Deposition and tectonic setting of the Palaeoproterozoic Castelo dos Sonhos metasedimentary formation, Tapajós Gold Province, Amazonian Craton, Brazil: age and isotopic constraints
In: International Geology Review, Band 59, Heft 7, S. 864-883
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In: International Geology Review, Band 59, Heft 7, S. 864-883
In: https://www.repository.cam.ac.uk/handle/1810/249243
OBJECTIVES: Pancreatic cancer (PCa) is treatable by surgery when detected at an early stage. Non-invasive imaging methods able to detect both established tumours and their precursor lesions are needed to select patients for surgery. We investigated here whether pancreatic preneoplasia could be detected prior to the development of invasive cancers in genetically engineered mouse models of PCa using metabolic imaging. DESIGN: The concentrations of alanine and lactate and the activities of lactate dehydrogenase (LDH) and alanine aminotransferase (ALT) were measured in extracts prepared from the pancreas of animals at different stages of disease progression; from pancreatitis, through tissue with predominantly low-grade and then high-grade pancreatic intraepithelial neoplasia and then tumour. (13)C magnetic resonance spectroscopic imaging ((13)C-MRSI) was used to measure non-invasively changes in (13)C labelling of alanine and lactate with disease progression, following injection of hyperpolarised [1-(13)C]pyruvate. RESULTS: Progressive decreases in the alanine/lactate concentration ratio and ALT/LDH activity ratio with disease progression were accompanied by a corresponding decrease in the [1-(13)C]alanine/[1-(13)C]lactate signal ratio observed in (13)C-MRSI images of the pancreas. CONCLUSIONS: Metabolic imaging with hyperpolarised [1-(13)C]pyruvate enables detection and monitoring of the progression of PCa precursor lesions. Translation of this MRI technique to the clinic has the potential to improve the management of patients at high risk of developing PCa. ; The work was supported by a Cancer Research UK Programme grant (17242) to K.M.B. E.M.S. is a recipient of a fellowship from the European Union Seventh Framework Programme (FP7/2007-2013) under the Marie Curie Initial Training Network METAFLUX (project number 264780). T.B.R. is a recipient of an Intra- European Marie Curie (FP7-PEOPLE-2009-IEF, Imaging Lymphoma) fellowship and a Long-term European Molecular Biology Organization (EMBO-ALT-1145-2009) fellowship. E.M.S. and J.A. acknowledge the educational support of Programme for Advanced Medical Education from Calouste Gulbenkian Foundation, Champalimaud Foundation, Ministerio de Saude and Fundacao para a Ciencia e Tecnologia, Portugal. The polarizer and related materials were provided by GE Healthcare. The polarimeter was provided by NIHR Cambridge Biomedical Centre. The laboratory is a member of and receives support from the Cancer Research UK & Engineering and Physical Science Research Council Cancer Imaging Center in Cambridge and Manchester. The authors would also like to acknowledge Dr. Judit Espana, Dr. Athena Matakidou, Dr. Madhu Basetti, Dr. Jose Sandoval and Sarah McGuire for their help with experiments as well as the Tumor Models Core of Cancer Research UK-Cambridge Institute. ; This is the final version of the article. It first appeared from BMJ Group via http://dx.doi.org/10.1136/gutjnl-2015-310114
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Historically, genetically engineered (GE) plants that have incorporated genes conferring insect protection have primarily used Cry proteins derived from Bacillus thuringiensis (Bt) to achieve their insecticidal phenotype. As a result, regulators have developed a level of familiarity and confidence in reviewing plants incorporating these insecticidal proteins. However, new technologies have been developed that produce GE plants that incorporate pest protection by triggering an RNA interference (RNAi) response or proteins other than Bt Cry proteins. These technologies have new modes of action. Although the overall assessment paradigm for GE plants is robust, there are ongoing discussions about the appropriate tests and measurement endpoints needed to inform non-target arthropod assessment for technologies that have a different mode of action than the Bt Cry proteins. As a result, increasing attention is being paid to the use of sublethal endpoints and their value for environmental risk assessment (ERA). This review focuses on the current status and history of sublethal endpoint use in insect-active GE crops, and evaluates the future use of sublethal endpoints for new and emerging technologies. It builds upon presentations made at the Workshop on Sublethal Endpoints for Non-target Organism Testing for Non-Bt GE Crops (Washington DC, USA, 4–5 March 2019), and the discussions of government, academic and industry scientists convened for the purpose of reviewing the progress and status of sublethal endpoint testing in non-target organisms.
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In: https://www.repository.cam.ac.uk/handle/1810/249221
PURPOSE: Dissolution dynamic nuclear polarization can increase the sensitivity of the (13) C magnetic resonance spectroscopy experiment by at least four orders of magnitude and offers a novel approach to the development of MRI gene reporters based on enzymes that metabolize (13) C-labeled tracers. We describe here a gene reporter based on the enzyme pyruvate decarboxylase (EC 4.1.1.1), which catalyzes the decarboxylation of pyruvate to produce acetaldehyde and carbon dioxide. METHODS: Pyruvate decarboxylase from Zymomonas mobilis (zmPDC) and a mutant that lacked enzyme activity were expressed using an inducible promoter in human embryonic kidney (HEK293T) cells. Enzyme activity was measured in the cells and in xenografts derived from the cells using (13) C MRS measurements of the conversion of hyperpolarized [1-(13) C] pyruvate to H(13) CO3-. RESULTS: Induction of zmPDC expression in the cells and in the xenografts derived from them resulted in an approximately two-fold increase in the H(13) CO3-/[1-(13) C] pyruvate signal ratio following intravenous injection of hyperpolarized [1-(13) C] pyruvate. CONCLUSION: We have demonstrated the feasibility of using zmPDC as an in vivo reporter gene for use with hyperpolarized (13) C MRS. Magn Reson Med 76:391-401, 2016. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. ; PD was in receipt of a studentship funded by CRUK and S.-S.T. a Yousef Jameel studentship. TBR was in receipt of an Intra-European Marie Curie (FP7-PEOPLE- 2009-IEF, Imaging Lymphoma) and Long-term EMBO (EMBO-ALT-1145-2009) fellowships and E.M.S. and I.M.R were recipients of fellowships from the European Union Seventh Framework Programme (FP7/2007-2013) under the Marie Curie Initial Training Network METAFLUX (project number 264780). E.M.S. also acknowledges the educational support of Programme for Advanced Medical Education from Calouste Gulbenkian Foundation, Champalimaud Foundation, Ministerio de Saude and Fundacao para a Ciencia e Tecnologia, Portugal. The work was supported by a CRUK Programme Grant (17242) to KMB. The polarizer and related materials were provided by GE-Healthcare. ; This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/mrm.25879
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) ; Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) ; Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) ; FINEP (Brazil) ; NSFC (China) ; CNRS/IN2P3 (France) ; BMBF (Germany) ; DFG (Germany) ; HGF (Germany) ; SFI (Ireland) ; INFN (Italy) ; NASU (Ukraine) ; STFC (UK) ; NSF (USA) ; BMWFW (Austria) ; FWF (Austria) ; FNRS (Belgium) ; FWO (Belgium) ; Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) ; MES (Bulgaria) ; CAS (China) ; MoST (China) ; COLCIENCIAS (Colombia) ; MSES (Croatia) ; CSF (Croatia) ; RPF (Cyprus) ; MoER (Estonia) ; ERC IUT (Estonia) ; ERDF (Estonia) ; Academy of Finland (Finland) ; MEC (Finland) ; HIP (Finland) ; CEA (France) ; GSRT (Greece) ; OTKA (Hungary) ; NIH (Hungary) ; DAE (India) ; DST (India) ; IPM (Iran) ; NRF (Republic of Korea) ; WCU (Republic of Korea) ; LAS (Lithuania) ; MOE (Malaysia) ; UM (Malaysia) ; CINVESTAV (Mexico) ; CONACYT (Mexico) ; SEP (Mexico) ; UASLP-FAI (Mexico) ; MBIE (New Zealand) ; PAEC (Pakistan) ; MSHE (Poland) ; NSC (Poland) ; FCT (Portugal) ; JINR (Dubna) ; MON (Russia) ; RosAtom (Russia) ; RAS (Russia) ; RFBR (Russia) ; MESTD (Serbia) ; SEIDI (Spain) ; CPAN (Spain) ; MST (Taipei) ; ThEPCenter (Thailand) ; IPST (Thailand) ; STAR (Thailand) ; NSTDA (Thailand) ; TUBITAK (Turkey) ; TAEK (Turkey) ; SFFR (Ukraine) ; DOE (USA) ; MPG (Germany) ; FOM (The Netherlands) ; NWO (The Netherlands) ; MNiSW (Poland) ; NCN (Poland) ; MEN/IFA (Romania) ; MinES (Russia) ; FANO (Russia) ; MinECo (Spain) ; SNSF (Switzerland) ; SER (Switzerland) ; Marie-Curie programme ; European Research Council ; EPLANET (European Union) ; Leventis Foundation ; A. P. Sloan Foundation ; Alexander von Humboldt Foundation ; Belgian Federal Science Policy Office ; Fonds pour la Formation a la Recherche dans l'Industrie et dans l'Agriculture (FRIABelgium) ; Agentschap voor Innovatie door Wetenschap en Technologie (IWT-Belgium) ; Ministry of Education, Youth and Sports (MEYS) of the Czech Republic ; Council of Science and Industrial Research, India ; Foundation for Polish Science ; European Union, Regional Development Fund ; Compagnia di San Paolo (Torino) ; Consorzio per la Fisica (Trieste) ; MIUR (Italy) ; Thalis programme ; Aristeia programme ; EU-ESF ; Greek NSRF ; National Priorities Research Program by Qatar National Research Fund ; EPLANET ; Marie Sklodowska-Curie Actions ; ERC (European Union) ; Conseil general de Haute-Savoie ; Labex ENIGMASS ; OCEVU ; Region Auvergne (France) ; XuntaGal (Spain) ; GENCAT (Spain) ; Royal Society (UK) ; Royal Commission for the Exhibition of 1851 (UK) ; MIUR (Italy): 20108T4XTM ; The standard model of particle physics describes the fundamental particles and their interactions via the strong, electromagnetic and weak forces. It provides precise predictions for measurable quantities that can be tested experimentally. The probabilities, or branching fractions, of the strange B meson (B-s(0)) and the B-0 meson decaying into two oppositely charged muons (mu(+) and mu(-)) are especially interesting because of their sensitivity to theories that extend the standard model. The standard model predicts that the B-s(0)->mu(+)mu(-) and B-0 ->mu(+)mu(-) decays are very rare, with about four of the former occurring for every billion B-s(0) mesons produced, and one of the latter occurring for every ten billion B-0 mesons(1). A difference in the observed branching fractions with respect to the predictions of the standard model would provide a direction in which the standard model should be extended. Before the Large Hadron Collider (LHC) at CERN2 started operating, no evidence for either decay mode had been found. Upper limits on the branching fractions were an order of magnitude above the standard model predictions. The CMS (Compact Muon Solenoid) and LHCb(Large Hadron Collider beauty) collaborations have performed a joint analysis of the data from proton-proton collisions that they collected in 2011 at a centre-of-mass energy of seven teraelectronvolts and in 2012 at eight teraelectronvolts. Here we report the first observation of the B-s(0)->mu(+)mu(-) decay, with a statistical significance exceeding six standard deviations, and the best measurement so far of its branching fraction. Furthermore, we obtained evidence for the B-0 ->mu(+)mu(-) decay with a statistical significance of three standard deviations. Both measurements are statistically compatible with standard model predictions and allow stringent constraints to be placed on theories beyond the standard model. The LHC experiments will resume taking data in 2015, recording proton-proton collisions at a centre-of-mass energy of 13 teraelectronvolts, which will approximately double the production rates of B-s(0) and B-0 mesons and lead to further improvements in the precision of these crucial tests of the standard model.
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