31 research outputs found
Refined high-content imaging-based phenotypic drug screening in zebrafish xenografts
- Author
- Publication venue
- Nature Publishing Group
- Publication date
- 18/05/2023
- Field of study
Full text linkZebrafish xenotransplantation models are increasingly applied for phenotypic drug screening to identify small compounds for precision oncology. Larval zebrafish xenografts offer the opportunity to perform drug screens at high-throughput in a complex in vivo environment. However, the full potential of the larval zebrafish xenograft model has not yet been realized and several steps of the drug screening workflow still await automation to increase throughput. Here, we present a robust workflow for drug screening in zebrafish xenografts using high-content imaging. We established embedding methods for high-content imaging of xenografts in 96-well format over consecutive days. In addition, we provide strategies for automated imaging and analysis of zebrafish xenografts including automated tumor cell detection and tumor size analysis over time. We also compared commonly used injection sites and cell labeling dyes and show specific site requirements for tumor cells from different entities. We demonstrate that our setup allows us to investigate proliferation and response to small compounds in several zebrafish xenografts ranging from pediatric sarcomas and neuroblastoma to glioblastoma and leukemia. This fast and cost-efficient assay enables the quantification of anti-tumor efficacy of small compounds in large cohorts of a vertebrate model system in vivo. Our assay may aid in prioritizing compounds or compound combinations for further preclinical and clinical investigations
Neuroblastoma-associated chromosomal aberrations drive cell identity loss in human neural crest via disruption of developmental regulators
- Author
- Andrews P.W.
- Barbaric I.
- Bernkopf M.
- Bozatzi P.
- Bozsaky E.
- Bryant H.E.
- Buri M.C.
- Distel M.
- Farlik M.
- Fetahu I.S.
- Guarini M.
- Hafemeister C.
- Halbritter F.
- Montano-Gutierrez L.F.
- Putz E.M.
- Saldana-Guerrero I.M.
- Shaw L.E.
- Shoeb M.R.
- Souilhol C.
- Stavish D.
- Sturtzel C.
- Tarelli S.
- Taschner-Mandl S.
- Tsakiridis A.
- Wenninger-Weinzierl A.
- Publication venue
- 'Cold Spring Harbor Laboratory'
- Publication date
- Field of study
Get PDFA human neural crest model reveals the developmental impact of neuroblastoma-associated chromosomal aberrations
- Author
- Andrews P.W.
- Barbaric I.
- Bernkopf M.
- Boswell K.
- Bozatzi P.
- Bozsaky E.
- Bryant H.E.
- Buri M.C.
- Chesler L.
- Cresswell G.D.
- Distel M.
- Farlik M.
- Fetahu I.S.
- Guarini M.
- Hafemeister C.
- Halbritter F.
- Huang M.
- Ladenstein R.
- Lea R.A.
- Montano-Gutierrez L.F.
- Poon E.
- Putz E.M.
- Pötschger U.
- Rados M.
- Saldana-Guerrero I.M.
- Shaw L.E.
- Shoeb M.R.
- Souilhol C.
- Stavish D.
- Sturtzel C.
- Tarelli S.
- Taschner-Mandl S.
- Tsakiridis A.
- Weninger W.
- Wenninger-Weinzierl A.
- Wernig-Zorc S.
- Zoescher P.
- Publication venue
- Nature Research
- Publication date
- 03/05/2024
- Field of study
Get PDFEarly childhood tumours arise from transformed embryonic cells, which often carry large copy number alterations (CNA). However, it remains unclear how CNAs contribute to embryonic tumourigenesis due to a lack of suitable models. Here we employ female human embryonic stem cell (hESC) differentiation and single-cell transcriptome and epigenome analysis to assess the effects of chromosome 17q/1q gains, which are prevalent in the embryonal tumour neuroblastoma (NB). We show that CNAs impair the specification of trunk neural crest (NC) cells and their sympathoadrenal derivatives, the putative cells-of-origin of NB. This effect is exacerbated upon overexpression of MYCN, whose amplification co-occurs with CNAs in NB. Moreover, CNAs potentiate the pro-tumourigenic effects of MYCN and mutant NC cells resemble NB cells in tumours. These changes correlate with a stepwise aberration of developmental transcription factor networks. Together, our results sketch a mechanistic framework for the CNA-driven initiation of embryonal tumours
HE-LHC: The High-Energy Large Hadron Collider – Future Circular Collider Conceptual Design Report Volume 4
- Author
- Abada A.
- Abbrescia M.
- AbdusSalam S. S.
- Abdyukhanov I.
- Abelleira Fernandez J.
- Abramov A.
- Aburaia M.
- Acar A. O.
- Adzic P. R.
- Agrawal P.
- Aguilar-Saavedra J. A.
- Aguilera-Verdugo J. J.
- Ahnen J. von
- Aiba M.
- Aichinger I.
- Aielli G.
- Akay A.
- Akhundov A.
- Aksakal H.
- Albacete J. L.
- Albergo S.
- Alekou A.
- Aleksa M.
- Aleksan R.
- Alemany Fernandez R. M.
- Alexahin Y.
- Alioli S.
- Alipour Tehrani N.
- Allanach B. C.
- Allport P. P.
- Altınlı M.
- Altmannshofer W.
- Alía R. G.
- Ambrosio G.
- Amorim D.
- Amstutz O.
- Anderlini L.
- Andreazza A.
- Andreini M.
- Andriatis A.
- Andris C.
- Andronic A.
- Angelucci M.
- Antinori F.
- Antipov S. A.
- Antonelli M.
- Antonello M.
- Antonioli P.
- Antusch S.
- Anulli F.
- Apolinário L.
- Apollinari G.
- Apollonio A.
- Appelö D.
- Appleby R. B.
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- Publication venue
- Springer Verlag
- Publication date
- 09/02/2021
- Field of study
Get PDFIn response to the 2013 Update of the European Strategy for Particle Physics (EPPSU), the Future Circular Collider (FCC) study was launched as a world-wide international collaboration hosted by CERN. The FCC study covered an energy-frontier hadron collider (FCC-hh), a highest-luminosity high-energy lepton collider (FCC-ee), the corresponding 100 km tunnel infrastructure, as well as the physics opportunities of these two colliders, and a high-energy LHC, based on FCC-hh technology. This document constitutes the third volume of the FCC Conceptual Design Report, devoted to the hadron collider FCC-hh. It summarizes the FCC-hh physics discovery opportunities, presents the FCC-hh accelerator design, performance reach, and staged operation plan, discusses the underlying technologies, the civil engineering and technical infrastructure, and also sketches a possible implementation. Combining ingredients from the Large Hadron Collider (LHC), the high-luminosity LHC upgrade and adding novel technologies and approaches, the FCC-hh design aims at significantly extending the energy frontier to 100 TeV. Its unprecedented centre-of-mass collision energy will make the FCC-hh a unique instrument to explore physics beyond the Standard Model, offering great direct sensitivity to new physics and discoveries
FCC-ee: The Lepton Collider – Future Circular Collider Conceptual Design Report Volume 2
- Author
- Abada A.
- Abbrescia M.
- AbdusSalam S. S.
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- Zupan J.
- Zurita J.
- Özcan V.
- Özdemir K.
- Publication venue
- Springer Verlag
- Publication date
- 14/11/2019
- Field of study
Get PDFFCC-ee: The Lepton Collider: Future Circular Collider Conceptual Design Report Volume 2
- Author
- Abada A
- Abbrescia M
- AbdusSalam SS
- Abdyukhanov I
- Abramov A
- Aburaia M
- Acar AO
- Adzic PR
- Agaliotis EL
- Agrawal P
- Aguilar-Saavedra JA
- Aguilera-Verdugo JJ
- Aiba M
- Aichinger I
- Aielli G
- Akay A
- Akhundov A
- Aksakal H
- Alaniz EC
- Albacete JL
- Albergo S
- Alekou A
- Aleksa M
- Aleksan R
- Alexahin Y
- Alia RG
- Alioli S
- Allanach BC
- Allport PP
- Altinli M
- Altmannshofer W
- Ambrosio G
- Amorim D
- Amstutz O
- Anderlini L
- Andreazza A
- Andreini M
- Andriatis A
- Andris C
- Andronic A
- Angelucci M
- Antinori F
- Antipov SA
- Antonelli M
- Antonello M
- Antonioli P
- Antusch S
- Anulli F
- Apolinario L
- Apollinari G
- Apollonio A
- Appelo D
- Appleby RB
- Apyan A
- Apyan A
- Arbey A
- Arbuzov A
- Arduini G
- Ari V
- Arias S
- Armesto N
- Arnaldi R
- Arsenyev SA
- Arzeo M
- Asai S
- Aslanides E
- Assmann RW
- Astapovych D
- Atanasov M
- Atieh S
- Attie D
- Auchmann B
- Audurier A
- Aull S
- Aumon S
- Aune S
- Avino F
- Avrillaud G
- Aydin G
- Azatov A
- Azuelos G
- Azzi P
- Azzolini O
- Azzurri P
- Bacchetta N
- Bacchiocchi E
- Bachacou H
- Baek YW
- Baglin V
- Bai Y
- Baird S
- Baker MJ
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- Yilmaz A
- Yilmaz A
- Yoo H-D
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- Zaborowska A
- Zadeh SG
- Zadeh SG
- Zahnd M
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- Zhang C
- Zhang H
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- Zhang Z
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- Zhong Y-M
- Zhou D
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- Zhuang P
- Zick G
- Zimmermann F
- Zinn-Justin J
- Zivkovic L
- Zlobin AV
- Zobov M
- Zupan J
- Zurita J
- Publication venue
- SPRINGER HEIDELBERG
- Publication date
- 01/06/2019
- Field of study
Get PDFIn response to the 2013 Update of the European Strategy for Particle Physics, the Future Circular Collider (FCC) study was launched, as an international collaboration hosted by CERN. This study covers a highest-luminosity high-energy lepton collider (FCC-ee) and an energy-frontier hadron collider (FCC-hh), which could, successively, be installed in the same 100 km tunnel. The scientific capabilities of the integrated FCC programme would serve the worldwide community throughout the 21st century. The FCC study also investigates an LHC energy upgrade, using FCC-hh technology. This document constitutes the second volume of the FCC Conceptual Design Report, devoted to the electron-positron collider FCC-ee. After summarizing the physics discovery opportunities, it presents the accelerator design, performance reach, a staged operation scenario, the underlying technologies, civil engineering, technical infrastructure, and an implementation plan. FCC-ee can be built with today’s technology. Most of the FCC-ee infrastructure could be reused for FCC-hh. Combining concepts from past and present lepton colliders and adding a few novel elements, the FCC-ee design promises outstandingly high luminosity. This will make the FCC-ee a unique precision instrument to study the heaviest known particles (Z, W and H bosons and the top quark), offering great direct and indirect sensitivity to new physics
FCC Physics Opportunities: Future Circular Collider Conceptual Design Report Volume 1
- Author
- Abada A
- Abbrescia M
- AbdusSalam SS
- Abdyukhanov I
- Abramov A
- Aburaia M
- Acar AO
- Adzic PR
- Agrawal P
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- Ahnen JV
- Aiba M
- Aichinger I
- Aielli G
- Akay A
- Akhundov A
- Aksakal H
- Alaniz EC
- Albacete JL
- Albergo S
- Alekou A
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- Alexahin Y
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- Yang G
- Yang HJ
- Yao W-M
- Yazgan E
- Yermolchik V
- Yildiz HD
- Yilmaz A
- Yilmaz A
- Yoo H-D
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- Zaborowska A
- Zadeh SG
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- Zahnd M
- Zanetti M
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- Zawiejski L
- Zeiler P
- Zerlauth M
- Zernov SM
- Zevi Dell Porta G
- Zhang C
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- Zhao Z
- Zhong Y-M
- Zhou D
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- Zlobin AV
- Zobov M
- Zupan J
- Zurita J
- Publication venue
- 'Springer Fachmedien Wiesbaden GmbH'
- Publication date
- 01/06/2019
- Field of study
Get PDFWe review the physics opportunities of the Future Circular Collider, covering its e+e-, pp, ep and heavy ion programmes. We describe the measurement capabilities of each FCC component, addressing the study of electroweak, Higgs and strong interactions, the top quark and flavour, as well as phenomena beyond the Standard Model. We highlight the synergy and complementarity of the different colliders, which will contribute to a uniquely coherent and ambitious research programme, providing an unmatchable combination of precision and sensitivity to new physics
HE-LHC: The High-Energy Large Hadron Collider: Future Circular Collider Conceptual Design Report Volume 4
- Author
- Abada A
- Abbrescia M
- AbdusSalam SS
- Abdyukhanov I
- Abelleira Fernandez J
- Abramov A
- Aburaia M
- Acar AO
- Adzic PR
- Agrawal P
- Aguilar-Saavedra JA
- Aguilera-Verdugo JJ
- Aiba M
- Aichinger I
- Aielli G
- Akay A
- Akhundov A
- Aksakal H
- Albacete JL
- Albergo S
- Alekou A
- Aleksa M
- Aleksan R
- Alemany Fernandez RM
- Alexahin Y
- Alia RG
- Alioli S
- Alipour Tehrani N
- Allanach BC
- Allport PP
- Altinli M
- Altmannshofer W
- Ambrosio G
- Amorim D
- Amstutz O
- Anderlini L
- Andreazza A
- Andreini M
- Andriatis A
- Andris C
- Andronic A
- Angelucci M
- Antinori F
- Antipov SA
- Antonelli M
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- Ari V
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- Aull S
- Aumon S
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- Avino F
- Avrillaud G
- Aydin G
- Azatov A
- Azuelos G
- Azzi P
- Azzolini O
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- Bachacou H
- Baek YW
- Baglin V
- Bai Y
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- Ball AH
- Ballarino A
- Banerjee S
- Barber DP
- Barducci D
- Barjhoux P
- Barna D
- Barnafoldi GG
- Barnes MJ
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- Publication venue
- SPRINGER HEIDELBERG
- Publication date
- 01/07/2019
- Field of study
Get PDFIn response to the 2013 Update of the European Strategy for Particle Physics (EPPSU), the Future Circular Collider (FCC) study was launched as a world-wide international collaboration hosted by CERN. The FCC study covered an energy-frontier hadron collider (FCC-hh), a highest-luminosity high-energy lepton collider (FCC-ee), the corresponding 100 km tunnel infrastructure, as well as the physics opportunities of these two colliders, and a high-energy LHC, based on FCC-hh technology. This document constitutes the third volume of the FCC Conceptual Design Report, devoted to the hadron collider FCC-hh. It summarizes the FCC-hh physics discovery opportunities, presents the FCC-hh accelerator design, performance reach, and staged operation plan, discusses the underlying technologies, the civil engineering and technical infrastructure, and also sketches a possible implementation. Combining ingredients from the Large Hadron Collider (LHC), the high-luminosity LHC upgrade and adding novel technologies and approaches, the FCC-hh design aims at significantly extending the energy frontier to 100 TeV. Its unprecedented centre-of-mass collision energy will make the FCC-hh a unique instrument to explore physics beyond the Standard Model, offering great direct sensitivity to new physics and discoveries
FCC-hh: The Hadron Collider: Future Circular Collider Conceptual Design Report Volume 3
- Author
- Abada A
- Abbrescia M
- AbdusSalam SS
- Abdyukhanov I
- Abelleira Fernandez J
- Abramov A
- Aburaia M
- Acar AO
- Adzic PR
- Agrawal P
- Aguilar-Saavedra JA
- Aguilera-Verdugo JJ
- Aiba M
- Aichinger I
- Aielli G
- Akay A
- Akhundov A
- Aksakal H
- Albacete JL
- Albergo S
- Alekou A
- Aleksa M
- Aleksan R
- Alemany Fernandez RM
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- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 18/12/2018
- Field of study
Get PDFIn response to the 2013 Update of the European Strategy for Particle Physics (EPPSU), the Future Circular Collider (FCC) study was launched as a world-wide international collaboration hosted by CERN. The FCC study covered an energy-frontier hadron collider (FCC-hh), a highest-luminosity high-energy lepton collider (FCC-ee), the corresponding 100 km tunnel infrastructure, as well as the physics opportunities of these two colliders, and a high-energy LHC, based on FCC-hh technology. This document constitutes the third volume of the FCC Conceptual Design Report, devoted to the hadron collider FCC-hh. It summarizes the FCC-hh physics discovery opportunities, presents the FCC-hh accelerator design, performance reach, and staged operation plan, discusses the underlying technologies, the civil engineering and technical infrastructure, and also sketches a possible implementation. Combining ingredients from the Large Hadron Collider (LHC), the high-luminosity LHC upgrade and adding novel technologies and approaches, the FCC-hh design aims at significantly extending the energy frontier to 100 TeV. Its unprecedented centre of-mass collision energy will make the FCC-hh a unique instrument to explore physics beyond the Standard Model, offering great direct sensitivity to new physics and discoveries
HE-LHC: The High-Energy Large Hadron Collider
- Author
- Abada A
- Abbrescia M
- AbdusSalam SS
- Abdyukhanov I
- Abelleira Fernandez J
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- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 18/12/2018
- Field of study
Get PDFIn response to the 2013 Update of the European Strategy for Particle Physics (EPPSU), the Future Circular Collider (FCC) study was launched as a world-wide international collaboration hosted by CERN. The FCC study covered an energy-frontier hadron collider (FCC-hh), a highest-luminosity high-energy lepton collider (FCC-ee), the corresponding 100 km tunnel infrastructure, as well as the physics opportunities of these two colliders, and a high-energy LHC, based on FCC-hh technology. This document constitutes the third volume of the FCC Conceptual Design Report, devoted to the hadron collider FCC-hh. It summarizes the FCC-hh physics discovery opportunities, presents the FCC-hh accelerator design, performance reach, and staged operation plan, discusses the underlying technologies, the civil engineering and technical infrastructure, and also sketches a possible implementation. Combining ingredients from the Large Hadron Collider (LHC), the high-luminosity LHC upgrade and adding novel technologies and approaches, the FCC-hh design aims at significantly extending the energy frontier to 100 TeV. Its unprecedented centre-of-mass collision energy will make the FCC-hh a unique instrument to explore physics beyond the Standard Model, offering great direct sensitivity to new physics and discoveries
