Insertion Device Alignment for the Diamond Light Source A
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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. -
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. -
Chapter 3: Front Ends and Insertion Devices
Advanced Photon Source Upgrade Project Final Design Report May 2019 Chapter 3: Front Ends and Insertion Devices Document Number : APSU-2.01-RPT-003 ICMS Content ID : APSU_2032071 Advanced Photon Source Upgrade Project 3–ii • Table of Contents Table of Contents 3 Front Ends and Insertion Devices 1 3-1 Introduction . 1 3-2 Front Ends . 2 3-2.1 High Heat Load Front End . 6 3-2.2 Canted Undulator Front End . 11 3-2.3 Bending Magnet Front End . 16 3-3 Insertion Devices . 20 3-3.1 Storage Ring Requirements . 22 3-3.2 Overview of Insertion Device Straight Sections . 23 3-3.3 Permanent Magnet Undulators . 24 3-3.4 Superconducting Undulators . 30 3-3.5 Insertion Device Vacuum Chamber . 33 3-4 Bending Magnet Sources . 36 References 39 Advanced Photon Source Upgrade Project List of Figures • 3–iii List of Figures Figure 3.1: Overview of ID and BM front ends in relation to the storage ring components. 2 Figure 3.2: Layout of High Heat Load Front End for APS-U. 6 Figure 3.3: Model of the GRID XBPM for the HHL front end. 8 Figure 3.4: Layout of Canted Undulator Front End for APS-U. 11 Figure 3.5: Model of the GRID XBPM for the CU front end. 13 Figure 3.6: Horizontal fan of radiation from different dipoles for bending magnet beamlines. 16 Figure 3.7: Layout of Original APS Bending Magnet Front End in current APS. 17 Figure 3.8: Layout of modified APSU Bending Magnet Front End to be installed in APSU. -
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. -
Insertion Devices Lecture 4 Undulator Magnet Designs
Insertion Devices Lecture 4 Undulator Magnet Designs Jim Clarke ASTeC Daresbury Laboratory Hybrid Insertion Devices – Inclusion of Iron Simple hybrid example Top Array e- Bottom Array 2 Lines of Magnetic Flux Including a non-linear material like iron means that simple analytical formulae can no longer be derived – linear superposition no longer works! Accurate predictions for particular designs can only be made using special magnetostatic software in either 2D (fast) or 3D (slow) e- 3 Field Levels for Hybrid and PPM Insertion Devices Assuming Br = 1.1T and gap of 20 mm When g/u is small the impact of the iron is very significant 4 Introduction We now have an understanding for how we can use Permanent Magnets to create the sinusoidal fields required by Insertion Devices Next we will look at creating more complex field shapes, such as those required for variable polarisation Later we will look at other technical issues such as the challenge of in-vacuum undulators, dealing with the large magnetic forces involved, correcting field errors, and also how and why we might cool undulators to ~150K Finally, electromagnetic alternatives will be considered 5 Helical (or Elliptical) Undulators for Variable Polarisation We need to include a finite horizontal field of the same period so the electron takes an elliptical path when it is viewed head on We want two orthogonal fields of equal period but of different amplitude and phase 3 independent variables Three independent variables are required for the arbitrary selection of any polarisation state -
A Review of High-Gain Free-Electron Laser Theory
atoms Review A Review of High-Gain Free-Electron Laser Theory Nicola Piovella 1,* and Luca Volpe 2 1 Dipartimento di Fisica “Aldo Pontremoli”, Università degli Studi di Milano, Via Celoria 16, 20133 Milano, Italy 2 Centro de Laseres Pulsados (CLPU), Parque Cientifico, 37185 Salamanca, Spain; [email protected] * Correspondence: [email protected] Abstract: High-gain free-electron lasers, conceived in the 1980s, are nowadays the only bright sources of coherent X-ray radiation available. In this article, we review the theory developed by R. Bonifacio and coworkers, who have been some of the first scientists envisaging its operation as a single-pass amplifier starting from incoherent undulator radiation, in the so called self-amplified spontaneous emission (SASE) regime. We review the FEL theory, discussing how the FEL parameters emerge from it, which are fundamental for describing, designing and understanding all FEL experiments in the high-gain, single-pass operation. Keywords: free-electron laser; X-ray emission; collective effects 1. Basic Concepts The free-electron laser is essentially a device that transforms the kinetic energy of a relativistic electron beam (e-beam) into e.m. radiation [1–4]. The e-beam passing through a transverse periodic magnetic field oscillates in a direction perpendicular to the magnetic Citation: Piovella, N.; Volpe, L. field and the propagation axis, and emits radiation confined in a narrow cone along the A Review of High-Gain Free-Electron propagation direction. The periodic magnetic field is provided by the so-called undulator, an Laser Theory. Atoms 2021, 9, 28. insertion device usually realized with two arrays of permanent magnets with alternating https://doi.org/10.3390/atoms9020028 polarities (see Figure1) or with two helical coils with current circulating in opposite directions. -
Third-Generation Synchrotron X-Ray Diffraction of 6- M Crystal of Raite, Na
Proc. Natl. Acad. Sci. USA Vol. 94, pp. 12263–12267, November 1997 Geology Third-generation synchrotron x-ray diffraction of 6-mm crystal of raite, 'Na3Mn3Ti0.25Si8O20(OH)2z10H2O, opens up new chemistry and physics of low-temperature minerals (crystal structureymicrocrystalyphyllosilicate) JOSEPH J. PLUTH*, JOSEPH V. SMITH*†,DMITRY Y. PUSHCHAROVSKY‡,EUGENII I. SEMENOV§,ANDREAS BRAM¶, CHRISTIAN RIEKEL¶,HANS-PETER WEBER¶, AND ROBERT W. BROACHi *Department of Geophysical Sciences, Center for Advanced Radiation Sources, GeologicalySoilyEnvironmental, and Materials Research Science and Engineering Center, 5734 South Ellis Avenue, University of Chicago, Chicago, IL 60637; ‡Department of Geology, Moscow State University, Moscow, 119899, Russia; §Fersman Mineralogical Museum, Russian Academy of Sciences, Moscow, 117071, Russia; ¶European Synchrotron Radiation Facility, BP 220, 38043, Grenoble, France; and UOP Research Center, Des Plaines, IL 60017 Contributed by Joseph V. Smith, September 3, 1997 ABSTRACT The crystal structure of raite was solved and the energy and metal industries, hydrology, and geobiology. refined from data collected at Beamline Insertion Device 13 at Raite lies in the chemical cooling sequence of exotic hyperal- the European Synchrotron Radiation Facility, using a 3 3 3 3 kaline rocks of the Kola Peninsula, Russia, and the 65 mm single crystal. The refined lattice constants of the Monteregian Hills, Canada (2). This hydrated sodium- monoclinic unit cell are a 5 15.1(1) Å; b 5 17.6(1) Å; c 5 manganese silicate extends the already wide range of manga- 5.290(4) Å; b 5 100.5(2)°; space group C2ym. The structure, nese crystal chemistry (3), which includes various complex including all reflections, refined to a final R 5 0.07. -
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. -
The Diamond Light Source
The Diamond Light Source ... a bright future for UK and World science Richard P. Walker, Technical Director What is Diamond ? • The largest scientific investment in the UK for 30 years • A synchrotron light source producing pinpoint UV and X-ray light beams of exceptional brightness • A ‘super microscope’ for new research opportunities into the structure and properties of matter What is Diamond ? • A Power Converter ! 15 MW of electrical power from the grid … 300-500 kW of X-rays … … but most of which only produces unwanted heat; only a fraction is selected for use in experiments. What is Synchrotron Radiation ? SR is electromagnetic radiation emitted when a high energy beam of charged particles (electrons) is deflected by a magnetic field. What’s so special about Synchrotron Radiation ? SR SR is emitted over a wide range of the electromagnetic spectrum, from Infra-red to hard X-rays Any desired radiation wavelength can be produced - enabling a very wide range of scientific and technological applications What’s so special about Synchrotron Radiation ? SR is very intense, and has extremely high brightness (emitted from a small area, with small angular divergence, determined by the properties of the electron beam) High brightness means: - it can be focused to sub-micron spot sizes: possibility of examining extremely small samples or investigating the structure and properties of objects with very fine spatial resolution - experiments can be carried out much more quickly: high through-put of samples or ability to follow chemical and biological reactions in real-time Diamond is a “third-generation” synchrotron radiation source • 1st generation: machines originally built for other purposes e.g. -
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.