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A Novel Optical Microscope for Imaging Large
RESEARCH ARTICLE A novel optical microscope for imaging large embryos and tissue volumes with sub-cellular resolution throughout Gail McConnell1*, Johanna Tra¨ ga˚ rdh1, Rumelo Amor1, John Dempster1, Es Reid1, William Bradshaw Amos1,2 1Centre for Biophotonics, Strathclyde Institute for Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom; 2MRC Laboratory of Molecular Biology, Cambridge, United Kingdom Abstract Current optical microscope objectives of low magnification have low numerical aperture and therefore have too little depth resolution and discrimination to perform well in confocal and nonlinear microscopy. This is a serious limitation in important areas, including the phenotypic screening of human genes in transgenic mice by study of embryos undergoing advanced organogenesis. We have built an optical lens system for 3D imaging of objects up to 6 mm wide and 3 mm thick with depth resolution of only a few microns instead of the tens of microns currently attained, allowing sub-cellular detail to be resolved throughout the volume. We present this lens, called the Mesolens, with performance data and images from biological specimens including confocal images of whole fixed and intact fluorescently-stained 12.5-day old mouse embryos. DOI: 10.7554/eLife.18659.001 Introduction During experiments with laser scanning confocal microscopes in the mid-1980s, it became obvious that the optical sectioning, which is the main advantage of the confocal method, did not work with *For correspondence: the available low-magnification objectives, because of their low numerical aperture (N.A.) [email protected] (White et al., 1987). In specimens such as mouse embryos at the 10–12.5 day stage, when the major Competing interest: See organs are developing (Kaufman, 1992), it was impossible to see individual cells in the interior page 14 despite the lateral (XY) resolution being sufficient. -
Causal Diagrams for Interference Elizabeth L
STATISTICAL SCIENCE Volume 29, Number 4 November 2014 Special Issue on Semiparametrics and Causal Inference Causal Etiology of the Research of James M. Robins ..............................................Thomas S. Richardson and Andrea Rotnitzky 459 Doubly Robust Policy Evaluation and Optimization ..........................Miroslav Dudík, Dumitru Erhan, John Langford and Lihong Li 485 Statistics,CausalityandBell’sTheorem.....................................Richard D. Gill 512 Standardization and Control for Confounding in Observational Studies: A Historical Perspective..............................................Niels Keiding and David Clayton 529 CausalDiagramsforInterference............Elizabeth L. Ogburn and Tyler J. VanderWeele 559 External Validity: From do-calculus to Transportability Across Populations .........................................................Judea Pearl and Elias Bareinboim 579 Nonparametric Bounds and Sensitivity Analysis of Treatment Effects .................Amy Richardson, Michael G. Hudgens, Peter B. Gilbert and Jason P. Fine 596 The Bayesian Analysis of Complex, High-Dimensional Models: Can It Be CODA? .......................................Y.Ritov,P.J.Bickel,A.C.GamstandB.J.K.Kleijn 619 Q-andA-learning Methods for Estimating Optimal Dynamic Treatment Regimes .............. Phillip J. Schulte, Anastasios A. Tsiatis, Eric B. Laber and Marie Davidian 640 A Uniformly Consistent Estimator of Causal Effects under the k-Triangle-Faithfulness Assumption...................................................Peter Spirtes -
Main Panel B
MAIN PANEL B Sub-panel 7: Earth Systems and Environmental Sciences Sub-panel 8: Chemistry Sub-panel 9: Physics Sub-panel 10: Mathematical Sciences Sub-panel 11: Computer Science and Informatics Sub-panel 12: Engineering Where required, specialist advisers have been appointed to the REF sub-panels to provide advice to the REF sub-panels on outputs in languages other than English, and / or English-language outputs in specialist areas, that the panel is otherwise unable to assess. This may include outputs containing a substantial amount of code, notation or technical terminology analogous to another language In addition to these appointments, specialist advisers will be appointed for the assessment of classified case studies and are not included in the list of appointments. Main Panel B Main Panel B Chair Professor David Price University College London Deputy Chair Professor Dame Muffy Calder* University of Glasgow Members Professor Mike Ashfold University of Bristol Professor John Clarkson University of Cambridge Dr Peter Costigan Independent Professor Paula Eerola University of Helsinki Professor Alison Etheridge University of Oxford Dr Giles Graham Defence Science Technology Laboratory Professor Michael Hinton High Value Manufacturing Catapult Professor Andrew Holmes University of Melbourne Professor Raymond Jeanloz University of California, Berkeley Mr Ben Johnson Graphic Science Ltd Professor Hilary Lappin-Scott Cardiff University Professor John Ludden Heriot-Watt University Professor Miles Padgett University of Glasgow Professor Simon -
Annual Report 2017-2018
Annual Review 2017 | 2018 ONTENTS C 1 Overview 1 2 Profile 4 3 Research 6 4 Events 9 5 Personnel 13 6 Mentoring 17 7 Structures 18 APPENDICES R1 Highlighted Papers 20 R2 Complete List of Papers 23 E1 HIMR-run Events 29 E2 HIMR-sponsored Events 31 E3 Focused Research Events 39 E4 Future Events 54 P1 Fellows Joining in 2017|2018 59 P2 Fellows Leaving since September 2017 60 P3 Fellows Moving with 3-year Extensions 62 P4 Future Fellows 63 M1 Mentoring Programme 64 1. Overview This has been another excellent year for the Heilbronn Institute, which is now firmly established as a major national mathematical research centre. HIMR has developed a strong brand and is increasingly influential in the UK mathematics community. There is currently an outstanding cohort of Heilbronn Research Fellows doing first-rate research. Recruitment of new Fellows has been most encouraging, as is the fact that many distinguished academic mathematicians continue to work with the Institute. The research culture at HIMR is excellent. Members have expressed a high level of satisfaction. This is especially the case with the Fellows, many of whom have chosen to continue their relationships with the Institute. Our new Fellows come from leading mathematics departments and have excellent academic credentials. Those who left have moved to high-profile groups, including several to permanent academic positions. We currently have 29 Fellows, hosted by 6 universities. We are encouraged by the fact that of the 9 Fellows joining us this year, 5 are women. The achievements of our Fellows this year again range from winning prestigious prizes to publishing in the elite mathematical journals and organising major mathematical meetings. -
Urban Pamphleteer #2 Regeneration Realities
Regeneration Realities Urban Pamphleteer 2 p.1 Duncan Bowie# p.3 Emma Dent Coad p.5 Howard Read p.6 Loretta Lees, Just Space, The London Tenants’ Federation and SNAG (Southwark Notes Archives Group) p.11 David Roberts and Andrea Luka Zimmerman p.13 Alexandre Apsan Frediani, Stephanie Butcher, and Paul Watt p.17 Isaac Marrero- Guillamón p.18 Alberto Duman p.20 Martine Drozdz p.22 Phil Cohen p.23 Ben Campkin p.24 Michael Edwards p.28 isik.knutsdotter Urban PamphleteerRunning Head Ben Campkin, David Roberts, Rebecca Ross We are delighted to present the second issue of Urban Pamphleteer In the tradition of radical pamphleteering, the intention of this series is to confront key themes in contemporary urban debate from diverse perspectives, in a direct and accessible – but not reductive – way. The broader aim is to empower citizens, and inform professionals, researchers, institutions and policy- makers, with a view to positively shaping change. # 2 London: Regeneration Realities The term ‘regeneration’ has recently been subjected to much criticism as a pervasive metaphor applied to varied and often problematic processes of urban change. Concerns have focused on the way the concept is used as shorthand in sidestepping important questions related to, for example, gentrification and property development. Indeed, it is an area where policy and practice have been disconnected from a rigorous base in research and evidence. With many community groups affected by regeneration evidently feeling disenfranchised, there is a strong impetus to propose more rigorous approaches to researching and doing regeneration. The Greater London Authority has also recently opened a call for the public to comment on what regeneration is, and feedback on what its priorities should be. -
A Novel Optical Microscope for Imaging Large Embryos And
RESEARCH ARTICLE A novel optical microscope for imaging large embryos and tissue volumes with sub-cellular resolution throughout Gail McConnell1*, Johanna Tra¨ ga˚ rdh1, Rumelo Amor1, John Dempster1, Es Reid1, William Bradshaw Amos1,2 1Centre for Biophotonics, Strathclyde Institute for Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom; 2MRC Laboratory of Molecular Biology, Cambridge, United Kingdom Abstract Current optical microscope objectives of low magnification have low numerical aperture and therefore have too little depth resolution and discrimination to perform well in confocal and nonlinear microscopy. This is a serious limitation in important areas, including the phenotypic screening of human genes in transgenic mice by study of embryos undergoing advanced organogenesis. We have built an optical lens system for 3D imaging of objects up to 6 mm wide and 3 mm thick with depth resolution of only a few microns instead of the tens of microns currently attained, allowing sub-cellular detail to be resolved throughout the volume. We present this lens, called the Mesolens, with performance data and images from biological specimens including confocal images of whole fixed and intact fluorescently-stained 12.5-day old mouse embryos. DOI: 10.7554/eLife.18659.001 Introduction During experiments with laser scanning confocal microscopes in the mid-1980s, it became obvious *For correspondence: that the optical sectioning, which is the main advantage of the confocal method, did not work with [email protected] the available low-magnification objectives, because of their low numerical aperture (N.A.) Competing interest: See (White et al., 1987). In specimens such as mouse embryos at the 10–12.5 day stage, when the major page 14 organs are developing (Kaufman, 1992), it was impossible to see individual cells in the interior despite the lateral (XY) resolution being sufficient. -
NEWSLETTER Issue: 481 - March 2019
i “NLMS_481” — 2019/2/13 — 11:04 — page 1 — #1 i i i NEWSLETTER Issue: 481 - March 2019 HILBERT’S FRACTALS CHANGING SIXTH AND A-LEVEL PROBLEM GEOMETRY STANDARDS i i i i i “NLMS_481” — 2019/2/13 — 11:04 — page 2 — #2 i i i EDITOR-IN-CHIEF COPYRIGHT NOTICE Iain Moatt (Royal Holloway, University of London) News items and notices in the Newsletter may [email protected] be freely used elsewhere unless otherwise stated, although attribution is requested when reproducing whole articles. Contributions to EDITORIAL BOARD the Newsletter are made under a non-exclusive June Barrow-Green (Open University) licence; please contact the author or photog- Tomasz Brzezinski (Swansea University) rapher for the rights to reproduce. The LMS Lucia Di Vizio (CNRS) cannot accept responsibility for the accuracy of Jonathan Fraser (University of St Andrews) information in the Newsletter. Views expressed Jelena Grbic´ (University of Southampton) do not necessarily represent the views or policy Thomas Hudson (University of Warwick) of the Editorial Team or London Mathematical Stephen Huggett (University of Plymouth) Society. Adam Johansen (University of Warwick) Bill Lionheart (University of Manchester) ISSN: 2516-3841 (Print) Mark McCartney (Ulster University) ISSN: 2516-385X (Online) Kitty Meeks (University of Glasgow) DOI: 10.1112/NLMS Vicky Neale (University of Oxford) Susan Oakes (London Mathematical Society) David Singerman (University of Southampton) Andrew Wade (Durham University) NEWSLETTER WEBSITE The Newsletter is freely available electronically Early Career Content Editor: Vicky Neale at lms.ac.uk/publications/lms-newsletter. News Editor: Susan Oakes Reviews Editor: Mark McCartney MEMBERSHIP CORRESPONDENTS AND STAFF Joining the LMS is a straightforward process. -
Design and Analysis Issues in Family-Based Association
Emerging Challenges in Statistical Genetics Duncan Thomas University of Southern California Human Genetics in the Big Science Era • “Big Data” – large n and large p and complexity e.g., NIH Biomedical Big Data Initiative (RFA-HG-14-020) • Large n: challenge for computation and data storage, but not conceptual • Large p: many data mining approaches, few grounded in statistical principles • Sparse penalized regression & hierarchical modeling from Bayesian and frequentist perspectives • Emerging –omics challenges Genetics: from Fisher to GWAS • Population genetics & heritability – Mendel / Fisher / Haldane / Wright • Segregation analysis – Likelihoods on complex pedigrees by peeling: Elston & Stewart • Linkage analysis (PCR / microsats / SNPs) – Multipoint: Lander & Green – MCMC: Thompson • Association – TDT, FBATs, etc: Spielman, Laird – GWAS: Risch & Merikangas – Post-GWAS: pathway mining, next-gen sequencing Association: From hypothesis-driven to agnostic research Candidate pathways Candidate Hierarchical GWAS genes models (ht-SNPs) Ontologies Pathway mining MRC BSU SGX Plans Objectives: – Integrating structural and prior information for sparse regression analysis of high dimensional data – Clustering models for exposure-disease associations – Integrating network information – Penalised regression and Bayesian variable selection – Mechanistic models of cellular processes – Statistical computing for large scale genomics data Targeted areas of impact : – gene regulation and immunological response – biomarker based signatures – targeting -
BIOLOGY 639 SCIENCE ONLINE the Unexpected Brains Behind Blood Vessel Growth 641 THIS WEEK in SCIENCE 668 U.K
4 February 2005 Vol. 307 No. 5710 Pages 629–796 $10 07%.'+%#%+& 2416'+0(70%6+10 37#06+6#6+8' 51(69#4' #/2.+(+%#6+10 %'..$+1.1); %.10+0) /+%41#44#;5 #0#.;5+5 #0#.;5+5 2%4 51.76+105 Finish first with a superior species. 50% faster real-time results with FullVelocity™ QPCR Kits! Our FullVelocity™ master mixes use a novel enzyme species to deliver Superior Performance vs. Taq -Based Reagents FullVelocity™ Taq -Based real-time results faster than conventional reagents. With a simple change Reagent Kits Reagent Kits Enzyme species High-speed Thermus to the thermal profile on your existing real-time PCR system, the archaeal Fast time to results FullVelocity technology provides you high-speed amplification without Enzyme thermostability dUTP incorporation requiring any special equipment or re-optimization. SYBR® Green tolerance Price per reaction $$$ • Fast, economical • Efficient, specific and • Probe and SYBR® results sensitive Green chemistries Need More Information? Give Us A Call: Ask Us About These Great Products: Stratagene USA and Canada Stratagene Europe FullVelocity™ QPCR Master Mix* 600561 Order: (800) 424-5444 x3 Order: 00800-7000-7000 FullVelocity™ QRT-PCR Master Mix* 600562 Technical Services: (800) 894-1304 Technical Services: 00800-7400-7400 FullVelocity™ SYBR® Green QPCR Master Mix 600581 FullVelocity™ SYBR® Green QRT-PCR Master Mix 600582 Stratagene Japan K.K. *U.S. Patent Nos. 6,528,254, 6,548,250, and patents pending. Order: 03-5159-2060 Purchase of these products is accompanied by a license to use them in the Polymerase Chain Reaction (PCR) Technical Services: 03-5159-2070 process in conjunction with a thermal cycler whose use in the automated performance of the PCR process is YYYUVTCVCIGPGEQO covered by the up-front license fee, either by payment to Applied Biosystems or as purchased, i.e., an authorized thermal cycler. -
XXXX LEVER JAN15 NEWSLTTR.Indd 1 28/01/2015 11:34 DIRECTOR’S NOTE FUNDING UPDATES COMPETITIONS SCHEME NEWS OLD and NEW
SCHOLARSHIPS FOR RESEARCH AND EDUCATION JANUARY 2015 ROUND MOUNDS Were they really built by Normans? INSIDE THIS ISSUE The ‘me’ in memory Exploring the developing self The American steppe Russian influences on the Great Plains GEMOLOGY NANOSYNTHESIS New materials, new worlds Jewellers, travellers and the A new method of nanostructure Understanding the uses of Bronze Age axes science of gems in France in fi lms XXXX LEVER JAN15 NEWSLTTR.indd 1 28/01/2015 11:34 DIRECTOR’S NOTE FUNDING UPDATES COMPETITIONS SCHEME NEWS OLD AND NEW Award winners in no fewer than seven and the latest round produced over LEVERHULME RESEARCH funding streams are announced in this 750 applications, so we were very CENTRES edition of the Newsletter. pleased to be able to make 100 awards. We congratulate the recipients of Competition to secure one of these The Leverhulme Trust has announced our new Leverhulme Doctoral Scholarship Fellowships is obviously fierce – so many the launch of a major new initiative to Awards. Fourteen universities will each congratulations to those who succeeded establish Leverhulme Research Centres receive £1 million, over three years, to in this particular round. in the UK, representing a commitment provide 15 scholarships per institution For the first time, our popular of up to £10 million over 10 years for to address topics as diverse as Artist in Residence Grants were made each Centre. The objective is to fund understanding maritime futures, climate via the competitive mechanism of a innovative research of the greatest justice, genetics journeys into history and single ‘gathered field’. Over 100 bids originality and to encourage bold, mathematics for a sustainable society. -
A Joint Spatio-Temporal Model of Opioid Associated Deaths and Treatment Admissions in Ohio
A JOINT SPATIO-TEMPORAL MODEL OF OPIOID ASSOCIATED DEATHS AND TREATMENT ADMISSIONS IN OHIO BY YIXUAN JI A Thesis Submitted to the Graduate Faculty of WAKE FOREST UNIVERSITY GRADUATE SCHOOL OF ARTS AND SCIENCES in Partial Fulfillment of the Requirements for the Degree of MASTER OF ARTS Mathematics and Statistics May 2019 Winston-Salem, North Carolina Approved By: Staci Hepler, Ph.D., Advisor Miaohua Jiang, Ph.D., Chair Robert Erhardt, Ph.D. Acknowledgments First and foremost, I would like to express my sincere gratitude and appreciation to my advisor, Dr. Staci A. Hepler. Without your continuous support and inspiration, I could not have achieved this thesis research. Thank you so much for your patience, motivation, enthusiasm, and immense knowledge, which made this research even more enjoyable. In addition to my advisor, I would also like to thank Dr. Miaohua Jiang and Dr. Robert Erhardt, for the constant encouragement and advice, and for serving on my thesis committee. Furthermore, this thesis benefited greatly from various courses that I took, including Bayesian statistics from Dr. Hepler, factor analysis and Markov Chain from Dr. Berenhaut, poisson linear model from Dr. Erhardt's Generalized Linear Model class, R programming skills from Dr. Nicole Dalzell and also reasoning skills from Dr. John Gemmer's Real Analysis class. Additionally, I would like to extend my thanks to Dr. Ellen Kirkman, Dr. Stephen Robinson and Dr. Sarah Raynor for their special attention and support to me, as an international student. Last but not least, I would like to thank my family for their sincere mental support throughout my life. -
Alan Agresti
Historical Highlights in the Development of Categorical Data Analysis Alan Agresti Department of Statistics, University of Florida UF Winter Workshop 2010 CDA History – p. 1/39 Karl Pearson (1857-1936) CDA History – p. 2/39 Karl Pearson (1900) Philos. Mag. Introduces chi-squared statistic (observed − expected)2 X2 = X expected df = no. categories − 1 • testing values for multinomial probabilities (Monte Carlo roulette runs) • testing fit of Pearson curves • testing statistical independence in r × c contingency table (df = rc − 1) CDA History – p. 3/39 Karl Pearson (1904) Advocates measuring association in contingency tables by approximating the correlation for an assumed underlying continuous distribution • tetrachoric correlation (2 × 2, assuming bivariate normality) X2 2 • contingency coefficient 2 based on for testing q X +n X independence in r × c contingency table • introduces term “contingency” as a “measure of the total deviation of the classification from independent probability.” CDA History – p. 4/39 George Udny Yule (1871-1951) (1900) Philos. Trans. Royal Soc. London (1912) JRSS Advocates measuring association using odds ratio n11 n12 n21 n22 n n n n − n n θˆ = 11 22 Q = 11 22 12 21 = (θˆ − 1)/(θˆ + 1) n12n21 n11n22 + n12n21 “At best the normal coefficient can only be said to give us. a hypothetical correlation between supposititious variables. The introduction of needless and unverifiable hypotheses does not appear to me a desirable proceeding in scientific work.” (1911) An Introduction to the Theory of Statistics (14 editions) CDA History – p. 5/39 K. Pearson, with D. Heron (1913) Biometrika “Unthinking praise has been bestowed on a textbook which can only lead statistical students hopelessly astray.” .