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  • 1
    Call number: YY Diss Sim/Mag
    Keywords: DKFZ-publications / academic dissertations
    Pages: 148 p.
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    YY Diss Sim/Mag departmental collection or stack – please contact the library
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  • 2
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  GMS Journal for Medical Education; VOL: 36; DOC37 /20190815/
    Publication Date: 2019-08-16
    Description: Background: It is unavoidable for learners undergoing health professions training to encounter different complex clinical scenarios related to diagnoses, treatment and ethical dilemmas. The lack of standard answers to such clinical challenges can cause uncertainty in the process of teaching, learning and assessment as learners grapple with the need to critically appraise the specific context, past practices and extant literature to arrive at a thoughtful decision. In this aspect, debate can be a useful pedagogical tool to consider multiple, different perspectives regarding these issues. As the use of debate within the health professions education has not been reviewed, we conducted a systematic review of the current literature on the adoption of debate as a pedagogical tool to clarify the specific context of use as well as its effectiveness in the learning of skills and content within the health professions education. Methods: A systematic review was conducted on relevant published literature in English within journal databases until September 2018 that employed debate as a pedagogical tool within health professions education. Results: Out of 626 screened articles, 12 studies were finally included based on inclusion/exclusion criteria. The 12 studies (9 undergraduate, 3 postgraduate) covered a diverse range of disciplines and debate in health professions education was adopted for acquisition of skills (such as critical thinking, communication skills, teamwork), or learning of specific topics (such as patient safety, ethical issues, teaching of new topics) as well as to examine evidence based practice. In the majority of studies (10 of 12 studies, 83.3%), debate has been deemed by the learners to be effective in facilitating the learning of new content and skills such as communication and critical thinking, which are related to processes aligned with adult learning, motivational, reflective and social learning theories.Conclusion: Overall, sparse studies to date with relatively low risk of bias found debate to be effective in enabling the learning of skills and content within health professions education. Future studies may want to incorporate more objective measures of the learning outcomes of learners following the adoption of debate as a teaching tool as well as to examine the combinatorial use of debate with other pedagogical tools and their longitudinal impact on learners and learning.
    Description: Hintergrund: Für Lernende während der ärztlichen Ausbildung ist es unvermeidbar, verschiedenen komplexen klinischen Szenarien hinsichtlich Diagnose, Behandlung und ethischer Dilemmata zu begegnen. Der Mangel an Standardantworten auf solche klinischen Herausforderungen kann zu Unsicherheit im Prozess des Lehrens, Lernens und der Einschätzung führen, da die Lernenden sich mit dem Bedürfnis nach kritischer Bewertung eines spezifischen Kontextes, vergangenen Praktiken und vorhandener Literatur auseinandersetzen müssen, um zu einer durchdachten Entscheidung zu gelangen. In dieser Hinsicht kann die Debatte ein nützliches pädagogisches Werkzeug sein, um verschiedenartige, multiple Perspektiven bezüglich dieser Probleme zu berücksichtigen. Da der Nutzen von Debatten innerhalb der ärztlichen Ausbildung noch nicht überprüft worden ist, haben wir einen systematischen Überblick über die aktuelle Literatur zur Einbeziehung von Debatten als pädagogisches Werkzeug vorgenommen, um deren spezifischen Nutzungskontext sowie Effektivität beim Erlernen von Fähigkeiten und Inhalten innerhalb der ärztlichen Ausbildung zu klären. Methoden: Es wurde eine systematische Überprüfung der relevanten, bis September 2018 veröffentlichten englischsprachigen Literatur in Zeitschriftendatenbanken durchgeführt, die sich mit Debatten als pädagogischem Werkzeug innerhalb der Ausbildung von Gesundheitsberufen befassten. Ergebnisse: Von 626 angezeigten Artikeln wurden schließlich 12 Studien basierend auf Inklusions-/Exklusionskriterien einbezogen. Diese 12 Studien (9 universitäre, 3 postgraduierte) deckten ganz verschiedene Bereiche und Disziplinen ab, und die Debatte in der Ausbildung von Gesundheitsberufen wurde zum Erwerb von Fähigkeiten (wie z. B. kritisches Denken, kommunikative Fähigkeiten, Teamwork) oder zum Erlernen spezifischer Themen (wie z. B. Patientensicherheit, ethische Probleme, Unterrichten neuer Themenbereiche) sowie zur Überprüfung Evidenz-basierter Praxis genutzt. Bei der Mehrheit der Studien (10 von 12 Studien, 83,3%) wurden Debatten seitens der Lernenden als effektiv bei der Erleichterung des Erlernens neuer Inhalte und Fähigkeiten, wie z. B. bei der Kommunikation und dem kritischen Denken, eingeschätzt, die verbunden sind mit Prozessen, die am Lernen im Erwachsenenalter, an Motivations-, Reflexions- und sozialen Lerntheorien ausgerichtet sind.Schlussfolgerung: Insgesamt schätzten die bislang nur spärlich vorhandenen Studien mit einem relativ niedrigen Risiko der systematischen Verzerrung Debatten als effektiv bei der Ermöglichung des Erlernens von Fähigkeiten und Inhalten innerhalb der Ausbildung von Gesundheitsberufen ein. Zukünftige Studien sollten eventuell objektivere Maßstäbe bzgl. der Lernergebnisse nach Einbeziehung von Debatten als Lehrwerkzeug anlegen, sowie die kombinierte Nutzung von Debatten zusammen mit anderen pädagogischen Werkzeugen und deren langfristigen Einfluss auf Lernende und Lernen untersuchen.
    Keywords: education ; health professions ; debate ; Ausbildung ; Gesundheitsberufe ; Debatte ; ddc: 610
    Language: English
    Type: article
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  • 3
    Publication Date: 2014-07-22
    Description: Tumour oncogenes include transcription factors that co-opt the general transcriptional machinery to sustain the oncogenic state, but direct pharmacological inhibition of transcription factors has so far proven difficult. However, the transcriptional machinery contains various enzymatic cofactors that can be targeted for the development of new therapeutic candidates, including cyclin-dependent kinases (CDKs). Here we present the discovery and characterization of a covalent CDK7 inhibitor, THZ1, which has the unprecedented ability to target a remote cysteine residue located outside of the canonical kinase domain, providing an unanticipated means of achieving selectivity for CDK7. Cancer cell-line profiling indicates that a subset of cancer cell lines, including human T-cell acute lymphoblastic leukaemia (T-ALL), have exceptional sensitivity to THZ1. Genome-wide analysis in Jurkat T-ALL cells shows that THZ1 disproportionally affects transcription of RUNX1 and suggests that sensitivity to THZ1 may be due to vulnerability conferred by the RUNX1 super-enhancer and the key role of RUNX1 in the core transcriptional regulatory circuitry of these tumour cells. Pharmacological modulation of CDK7 kinase activity may thus provide an approach to identify and treat tumour types that are dependent on transcription for maintenance of the oncogenic state.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4244910/" 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/PMC4244910/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kwiatkowski, Nicholas -- Zhang, Tinghu -- Rahl, Peter B -- Abraham, Brian J -- Reddy, Jessica -- Ficarro, Scott B -- Dastur, Anahita -- Amzallag, Arnaud -- Ramaswamy, Sridhar -- Tesar, Bethany -- Jenkins, Catherine E -- Hannett, Nancy M -- McMillin, Douglas -- Sanda, Takaomi -- Sim, Taebo -- Kim, Nam Doo -- Look, Thomas -- Mitsiades, Constantine S -- Weng, Andrew P -- Brown, Jennifer R -- Benes, Cyril H -- Marto, Jarrod A -- Young, Richard A -- Gray, Nathanael S -- CA109901/CA/NCI NIH HHS/ -- CA178860-01/CA/NCI NIH HHS/ -- HG002668/HG/NHGRI NIH HHS/ -- P01 NS047572/NS/NINDS NIH HHS/ -- P01 NS047572-10/NS/NINDS NIH HHS/ -- P30 CA014051/CA/NCI NIH HHS/ -- R01 CA130876/CA/NCI NIH HHS/ -- R01 CA130876-04/CA/NCI NIH HHS/ -- R01 CA179483/CA/NCI NIH HHS/ -- R01 HG002668/HG/NHGRI NIH HHS/ -- R21 CA178860/CA/NCI NIH HHS/ -- T32 GM008042/GM/NIGMS NIH HHS/ -- U54 HG006097/HG/NHGRI NIH HHS/ -- U54 HG006097-02/HG/NHGRI NIH HHS/ -- England -- Nature. 2014 Jul 31;511(7511):616-20. doi: 10.1038/nature13393. Epub 2014 Jun 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA [2] Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA [3] Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA [4]. ; 1] Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA [2] Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA [3]. ; Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA. ; 1] Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA [2] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. ; 1] Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA [2] Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA [3] Blais Proteomics Center, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA. ; Department of Medicine Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts 02129, USA. ; 1] Department of Medicine Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts 02129, USA [2] Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA. ; 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. ; Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada. ; 1] Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02215, USA [2] Cancer Science Institute of Singapore, National University of Singapore, 117599 Singapore. ; Chemical Kinomics Research Center, Korea Institute of Science and Technology, 39-1, Hawolgok-dong, Seongbuk-gu, Seoul 136-791, Korea, and KU-KIST Graduate School of Converging Science and Technology, 145, Anam-ro, Seongbuk-gu, Seoul 136-713, Korea. ; Daegu-Gyeongbuk Medical Innovation Foundation, 2387 dalgubeol-daero, Suseong-gu, Daegu 706-010, Korea. ; 1] Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02215, USA [2] Division of Hematology/Oncology, Children's Hospital, Boston, Massachusetts 02115 USA. ; 1] Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA [2] Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25043025" target="_blank"〉PubMed〈/a〉
    Keywords: Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Core Binding Factor Alpha 2 Subunit/metabolism ; Cyclin-Dependent Kinases/antagonists & inhibitors ; Cysteine/metabolism ; Enzyme Inhibitors/*pharmacology ; Gene Expression Regulation, Neoplastic/*drug effects ; Humans ; Jurkat Cells ; Phenylenediamines/*pharmacology ; Phosphorylation/drug effects ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/*enzymology ; Pyrimidines/*pharmacology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2018-11-02
    Description: The most commonly utilized class of chemotherapeutic agents administered as a first-line therapy are antimitotic drugs; however, their clinical success is often impeded by chemoresistance and disease relapse. Hence, a better understanding of the cellular pathways underlying escape from cell death is critical. Mitotic slippage describes the cellular process where cells exit antimitotic drug-enforced mitotic arrest and "slip" into interphase without proper chromosome segregation and cytokinesis. The current report explores the cell fate consequence following mitotic slippage and assesses a major outcome following treatment with many chemotherapies, therapy-induced senescence. It was found that cells postslippage entered senescence and could impart the senescence-associated secretory phenotype (SASP). SASP factor production elicited paracrine protumorigenic effects, such as migration, invasion, and vascularization. Both senescence and SASP factor development were found to be dependent on autophagy. Autophagy induction during mitotic slippage involved the autophagy activator AMPK and endoplasmic reticulum stress response protein PERK. Pharmacologic inhibition of autophagy or silencing of autophagy-related ATG5 led to a bypass of G 1 arrest senescence, reduced SASP-associated paracrine tumorigenic effects, and increased DNA damage after S-phase entry with a concomitant increase in apoptosis. Consistent with this, the autophagy inhibitor chloroquine and microtubule-stabilizing drug paclitaxel synergistically inhibited tumor growth in mice. Sensitivity to this combinatorial treatment was dependent on p53 status, an important factor to consider before treatment. Implications: Clinical regimens targeting senescence and SASP could provide a potential effective combinatorial strategy with antimitotic drugs. Mol Cancer Res; 16(11); 1625–40. ©2018 AACR .
    Print ISSN: 1541-7786
    Electronic ISSN: 1557-3125
    Topics: Medicine
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  • 5
    Publication Date: 2018-11-27
    Description: The renin angiotensin system (RAS) mediates bifunctional growth regulation in melanoma and is a novel target for therapeutic intervention The renin angiotensin system (RAS) mediates bifunctional growth regulation in melanoma and is a novel target for therapeutic intervention, Published online: 26 November 2018; doi:10.1038/s41388-018-0563-y The renin angiotensin system (RAS) mediates bifunctional growth regulation in melanoma and is a novel target for therapeutic intervention
    Print ISSN: 0950-9232
    Topics: Medicine
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  • 6
    Publication Date: 2014-03-29
    Description: Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly 'housekeeping', whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529748/" 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/PMC4529748/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉FANTOM Consortium and the RIKEN PMI and CLST (DGT) -- Forrest, Alistair R R -- Kawaji, Hideya -- Rehli, Michael -- Baillie, J Kenneth -- de Hoon, Michiel J L -- Haberle, Vanja -- Lassmann, Timo -- Kulakovskiy, Ivan V -- Lizio, Marina -- Itoh, Masayoshi -- Andersson, Robin -- Mungall, Christopher J -- Meehan, Terrence F -- Schmeier, Sebastian -- Bertin, Nicolas -- Jorgensen, Mette -- Dimont, Emmanuel -- Arner, Erik -- Schmidl, Christian -- Schaefer, Ulf -- Medvedeva, Yulia A -- Plessy, Charles -- Vitezic, Morana -- Severin, Jessica -- Semple, Colin A -- Ishizu, Yuri -- Young, Robert S -- Francescatto, Margherita -- Alam, Intikhab -- Albanese, Davide -- Altschuler, Gabriel M -- Arakawa, Takahiro -- Archer, John A C -- Arner, Peter -- Babina, Magda -- Rennie, Sarah -- Balwierz, Piotr J -- Beckhouse, Anthony G -- Pradhan-Bhatt, Swati -- Blake, Judith A -- Blumenthal, Antje -- Bodega, Beatrice -- Bonetti, Alessandro -- Briggs, James -- Brombacher, Frank -- Burroughs, A Maxwell -- Califano, Andrea -- Cannistraci, Carlo V -- Carbajo, Daniel -- Chen, Yun -- Chierici, Marco -- Ciani, Yari -- Clevers, Hans C -- Dalla, Emiliano -- Davis, Carrie A -- Detmar, Michael -- Diehl, Alexander D -- Dohi, Taeko -- Drablos, Finn -- Edge, Albert S B -- Edinger, Matthias -- Ekwall, Karl -- Endoh, Mitsuhiro -- Enomoto, Hideki -- Fagiolini, Michela -- Fairbairn, Lynsey -- Fang, Hai -- Farach-Carson, Mary C -- Faulkner, Geoffrey J -- Favorov, Alexander V -- Fisher, Malcolm E -- Frith, Martin C -- Fujita, Rie -- Fukuda, Shiro -- Furlanello, Cesare -- Furino, Masaaki -- Furusawa, Jun-ichi -- Geijtenbeek, Teunis B -- Gibson, Andrew P -- Gingeras, Thomas -- Goldowitz, Daniel -- Gough, Julian -- Guhl, Sven -- Guler, Reto -- Gustincich, Stefano -- Ha, Thomas J -- Hamaguchi, Masahide -- Hara, Mitsuko -- Harbers, Matthias -- Harshbarger, Jayson -- Hasegawa, Akira -- Hasegawa, Yuki -- Hashimoto, Takehiro -- Herlyn, Meenhard -- Hitchens, Kelly J -- Ho Sui, Shannan J -- Hofmann, Oliver M -- Hoof, Ilka -- Hori, Furni -- Huminiecki, Lukasz -- Iida, Kei -- Ikawa, Tomokatsu -- Jankovic, Boris R -- Jia, Hui -- Joshi, Anagha -- Jurman, Giuseppe -- Kaczkowski, Bogumil -- Kai, Chieko -- Kaida, Kaoru -- Kaiho, Ai -- Kajiyama, Kazuhiro -- Kanamori-Katayama, Mutsumi -- Kasianov, Artem S -- Kasukawa, Takeya -- Katayama, Shintaro -- Kato, Sachi -- Kawaguchi, Shuji -- Kawamoto, Hiroshi -- Kawamura, Yuki I -- Kawashima, Tsugumi -- Kempfle, Judith S -- Kenna, Tony J -- Kere, Juha -- Khachigian, Levon M -- Kitamura, Toshio -- Klinken, S Peter -- Knox, Alan J -- Kojima, Miki -- Kojima, Soichi -- Kondo, Naoto -- Koseki, Haruhiko -- Koyasu, Shigeo -- Krampitz, Sarah -- Kubosaki, Atsutaka -- Kwon, Andrew T -- Laros, Jeroen F J -- Lee, Weonju -- Lennartsson, Andreas -- Li, Kang -- Lilje, Berit -- Lipovich, Leonard -- Mackay-Sim, Alan -- Manabe, Ri-ichiroh -- Mar, Jessica C -- Marchand, Benoit -- Mathelier, Anthony -- Mejhert, Niklas -- Meynert, Alison -- Mizuno, Yosuke -- de Lima Morais, David A -- Morikawa, Hiromasa -- Morimoto, Mitsuru -- Moro, Kazuyo -- Motakis, Efthymios -- Motohashi, Hozumi -- Mummery, Christine L -- Murata, Mitsuyoshi -- Nagao-Sato, Sayaka -- Nakachi, Yutaka -- Nakahara, Fumio -- Nakamura, Toshiyuki -- Nakamura, Yukio -- Nakazato, Kenichi -- van Nimwegen, Erik -- Ninomiya, Noriko -- Nishiyori, Hiromi -- Noma, Shohei -- Noazaki, Tadasuke -- Ogishima, Soichi -- Ohkura, Naganari -- Ohimiya, Hiroko -- Ohno, Hiroshi -- Ohshima, Mitsuhiro -- Okada-Hatakeyama, Mariko -- Okazaki, Yasushi -- Orlando, Valerio -- Ovchinnikov, Dmitry A -- Pain, Arnab -- Passier, Robert -- Patrikakis, Margaret -- Persson, Helena -- Piazza, Silvano -- Prendergast, James G D -- Rackham, Owen J L -- Ramilowski, Jordan A -- Rashid, Mamoon -- Ravasi, Timothy -- Rizzu, Patrizia -- Roncador, Marco -- Roy, Sugata -- Rye, Morten B -- Saijyo, Eri -- Sajantila, Antti -- Saka, Akiko -- Sakaguchi, Shimon -- Sakai, Mizuho -- Sato, Hiroki -- Savvi, Suzana -- Saxena, Alka -- Schneider, Claudio -- Schultes, Erik A -- Schulze-Tanzil, Gundula G -- Schwegmann, Anita -- Sengstag, Thierry -- Sheng, Guojun -- Shimoji, Hisashi -- Shimoni, Yishai -- Shin, Jay W -- Simon, Christophe -- Sugiyama, Daisuke -- Sugiyama, Takaai -- Suzuki, Masanori -- Suzuki, Naoko -- Swoboda, Rolf K -- 't Hoen, Peter A C -- Tagami, Michihira -- Takahashi, Naoko -- Takai, Jun -- Tanaka, Hiroshi -- Tatsukawa, Hideki -- Tatum, Zuotian -- Thompson, Mark -- Toyodo, Hiroo -- Toyoda, Tetsuro -- Valen, Elvind -- van de Wetering, Marc -- van den Berg, Linda M -- Verado, Roberto -- Vijayan, Dipti -- Vorontsov, Ilya E -- Wasserman, Wyeth W -- Watanabe, Shoko -- Wells, Christine A -- Winteringham, Louise N -- Wolvetang, Ernst -- Wood, Emily J -- Yamaguchi, Yoko -- Yamamoto, Masayuki -- Yoneda, Misako -- Yonekura, Yohei -- Yoshida, Shigehiro -- Zabierowski, Susan E -- Zhang, Peter G -- Zhao, Xiaobei -- Zucchelli, Silvia -- Summers, Kim M -- Suzuki, Harukazu -- Daub, Carsten O -- Kawai, Jun -- Heutink, Peter -- Hide, Winston -- Freeman, Tom C -- Lenhard, Boris -- Bajic, Vladimir B -- Taylor, Martin S -- Makeev, Vsevolod J -- Sandelin, Albin -- Hume, David A -- Carninci, Piero -- Hayashizaki, Yoshihide -- BB/F003722/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/G022771/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BB/I001107/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- MC_PC_U127597124/Medical Research Council/United Kingdom -- MC_UP_1102/1/Medical Research Council/United Kingdom -- R01 DE022969/DE/NIDCR NIH HHS/ -- R01 GM084875/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 Mar 27;507(7493):462-70. doi: 10.1038/nature13182.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670764" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Atlases as Topic ; Cell Line ; Cells, Cultured ; Cluster Analysis ; Conserved Sequence/genetics ; Gene Expression Regulation/genetics ; Gene Regulatory Networks/genetics ; Genes, Essential/genetics ; Genome/genetics ; Humans ; Mice ; *Molecular Sequence Annotation ; Open Reading Frames/genetics ; Organ Specificity ; Promoter Regions, Genetic/*genetics ; RNA, Messenger/analysis/genetics ; Transcription Factors/metabolism ; Transcription Initiation Site ; Transcription, Genetic/genetics ; Transcriptome/*genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2018-12-05
    Description: Concerns about malaria parasite resistance to treatment with artemisinin drugs (ARTs) have grown with findings of prolonged parasite clearance t1/2s (〉5 h) and their association with mutations in Plasmodium falciparum Kelch-propeller protein K13. Here, we describe a P. falciparum laboratory cross of K13 C580Y mutant with C580 wild-type parasites to...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 8
    Publication Date: 2013-10-18
    Description: Super-luminous supernovae that radiate more than 10(44) ergs per second at their peak luminosity have recently been discovered in faint galaxies at redshifts of 0.1-4. Some evolve slowly, resembling models of 'pair-instability' supernovae. Such models involve stars with original masses 140-260 times that of the Sun that now have carbon-oxygen cores of 65-130 solar masses. In these stars, the photons that prevent gravitational collapse are converted to electron-positron pairs, causing rapid contraction and thermonuclear explosions. Many solar masses of (56)Ni are synthesized; this isotope decays to (56)Fe via (56)Co, powering bright light curves. Such massive progenitors are expected to have formed from metal-poor gas in the early Universe. Recently, supernova 2007bi in a galaxy at redshift 0.127 (about 12 billion years after the Big Bang) with a metallicity one-third that of the Sun was observed to look like a fading pair-instability supernova. Here we report observations of two slow-to-fade super-luminous supernovae that show relatively fast rise times and blue colours, which are incompatible with pair-instability models. Their late-time light-curve and spectral similarities to supernova 2007bi call the nature of that event into question. Our early spectra closely resemble typical fast-declining super-luminous supernovae, which are not powered by radioactivity. Modelling our observations with 10-16 solar masses of magnetar-energized ejecta demonstrates the possibility of a common explosion mechanism. The lack of unambiguous nearby pair-instability events suggests that their local rate of occurrence is less than 6 x 10(-6) times that of the core-collapse rate.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nicholl, M -- Smartt, S J -- Jerkstrand, A -- Inserra, C -- McCrum, M -- Kotak, R -- Fraser, M -- Wright, D -- Chen, T-W -- Smith, K -- Young, D R -- Sim, S A -- Valenti, S -- Howell, D A -- Bresolin, F -- Kudritzki, R P -- Tonry, J L -- Huber, M E -- Rest, A -- Pastorello, A -- Tomasella, L -- Cappellaro, E -- Benetti, S -- Mattila, S -- Kankare, E -- Kangas, T -- Leloudas, G -- Sollerman, J -- Taddia, F -- Berger, E -- Chornock, R -- Narayan, G -- Stubbs, C W -- Foley, R J -- Lunnan, R -- Soderberg, A -- Sanders, N -- Milisavljevic, D -- Margutti, R -- Kirshner, R P -- Elias-Rosa, N -- Morales-Garoffolo, A -- Taubenberger, S -- Botticella, M T -- Gezari, S -- Urata, Y -- Rodney, S -- Riess, A G -- Scolnic, D -- Wood-Vasey, W M -- Burgett, W S -- Chambers, K -- Flewelling, H A -- Magnier, E A -- Kaiser, N -- Metcalfe, N -- Morgan, J -- Price, P A -- Sweeney, W -- Waters, C -- England -- Nature. 2013 Oct 17;502(7471):346-9. doi: 10.1038/nature12569.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Astrophysics Research Centre, School of Mathematics and Physics, Queen's University Belfast, Belfast BT7 1NN, UK. mnicholl03@qub.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24132291" target="_blank"〉PubMed〈/a〉
    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: 2011-09-10
    Description: Our goal is to develop a vaccine that sustainably prevents Plasmodium falciparum (Pf) malaria in 〉/=80% of recipients. Pf sporozoites (PfSPZ) administered by mosquito bites are the only immunogens shown to induce such protection in humans. Such protection is thought to be mediated by CD8(+) T cells in the liver that secrete interferon-gamma (IFN-gamma). We report that purified irradiated PfSPZ administered to 80 volunteers by needle inoculation in the skin was safe, but suboptimally immunogenic and protective. Animal studies demonstrated that intravenous immunization was critical for inducing a high frequency of PfSPZ-specific CD8(+), IFN-gamma-producing T cells in the liver (nonhuman primates, mice) and conferring protection (mice). Our results suggest that intravenous administration of this vaccine will lead to the prevention of infection with Pf malaria.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Epstein, J E -- Tewari, K -- Lyke, K E -- Sim, B K L -- Billingsley, P F -- Laurens, M B -- Gunasekera, A -- Chakravarty, S -- James, E R -- Sedegah, M -- Richman, A -- Velmurugan, S -- Reyes, S -- Li, M -- Tucker, K -- Ahumada, A -- Ruben, A J -- Li, T -- Stafford, R -- Eappen, A G -- Tamminga, C -- Bennett, J W -- Ockenhouse, C F -- Murphy, J R -- Komisar, J -- Thomas, N -- Loyevsky, M -- Birkett, A -- Plowe, C V -- Loucq, C -- Edelman, R -- Richie, T L -- Seder, R A -- Hoffman, S L -- 5R44AI055229-07/AI/NIAID NIH HHS/ -- 5R44AI058375-05/AI/NIAID NIH HHS/ -- 5R44AI058499-05/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Oct 28;334(6055):475-80. doi: 10.1126/science.1211548. Epub 2011 Sep 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉U.S. Military Malaria Vaccine Program, Naval Medical Research Center, Silver Spring, MD 20910, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21903775" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Animals ; Antibodies, Protozoan/blood/immunology ; Antigens, Protozoan/immunology ; CD8-Positive T-Lymphocytes/*immunology ; Humans ; Injections, Intravenous ; Injections, Subcutaneous ; Interferon-gamma/biosynthesis/immunology ; Liver/*immunology ; Macaca mulatta ; Malaria Vaccines/administration & dosage/adverse effects/*immunology ; Malaria, Falciparum/*prevention & control ; Mice ; Middle Aged ; Plasmodium falciparum/*immunology ; Rabbits ; Sporozoites/*immunology ; Vaccines, Attenuated/administration & dosage/adverse effects/immunology ; Young Adult
    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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  • 10
    Publication Date: 2011-07-02
    Description: The composition of sulfur isotopes in sedimentary sulfides and sulfates traces the sulfur cycle throughout Earth's history. In particular, depletions of sulfur-34 ((34)S) in sulfide relative to sulfate exceeding 47 per mil ( per thousand) often serve as a proxy for the disproportionation of intermediate sulfur species in addition to sulfate reduction. Here, we demonstrate that a pure, actively growing culture of a marine sulfate-reducing bacterium can deplete (34)S by up to 66 per thousand during sulfate reduction alone and in the absence of an extracellular oxidative sulfur cycle. Therefore, similar magnitudes of sulfur isotope fractionation in sedimentary rocks do not unambiguously record the presence of other sulfur-based metabolisms or the stepwise oxygenation of Earth's surface environment during the Proterozoic.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sim, Min Sub -- Bosak, Tanja -- Ono, Shuhei -- New York, N.Y. -- Science. 2011 Jul 1;333(6038):74-7. doi: 10.1126/science.1205103.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Earth, Atmospheric, and Planetary Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. mssim@mit.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21719675" target="_blank"〉PubMed〈/a〉
    Keywords: Desulfovibrio/growth & development/isolation & purification/*metabolism ; Geologic Sediments/microbiology ; Glucose/metabolism ; Oxidation-Reduction ; Seawater/chemistry/microbiology ; Sulfates/*metabolism ; Sulfides/metabolism ; Sulfur/metabolism ; Sulfur Isotopes/*metabolism ; Time
    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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