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Wellcome Trust Annual Report and Financial Statements 2017 Contents
Annual Report and Financial Statements 2017 2 Wellcome Trust Annual Report and Financial Statements 2017 Contents Report from the Chair and the Director 5 Trustee’s Report 8 What we do 8 Review of Charitable Activities 9 Review of Investment Activities 18 Financial Review 29 Structure and Governance 34 Risk Management 37 Remuneration Report 40 Audit Committee Report 43 Independent Auditor’s Report 45 Financial Statements 58 Consolidated Statement of Financial Activities 58 Consolidated Balance Sheet 59 Statement of Financial Activities of the Trust 60 Balance Sheet of the Trust 61 Consolidated Cash Flow Statement 62 Notes to the Financial Statements 63 Reference and Administrative Details 117 3 Wellcome Trust Annual Report and Financial Statements 2017 “ At Wellcome, we believe in the power of ideas to improve health” Jeremy Farrar Director 4 Wellcome Trust Annual Report and Financial Statements 2017 Report from the Chair and the Director “Our core approach is funding people to explore great ideas, at every step of the way from discovery to impact” At Wellcome, we believe in the power of ideas to improve cause of maternal mortality in the world. It also includes health. Funded from our independent investment portfolio, supporting research in the humanities and social sciences, we support thousands of scientists and researchers in more such as a project which this year published ethical guidelines than 70 countries, as well as innovators, educators and artists. for involving pregnant women in Zika vaccine research. Together, we take on big problems, fuel imaginations and spark And resources like the Human Induced Pluripotent Stem Cell debate, working always to achieve better health for everyone. -
The Electron Microscopy Science Technology Platform at the Francis
The Francis Crick Institute is a The Electron biomedical discovery institute Microscopy dedicated to understanding the fundamental biology underlying Science health and disease. Its work Technology is helping to understand why disease develops and to translate Platform at discoveries into new ways to the Francis prevent, diagnose and treat illnesses such as cancer, heart Crick Institute disease, stroke, infections, and Lucy Collinson neurodegenerative diseases. An independent organisation, its founding partners are the Medical Research Council (MRC), Cancer Research UK, Wellcome, University College London, Imperial College London and King’s College London. The Crick was formed in 2015, with many of the Crick’s scientists joining from two ‘parent’ institutes, the MRC’s National Institute for Medical Research and Cancer Research UK’s London Research Institute, and in 2016 it moved into a brand new state-of- the-art building in central London which brings together 1500 scientists and support staff working collaboratively across disciplines, making it the biggest biomedical research facility under a single roof in Europe. © Nick Guttridge 4 ISSUE 46 JUNE 2017 5 Each microscope room is a six-sided shielded box, • The Phenom-World DelPhi benchtop SEM with walls that contain complex metallic layers has an integrated fluorescence microscope to attenuate DC fields, and an active cancellation for correlative imaging system to attenuate AC fields. Under each • The FEI Twin 120 kV TEM has a cryo stage for microscope is a concrete platform, cast in place, and screening vitrified macromolecular samples supported by air springs that remove environmental prior to imaging on 200 kV and 300 kV TEMs vibration to <1 Hz. -
FEL Physics Summary
VUV and X-Ray Free Electron Lasers: The Technology and Its Scientific Promise William Barletta and Carlo Rizzuto Sections I & III – Motivations & FEL Physics List of symbols fine structure constant dimensionless vector potential aw horizontal Twiss x bunching parameter b mean resolution error of BPMs BPMres position error of BPMs BPMpos remanent field BR undulator magnetic field strength Bw horizontal Twiss x speed of light c mean phase error in undulator penetration depth δp horizontal dispersion Dx derivative of Dx D´x FEL beam diameter on optic Dw energy chirp from CSR E/E beam emittance electron charge e beam energy E peak electric field in gun Eo normalized emittance n energy in the FEL pulse EPulse longitudinal space charge force Fsc angle of incidence j i 1 2 relativistic factor (E/ me c ) optical function in transport H magnetic coercivity HC Alfven current at =1 IAo beam current Ib BBU threshold current IBBU undulator parameter K mean undulator strength Krms undulator spatial frequency kw gain length LG th m harmonic wavelength m plasma wavelength P radiation wavelength r undulator wavelength w root of gain equation harmonic number m electron mass me number of electrons Ne electron density ne number of undulator periods Nu radiation power P input laser power Plaser noise power Pn pole roll angle error BNP (or Pierce) parameter quantum FEL parameter ´ atom density A quality factor Q dipole quality factor Qdipole FEL energy constraint ratio r1 FEL emittance constraint ratio r2 FEL diffraction constraint ratio r3 classical radius of electron re bend angle in undulator bend angle in achromat 2 th phase of i electron i kick relative to each pole error j mean energy spread of electrons e bunch length z relativistic plasma frequency p distance along undulator z mean longitudinal velocity <vz> impedance of free space Zo Rayleigh range ZR 3 I. -
Bilateral NIST-PTB Comparison of Spectral Responsivity in the VUV
Bilateral NIST-PTB Comparison of Spectral Responsivity in the VUV A Gottwald 1, M Richter 1, P-S Shaw 2, Z Li 2 and U Arp 2 1Physikalisch-Technische Bundesanstalt, Abbestraße 2-12, 10587 Berlin, Germany 2National Institute for Standards and Technology, 100 Bureau Dr., Gaithersburg, MD 20899-8410, U.S.A. E-mail: [email protected] Abstract. To compare the calibration capabilities for the spectral responsivity in the vacuum-ultraviolet spectral region between 135 nm and 250 nm, PTB and NIST agreed on a bilateral comparison. Calibrations of semiconductor photodiodes as transfer detectors were performed using monochromatized synchrotron radiation and cryogenic electrical substitution radiometers as primary detector standards. Great importance was attached to the selection of suitable transfer detector standards due to their critical issues in that wavelength regime. The uncertainty budgets were evaluated in detail. The comparison showed a reasonable agreement between the participants. However, it got obvious that the uncertainty level for this comparison cannot easily be further reduced due to the lack of sufficiently radiation-hard and long-term stable transfer standard detectors. Keywords: PACS: 07.60.Dq, 07.85.Qe, 85.60.Dw, 06.20.fb Bilateral NIST-PTB Comparison of Spectral Responsivity in the VUV 2 1. Introduction The last decade has seen numerous key comparisons in the field of photometry and radiometry between different national metrology institutes (NMIs) in the context of the Mutual Recognition Arrangement. At first, these comparisons were restricted to wavelengths longer than 200 nm, with just the exception of a recent pilot comparison from 10 nm to 20 nm [1]. -
Structure of Human Aspartyl Aminopeptidase Complexed With
Chaikuad et al. BMC Structural Biology 2012, 12:14 http://www.biomedcentral.com/1472-6807/12/14 RESEARCH ARTICLE Open Access Structure of human aspartyl aminopeptidase complexed with substrate analogue: insight into catalytic mechanism, substrate specificity and M18 peptidase family Apirat Chaikuad1, Ewa S Pilka1, Antonio De Riso2, Frank von Delft1, Kathryn L Kavanagh1, Catherine Vénien-Bryan2, Udo Oppermann1,3 and Wyatt W Yue1* Abstract Backround: Aspartyl aminopeptidase (DNPEP), with specificity towards an acidic amino acid at the N-terminus, is the only mammalian member among the poorly understood M18 peptidases. DNPEP has implicated roles in protein and peptide metabolism, as well as the renin-angiotensin system in blood pressure regulation. Despite previous enzyme and substrate characterization, structural details of DNPEP regarding ligand recognition and catalytic mechanism remain to be delineated. Results: The crystal structure of human DNPEP complexed with zinc and a substrate analogue aspartate-β- hydroxamate reveals a dodecameric machinery built by domain-swapped dimers, in agreement with electron microscopy data. A structural comparison with bacterial homologues identifies unifying catalytic features among the poorly understood M18 enzymes. The bound ligands in the active site also reveal the coordination mode of the binuclear zinc centre and a substrate specificity pocket for acidic amino acids. Conclusions: The DNPEP structure provides a molecular framework to understand its catalysis that is mediated by active site loop swapping, a mechanism likely adopted in other M18 and M42 metallopeptidases that form dodecameric complexes as a self-compartmentalization strategy. Small differences in the substrate binding pocket such as shape and positive charges, the latter conferred by a basic lysine residue, further provide the key to distinguishing substrate preference. -
A Critical Base Pair in K-Turns That Confers Folding Characteristics and Correlates with Biological Function
ARTICLE Received 16 Apr 2014 | Accepted 2 Sep 2014 | Published 29 Oct 2014 DOI: 10.1038/ncomms6127 OPEN A critical base pair in k-turns that confers folding characteristics and correlates with biological function Scott A. McPhee1, Lin Huang1 & David M.J. Lilley1 Kink turns (k-turns) are widespread elements in RNA that mediate tertiary contacts by kinking the helical axis. We have found that the ability of k-turns to undergo ion-induced folding is conferred by a single base pair that follows the conserved AG pairs, that is, the 3b3n position. A Watson–Crick pair leads to an inability to fold in metal ions alone, while 3n ¼ Gor3b¼ C (but not both) permits folding. Crystallographic study reveals two hydrated metal ions coordinated to O6 of G3n and G2n of Kt-7. Removal of either atom impairs Mg2 þ - induced folding in solution. While SAM-I riboswitches have 3b3n sequences that would predispose them to ion-induced folding, U4 snRNA are strongly biased to an inability to such folding. Thus riboswitch sequences allow folding to occur independently of protein binding, while U4 should remain unfolded until bound by protein. The empirical rules deduced for k-turn folding have strong predictive value. 1 Cancer Research UK Nucleic Acid Structure Research Group, MSI/WTB Complex, The University of Dundee, Dow Street, Dundee DD1 5EH, UK. Correspondence and requests for materials should be addressed to D.M.J.L. (email: [email protected]). NATURE COMMUNICATIONS | 5:5127 | DOI: 10.1038/ncomms6127 | www.nature.com/naturecommunications 1 & 2014 Macmillan Publishers Limited. -
Living Healthier for Longer Sharing Data Saves Lives
News from the Medical Research Council network Spring 2014 Leading science for better health MEASUREto How some MRC scientific workshops are making custom-made kit to enable pioneering research Living healthier for longer Supporting innovative ageing research through the Lifelong Health and Wellbeing initiative Sharing data saves lives Opinions from two MRC researchers Network can also be downloaded as a PDF at: www.mrc.ac.uk/network CONTENTS NEWS News COMMENT FROM £39.1m for improving data research 3 £39.1m for improving Science festival fun 4 John Let’s talk about dementia 7 data research Savill A £32m MRC investment, announced by Universities and Science the MRC Consortium for Medical Microbial Bioinformatics led by Minister David Willetts at the High Performance Computing and Warwick University, the Medical Bioinformatics partnership led People CHIEF EXECUTIVE Big Data Conference in London on 6 February, plus an additional by Imperial College London and University College London £7.1m, is the latest instalment of a £90m funding initiative to Partners which includes the Francis Crick Institute, will also Dr Jane Cope on the power of persuasion 9 In February, the Minister for tackle health and bioinformatics challenges for the advancement support career opportunities for computational scientists, Universities and Science David of medical research. technologists and programme leaders, enhancing the UK’s skills Willetts announced a £32m MRC in this area. investment into improving the UK’s Six major strategic awards will strengthen collaborative links, capability in, and capacity for, improve tools and infrastructure for researchers and support the Mr Willets said: “Making the most of large and complex data is a Latest discoveries medical bioinformatics. -
Collimation System for the Bessy Fel∗
T. Kamps / Proceedings of the 2004 FEL Conference, 381-384 381 COLLIMATION SYSTEM FOR THE BESSY FEL∗ T. Kamps Berliner Elektronenspeicherring-Gesellschaft fur¨ Synchrotronstrahlung BESSY, D-12489 Berlin, Germany Abstract magnet undulators. Each undulator is composed of mod- ules with length ranging from 1.6 m to 3.9 m, the total Beam collimation is an essential element for the success- length of the high energy FEL line is 70 m. A FODO lat- ful running of a linear accelerator based free electron laser. tice is superimposed onto the undulator structure with the The task of the collimation system is to protect the undu- quadrupole magnets located at the intersections between lator modules against mis-steered beam and dark-current. the undulator modules. For the present analysis in total 14 This is achieved by a set of apertures limiting the succeed- undulator modules are taken into account for the simulation ing transverse phase space volume and magnetic dogleg studies. The gap between the undulator poles is 10 mm, the structure for the longitudinal phase space. In the follow- beampipe radius is 4 mm. The undulator magnets are made ing the design of the BESSY FEL collimation system is of NdFeB in order to obtain large undulator K parameters. described together with detailed simulation studies. This material is very sensitive to irradiation, especially to the reduced dose deposited by high-energy electrons (> MOTIVATION 20 MeV). From studies with NdFeB under electron irra- Experiences from linac driven FEL operation (for exam- diation [4] the limit for acceptable beam loss in the undula- ple at TTF1 [1]) indicate that beam collimation is essential tor chamber has been derived. -
Structural Basis of Mammalian Mucin Processing by the Human Gut O
ARTICLE https://doi.org/10.1038/s41467-020-18696-y OPEN Structural basis of mammalian mucin processing by the human gut O-glycopeptidase OgpA from Akkermansia muciniphila ✉ ✉ Beatriz Trastoy 1,4, Andreas Naegeli2,4, Itxaso Anso 1,4, Jonathan Sjögren 2 & Marcelo E. Guerin 1,3 Akkermansia muciniphila is a mucin-degrading bacterium commonly found in the human gut that promotes a beneficial effect on health, likely based on the regulation of mucus thickness 1234567890():,; and gut barrier integrity, but also on the modulation of the immune system. In this work, we focus in OgpA from A. muciniphila,anO-glycopeptidase that exclusively hydrolyzes the peptide bond N-terminal to serine or threonine residues substituted with an O-glycan. We determine the high-resolution X-ray crystal structures of the unliganded form of OgpA, the complex with the glycodrosocin O-glycopeptide substrate and its product, providing a comprehensive set of snapshots of the enzyme along the catalytic cycle. In combination with O-glycopeptide chemistry, enzyme kinetics, and computational methods we unveil the molecular mechanism of O-glycan recognition and specificity for OgpA. The data also con- tribute to understanding how A. muciniphila processes mucins in the gut, as well as analysis of post-translational O-glycosylation events in proteins. 1 Structural Biology Unit, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, 48160 Derio, Spain. 2 Genovis AB, Box 790, 22007 Lund, Sweden. 3 IKERBASQUE, Basque Foundation for Science, 48013 ✉ Bilbao, Spain. 4These authors contributed equally: Beatriz Trastoy, Andreas Naegeli, Itxaso Anso. -
Structure and Ligand Binding of the ADP-Binding Domain of the NAD+ Riboswitch
Downloaded from rnajournal.cshlp.org on October 6, 2021 - Published by Cold Spring Harbor Laboratory Press Structure and ligand binding of the ADP-binding domain of the NAD+ riboswitch Lin Huang1, Jia Wang and David M. J. Lilley* Cancer Research UK Nucleic Acid Structure Research Group, MSI/WTB Complex, The University of Dundee, Dow Street, Dundee DD1 5EH, U.K. * To whom correspondence should be addressed 1. Current address : Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 , P. R. China and RNA Biomedical Institute, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, P. R. China Keywords : Riboregulation; RNA structure; X-ray crystallography; metal ions; nucleotide binding Running title: The structure of the NAD+ riboswitch Submitted to the RNA journal 20 January 2020 Editorial enquiries to Professor Lilley: Tel: (+44)-1382-384243 Email: [email protected] Downloaded from rnajournal.cshlp.org on October 6, 2021 - Published by Cold Spring Harbor Laboratory Press ABSTRACT The nadA motif is the first known NAD+-dependent riboswitch, comprising two similar tandem bulged stem-loop structures. We have determined the structure of the 5’ domain 1 of the riboswitch. It has three coaxial helical segments, separated by an ACANCCCC bulge and by an internal loop, with a tertiary contact between them that includes two C:G base pairs. We have determined the structure with a number of ligands related to NADH, but in each case only the ADP moiety is observed. The adenosine adopts an anti conformation, and forms multiple hydrogen bonds across the width of the sugar edge of the penultimate C:G base pair of the helix preceding the bulge, and the observed contacts have been confirmed by mutagenesis and calorimetry. -
The Tesla Free Electron Laser J
THE TESLA FREE ELECTRON LASER J. Rossbach, for the TESLA FEL collaboration DESY, Notkestrasse 85, D22603 Hamburg, Germany Abstract occupied many scientists, a practical solution to this prob- lem has not yet been realized. To be an efficient research The TESLA Free Electron Laser (FEL) makes use of the tool, such a source would have to provide stable intensities high electron beam quality that can be provided by the su- with short pulses and repetition frequencies similar to what perconducting TESLA linac to drive a single pass FEL at is found in optical lasers. Exactly this seems to be possible wavelengths far below the visible. To reach a wavelength by using the so-called self amplified spontaneous emission of 6 nanometers, the TESLA Test Facility (TTF) currently process SASE. under construction at DESY will be extended to 1 GeV The basic principle [1] makes use of the fact that an elec- beam energy. Because there are no mirrors and seed-lasers tron beam of sufficient quality, passing a long undulator in this wavelength regime, the principle of Self-Amplified- magnet, exponentially amplifies an initially existing radi- Spontaneous-Emission (SASE) will be employed. A first ation field, if the photon wavelength λph matches a reso- test of both the principle and technical components is fore- nance condition determined by undulator parameters and seen at a photon wavelength larger than 42 nanometers. the beam energy: With respect to linac technology, the key prerequisite for such single-pass, high-gain FELs is a high intensity, λu 2 λph = (1 + K ) (1) diffraction limited, electron beam to be generated and ac- 2γ2 celerated without degradation. -
Wellcome Trust Annual Report and Financial Statements 2019 Is © the Wellcome Trust and Is Licensed Under Creative Commons Attribution 2.0 UK
Annual Report and Financial Statements 2019 Table of contents Report from Chair 3 Report from Director 5 Trustee’s Report 7 What we do 8 Review of Charitable Activities 9 Review of Investment Activities 21 Financial Review 31 Structure and Governance 36 Social Responsibility 40 Risk Management 42 Remuneration Report 44 Remuneration Committee Report 46 Nomination Committee Report 47 Investment Committee Report 48 Audit and Risk Committee Report 49 Independent Auditor’s Report 52 Financial Statements 61 Consolidated Statement of Financial Activities 62 Consolidated Balance Sheet 63 Statement of Financial Activities of the Trust 64 Balance Sheet of the Trust 65 Consolidated Cash Flow Statement 66 Notes to the Financial Statements 67 Alternative Performance Measures and Key Performance Indicators 114 Glossary of Terms 115 Reference and Administrative Details 116 Table of Contents Wellcome Trust Annual Report 2019 | 2 Report from Chair During my tenure at Wellcome, which ends in The macro environment is increasingly challenging, 2020, I count myself lucky to have had the which has created volatility in financial markets. opportunity to meet inspiring people from a rich Q4 2018 was a very difficult quarter, but the diversity of sectors, backgrounds, specialisms resumption of interest rate cuts by the US Federal and scientific fields. Reserve underpinned another year of gains for our portfolio. We recognise that the cycle is extended, Wellcome’s achievements belong to the people and that the portfolio is likely to face more who work here and to the people we fund – it is challenging times ahead. a partnership that continues to grow stronger, more influential and more ambitious, spurred by The team is working hard to ensure that our independence.