International Review of Mathematical Sciences in the UK
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D3.3 Initial Technical & Logical Architecture and Future Work
D3.3 Initial Technical & Logical Architecture and future work recommendations ECP 2008 DILI 558001 Europeana v1.0 D3.3 Initial Technical & Logical Architecture and future work recommendations Deliverable number D3.3 Dissemination level Public Delivery date 30 July 2010 Status Final Makx Dekkers, Stefan Gradmann, Jan Author(s) Molendijk eContentplus This project is funded under the eContentplus programme1, a multiannual Community programme to make digital content in Europe more accessible, usable and exploitable. 1 OJ L 79, 24.3.2005, p. 1. 1/14 D3.3 Initial Technical & Logical Architecture and future work recommendations 1. Introduction This deliverable has two tasks: To characterise the technical and logical architecture of Europeana as a system in its 1.0 state (that is to say by the time of the ‘Rhine’ release To outline the future work recommendations that can reasonably be made at that moment. This also provides a straightforward and logical structure to the document: characterisation comes first followed by the recommendations for future work. 2. Technical and Logical Architecture From a high-level architectural point of view, Europeana.eu is best characterized as a search engine and a database. It loads metadata delivered by providers and aggregators into a database, and uses that database to allow users to search for cultural heritage objects, and to find links to those objects. Various methods of searching and browsing the objects are offered, including a simple and an advanced search form, a timeline, and an openSearch API. It is also important to describe what Europeana.eu does not do, even though people sometimes expect it to. -
A Knowledge Discovery Approach
Semantic XML Tagging of Domain-Specific Text Archives: A Knowledge Discovery Approach Dissertation zur Erlangung des akademisches Grades Doktoringenieur (Dr.-Ing.) angenommen durch die Fakult¨at fur¨ Informatik der Otto-von-Guericke-Universit¨at Magdeburg von Diplom-Kaufmann Peter Karsten Winkler, geboren am 1. Oktober 1971 in Berlin Gutachterinnen und Gutachter: Prof. Dr. Myra Spiliopoulou Prof. Dr. Gunter Saake Prof. Dr. Stefan Conrad Ort und Datum des Promotionskolloquiums: Magdeburg, 22. Januar 2009 Karsten Winkler. Semantic XML Tagging of Domain-Specific Text Archives: A Knowl- edge Discovery Approach. Dissertation, Faculty of Computer Science, Otto von Guericke University Magdeburg, Magdeburg, Germany, January 2009. Contents List of Figures v List of Tables vii List of Algorithms xi Abstract xiii Zusammenfassung xv Acknowledgments xvii 1 Introduction 1 1.1 TheAbundanceofText ............................ 1 1.2 Defining Semantic XML Markup . 3 1.3 BenefitsofSemanticXMLMarkup . 9 1.4 ResearchQuestions ............................... 12 1.5 ResearchMethodology ............................. 14 1.6 Outline...................................... 16 2 Literature Review 19 2.1 Storage, Retrieval, and Analysis of Textual Data . ....... 19 2.1.1 Knowledge Discovery in Textual Databases . 19 2.1.2 Information Storage and Retrieval . 23 2.1.3 InformationExtraction. 25 2.2 Discovering Concepts in Textual Data . 26 2.2.1 Topic Discovery in Text Documents . 27 2.2.2 Extracting Relational Tuples from Text . 31 2.2.3 Learning Taxonomies, Thesauri, and Ontologies . 35 2.3 Semantic Annotation of Text Documents . 39 2.3.1 Manual Semantic Text Annotation . 40 2.3.2 Semi-Automated Semantic Text Annotation . 43 2.3.3 Automated Semantic Text Annotation . 47 2.4 Schema Discovery in Marked-Up Text Documents . -
Pila, O-Minimality and Diophantine Geometry
O-minimality and Diophantine geometry Jonathan Pila Abstract. This lecture is concerned with some recent applications of mathematical logic to Diophantine geometry. More precisely it concerns applications of o-minimality, a branch of model theory which treats tame structures in real geometry, to certain finiteness problems descending from the classical conjecture of Mordell. Mathematics Subject Classification (2010). Primary 03C64, 11G18. Keywords. O-minimal structure, Andr´e-Oortconjecture, Zilber-Pink conjecture. 1. Introduction This is a somewhat expanded version of my lecture at ICM 2014 in Seoul. It surveys some recent interactions between model theory and Diophantine geometry. The Diophantine problems to be considered are of a type descending from the classical Mordell conjecture (theorem of Faltings). I will describe the passage from Mordell's conjecture to the far-reaching Zilber-Pink conjecture, which is very much open and the subject of lively study by a variety of methods on several fronts. The model theory is \o-minimality", which studies tame structures in real geometry, and offers powerful tools applicable to certain “definable” sets. In combination with an elementary analytic method for \counting rational points" it leads to a general result about the height distribution of rational points on definable sets. This result can be successfully applied to Zilber-Pink problems in the presence of certain functional transcendence and arithmetic ingredients which are known in many cases but seemingly quite difficult in general. Both the methods and problems have connections with transcendental number theory. My further objective is to explain these connections and to bring out the pervasive presence of Schanuel's conjecture. -
NCI RAS Initiative Update
Ras Initiative Update Frank McCormick and Levi Garraway DEPARTMENT OF HEALTH AND HUMAN SERVICES • National Institutes of Health • National Cancer Institute The Frederick National Laboratory is a Federally Funded Research and Development Center operated by Leidos Biomedical Research, Inc., for the National Cancer Institute RAS Initiative Accomplishments: Evaluating Ras dependency 2 SiREN assay for Ras dependency SiREN assay for Ras dependency 70% KD siEGFP 0-10% KD 50% KD 100% KD SiREN assay for Ras dependency RAS Initiative Accomplishments: Biophysical and structural analysis 7 Ras proteins 1 -166 167-185,6 Raf, PI 3’ kinase RalGDS, GAPs Raf, PI 3’ kinase RalGDS, GAPs Raf, PI 3’ kinase RalGDS, GAPs Raf, PI 3’ kinase RalGDS, GAPs Palmitoyl Farnesyl Fully processed KRAS4b A. Gorfe, U-Texas Houston Engineering baculovirus for improved production of processed KRAS • recombineering used to insert FNTA/FNTB genes into the baculovirus genome • eliminated issues with coinfection of multiple viruses • maltose-binding protein (MBP) fusion for greater yield and solubility • Trichoplusia ni (Hi5) insect cells for increased yield Carissa Grose, Dom Esposito, Bill Gillette Processed KRAS4b characterization • Extensive protein characterization – Purified to homogeneity; yield >7mg/L – Intact mass – Predominantly monomeric – Secondary structure equivalent to non-processed KRAS4b KRAS4b- FME – Lower thermal stability Intact mass analysis Analytical ultracentrifugation Secondary structure by CD 2.14 S 25.7 kDa 10 Bill Gillette, Zhaojing Meng, Shelley Perkins, -
Miriam Molina Arcas
CV Miriam Molina Arcas Miriam Molina Arcas Principal Laboratory Research Scientist The Francis Crick Institute 1 Midland Road, NW1 1AT London +442037963313 [email protected] EDUCATION 1999-2005 PhD in Biomedicine, University of Barcelona, Spain Role of equilibrative nucleoside transporters in the sensitivity to antineoplasic drugs. Supervisors: Prof. Marçal Pastor-Anglada and Dr. F. Javier Casado 1994-1999 BSc Biochemistry, University of Barcelona, Spain RESEARCH AND PROFESSIONAL EXPERIENCE June 2016- present Senior Laboratory Research Scientist, Oncogene Biology Laboratory, The Francis Crick Institute. Prof. Julian Downward. Studied combination approaches that improve the efficacy of KRAS inhibitors and reduce resistance mechanisms. March 2015- May 2016 Postdoctoral Fellow, Lung Cancer Team, Institute of Cancer Research. Prof. Julian Downward. Designed and optimized a whole-genome shRNA screen to identify synthetic lethal interactions with MEK and IGF1R inhibitors. Sep 2008- Feb 2015 Postdoctoral Fellow, Signal Transduction Laboratory, Cancer Research UK- London Research Institute. Prof. Julian Downward Using RNA interfering and drug screens, identified new therapeutic strategies to treat tumours harbouring KRAS mutations 2006- Aug 2008 Postdoctoral Fellow, University of Barcelona, Spain Prof. Marçal Pastor-Anglada Studied the role of membrane transporters in nucleoside-derived drug response in cancer and HIV. TEACHING AND MENTORING EXPERIENCE 2018-2021 Honorary Research Associate in the School of Life & Medical Sciences, University College London, part of the Certificate in Core Teaching Practices. 2007-2008 Part-time lecturer of Biochemistry and Molecular Biology (University of Barcelona). 180h of theory and practical lessons. 2003-2005 Teaching assistant of Biochemistry and Molecular Biology (University of Barcelona). 60h of practical lessons. September 2019 Co-supervisor of MSc Experimental Pharmacology and Therapeutics Research of Pablo Romero Clavijo at the University College London. -
![Bibliography [Abiteboul and Kanellakis, 1989] Serge Abiteboul and Paris Kanellakis](https://docslib.b-cdn.net/cover/1320/bibliography-abiteboul-and-kanellakis-1989-serge-abiteboul-and-paris-kanellakis-221320.webp)
Bibliography [Abiteboul and Kanellakis, 1989] Serge Abiteboul and Paris Kanellakis
507 Bibliography [Abiteboul and Kanellakis, 1989] Serge Abiteboul and Paris Kanellakis. Object identity as a query language primitive. In Proc. of the ACM SIGMOD Int. Conf. on Management of Data, pages 159–173, 1989. [Abiteboul et al., 1995] Serge Abiteboul, Richard Hull, and Victor Vianu. Foundations of Databases. Addison Wesley Publ. Co., Reading, Massachussetts, 1995. [Abiteboul et al., 1997] Serge Abiteboul, Dallan Quass, Jason McHugh, Jennifer Widom, and Janet L. Wiener. The Lorel query language for semistructured data. Int. J. on Digital Libraries, 1(1):68–88, 1997. [Abiteboul et al., 2000] Serge Abiteboul, Peter Buneman, and Dan Suciu. Data on the Web: from Relations to Semistructured Data and XML. Morgan Kaufmann, Los Altos, 2000. [Abiteboul, 1997] Serge Abiteboul. Querying semi-structured data. In Proc. of the 6th Int. Conf. on Database Theory (ICDT’97), pages 1–18, 1997. [Abrahams et al., 1996] Merryll K. Abrahams, Deborah L. McGuinness, Rich Thomason, Lori Alperin Resnick, Peter F. Patel-Schneider, Violetta Cavalli-Sforza, and Cristina Conati. NeoClassic tutorial: Version 1.0. Technical report, Artificial Intelligence Prin- ciples Research Department, AT&T Labs Research and University of Pittsburgh, 1996. Available as http://www.bell-labs.com/project/classic/papers/NeoTut/NeoTut. html. [Abrett and Burstein, 1987] Glen Abrett and Mark H. Burstein. The KREME knowledge editing environment. Int. J. of Man-Machine Studies, 27(2):103–126, 1987. [Abrial, 1974] J. R. Abrial. Data semantics. In J. W. Klimbie and K. L. Koffeman, editors, Data Base Management, pages 1–59. North-Holland Publ. Co., Amsterdam, 1974. [Achilles et al., 1991] E. Achilles, B. -
Unveiling New Disease, Pathway, and Gene Associations Via Multi-Scale Neural Networks
Unveiling new disease, pathway, and gene associations via multi-scale neural networks Thomas Gaudelet 1, No¨elMalod-Dognin 2, Jon S´anchez-Valle 2, Vera Pancaldi 2,3,4, Alfonso Valencia 2,5,6 and NataˇsaPrˇzulj 2,5,∗ 1 Department of Computer Science, University College London, London, WC1E 6BT 2 Department of Life Sciences, Barcelona Supercomputing Center (BSC), Barcelona, 08034 Spain 3 Centre de Recherches en Canc´erologiede Toulouse (CRCT), UMR1037 Inserm, ERL5294 CNRS, 31037 Toulouse, France 4 University Paul Sabatier III, Toulouse, France 5 ICREA, Pg. Llu´ısCompanys 23, 08010 Barcelona, Spain 6 Coordination Node. Spanish National Bioinformatics Institute, ELIXIR-Spain (INB, ELIXIR-ES), Spain ∗ [email protected]. Abstract Diseases involve complex modifications to the cellular machinery. The gene expression profile of the affected cells contains characteristic patterns linked to a disease. Hence, new biological knowledge about a disease can be extracted from these profiles, improving our ability to diagnose and assess disease risks. This knowledge can be used for drug re-purposing, or by physicians to evaluate a patient's condition and co-morbidity risk. Here, we consider differential gene expressions obtained by microarray technology for patients diagnosed with various diseases. Based on these data and cellular multi-scale organization, we aim at uncovering disease{disease, disease{gene and disease{pathway associations. We propose a neural network with structure based on the multi- scale organization of proteins in a cell into biological pathways. We show that this model is able to correctly predict the diagnosis for the majority of patients. Through the analysis of the trained model, we predict disease{ disease, disease{pathway, and disease{gene associations and validate the predictions by comparisons to known interactions and literature search, proposing putative explanations for the predictions. -
Fellows Opted out of the Mentoring Programme As of 21 July 2020 1 of 3 Professor Chris Abell FRS Fmedsci Professor Philip Jones
Fellows opted out of the Mentoring programme as of 21 July 2020 Professor Chris Abell FRS FMedSci Professor Philip Jones FMedSci Professor David Adams FMedSci Professor Roger Jones FMedSci Professor Judith Allen FRSE FMedSci Professor Kamlesh Khunti FMedSci Professor Thomas Kirkwood CBE Professor Desmond Archer OBE FMedSci FMedSci Professor Louise Arseneault FMedSci Professor Robb Krumlauf FMedSci Professor Charalambos Kyriacou Professor Michael Arthur FMedSci FMedSci Professor Deborah Ashby OBE FMedSci Sir Peter Lachmann FRS FMedSci Professor Dame Frances Ashcroft DBE Professor Leon Lagnado FMedSci FRS FMedSci Professor Anthony Barrett FRS FMedSci Professor Ajit Lalvani FMedSci Professor Gillian Bates FRS FMedSci Professor Deborah Lawlor CBE FMedSci Professor Facundo Batista FMedSci Professor Joy Lawn FMedSci Professor Stephan Beck FMedSci Professor Susan Lea FMedSci Professor Jill Belch OBE FMedSci Professor Sir Robert Lechler PMedSci Professor Sir John Bell GBE FRS Dr Melanie Lee CBE FMedSci HonFREng FMedSci Professor Wendy Bickmore FRS FRSE Professor Andrew Lees FMedSci FMedSci Professor Sir Adrian Bird CBE FRS FRSE Professor Stafford Lightman FRS FMedSci FMedSci Professor Ewan Birney CBE FRS Professor Janet Lord FMedSci FMedSci Professor Dorothy Bishop FRS FBA Professor Thomas MacDonald FMedSci FMedSci Professor Rona MacKie CBE FRSE Professor Jane Blazeby FMedSci Sir Stephen Bloom FRS FMedSci Professor Giovanna Mallucci FMedSci Sir Tom Blundell FRS FMedSci Dr Fiona Marshall FMedSci Professor Dame Theresa Marteau DBE Professor Peter -
Algebra & Number Theory Vol. 7 (2013)
Algebra & Number Theory Volume 7 2013 No. 3 msp Algebra & Number Theory msp.org/ant EDITORS MANAGING EDITOR EDITORIAL BOARD CHAIR Bjorn Poonen David Eisenbud Massachusetts Institute of Technology University of California Cambridge, USA Berkeley, USA BOARD OF EDITORS Georgia Benkart University of Wisconsin, Madison, USA Susan Montgomery University of Southern California, USA Dave Benson University of Aberdeen, Scotland Shigefumi Mori RIMS, Kyoto University, Japan Richard E. Borcherds University of California, Berkeley, USA Raman Parimala Emory University, USA John H. Coates University of Cambridge, UK Jonathan Pila University of Oxford, UK J-L. Colliot-Thélène CNRS, Université Paris-Sud, France Victor Reiner University of Minnesota, USA Brian D. Conrad University of Michigan, USA Karl Rubin University of California, Irvine, USA Hélène Esnault Freie Universität Berlin, Germany Peter Sarnak Princeton University, USA Hubert Flenner Ruhr-Universität, Germany Joseph H. Silverman Brown University, USA Edward Frenkel University of California, Berkeley, USA Michael Singer North Carolina State University, USA Andrew Granville Université de Montréal, Canada Vasudevan Srinivas Tata Inst. of Fund. Research, India Joseph Gubeladze San Francisco State University, USA J. Toby Stafford University of Michigan, USA Ehud Hrushovski Hebrew University, Israel Bernd Sturmfels University of California, Berkeley, USA Craig Huneke University of Virginia, USA Richard Taylor Harvard University, USA Mikhail Kapranov Yale University, USA Ravi Vakil Stanford University, -
Ontology-Based Methods for Analyzing Life Science Data
Habilitation a` Diriger des Recherches pr´esent´ee par Olivier Dameron Ontology-based methods for analyzing life science data Soutenue publiquement le 11 janvier 2016 devant le jury compos´ede Anita Burgun Professeur, Universit´eRen´eDescartes Paris Examinatrice Marie-Dominique Devignes Charg´eede recherches CNRS, LORIA Nancy Examinatrice Michel Dumontier Associate professor, Stanford University USA Rapporteur Christine Froidevaux Professeur, Universit´eParis Sud Rapporteure Fabien Gandon Directeur de recherches, Inria Sophia-Antipolis Rapporteur Anne Siegel Directrice de recherches CNRS, IRISA Rennes Examinatrice Alexandre Termier Professeur, Universit´ede Rennes 1 Examinateur 2 Contents 1 Introduction 9 1.1 Context ......................................... 10 1.2 Challenges . 11 1.3 Summary of the contributions . 14 1.4 Organization of the manuscript . 18 2 Reasoning based on hierarchies 21 2.1 Principle......................................... 21 2.1.1 RDF for describing data . 21 2.1.2 RDFS for describing types . 24 2.1.3 RDFS entailments . 26 2.1.4 Typical uses of RDFS entailments in life science . 26 2.1.5 Synthesis . 30 2.2 Case study: integrating diseases and pathways . 31 2.2.1 Context . 31 2.2.2 Objective . 32 2.2.3 Linking pathways and diseases using GO, KO and SNOMED-CT . 32 2.2.4 Querying associated diseases and pathways . 33 2.3 Methodology: Web services composition . 39 2.3.1 Context . 39 2.3.2 Objective . 40 2.3.3 Semantic compatibility of services parameters . 40 2.3.4 Algorithm for pairing services parameters . 40 2.4 Application: ontology-based query expansion with GO2PUB . 43 2.4.1 Context . 43 2.4.2 Objective . -
Drugging the Undruggable: Advances on RAS Targeting in Cancer
G C A T T A C G G C A T genes Review Drugging the Undruggable: Advances on RAS Targeting in Cancer Miriam Molina-Arcas 1,*, Amit Samani 1,2,* and Julian Downward 1,3 1 Oncogene Biology Laboratory, Francis Crick Institute, London NW1 1AT, UK; [email protected] 2 Department of Medical Oncology, Imperial College Healthcare NHS Trust, London W2 1NY, UK 3 Lung Cancer Group, Institute of Cancer Research, London SW3 6JB, UK * Correspondence: [email protected] (M.M.-A.); [email protected] (A.S.) Abstract: Around 20% of all malignancies harbour activating mutations in RAS isoforms. Despite this, there is a deficiency of RAS-targeting agents licensed for therapeutic use. The picomolar affinity of RAS for GTP, and the lack of suitable pockets for high-affinity small-molecule binding, precluded effective therapies despite decades of research. Recently, characterisation of the biochemical properties of KRAS-G12C along with discovery of its ‘switch-II pocket’ have allowed development of effective mutant-specific inhibitors. Currently seven KRAS-G12C inhibitors are in clinical trials and sotorasib has become the first one to be granted FDA approval. Here, we discuss historical efforts to target RAS directly and approaches to target RAS effector signalling, including combinations that overcome limitations of single-agent targeting. We also review pre-clinical and clinical evidence for the efficacy of KRAS-G12C inhibitor monotherapy followed by an illustration of combination therapies designed to overcome primary resistance and extend durability of response. Finally, we briefly discuss novel approaches to targeting non-G12C mutant isoforms. -
Ax-Schanuel and Strong Minimality for the $ J $-Function
AX-SCHANUEL AND STRONG MINIMALITY FOR THE j-FUNCTION VAHAGN ASLANYAN Abstract. Let K := (K;+, ·, D, 0, 1) be a differentially closed field of character- istic 0 with field of constants C. In the first part of the paper we explore the connection between Ax-Schanuel type theorems (predimension inequalities) for a differential equation E(x, y) and the geometry of the fibres Us := {y : E(s,y) ∧ y∈ / C} where s is a non-constant element. We show that certain types of predimension inequalities imply strong minimality and geometric triviality of Us. Moreover, the induced structure on the Cartesian powers of Us is given by special subvarieties. In particular, since the j-function satisfies an Ax-Schanuel inequality of the required form (due to Pila and Tsimerman), applying our results to the j-function we recover a theorem of Freitag and Scanlon stating that the differential equation of j defines a strongly minimal set with trivial geometry. In the second part of the paper we study strongly minimal sets in the j-reducts of differentially closed fields. Let Ej (x, y) be the (two-variable) differential equation of the j-function. We prove a Zilber style classification result for strongly minimal sets in the reduct K := (K;+, ·, Ej ). More precisely, we show that in K all strongly minimal sets are geometrically trivial or non-orthogonal to C. Our proof is based on the Ax-Schanuel theorem and a matching Existential Closedness statement which asserts that systems of equations in terms of Ej have solutions in K unless having a solution contradicts Ax-Schanuel.