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Tumor heterogeneity and therapy resistance-implications for future treatments of prostate cancer

Journal of Cancer Metastasis and Treatment 2017年第1期3卷 302-314页

作者： Fiona M.Frame Amanda R.Noble sandra klein Hannah F.Walker Rakesh Suman Richard Kasprowicz Vin M.Mann Matt S.Simms Norman J.Maitland Cancer Research Unit Department of BiologyUniversity of YorkHeslingtonNorth Yorkshire YO105DDUK Black Family Stem Cell Institute Icahn School of Medicine at Mount SinaiNew YorkNY 10029USA Phase Focus Limited Electric WorksSheffield Digital CampusSheffield S12BJUK Department of Urology Castle Hill Hospital(Hull and East Yorkshire Hospitals NHS Trust)Cottingham HU165JQUK Hull York Medical School University of HullHull HU67RXUK.

Aim:To develop new therapies for prostate cancer,disease heterogeneity must be *** includes patient variation,multi-focal disease,cellular heterogeneity,genomic changes and epigenetic *** requires more representative models to be used in more innovative ***:This study used a panel of cell lines and primary prostate epithelial cell cultures derived from patient *** assays were used;alamar blue,colony forming assays,γH2AX and Ki67 immunofluorescence and comet *** quantitative phase imaging(QPI),a label-free imaging technique,combined with Cell Analysis Toolbox software,was implemented to carry out real-time analysis of cells and to retrieve morphological,kinetic and population ***:A combination of radiation and Vorinostat may be more effective than radiation *** prostate cancer stem-like cells are more resistant to etoposide than more differentiated *** of QPI images showed that cell lines and primary cells differ in their size,motility and proliferation rate.A QPI signature was developed in order to identify two subpopulations of cells within a heterogeneous primary ***:Use of primary prostate epithelial cultures allows assessment of therapies whilst taking into account cellular *** of rare cell populations and embracing novel techniques may ultimately lead to identifying and overcoming treatment resistance.

关键词： Prostate ptychography live-cell imaging primary cells quantitative phase imaging

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Catalytic domain of PDC-E2 contains epitopes recognized by antimitochondrial antibodies in primary biliary cirrhosis

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World Journal of Gastroenterology 2010年第8期16卷 973-981页

作者： sandra Braun Christoph Berg sandra Buck Michael Gregor Reinhild klein Department of Internal Medicine University of Tuebingen Department of Internal Medicine University of Tuebingen

AIM:To search for further immunodominant peptides of the pyruvate dehydrogenase complex E2-component (PDC-E2) recognized by antimitochondrial antibodies (AMA) in primary biliary cirrhosis (PBC). METHODS:Sera from 95 patients with PBC were tested by enzyme-linked immunosorbent assay against 33 synthetic overlapping peptides (25 amino acids; aa) covering the entire length of the E2-subunit of PDC-E2. Furthermore,the inner lipoyl peptide 167-184 was used in an unlip oylated and a lipoylated form as well as coupled to ovalbumin. Sera from 11 AMA negative/ANA posit ive PBC patients,63 patients with other liver disorders and 22 healthy blood donors served as ***:Of the 95 PBC-sera,74% reacted with the peptide 475-499 and 58% with the pept ide 407-431 located within the catalytic domain of PDC-E2. Patients with other disorders or healthy controls were positive in only up to 18%. Antibodies to the unlipoylatedand lip oylated pept ide 167-184 within the inner lipoyl domain were found in only 5% and 11% of the PBC sera,respectively; using ovalbumin-coupled peptides,the incidence increased up to 57% (unlipoylated form). CONCLUSION:Peptides within the catalytic site of PDC-E2 rather than the previously reported lipoyl binding peptide 167-184 may represent major immunodomin ant epitopes recognized by AMA in PBC.

关键词： Anti-M2 Epitope mapping E2-subunit Pyruvate dehydrogenase complex Inner lipoyl domain Active site Catalytic domain Primary biliary cirrhosis

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The Giant Radio Array for Neutrino Detection(GRAND):Science and design

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Science China(Physics,Mechanics & Astronomy) 2020年第1期63卷 1-43页

作者： Jaime Alvarez-Muniz Rafael Alves Batista Aswathi Balagopal V. Julien Bolmont Mauricio Bustamante Washington Carvalho Jr. Didier Charrier Ismael Cognard Valentin Decoene Peter B.Denton Sijbrand De Jong Krijn D.De Vries Ralph Engel Ke Fang Chad Finley Stefano Gabici Quan Bu Gou Jun Hua Gu Claire Guépin Hong Bo Hu Yan Huang Kumiko Kotera sandra Le Coz Jean-Philippe Lenain Guo Liang Léü Olivier Martineau-Huynh Miguel Mostafá Fabrice Mottez Kohta Murase Valentin Niess Foteini Oikonomou Tanguy Pierog Xiang Li Qian Bo Qin Duan Ran Nicolas Renault-Tinacci Markus Roth Frank G.Schroder Fabian Schüssler Cyril Tasse Charles Timmerman Matías Tueros Xiang Ping Wu Philippe Zarka Andreas Zech B.Theodore Zhang Jian Li Zhang Yi Zhang Qian Zheng Anne Zilles Departamento de Fisica de Particulas&lnstituto Galego de Fisica de Altas Enerxias Universidad de Santiago de CompostelaSantiago de Compostela 15782Spain Instituto de Astronomia Geofisica e Ciencias AtmosfericasUniversidade de Sao PauloSao Paulo-SP 05508-090Brazil Department of Physics-Astrophysics University of OxfordDWBOxford 0X13RHUK Institute of Experimental Particle Physics(ETP) Karlsruhe Institute of Technology(KIT)Karlsru he D-76021Germany Laboratoire de Physique Nucleeaire et de Hautes Energies(LPNHE) Sorbonne UniversiteUniversite Paris DiderotSorbonne Paris CiteCNRS place Jussieu F-75252Paris Cedex 5France Niels Bohr International Academy and DARK Niels Bohr InstituteCopenhagen 2100Denmark Discovery Center Niels Bohr InstituteCopenhagen 2100Denmark Center for Cosmology and AstroParticle Physics(CCA.PP)&Department of Physics Ohio State UniversityColumbus OH 43210USA Universidade de Santiago de Compostela Santiago de Compostela 15782Spain 0SUBATECH Institut Mines-Telecom Atlantique-CNRS/IN2P3-Universite de NantesNantes 44300France Laboratoire de Physique et Chimie de KEnvironnement et de VEspace LPC2E CNRS-Universite d'Orleans Orleans F-45071France Station de Radioastronomie de Nancay Observatoire de ParisCNRS/INSU F-18330 NangayFrance Sorbonne Universite UMR 7095Institut d'Astrophysique de Paris98 bis bd AragoParis 75014France Institute for Mathematics Astrophysics and Particle Physics(IMAPP)Radboud UniversiteitNijmegen 6500Netherlands Nationaal Instituut voor Kemfysica en Hoge Energie Fysica(NIKHEF) Amsterdam NL-1009Netherlands IIHE/ELEM Vrije Universiteit BrusselPleinlaan 2Brussels 1050Belgium Institute for Nuclear Physics(IKP) Karlsruhe Institute of Technology(KIT)Karlsruhe D-76021Germany Einstein Fellow Stanford UniversityStanford CA 94305USA Department of Astronomy University of MarylandCollege Park MD 20742-2421USA Joint Space-Science Institute College Park MD 20742-2421USA Oskar klein Centre Stockholm UniversityStockholm SE-10691Sweden Department of Phy

The Giant Radio Array for Neutrino Detection(GRAND)is a planned large-scale observatory of ultra-high-energy(UHE)cosmic particles,with energies exceeding 10~8 Ge *** goal is to solve the long-standing mystery of the origin of UHE cosmic *** do this,GRAND will detect an unprecedented number of UHE cosmic rays and search for the undiscovered UHE neutrinos and gamma rays associated to them with unmatched *** will use large arrays of antennas to detect the radio emission coming from extensive air showers initiated by UHE particles in the *** design is modular:20 separate,independent sub-arrays,each of 10000 radio antennas deployed over 10000 km^2.A staged construction plan will validate key detection techniques while achieving important science goals *** we present the science goals,detection strategy,preliminary design,performance goals,and construction plans for GRAND.

关键词： radio telescopes neutrinos in astronomical observations cosmic rays in astronomical observations radiowave radiation:sources galactic and extragalactic cosmic rays:galactic and extragalactic

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The Giant Radio Array for Neutrino Detection(GRAND):Science and design

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Science China(Physics,Mechanics & Astronomy) 2020年第1期Mechanics & Astronomy) .卷 5-47页

作者： Jaime álvarez-Mu?iz Rafael Alves Batista Aswathi Balagopal V. Julien Bolmont Mauricio Bustamante Washington Carvalho Jr. Didier Charrier Isma?l Cognard Valentin Decoene Peter B.Denton Sijbrand De Jong Krijn D.De Vries Ralph Engel Ke Fang Chad Finley Stefano Gabici Quan Bu Gou Jun Hua Gu Claire Guépin Hong Bo Hu Yan Huang Kumiko Kotera sandra Le Coz Jean-Philippe Lenain Guo Liang Léü Olivier Martineau-Huynh Miguel Mostafá Fabrice Mottez Kohta Murase Valentin Niess Foteini Oikonomou Tanguy Pierog Xiang Li Qian Bo Qin Duan Ran Nicolas Renault-Tinacci Markus Roth Frank G.Schr ?der Fabian Schüssler Cyril Tasse Charles Timmerman Matías Tueros Xiang Ping Wu Philippe Zarka Andreas Zech B.Theodore Zhang Jian Li Zhang Yi Zhang Qian Zheng Anne Zilles Departamento de Física de Partículas & Instituto Galego de Física de Altas Enerxías Universidad de Santiago de Compostela Instituto de Astronomia Geofísica e Ciências Atmosféricas Universidade de S?o Paulo Department of Physics—Astrophysics University of Oxford DWB Institute of Experimental Particle Physics (ETP) Karlsruhe Institute of Technology (KIT) Laboratoire de Physique Nucléeaire et de Hautes Energies (LPNHE) Sorbonne Université Université Paris Diderot Sorbonne Paris Cité Niels Bohr International Academy and DARK Niels Bohr Institute Discovery Center Niels Bohr Institute Center for Cosmology and Astro Particle Physics (CCAPP) & Department of Physics Ohio State University Universidade de Santiago de Compostela SUBATECH Institut Mines-Telecom Atlantique – CNRS/IN2P3 – Université de Nantes Laboratoire de Physique et Chimie de l’Environnement et de l’Espace LPC2E CNRS-Université d’Orléans Station de Radioastronomie de Nan?cay Observatoire de Paris Sorbonne Université UMR 7095 Institut d’Astrophysique de Paris Institute for Mathematics Astrophysics and Particle Physics (IMAPP) Radboud Universiteit Nationaal Instituut voor Kernfysica en Hoge Energie Fysica (NIKHEF) IIHE/ELEM Vrije Universiteit Brussel Institute for Nuclear Physics (IKP) Karlsruhe Institute of Technology (KIT) Einstein Fellow Stanford University Department of Astronomy University of Maryland Joint Space-Science Institute Oskar klein Centre Stockholm University Department of Physics Stockholm University Astro Particule et Cosmologie (APC) Université Paris Diderot CNRS/IN2P3 CEA/Irfu Observatoire de Paris Institute of High Energy Physics Chinese Academy of Sciences National Astronomical Observatories Chinese Academy of Sciences School of Physical Science and Technology Xinjiang University Center for Particle and Gravitational Astrophysics Pennsylvania State University Department of Physics Pennsylvania State University Department of Astronomy & Astrophysics Pennsylvania State University LUTH Observatoire de Paris

The Giant Radio Array for Neutrino Detection（GRAND） is a planned large-scale observatory of ultra-high-energy（UHE） cosmic particles, with energies exceeding 10～8 Ge V. Its goal is to solve the long-standing mystery of the origin of UHE cosmic rays. To do this, GRAND will detect an unprecedented number of UHE cosmic rays and search for the undiscovered UHE neutrinos and gamma rays associated to them with unmatched sensitivity. GRAND will use large arrays of antennas to detect the radio emission coming from extensive air showers initiated by UHE particles in the atmosphere. Its design is modular: 20 separate, independent sub-arrays, each of 10000 radio antennas deployed over 10000 km2. A staged construction plan will validate key detection techniques while achieving important science goals early. Here we present the science goals, detection strategy, preliminary design, performance goals, and construction plans for GRAND.

关键词： radio telescopes neutrinos in astronomical observations cosmic rays in astronomical observations radiowave radiation: sources galactic and extragalactic cosmic rays

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