinski, Christopher -- Lee, Seungkyu -- D'Avanzo, Carla -- Chen, Hechao -- Hooli, Basavaraj -- Asselin, Caroline -- Muffat, Julien -- Klee, Justin B -- Zhang, Can -- Wainger, Brian J -- Peitz, Michael -- Kovacs, Dora M -- Woolf, Clifford J -- Wagner, Steven L -- Tanzi, Rudolph E -- Kim, Doo Yeon -- 5P01AG15379/AG/NIA NIH HHS/ -- 5R37MH060009/MH/NIMH NIH HHS/ -- P01 AG004953/AG/NIA NIH HHS/ -- P01 AG015379/AG/NIA NIH HHS/ -- P30 HD018655/HD/NICHD NIH HHS/ -- P30 NS045776/NS/NINDS NIH HHS/ -- P50 AG005134/AG/NIA NIH HHS/ -- R01 AG014713/AG/NIA NIH HHS/ -- R01 NS045860/NS/NINDS NIH HHS/ -- R21 AG031483/AG/NIA NIH HHS/ -- RF1 AG048080/AG/NIA NIH HHS/ -- England -- Nature. 2014 Nov 13;515(7526):274-8. doi: 10.1038/nature13800. Epub 2014 Oct 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA [2]. ; 1] Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA [2] Division of Mass Spectrometry Research, Korea Basic Science Institute, Cheongju-si, Chungbuk 363-883, South Korea [3]. ; 1] Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA [2] Institute of Reconstructive Neurobiology, Life and Brain Center, University of Bonn and Hertie Foundation, 53127 Bonn, Germany. ; Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA. ; FM Kirby Neurobiology Center, Boston Children's Hospital and Harvard Stem Cell Institute, Boston, Massachusetts 02115, USA. ; The Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA. ; Institute of Reconstructive Neurobiology, Life and Brain Center, University of Bonn and Hertie Foundation, 53127 Bonn, Germany. ; Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25307057" target="_blank"〉PubMed〈/a〉

Description: We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Deltaex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉George, Julie -- Lim, Jing Shan -- Jang, Se Jin -- Cun, Yupeng -- Ozretic, Luka -- Kong, Gu -- Leenders, Frauke -- Lu, Xin -- Fernandez-Cuesta, Lynnette -- Bosco, Graziella -- Muller, Christian -- Dahmen, Ilona -- Jahchan, Nadine S -- Park, Kwon-Sik -- Yang, Dian -- Karnezis, Anthony N -- Vaka, Dedeepya -- Torres, Angela -- Wang, Maia Segura -- Korbel, Jan O -- Menon, Roopika -- Chun, Sung-Min -- Kim, Deokhoon -- Wilkerson, Matt -- Hayes, Neil -- Engelmann, David -- Putzer, Brigitte -- Bos, Marc -- Michels, Sebastian -- Vlasic, Ignacija -- Seidel, Danila -- Pinther, Berit -- Schaub, Philipp -- Becker, Christian -- Altmuller, Janine -- Yokota, Jun -- Kohno, Takashi -- Iwakawa, Reika -- Tsuta, Koji -- Noguchi, Masayuki -- Muley, Thomas -- Hoffmann, Hans -- Schnabel, Philipp A -- Petersen, Iver -- Chen, Yuan -- Soltermann, Alex -- Tischler, Verena -- Choi, Chang-min -- Kim, Yong-Hee -- Massion, Pierre P -- Zou, Yong -- Jovanovic, Dragana -- Kontic, Milica -- Wright, Gavin M -- Russell, Prudence A -- Solomon, Benjamin -- Koch, Ina -- Lindner, Michael -- Muscarella, Lucia A -- la Torre, Annamaria -- Field, John K -- Jakopovic, Marko -- Knezevic, Jelena -- Castanos-Velez, Esmeralda -- Roz, Luca -- Pastorino, Ugo -- Brustugun, Odd-Terje -- Lund-Iversen, Marius -- Thunnissen, Erik -- Kohler, Jens -- Schuler, Martin -- Botling, Johan -- Sandelin, Martin -- Sanchez-Cespedes, Montserrat -- Salvesen, Helga B -- Achter, Viktor -- Lang, Ulrich -- Bogus, Magdalena -- Schneider, Peter M -- Zander, Thomas -- Ansen, Sascha -- Hallek, Michael -- Wolf, Jurgen -- Vingron, Martin -- Yatabe, Yasushi -- Travis, William D -- Nurnberg, Peter -- Reinhardt, Christian -- Perner, Sven -- Heukamp, Lukas -- Buttner, Reinhard -- Haas, Stefan A -- Brambilla, Elisabeth -- Peifer, Martin -- Sage, Julien -- Thomas, Roman K -- 5R01CA114102-08/CA/NCI NIH HHS/ -- England -- Nature. 2015 Aug 6;524(7563):47-53. doi: 10.1038/nature14664. Epub 2015 Jul 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, 50931 Cologne, Germany. ; Departments of Pediatrics and Genetics, Stanford University, Stanford, California 94305, USA. ; Department of Pathology and Center for Cancer Genome Discovery, University of Ulsan College of Medicine, Asan Medical Center 88, Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea. ; Department of Pathology, University Hospital Cologne, 50937 Cologne, Germany. ; Department of Pathology, College of Medicine, Hanyang University. 222 Wangsimniro, Seongdong-gu, Seoul 133-791, Korea. ; Vancouver General Hospital, Terry Fox laboratory, Vancouver, British Columbia V5Z 1L3, Canada. ; European Molecular Biology Laboratory, Genome Biology Unit, 69117 Heidelberg, Germany. ; Institute of Pathology, Center of Integrated Oncology Cologne-Bonn, University Hospital of Bonn, 53127 Bonn, Germany. ; Center for Cancer Genome Discovery, University of Ulsan College of Medicine, Asan Medical Center 88, Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea. ; Department of Genetics, Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, North Carolina 27599-7295, USA. ; UNC Lineberger Comprehensive Cancer Center School of Medicine, University of North Carolina at Chapel Hill, North Carolina 27599-7295, USA. ; Institute of Experimental Gene Therapy and Cancer Research, Rostock University Medical Center, 18057 Rostock, Germany. ; Department I of Internal Medicine, Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne, 50937 Cologne, Germany. ; Department of Internal Medicine, University Hospital of Cologne, 50931 Cologne, Germany. ; Cologne Center for Genomics (CCG), University of Cologne, 50931 Cologne, Germany. ; 1] Cologne Center for Genomics (CCG), University of Cologne, 50931 Cologne, Germany. [2] Institute of Human Genetics, University Hospital Cologne, 50931 Cologne, Germany. ; 1] Division of Genome Biology, National Cancer Center Research Institute, Chuo-ku, Tokyo 1040045, Japan. [2] Genomics and Epigenomics of Cancer Prediction Program, Institute of Predictive and Personalized Medicine of Cancer (IMPPC), Barcelona 08916, Spain. ; Division of Genome Biology, National Cancer Center Research Institute, Chuo-ku, Tokyo 1040045, Japan. ; Department of Pathology and Clinical Laboratories, National Cancer Center Hospital Chuo-ku, Tokyo 1040045, Japan. ; Department of Pathology, Faculty of Medicine, University of Tsukuba, Ibaraki 305-8575, Japan. ; 1] Thoraxklinik at University Hospital Heidelberg, Amalienstrasse 5, 69126 Heidelberg, Germany. [2] Translational Lung Research Center Heidelberg (TLRC-H), Member of German Center for Lung Research (DZL), Amalienstrasse 5, 69126 Heidelberg, Germany. ; Thoraxklinik at University Hospital Heidelberg, Amalienstrasse 5, 69126 Heidelberg, Germany. ; 1] Translational Lung Research Center Heidelberg (TLRC-H), Member of German Center for Lung Research (DZL), Amalienstrasse 5, 69126 Heidelberg, Germany. [2] Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 220, 69120 Heidelberg, Germany. ; Institute of Pathology, Jena University Hospital, Friedrich-Schiller-University, 07743 Jena, Germany. ; Institute of Surgical Pathology, University Hospital Zurich, 8091 Zurich, Switzerland. ; Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea. ; Department of Thoracic and Cardiovascular Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea. ; Thoracic Program, Vanderbilt-Ingram Cancer Center PRB 640, 2220 Pierce Avenue, Nashville, Tennessee 37232, USA. ; University Hospital of Pulmonology, Clinical Center of Serbia, Medical School, University of Belgrade, 11000 Belgrade, Serbia. ; Department of Surgery, St. Vincent's Hospital, Peter MacCallum Cancer Centre, 3065 Melbourne, Victoria, Australia. ; Department of Pathology, St. Vincent's Hospital, Peter MacCallum Cancer Centre, 3065 Melbourne, Victoria, Australia. ; Department of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, 3065 Melbourne, Victoria, Australia. ; Asklepios Biobank fur Lungenerkrankungen, Comprehensive Pneumology Center Munich, Member of the German Center for Lung Research (DZL), Asklepios Fachkliniken Munchen-Gauting 82131, Germany. ; Laboratory of Oncology, IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini, 71013 San Giovanni, Rotondo, Italy. ; Roy Castle Lung Cancer Research Programme, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, The University of Liverpool Cancer Research Centre, 200 London Road, L69 3GA Liverpool, UK. ; University of Zagreb, School of Medicine, Department for Respiratory Diseases Jordanovac, University Hospital Center Zagreb, 10000 Zagreb, Croatia. ; Laboratory for Translational Medicine, Rudjer Boskovic Institute, 10000 Zagreb, Croatia. ; Charite Comprehensive Cancer Center, Charite Campus Mitte, 10115 Berlin, Germany. ; Tumor Genomics Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS - Istituto Nazionale Tumori, Via Venezian 1, 20133 Milan, Italy. ; Thoracic Surgery Unit, Department of Surgery, Fondazione IRCCS Istituto Nazionale Tumori, 20133 Milan, Italy. ; 1] Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, N-0424 Oslo, Norway. [2] Department of Oncology, Norwegian Radium Hospital, Oslo University Hospital, N-0310 Oslo, Norway. ; Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, N-0310 Oslo, Norway. ; Department of Pathology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands. ; 1] West German Cancer Center, Department of Medical Oncology, University Hospital Essen, 45147 Essen, Germany. [2] German Cancer Consortium (DKTK), 69120 Heidelberg, Germany. ; Departments of Immunology, Genetics and Pathology, and Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, 75185 Uppsala, Sweden. ; Genes and Cancer Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), 08908 Hospitalet de Llobregat, Barcelona, Spain. ; 1] Department of Clinical Science, Center for Cancer Biomarkers, University of Bergen, N-5058 Bergen, Norway. [2] Department of Gynecology and Obstetrics, Haukeland University Hospital, N-5058 Bergen, Norway. ; Computing Center, University of Cologne, 50931 Cologne, Germany. ; 1] Computing Center, University of Cologne, 50931 Cologne, Germany. [2] Department of Informatics, University of Cologne, 50931 Cologne, Germany. ; Institute of Legal Medicine, University of Cologne, 50823 Cologne, Germany. ; Gastrointestinal Cancer Group Cologne, Center of Integrated Oncology Cologne-Bonn, Department I for Internal Medicine, University Hospital of Cologne, 50937 Cologne, Germany. ; 1] Department I of Internal Medicine, Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne, 50937 Cologne, Germany. [2] Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany. ; Computational Molecular Biology Group, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany. ; Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, 464-8681 Nagoya, Japan. ; Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York 10065, USA. ; 1] Cologne Center for Genomics (CCG), University of Cologne, 50931 Cologne, Germany. [2] Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany. [3] Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany. ; Department of Pathology, CHU Grenoble INSERM U823, University Joseph Fourier, Institute Albert Bonniot 38043, CS10217 Grenoble, France. ; 1] Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, 50931 Cologne, Germany. [2] Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany. ; 1] Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, 50931 Cologne, Germany. [2] Department of Pathology, University Hospital Cologne, 50937 Cologne, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26168399" target="_blank"〉PubMed〈/a〉