Author: "Harmer A" / Topic: chemistry - Searchworks@Jio Institute Digital Library Search Results

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1. A Murder Mystery Gamification Session to Consolidate Analytical Biochemical Techniques Learning

Author: Alison M. Hill and Nicholas J. Harmer
Abstract: Gamification has a strong track record of improving student engagement and learning in the chemical sciences. Meta-analyses of different approaches to gamification have highlighted that providing a game fiction, encouraging students to work in teams, and breaking games into smaller "quests" are particularly effective. Here, we aimed to increase students' engagement and learning with four analytical biochemistry techniques (high-performance liquid chromatography, sodium dodecyl sulfate polyacrylamide gel electrophoresis, Western blot, and mass spectrometry) by creating a game that required them to use every method to solve a "murder mystery". Our game was based on the popular games "Mafia" and "Among Us" and introduced an original game fiction relevant to our setting. Students attending the formative gamified session gave highly positive feedback. They indicated that they enjoyed the session and increased confidence in the methods involved. Free text comments praised many of the elements deliberately introduced into the game. To our surprise, the main criticism was that the session was not challenging enough. We developed a revised session that required students to undertake more detailed data interpretation, which students reported gave the expected increase in difficulty. All materials and code for running our session and generating new mysteries with original data are available online.
Published: 2023
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2. 'CSI Vienna' -- Design and Evaluation of the Out-of-School Lab 'ELKE'

Author: Gross, Katharina and Harmer, Sandra Pia
Abstract: In the course of PISA and TIMSS a lot of out-of-school lab days have been established; as non-formal extracurricular learning environments they shall provide an efficient addition to formal learning at school. The "ELKE" project is a non-formal extracurricular learning lab that aims at linking curricular content and competence-centred activities. This makes it an effective addition to chemistry education at school. Additionally, "ELKE" is a teaching/learning-environment for university teacher training. The poster illustrates the general concept as well as the contextual design of "CSI Vienna", the Viennese experimentation day. Furthermore, it shows first results concerning the effectiveness of the "ELKE" student lab on learning. These results will also be related to the outcomes of studies on "ELKE" as a teaching/learning-environment for future chemistry teachers. [This paper was published in: "Research on Outdoor STEM Education in the digiTal Age. Proceedings of the ROSETA Online Conference in June 2020," edited by M. Ludwig, et al., WTM, 2020, pp. 205-208.]
Published: 2020

3. Inorganic Fe-O and Fe-S oxidoreductases: paradigms for prebiotic chemistry and the evolution of enzymatic activity in biology

Author: Xiao-Lan Huang, Jeffrey R. Harmer, Gerhard Schenk, and Gordon Southam
Subjects: oxidoreductases, biocatalysts, inorganic nanocatalysts, metal ion architecture, evolution, sustainability, Chemistry, QD1-999
Abstract: Oxidoreductases play crucial roles in electron transfer during biological redox reactions. These reactions are not exclusive to protein-based biocatalysts; nano-size (
Published: 2024
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4. Tin-Mining Extraction and Uses--a Malaysian School Project.

Author: Harmer, A. F.
Abstract: Describes a Malaysian school project which deals with tin, and extracting tin from its ore in the laboratory, as well as the economics involved and the locating and mining the ore. (HM)
Published: 1980

5. Antioxidants in Foods--An Investigation

Author: Harmer, A. F. and Angles, J.
Published: 1973

6. Industrial Chemistry for Teachers

Author: Harmer, D. E.
Published: 1970

7. The Cytochrome P450 OxyA from the Kistamicin Biosynthesis Cyclization Cascade is Highly Sensitive to Oxidative Damage

Author: Anja Greule, Thierry Izoré, Daniel Machell, Mathias H. Hansen, Melanie Schoppet, James J. De Voss, Louise K. Charkoudian, Ralf B. Schittenhelm, Jeffrey R. Harmer, and Max J. Cryle
Subjects: cytochrome P450, glycopeptide antibiotic biosynthesis, kistamicin, heme, biosynthesis, Chemistry, QD1-999
Abstract: Cytochrome P450 enzymes (P450s) are a superfamily of monooxygenases that utilize a cysteine thiolate–ligated heme moiety to perform a wide range of demanding oxidative transformations. Given the oxidative power of the active intermediate formed within P450s during their active cycle, it is remarkable that these enzymes can avoid auto-oxidation and retain the axial cysteine ligand in the deprotonated—and thus highly acidic—thiolate form. While little is known about the process of heme incorporation during P450 folding, there is an overwhelming preference for one heme orientation within the P450 active site. Indeed, very few structures to date contain an alternate heme orientation, of which two are OxyA homologs from glycopeptide antibiotic (GPA) biosynthesis. Given the apparent preference for the unusual heme orientation shown by OxyA enzymes, we investigated the OxyA homolog from kistamicin biosynthesis (OxyAkis), which is an atypical GPA. We determined that OxyAkis is highly sensitive to oxidative damage by peroxide, with both UV and EPR measurements showing rapid bleaching of the heme signal. We determined the structure of OxyAkis and found a mixed population of heme orientations present in this enzyme. Our analysis further revealed the possible modification of the heme moiety, which was only present in samples where the alternate heme orientation was present in the protein. These results suggest that the typical heme orientation in cytochrome P450s can help prevent potential damage to the heme—and hence deactivation of the enzyme—during P450 catalysis. It also suggests that some P450 enzymes involved in GPA biosynthesis may be especially prone to oxidative damage due to the heme orientation found in their active sites.
Published: 2022
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8. On the Dynamics of Moisture Absorption and Its Impact on Dielectric Properties of Epoxy Networks under DC and AC Voltages

Author: Yan Wang, Hashim Bhabha, Alun S. Vaughan, F. N. Alhabill, Dayuan Qiang, and Stuart Harmer
Subjects: Materials science, Absorption of water, Hydrogen, chemistry, Hydrogen bond, Analytical chemistry, Relaxation (physics), chemistry.chemical_element, Dielectric, Electrical and Electronic Engineering, Absorption (chemistry), Glass transition, Dielectric spectroscopy
Abstract: The effect of stoichiometry on the dynamics of moisture absorption in epoxy networks is reported. The results show that formulations containing an excess of epoxide groups are characterized by reduced water absorption. For all the considered formulations, water absorption is a reversible process. Water absorption reduces the glass transition temperature, T g , with each 1 wt% of absorbed water reducing T g by ~10 °C. We attribute this effect to water molecules masking network polar sites and, thereby, inhibiting the formation of intra- or inter-segmental hydrogen bonds. Dielectric spectroscopy reveals that a significant fraction of the absorbed water exhibits relaxation processes similar to the relaxation of the network polar groups and, thus, results in strengthening the existing relaxation peaks within the system. This phenomenon may be employed to magnify the presence of material polar groups, particularly when these groups have low concentration or cannot produce a detectable effect on the dielectric spectra. The presence of distributed absorbed water enhances charge transport, an effect reflected in a proportional reduction in DC breakdown strength. Conversely, AC breakdown strength is not critically affected for the levels of water absorption seen here.
Published: 2021
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9. Effect of wheat quality traits and glutenin composition on tortilla quality from the USDA Southern Regional Performance Nursery

Author: Michael Tilley, Guorong Zhang, Sarah Harmer, Sara E. Duke, Guihua Bai, Pingping Zhang, and Bradford W. Seabourn
Subjects: Glutenin, Agronomy, biology, Chemistry, media_common.quotation_subject, Organic Chemistry, biology.protein, Composition (visual arts), Quality (business), Food Science, media_common
Published: 2021
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10. Experimental observations of amorphization in multiple generations of boron carbide

Author: Christopher J. Marvel, Chawon Hwang, Richard A. Haber, Qirong Yang, Mo Rigen He, Martin P. Harmer, Kelvin Y. Xie, Jerry C. LaSalvia, and Kevin J. Hemker
Subjects: chemistry.chemical_compound, symbols.namesake, Materials science, chemistry, Transmission electron microscopy, Doping, Materials Chemistry, Ceramics and Composites, Analytical chemistry, symbols, Boron carbide, Raman spectroscopy
Published: 2021
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11. Applications of analytical electron microscopy to guide the design of boron carbide

Author: Christopher J. Marvel, Martin P. Harmer, Richard A. Haber, Qirong Yang, Kelvin Y. Xie, Scott D. Walck, Jerry C. LaSalvia, Kristopher D. Behler, and Masashi Watanabe
Subjects: chemistry.chemical_compound, Analytical electron microscopy, Materials science, chemistry, Transmission electron microscopy, Materials Chemistry, Ceramics and Composites, Grain boundary, Boron carbide, Composite material
Published: 2021
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12. Centrosymmetric or Noncentrosymmetric? Transition Metals Talking in K2TGe3S8(T = Co, Fe)

Author: Fei Wang, Jin Hu, Krishna Pandey, Jian Wang, Bingheng Ji, Kui Wu, and Colin P. Harmer
Subjects: Diffraction, 010405 organic chemistry, Chemistry, Crystal growth, Crystal structure, 010402 general chemistry, 01 natural sciences, 0104 chemical sciences, law.invention, Inorganic Chemistry, Crystallography, Transition metal, law, Electrical resistivity and conductivity, Antiferromagnetism, Physical and Theoretical Chemistry, Crystallization, Thermal analysis
Abstract: Two new quaternary sulfides K2TGe3S8(T = Co, Fe) have been synthesized by a high-temperature solid-state routine and flux growth method. The crystal growth process of K2TGe3S8(T = Co, Fe) was elucidated by in situ powder X-ray diffraction and DSC thermal analysis. The millimeter-sized crystals of K2TGe3S8(T = Co, Fe) were grown. K2CoGe3S8 crystallizes in a new structure type in centrosymmetric space group P1 (no. 2) with unit cell parameters of a = 7.016(1) A, b= 7.770(1) A, c = 14.342(1) A, α = 93.80(1)°, β = 92.65(1)°, γ = 114.04(1)°. K2FeGe3S8 crystallizes in the K2FeGe3Se8 structure type and the noncentrosymmetric space group P21 (no. 4) with unit cell parameters of a = 7.1089(5)A, b = 11.8823(8) A, c = 16.7588(11) A, β = 96.604(2)°. There is a high structural similarity between K2CoGe3S8 and K2FeGe3S8. The larger volume coupled with higher degrees of distortion of the [FeS4] tetrahedra compared to the [CoS4] tetrahedra accounts for the structure's shift from centrosymmetric to noncentrosymmetric. The theory simulation confirms that [TS4]T= Co or Fe tetrahedra play a crucial role in controlling the structure and properties of K2TGe3S8(T = Co, Fe). The measured optical bandgaps of K2CoGe3S8 and K2FeGe3S8 are 2.1(1) eV and 2.6(1) eV, respectively. K2FeGe3S8 shows antiferromagnetic ordering at 24 K while no magnetic ordering was detected in K2CoGe3S8. The magnetic measurements also demonstrate the divalent nature of transition metals in K2TGe3S8(T = Co, Fe).
Published: 2021
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13. Mapping the Pathway to Organocopper(II) Complexes Relevant to Atom Transfer Radical Polymerization

Author: Jeffrey Harmer, Paul V. Bernhardt, and Miguel A. Gonzálvez
Subjects: 010405 organic chemistry, Ligand, Atom-transfer radical-polymerization, 010402 general chemistry, 01 natural sciences, Spectral line, 0104 chemical sciences, law.invention, Inorganic Chemistry, Crystallography, chemistry.chemical_compound, chemistry, law, Density functional theory, Amine gas treating, Physical and Theoretical Chemistry, Electron paramagnetic resonance, Acetonitrile, Hyperfine structure
Abstract: The rare organocopper(II) complex [Cu(Metren)(CHCN)] (Metren = tris(2-(dimethylamino)ethyl)amine) has emerged as an important model of potential byproducts in copper-catalyzed atom transfer radical polymerization. This complex has been generated by controlled potential electrolysis of [Cu(Metren)(NCMe)] in the presence of BrCHCN. Time-resolved UV-vis and continuous wave and pulse electron paramagnetic resonance (EPR) spectra identified [Cu(Metren)Br] as an intermediate. Hyperfine sublevel correlation and electron nuclear double resonance spectroscopy of samples at different timepoints reveal signals that are assigned to a C-bound cyanomethylate ligand, with distinct N and H hyperfine coupling constants in comparison with the corresponding N-bound acetonitrile and bromido complexes. The experimental EPR data are supported by density functional theory calculations to understand how the geometries of the species involved produce distinct spectroscopic signatures, and a clear picture of how this unusual organocopper(II) complex is formed has emerged.
Published: 2021
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14. Self-assembly of an anion receptor with metal-dependent kinase inhibition and potent in vitro anti-cancer properties

Author: Emma Pinder, Christopher J. Clemett, Craig R. Rice, Jane Harmer, P. Jane Owen-Lynch, Roger M. Phillips, Hollie B. S. Griffiths, Robert A. Faulkner, Heiko Wurdak, Jarosław Bryk, Michael L. Ginger, and Simon J. Allison
Subjects: Anions, 0301 basic medicine, Cancer therapy, Cell Survival, Stereochemistry, Science, Blotting, Western, Cryptand, Supramolecular chemistry, General Physics and Astronomy, Antineoplastic Agents, Crystallography, X-Ray, 010402 general chemistry, 01 natural sciences, Article, General Biochemistry, Genetics and Molecular Biology, Cell Line, Inhibitory Concentration 50, 03 medical and health sciences, Coordination Complexes, Cell Line, Tumor, Neoplasms, Autophagy, Humans, Receptor, A549 cell, Multidisciplinary, Kinase, Chemistry, Phosphotransferases, Self-assembly, General Chemistry, HCT116 Cells, In vitro, 0104 chemical sciences, 030104 developmental biology, A549 Cells, Metals, Cell culture, Cancer cell, HT29 Cells
Abstract: One topical area of supramolecular chemistry is the binding of anionic species but despite the importance of anions in diverse cellular processes and for cancer development, anion receptors or ‘binders’ have received little attention as potential anti-cancer therapeutics. Here we report self-assembling trimetallic cryptands (e.g. [L2(Metal)3]6+ where Metal = Cu2+, Zn2+ or Mn2+) which can encapsulate a range of anions and which show metal-dependent differences in chemical and biological reactivities. In cell studies, both [L2Cu3]6+ and [L2Zn3]6+ complexes are highly toxic to a range of human cancer cell lines and they show significant metal-dependent selective activity towards cancer cells compared to healthy, non-cancerous cells (by up to 2000-fold). The addition of different anions to the complexes (e.g. PO43ˉ, SO42ˉ or PhOPO32ˉ) further alters activity and selectivity allowing the activity to be modulated via a self-assembly process. The activity is attributed to the ability to either bind or hydrolyse phosphate esters and mechanistic studies show differential and selective inhibition of multiple kinases by both [L2Cu3]6+ and [L2Zn3]6+ complexes but via different mechanisms., Artificial self-assembling systems such as anion receptors or ‘binders’ are largely unexplored for therapeutic applications. Here, the authors report self-assembling trimetallic cryptands containing copper, zinc or manganese that encapsulate a range of anions, are highly toxic to human cancer cell lines and show metal-dependent selectivity towards cancer vs. healthy cells linked to the selective inhibition of multiple kinases.
Published: 2021

15. IS26cannot move alone

Author: Ruth M. Hall and Christopher J. Harmer
Subjects: 0301 basic medicine, Microbiology (medical), Gibson assembly, 030106 microbiology, Transposases, medicine.disease_cause, Transposition (music), 03 medical and health sciences, Chloramphenicol Resistance, Plasmid, Gram-Negative Bacteria, Escherichia coli, medicine, Pharmacology (medical), Insertion sequence, Transposase, Pharmacology, Chemistry, Molecular biology, Anti-Bacterial Agents, 030104 developmental biology, Infectious Diseases, DNA Transposable Elements, pUC19, Plasmids
Abstract: BackgroundIS26 plays a major role in the dissemination of antibiotic resistance determinants in Gram-negative bacteria.ObjectivesTo determine whether insertion sequence IS26 is able to move alone (simple transposition) or if it exclusively forms cointegrates.MethodsA two-step PCR using outward-facing primers was used to search for circular IS26 molecules. Gibson assembly was used to clone a synthetic IS26 containing a catA1 chloramphenicol resistance gene downstream of the tnp26 transposase gene into pUC19. IS activity in a recA−Escherichia coli containing the non-conjugative pUC19-derived IS26::catA1 construct and the conjugative plasmid R388 was detected using a standard mating-out assay. Transconjugants were screened for resistance.ResultsCircular IS26 molecules that would form with a copy-out route were not detected by PCR. The synthetic IS26::catA1 construct formed CmRTpR transconjugants (where CmR and TpR stand for chloramphenicol resistant and trimethoprim resistant, respectively), representing an R388 derivative carrying the catA1 gene at a frequency of 5.6 × 10−7 CmRTpR transconjugants per TpR transconjugant, which is comparable to the copy-in activity of the unaltered IS26. To test for simple transposition of IS26::catA1 (without the plasmid backbone), 1200 CmRTpR colonies were screened and all were resistant to ampicillin, indicating that the pUC19 backbone was present. Hence, IS26::catA1 had only formed cointegrates.ConclusionsIS26 is unable to move alone and cointegrates are the exclusive end products of the reactions mediated by the IS26 transposase Tnp26. Consequently, when describing the formation of complex resistance regions, simple ‘transposition’ of a single IS26 should not be invoked.
Published: 2021
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16. Understanding the Mechanistic Requirements for Efficient and Stereoselective Alkene Epoxidation by a Cytochrome P450 Enzyme

Author: Paul V. Bernhardt, Joshua S. Harbort, Alicia M. Kirk, Stephen Bell, M.N. Podgorski, Elizabeth H. Krenske, Luke R. Churchman, Rebecca R. Chao, Jeffrey Harmer, John B. Bruning, T. Coleman, and James J. De Voss
Subjects: chemistry.chemical_classification, 010405 organic chemistry, Chemistry, Alkene, Stereochemistry, Reactive intermediate, Epoxide, General Chemistry, 010402 general chemistry, 01 natural sciences, Catalysis, 0104 chemical sciences, Hydroxylation, chemistry.chemical_compound, Catalytic cycle, Stereoselectivity, Chemoselectivity
Abstract: The cytochrome P450 (CYP) family of heme monooxygenase enzymes commonly catalyzes enantioselective hydroxylation and epoxidation reactions. Epoxidation reactions have been hypothesized to proceed via multiple mechanisms involving different reactive intermediates. Here, we use activity, spectroscopic, structural, and molecular dynamics data to investigate the activity and stereoselectivity of 4-vinylbenzoic acid epoxidation by the bacterial enzyme CYP199A4 from Rhodopseudomonas palustris HaA2. The epoxidation of 4-vinylbenzoic acid by CYP199A4 proceeded with high enantioselectivity, giving the (S)-epoxide in 99% ee at an activity of 220 nmol nmol-CYP–1 min–1. Optical and EPR spectroscopy, redox potential measurements, and the crystal structure of 4-vinylbenzoic acid-bound CYP199A4 indicated the partial retention of an aqua ligand at the heme center in the presence of the substrate, providing a justification of the lower activity (∼20%) compared to the oxidative demethylation of 4-methoxybenzoic acid. Mutagenesis at the conserved acid–alcohol pair (D251/T252), which perturbs the generation of the reactive oxygen intermediates, was employed to investigate their role in epoxidation reactions. The T252A mutant increased the rate of turnover of the catalytic cycle, but an elevation in hydrogen peroxide generation via uncoupling resulted in a similar rate of epoxide formation. The activity of epoxidation significantly reduced with the D251N mutant. The chemoselectivity and stereoselectivity of the epoxidation reaction were maintained in the turnovers by these mutants. Overall, there was little evidence that other intermediates, aside from the archetypal reactive ferryl porphyrin cation radical, Compound I, contributed significantly to the epoxidation reaction. The observation of the high selectivity for the (S)-enantiomer was rationalized by molecular dynamics simulations. When the arrangement of the alkene and the active intermediate approached an ideal transition state structure for epoxidation, one face of the alkene was more often exposed to the iron oxo unit.
Published: 2021
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17. Non-innocent Intercalation of Diamines into Tetragonal FeS Superconductor

Author: Chongin Pak, Joshua T. Greenfield, Kirill Kovnir, Eranga H. Gamage, Colin P. Harmer, and Adedoyin N. Adeyemi
Subjects: Superconductivity, Materials science, Solvothermal synthesis, Intercalation (chemistry), Energy Engineering and Power Technology, Ethylenediamine, Iron sulfide, Crystal structure, Crystallography, Tetragonal crystal system, chemistry.chemical_compound, chemistry, Materials Chemistry, Electrochemistry, Chemical Engineering (miscellaneous), Electrical and Electronic Engineering
Abstract: We report two solvothermal pathways toward intercalated iron sulfide, [Fe8S10]Fe(en)3·en0.5 (en = ethylenediamine), featuring [Fe8S10]2– layers stacked by [Fe(en)3]2+ cations and free ethylenediami...
Published: 2021
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18. A Trap-Door Mechanism for Zinc Acquisition by Streptococcus pneumoniae AdcA

Author: Jacqueline R. Morey, Michael Isselstein, Thorben Cordes, Christopher A. McDevitt, Jeffrey Harmer, James C. Paton, Stephanie L. Neville, Katherine Ganio, Evelyne Deplazes, Alina E. Motygullina, Bostjan Kobe, Victoria G. Pederick, Nikolaos Eleftheriadis, Zhenyao Luo, Aimee Tan, and Molecular Biophysics
Subjects: Protein Conformation, Protein domain, Virulence, chemistry.chemical_element, ATP-binding cassette transporter, Zinc, Molecular Dynamics Simulation, Microbiology, Host-Microbe Biology, 03 medical and health sciences, Protein structure, Bacterial Proteins, Protein Domains, Virology, Binding site, 030304 developmental biology, 0303 health sciences, Binding Sites, biology, Chemistry, 030302 biochemistry & molecular biology, Solute-binding protein, biology.organism_classification, QR1-502, respiratory tract diseases, Transport protein, Streptococcus pneumoniae, Biochemistry, ATP-Binding Cassette Transporters, ABC transporter, Bacteria, 0605 Microbiology, Research Article
Abstract: Zinc is an essential nutrient for the virulence of bacterial pathogens such as Streptococcus pneumoniae. Many Gram-positive bacteria use a two-domain lipoprotein for zinc acquisition, but how this class of metal-recruiting proteins acquire zinc and interact with the uptake machinery has remained poorly defined., Zinc is an essential element in all domains of life. Nonetheless, how prokaryotes achieve selective acquisition of zinc from the extracellular environment remains poorly understood. Here, we elucidate a novel mechanism for zinc-binding in AdcA, a solute-binding protein of Streptococcus pneumoniae. Crystal structure analyses reveal the two-domain organization of the protein and show that only the N-terminal domain (AdcAN) is necessary for zinc import. Zinc binding induces only minor changes in the global protein conformation of AdcA and stabilizes a highly mobile loop within the AdcAN domain. This loop region, which is conserved in zinc-specific solute-binding proteins, facilitates closure of the AdcAN binding site and is crucial for zinc acquisition. Collectively, these findings elucidate the structural and functional basis of selective zinc uptake in prokaryotes.
Published: 2021
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19. Lithium nickel borides: evolution of [NiB] layers driven by Li pressure

Author: Cai-Zhuang Wang, Colin P. Harmer, Xin Zhao, Raquel A. Ribeiro, Volodymyr Gvozdetskyi, Julia V. Zaikina, Scott L. Carnahan, Kai-Ming Ho, Aaron J. Rossini, Yang Sun, Gourab Bhaskar, Paul C. Canfield, and Feng Zhang
Subjects: Diffraction, Materials science, Hydride, Solid-state, chemistry.chemical_element, Nuclear magnetic resonance spectroscopy, Quantum chemistry, Synchrotron, law.invention, Inorganic Chemistry, Crystallography, Nickel, chemistry, law, Lithium
Abstract: Here we show the effect of Li chemical pressure on the structure of layered polymorphs with LiNiB composition: RT-LiNiB (room temperature polymorph) and HT-LiNiB (high temperature polymorph), resulting in stabilization of the novel RT-Li1+xNiB (x ∼ 0.17) and HT-Li1+yNiB (y ∼ 0.06) phases. Depending on the synthesis temperature and initial Li content, precisely controlled via hydride route synthesis, [NiB] layers undergo structural deformations, allowing for extra Li atoms to be accommodated between the layers. In situ variable temperature synchrotron and time-dependent laboratory powder X-ray diffraction studies suggest Li step-wise deintercalation processes: RT-Li1+xNiB → RT-LiNiB (high temp.) → LiNi3B1.8 → binary Ni borides and HT-Li1+yNiB → HT-LiNiB (high temp.) → LiNi3B1.8 → binary Ni borides. Quantum chemistry calculations and solid state 7Li and 11B NMR spectroscopy shed light on the complexity of real superstructures of these compounds determined from high resolution synchrotron powder diffraction data.
Published: 2021
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20. Athermal behavior of core-shell particles in nanocrystalline Cu-Ta

Author: Christopher J. Marvel, B.C. Hornbuckle, Joshua A. Smeltzer, Martin P. Harmer, and Kristopher A. Darling
Subjects: 010302 applied physics, Phase boundary, Materials science, Annealing (metallurgy), Mechanical Engineering, Metals and Alloys, Oxide, 02 engineering and technology, 021001 nanoscience & nanotechnology, Condensed Matter Physics, 01 natural sciences, Nanocrystalline material, Amorphous solid, law.invention, Core shell, chemistry.chemical_compound, chemistry, Chemical engineering, Mechanics of Materials, law, 0103 physical sciences, General Materials Science, Thermal stability, Electron microscope, 0210 nano-technology
Abstract: Nanocrystalline Cu-Ta is among the most successfully developed nanostructured alloys involving microstructural design, synthesis, characterization, and testing. However, the interplay of direct and indirect thermal stability mechanisms is still unclear. In this work, mechanically alloyed Cu-10at.%Ta was characterized with atomic-resolution electron microscopy to identify thermal stability mechanisms. A new mechanism involving athermal core-shell particles that were coarsening resistant was discovered after annealing between 100–800 °C up to 1000 h. Evidence suggests that oxide amorphous shells decreased the phase boundary energy thereby reducing the thermodynamic driving force for particle growth and indirectly maximizing thermal stability of Cu(Ta) grains.
Published: 2020
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21. Self‐Assembled Anion‐Binding Cryptand for the Selective Liquid–Liquid Extraction of Phosphate Anions

Author: Marco Molinari, Rebecca Andrews, Craig R. Rice, Gareth M.B. Parkes, Christopher J. Clemett, Philippe B. Wilson, Sabera Begum, Zuhlqurnain M. H. Qureshi, Robert A. Faulkner, Michael D. Ward, Jane Harmer, H. M. Williams, and Michael L. Ginger
Subjects: Cryptand, Supramolecular chemistry, chemistry.chemical_element, 010402 general chemistry, 01 natural sciences, Catalysis, chemistry.chemical_compound, Liquid–liquid extraction, Polymer chemistry, Anion binding, Self‐Assembly | Hot Paper, 010405 organic chemistry, Communication, structure elucidation, Extraction (chemistry), self-assembly, General Medicine, General Chemistry, Phosphate, Copper, Communications, 0104 chemical sciences, macrocycles, chemistry, copper, Self-assembly, anions
Abstract: The ligands L1 and L2 form trinuclear self‐assembled complexes with Cu2+ (i.e. [(L1)2Cu3]6+ or [(L2)2Cu3]6+) both of which act as a host to a variety of anions. Inclusion of long aliphatic chains on these ligands allows the assemblies to extract anions from aqueous media into organic solvents. Phosphate can be removed from water efficiently and highly selectively, even in the presence of other anions., The ligands L1 and L2 form trinuclear self‐assemblies with Cu2+ (i.e. [L 2Cu3]6+) both of which act as hosts to a variety of anions. Inclusion of long aliphatic chains on these ligands allows the self‐assemblies to extract anions from aqueous media into organic solvents. Phosphate anions can be removed from water efficiently and highly selectively in the presence of other anions.
Published: 2020
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22. Tuning Fe–Se Tetrahedral Frameworks by a Combination of [Fe(en)3]2+ Cations and Cl– Anions

Author: Michael Shatruk, Eranga H. Gamage, Liang Luo, Saeed Kamali, Joshua T. Greenfield, Colin P. Harmer, Jigang Wang, Colin D. Unger, Kirill Kovnir, and Judith K. Clark
Subjects: Inorganic Chemistry, chemistry.chemical_compound, Crystallography, chemistry, Chain (algebraic topology), 010405 organic chemistry, Tetrahedron, Ethylenediamine, Physical and Theoretical Chemistry, 010402 general chemistry, 01 natural sciences, 0104 chemical sciences
Abstract: A one-dimensional (1D) chain compound [Fe(en)3]3(FeSe2)4Cl2 (en = ethylenediamine), featuring tetrahedral FeSe2 chains separated by [Fe(en)3]2+ cations and Cl– anions, has been synthesized by a low...
Published: 2020
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23. Amyloid β chaperone — lipocalin-type prostaglandin D synthase acts as a peroxidase in the presence of heme

Author: Justin Ng Tze Yang, Jeffrey Harmer, Ralf Kather, Konstantin Pervushin, Bhuvaneswari Kannaian, Mu Yuguang, Margaret Phillips, and School of Biological Sciences
Subjects: 0301 basic medicine, Protein Conformation, Bilirubin, Heme, Molecular Dynamics Simulation, Ligands, Ferric Compounds, Biochemistry, Prostaglandin-D synthase, Electron-Paramagnetic-Resonance, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Biochemical Techniques & Resources, Alzheimer Disease, Structural Biology, Chemical Biology, L-PGDS, Extracellular, Humans, Benzothiazoles, Molecular Biology, Research Articles, Fluorescent Dyes, Peroxidase, Amyloid beta-Peptides, biology, Ligand binding assay, Electron Spin Resonance Spectroscopy, Biological sciences [Science], Transporter, Cell Biology, Lipocalins, Site-Directed Mutagenesis, Intramolecular Oxidoreductases, 030104 developmental biology, chemistry, Chaperone (protein), biology.protein, amyloid β, peroxidases, Hydrophobic and Hydrophilic Interactions, 030217 neurology & neurosurgery, Molecular Chaperones, Protein Binding
Abstract: The extracellular transporter, lipocalin-type prostaglandin D synthase (L-PGDS) binds to heme and heme metabolites with high affinity. It has been reported that L-PGDS protects neuronal cells against apoptosis induced by exposure to hydrogen peroxide. Our study demonstrates that when human WT L-PGDS is in complex with heme, it exhibits a strong peroxidase activity thus behaving as a pseudo-peroxidase. Electron paramagnetic resonance studies confirm that heme in the L-PGDS-heme complex is hexacoordinated with high-spin Fe(III). NMR titration of heme in L-PGDS points to hydrophobic interaction between heme and several residues within the β-barrel cavity of L-PGDS. In addition to the transporter function, L-PGDS is a key amyloid β chaperone in human cerebrospinal fluid. The presence of high levels of bilirubin and its derivatives, implicated in Alzheimer's disease, by binding to L-PGDS may reduce its chaperone activity. Nevertheless, our ThT binding assay establishes that heme and heme metabolites do not significantly alter the neuroprotective chaperone function of L-PGDS. Guided by NMR data we reconstructed the heme L-PGDS complex using extensive molecular dynamics simulations providing a platform for mechanistic interpretation of the catalytic and transporting functions and their modulation by secondary ligands like Aβ peptides and heme metabolites. Ministry of Education (MOE) Published version The research for this paper was supported by the MOE-Tier 2 grant M4020231. J.R.H. acknowledges support from the ARC (FT120100421).
Published: 2020
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24. Helical Peptides Design for Molecular Dipoles Functionalization of Wide Band Gap Oxides

Author: Elena Galoppini, Ryan Harmer, Sylvie Rangan, Robert Bartynski, Yuan Chen, and Jonathan Viereck
Subjects: Models, Molecular, Protein Folding, Aminoisobutyric Acids, Photoemission spectroscopy, Carboxylic acid, 010402 general chemistry, 01 natural sciences, Biochemistry, Protein Structure, Secondary, Catalysis, Isobutyric acid, Isophthalic acid, chemistry.chemical_compound, Colloid and Surface Chemistry, Spectroscopy, Fourier Transform Infrared, Monolayer, Titanium, chemistry.chemical_classification, Carboxybenzyl, Substrate (chemistry), General Chemistry, Chromophore, Nanostructures, 0104 chemical sciences, Crystallography, chemistry, Oligopeptides, Protein Binding
Abstract: The use of helical hexapeptides to establish a surface dipole layer on a TiO2 substrate, with the goal of influencing the energy levels of a coadsorbed chromophore, is explored. Two helical hexapeptides, synthesized from 2-amino isobutyric acid (Aib) residues, were protected at the N-terminus with a carboxybenzyl group (Z) and at the C-terminus carried either a carboxylic acid or an isophthalic acid (Ipa) anchor group to form Z-(Aib)6-COOH or Z-(Aib)6-Ipa, respectively. Using a combination of vibrational and photoemission spectroscopies, bonding of the two peptides to TiO2 surfaces (either nanostructured or single-crystal TiO2(110)) was found to be highly dependent on the anchor group, with Ipa establishing a monolayer much more efficiently than COOH. Furthermore, a monolayer of Z-(Aib)6-Ipa on TiO2(110) was exposed for different binding times to a solution of a zinc tetraphenylporphyrin (ZnTPP) derivative terminated with an Ipa anchor group (ZnTPP-P-Ipa). Photoemission spectroscopy revealed that ZnTPP-P-...
Published: 2020
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25. Oxidative Dissolution of Sulfide Minerals in Single and Mixed Sulfide Systems under Simulated Acid and Metalliferous Drainage Conditions

Author: Gujie Qian, Maria Angelica D. Rea, Jianyin Huang, Peter R. Teasdale, Roger St. C. Smart, Andrea R. Gerson, Russell C. Schumann, Allan Pring, Sarah L. Harmer, He Zhang, Rong Fan, Joël Brugger, Christopher T. Gibson, Qian, Gujie, Fan, Rong, Huang, Jianyin, Pring, Allan, Harmer, Sarah L, Zhang, He, Rea, Maria Angelica D, Brugger, Joël, Teasdale, Peter R, Gibson, Christopher T, Schumann, Russell C, Smart, Roger St C, and Gerson, Andrea R
Subjects: Sulfide, oxidation, sulfides, dissolution, 010501 environmental sciences, engineering.material, Sulfides, 01 natural sciences, Galena, Galvanic cell, Environmental Chemistry, Dissolution, 0105 earth and related environmental sciences, chemistry.chemical_classification, Minerals, Chalcopyrite, General Chemistry, minerals, pyrite, Sulfide minerals, Oxidative Stress, Sphalerite, chemistry, Solubility, visual_art, Environmental chemistry, engineering, visual_art.visual_art_medium, Pyrite, Acids
Abstract: Chalcopyrite, galena, and sphalerite commonly coexist with pyrite in sulfidic waste rocks. The aim of this work was to investigate their impact, potentially by galvanic interaction, on pyrite oxidation and acid generation rates under simulated acid and metalliferous drainage conditions. Kinetic leach column experiments using single-minerals and pyrite with one or two of the other sulfide minerals were carried out at realistic sulfide contents (total sulfide 47% for galena vs
Published: 2021

26. Mechanochemically Synthesised Flexible Electrodes Based on Bimetallic Metal–Organic Framework Glasses for the Oxygen Evolution Reaction

Author: Zhonghua Zhu, Zhiliang Wang, Jingwei Hou, Jeffrey Harmer, Sebastian Beyer, Wupeng Wang, Dominique R. T. Appadoo, Andraž Krajnc, Ana Guilherme Buzanich, Lianzhou Wang, Vicki Chen, Simon Smart, Linzhou Zhuang, Zhiheng Li, Rijia Lin, Gregor Mali, Thomas D. Bennett, Xuemei Li, and Mengran Li
Subjects: chemistry.chemical_classification, Materials science, 010405 organic chemistry, Oxygen evolution, chemistry.chemical_element, General Medicine, General Chemistry, 010402 general chemistry, 01 natural sciences, Catalysis, 0104 chemical sciences, Coordination complex, chemistry.chemical_compound, Chemical engineering, chemistry, Mechanochemistry, Imidazolate, Metal-organic framework, Bimetallic strip, Cobalt, Zeolitic imidazolate framework
Abstract: The melting behaviour of metal-organic frameworks (MOFs) has aroused significant research interest in the areas of materials science, condensed matter physics and chemical engineering. This work first introduces a novel method to fabricate a bimetallic MOF glass, through melt-quenching of the cobalt-based zeolitic imidazolate framework (ZIF) [ZIF-62(Co)] with an adsorbed ferric coordination complex. The high-temperature chemically reactive ZIF-62(Co) liquid facilitates the formation of coordinative bonds between Fe and imidazolate ligands, incorporating Fe nodes into the framework after quenching. The resultant Co-Fe bimetallic MOF glass therefore shows a significantly enhanced oxygen evolution reaction performance. The novel bimetallic MOF glass, when combined with the facile and scalable mechanochemical synthesis technique for both discrete powders and surface coatings on flexible substrates, enables significant opportunities for catalytic device assembly.
Published: 2021
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27. Inducing Ito,f and phase 1 repolarization of the cardiac action potential with a Kv4.3/KChIP2.1 bicistronic transgene

Author: Jules C. Hancox, Nan Wang, Stephen C Harmer, Ewan D. Fowler, Mark B. Cannell, and Eef Dries
Subjects: EXPRESSION, CURRENTS, Cardiac & Cardiovascular Systems, Ribosomal skipping, MOLECULAR PHYSIOLOGY, Transgene, Heart failure, REGIONAL DIFFERENCES, digestive system, VENTRICULAR MYOCYTES, Contractility, POTASSIUM CURRENT, Cardiac action potential, Repolarization, K+ CURRENT, Transient outward current, Transgene expression, Molecular Biology, 3-DIMENSIONAL STRUCTURE, Cardiac transient outward potassium current, Science & Technology, Chemistry, Cell Biology, CURRENT I-TO, Transfection, Excitation-contraction coupling, Cell biology, Cardiovascular System & Cardiology, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, Intracellular, K channels
Abstract: The fast transient outward potassium current (Ito,f) plays a key role in phase 1 repolarization of the human cardiac action potential (AP) and its reduction in heart failure (HF) contributes to the loss of contractility. Therefore, restoring Ito,f might be beneficial for treating HF. The coding sequence of a P2A peptide was cloned, in frame, between Kv4.3 and KChIP2.1 genes and ribosomal skipping was confirmed by Western blotting. Typical Ito,f properties with slowed inactivation and accelerated recovery from inactivation due to the association of KChIP2.1 with Kv4.3 was seen in transfected HEK293 cells. Both bicistronic components trafficked to the plasmamembrane and in adenovirus transduced rabbit cardiomyocytes both t-tubular and sarcolemmal construct labelling appeared. The resulting current was similar to Ito,f seen in human ventricular cardiomyocytes and was 50% blocked at ~0.8 mmol/l 4-aminopyridine and increased ~30% by 5 μmol/l NS5806 (an Ito,f agonist). Variation in the density of the expressed Ito,f, in rabbit cardiomyocytes recapitulated typical species-dependent variations in AP morphology. Simultaneous voltage recording and intracellular Ca2+ imaging showed that modification of phase 1 to a non-failing human phenotype improved the rate of rise and magnitude of the Ca2+ transient. Ito,f expression also reduced AP triangulation but did not affect ICa,L and INa magnitudes. This raises the possibility for a new gene-based therapeutic approach to HF based on selective phase 1 modification. ispartof: JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY vol:164 pages:29-41 ispartof: location:England status: published
Published: 2021
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28. Inhibition of the hERG potassium channel by phenanthrene - a polycyclic aromatic hydrocarbon pollutant

Author: Holly A. Shiels, Chunyun Du, Ehab Al-Moubarak, Jules C. Hancox, Stephen C Harmer, Yihong Zhang, Christopher E. Dempsey, and Oliver Hanington
Subjects: ERG1 Potassium Channel, congenital, hereditary, and neonatal diseases and abnormalities, Hydrocarbon, hERG, Polycyclic aromatic hydrocarbon, Pollutant, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Phenanthrene, Aromatic amino acids, Humans, KCNH2, Patch clamp, Potassium channel, cardiovascular diseases, Molecular Biology, Ion channel, Pharmacology, chemistry.chemical_classification, Dose-Response Relationship, Drug, biology, Mutagenesis, Cell Biology, PAH, Phenanthrenes, Electrophysiological Phenomena, Molecular Docking Simulation, HEK293 Cells, chemistry, Mutation, Mutagenesis, Site-Directed, biology.protein, Biophysics, Molecular Medicine, Original Article
Abstract: The lipophilic polycyclic aromatic hydrocarbon (PAH) phenanthrene is relatively abundant in polluted air and water and can access and accumulate in human tissue. Phenanthrene has been reported to interact with cardiac ion channels in several fish species. This study was undertaken to investigate the ability of phenanthrene to interact with hERG (human Ether-à-go-go-Related Gene) encoded Kv11.1 K+ channels, which play a central role in human ventricular repolarization. Pharmacological inhibition of hERG can be proarrhythmic. Whole-cell patch clamp recordings of hERG current (IhERG) were made from HEK293 cells expressing wild-type (WT) and mutant hERG channels. WT IhERG1a was inhibited by phenanthrene with an IC50 of 17.6 ± 1.7 µM, whilst IhERG1a/1b exhibited an IC50 of 1.8 ± 0.3 µM. WT IhERG block showed marked voltage and time dependence, indicative of dependence of inhibition on channel gating. The inhibitory effect of phenanthrene was markedly impaired by the attenuated inactivation N588K mutation. Remarkably, mutations of S6 domain aromatic amino acids (Y652, F656) in the canonical drug binding site did not impair the inhibitory action of phenanthrene; the Y652A mutation augmented IhERG block. In contrast, the F557L (S5) and M651A (S6) mutations impaired the ability of phenanthrene to inhibit IhERG, as did the S624A mutation below the selectivity filter region. Computational docking using a cryo-EM derived hERG structure supported the mutagenesis data. Thus, phenanthrene acts as an inhibitor of the hERG K+ channel by directly interacting with the channel, binding to a distinct site in the channel pore domain.
Published: 2021
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29. Optimization of cryogenic mechanical alloying parameters to synthesize ultrahard refractory high entropy materials

Author: B. Chad Hornbuckle, Anit K. Giri, Christopher J. Marvel, Joshua A. Smeltzer, Kristopher A. Darling, Mari-Therese Burton, and Martin P. Harmer
Subjects: Materials science, Precipitation (chemistry), Mechanical Engineering, Alloy, Metallurgy, Nanocrystalline, Nitride, engineering.material, Indentation hardness, Carbide, Hardness mechanisms, chemistry.chemical_compound, chemistry, Mechanics of Materials, Tungsten carbide, Impurity, Tool steel, engineering, TA401-492, General Materials Science, Impurity phase identification, High entropy alloy, Mechanical alloying, Scanning transmission electron microscopy, Materials of engineering and construction. Mechanics of materials
Abstract: Cryogenic mechanical alloying is a viable method to synthesize nanostructured alloys that exhibit improved mechanical properties without using highly contaminating, process control agents. However, cryogenically milled alloys still contain impurities introduced from the milling media and cryogenic fluid, and it is unclear how these milling parameters can be tailored to optimize alloy design. Here, milling media and cryogenic fluid were systematically varied and studied to quantify differences in impurity concentrations, microstructural evolution, and microhardness. Four derivatives of a Mo25Nb25Ta25W25 high entropy alloy were mechanically alloyed using tool steel or tungsten carbide milling media with either liquid N2 or Ar. Alloys were annealed for 100 h at 1000 °C or 1200 °C. Aberration-corrected scanning transmission electron microscopy (STEM) was primarily used to characterize as-milled and annealed specimens, and Vicker’s microindentation was used to compare hardness. Depending on the milling parameters, total impurity concentrations varied between 12 and 44 at.%, different impurity nitrides or carbides were identified in annealed specimens, and differences in hardness of up to 5 GPa were measured amongst the alloys. Overall, milling with LN2 led to the precipitation of ultrahard nitride phases that when combined with optimized heat treatments, improved the hardness beyond 17 GPa.
Published: 2021

30. Spinning sugars in antigen biosynthesis: a direct study of the Coxiella burnetii and Streptomyces griseus TDP-sugar epimerases

Author: Robert A. Field, Sergey A. Nepogodiev, Michail N. Isupov, Sumita Roy, Alice Cross, Mirella Vivoli Vega, Martin Rejzek, Joann L. Prior, Nicholas J. Harmer, Matthew J. Cliff, and Debbie Salmon
Subjects: chemistry.chemical_classification, biology, Active site, biology.organism_classification, Coxiella burnetii, DNA sequencing, chemistry.chemical_compound, Enzyme, chemistry, Biochemistry, Biosynthesis, Streptomycin, biology.protein, medicine, Streptomyces griseus, Bacteria, medicine.drug
Abstract: The sugars streptose and dihydrohydroxystreptose (DHHS) are unique to the bacteria Streptomyces griseus and Coxiella burnetii respectively. Streptose forms the central moiety of the antibiotic streptomycin, whilst DHHS is found in the O-antigen of the zoonotic pathogen C. burnetii. Biosynthesis of these sugars has been proposed to follow a similar path to that of TDP-rhamnose, catalysed by the enzymes RmlA/RmlB/RmlC/RmlD. Streptose and DHHS biosynthesis unusually require a ring contraction step that might be performed by the orthologues of RmlC or RmlD. Genome sequencing of S. griseus and C. burnetii proposed the StrM and CBU1838 proteins respectively as RmlC orthologues. Here, we demonstrate through both coupled and direct observation studies that both enzymes can perform the RmlC 3’’,5’’ double epimerisation activity; and that this activity supports TDP-rhamnose biosynthesis in vivo. We demonstrate that proton exchange is faster at the 3’’ position than the 5’’ position, in contrast to a previously studied orthologue. We solved the crystal structures of CBU1838 and StrM in complex with TDP and show that they form an active site highly similar to previously characterised enzymes. These results further support the hypothesis that streptose and DHHS are biosynthesised using the TDP pathway and are consistent with the ring contraction step being performed on a double epimerised substrate, most likely by the RmlD paralogue. This work will support the determination of the full pathways for streptose and DHHS biosynthesis.
Published: 2021
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31. Inhibition of The hERG Potassium Channel By The Polycyclic Aromatic Hydrocarbon Pollutant Phenanthrene

Author: Christopher E. Dempsey, Stephen C Harmer, Jules C. Hancox, Chunyun Du, Oliver Hanington, Ehab Al-Moubarak, Yihong Zhang, and Holly A. Shiels
Subjects: Pollutant, chemistry.chemical_classification, chemistry.chemical_compound, biology, chemistry, Environmental chemistry, hERG, biology.protein, Polycyclic aromatic hydrocarbon, Phenanthrene, Potassium channel
Abstract: The lipophilic polycyclic aromatic hydrocarbon (PAH) phenanthrene is relatively abundant in polluted air and water and can access and accumulate in human tissue. Phenanthrene has been reported to interact with cardiac ion channels in several fish species. This study was undertaken to investigate the ability of phenanthrene to interact with hERG (human Ether-à-go-go-Related Gene) encoded K+ channels, which play a central role in human ventricular repolarization. Pharmacological inhibition of hERG can be proarrhythmic. Whole-cell patch clamp recordings of hERG current (IhERG) were made from HEK293 cells expressing wild-type (WT) and mutant hERG channels. WT IhERG1a was inhibited by phenanthrene with an IC50 of 16.8 ± 1.7 µM, whilst IhERG1a/1b exhibited an IC50 of 1.8 ± 0.3 µM. WT IhERG block showed marked voltage and time-dependence, indicative of dependence of inhibition on channel gating. The inhibitory effect of phenanthrene was markedly impaired by the attenuated-inactivation N588K mutation. Remarkably, mutations of S6 domain aromatic amino acids (Y652, F656) in the canonical drug binding site did not impair the inhibitory action of phenanthrene; the Y652A mutation augmented IhERG block. In contrast, the F557L (S5) and M651A (S6) mutations impaired the ability of phenanthrene to inhibit IhERG, as did the S624A mutation below the selectivity filter region. Computational docking using a cryo-EM derived hERG structure supported the mutagenesis data. Thus, phenanthrene acts as an inhibitor of the hERG K+ channel by directly interacting with the channel, binding to a distinct site in the channel pore domain.
Published: 2021
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32. Fabrication and characterization of arc melted Si/B co-doped boron carbide

Author: Kevin J. Hemker, Atta U. Khan, Martin P. Harmer, Richard A. Haber, Jerry C. LaSalvia, Christopher J. Marvel, Qirong Yang, Ankur Chauhan, Vladislav Domnich, and Chawon Hwang
Subjects: inorganic chemicals, 010302 applied physics, Fabrication, Materials science, technology, industry, and agriculture, 02 engineering and technology, Boron carbide, 021001 nanoscience & nanotechnology, Microstructure, 01 natural sciences, Microanalysis, Characterization (materials science), symbols.namesake, chemistry.chemical_compound, Structural change, chemistry, 0103 physical sciences, Materials Chemistry, Ceramics and Composites, symbols, Shear strength, Composite material, 0210 nano-technology, Raman spectroscopy
Abstract: Boron carbide undergoes stress-induced amorphization when subjected to large non-hydrostatic stresses that exceed its elastic limit. This has been proposed as the source for the abrupt loss of shear strength in boron carbide which limits its engineering applications. Si/B co-doping was suggested as one of the means to suppress stress-induced amorphization but this has not been experimentally verified. Here, by utilizing arc melting, we prepared Si/B co-doped boron carbide with increased Si content as compared to conventional methods. Through Raman analysis in conjunction with indention and elemental analyses based on SEM and STEM (ζ-factor microanalysis), it is suggested that Si/B co-doping is a promising avenue for suppressing stress-induced amorphization. A comprehensive characterization of microstructure, chemistry, and structural change of boron carbide as a result of Si/B co-doping was elucidated.
Published: 2019
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33. From NaZn4Sb3 to HT-Na1–xZn4–ySb3: Panoramic Hydride Synthesis, Structural Diversity, and Thermoelectric Properties

Author: Tori Cox, Yang Sun, Julia V. Zaikina, Volodymyr Gvozdetskyi, Cai-Zhuang Wang, Sangki Hong, Feng Zhang, Kai-Ming Ho, Gourab Bhaskar, Bryan Owens-Baird, and Colin P. Harmer
Subjects: Materials science, Hydride, General Chemical Engineering, Sodium, chemistry.chemical_element, General Chemistry, Zinc, Crystal structure, Evaporation (deposition), Sodium hydride, chemistry.chemical_compound, Crystallography, chemistry, Thermoelectric effect, Materials Chemistry, Monoclinic crystal system
Abstract: Two new sodium zinc antimonides NaZn4Sb3 and HT-Na1–xZn4–ySb3 were synthesized by using reactive sodium hydride, NaH, as a precursor. The hydride route provides uniform mixing and comprehensive control over the composition, facilitating fast reactions and high-purity samples, whereas traditional synthesis using sodium metal results in inhomogeneous samples with a significant fraction of the more stable NaZnSb compound. NaZn4Sb3 crystallizes in the hexagonal P63/mmc space group (No. 194, Z = 2, a = 4.43579(4) A, c = 23.41553(9) A) and is stable upon heating in vacuum up to 736 K. The layered crystal structure of NaZn4Sb3 is related to the structure of the well-studied thermoelectric antimonides AeZn2Sb2 (Ae = Ca, Sr, Eu). Upon heating in vacuum, NaZn4Sb3 transforms to HT-Na1–xZn4–ySb3 (x = 0.047(3), y = 0.135(1)) due to partial Na/Zn evaporation/elimination, as was determined from high-temperature in situ synchrotron powder X-ray diffraction. HT-Na1–xZn4–ySb3 has a complex monoclinic structure with conside...
Published: 2019
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34. Engineering a Seven Enzyme Biotransformation using Mathematical Modelling and Characterized Enzyme Parts

Author: Jennifer A. Littlechild, Radka Snajdrova, Nicholas J. Harmer, Rhys Cutlan, Joseph P. Adams, and William Finnigan
Subjects: Process modeling, Process (engineering), Computer science, 010402 general chemistry, 01 natural sciences, Cofactor, Catalysis, Inorganic Chemistry, 03 medical and health sciences, Biotransformation, Genetic algorithm, Enzyme cascade, Reaction engineering, Physical and Theoretical Chemistry, 030304 developmental biology, Isolated enzymes, chemistry.chemical_classification, 0303 health sciences, Chemical reaction engineering, Full Paper, biology, 010405 organic chemistry, Organic Chemistry, Full Papers, In vitro, 0104 chemical sciences, Kinetics, Enzyme, chemistry, Cascade, Pathway optimization, biology.protein, Biochemical engineering
Abstract: Multi-step enzyme reactions offer considerable cost and productivity benefits. Process models offer a route to understanding the complexity of these reactions, and allow for their optimization. Despite the increasing prevalence of multi-step biotransformations, there are few examples of process models for enzyme reactions. From a toolbox of characterized enzyme parts, we demonstrate the construction of a process model for a seven enzyme, three step biotransformation using isolated enzymes. Enzymes for cofactor regeneration were employed to make thisin vitroreaction economical. Good modelling practice was critical in evaluating the impact of approximations and experimental error. We show that the use and validation of process models was instrumental in realizing and removing process bottlenecks, identifying divergent behavior, and for the optimization of the entire reaction using a genetic algorithm. We validated the optimized reaction to demonstrate that complex multi-step reactions with cofactor recycling involving at least seven enzymes can be reliably modelled and optimized.Significance statementThis study examines the challenge of modeling and optimizing multi-enzyme cascades. We detail the development, testing and optimization of a deterministic model of a three enzyme cascade with four cofactor regeneration enzymes. Significantly, the model could be easily used to predict the optimal concentrations of each enzyme in order to get maximum flux through the cascade. This prediction was strongly validated experimentally. The success of our model demonstrates that robust models of systems of at least seven enzymes are readily achievable. We highlight the importance of following good modeling practice to evaluate model quality and limitations. Examining deviations from expected behavior provided additional insight into the model and enzymes. This work provides a template for developing larger deterministic models of enzyme cascades.
Published: 2019
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35. Vitamin B6 in Pediatric Renal Transplant Recipients

Author: Rodney D. Gilbert, Stephen A. Wootton, Matthew Harmer, and Caroline Anderson
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Adolescent, Population, 030232 urology & nephrology, Nutritional Status, Medicine (miscellaneous), Reference range, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, Folic Acid, 0302 clinical medicine, Interquartile range, Internal medicine, medicine, Humans, Prospective Studies, Child, Prospective cohort study, education, Pyridoxal, Kidney transplantation, education.field_of_study, 030109 nutrition & dietetics, Nutrition and Dietetics, business.industry, medicine.disease, Kidney Transplantation, Transplant Recipients, Vitamin B 6, Diet, Transplantation, Vitamin B 12, chemistry, Nephrology, Child, Preschool, Pyridoxal Phosphate, Female, Observational study, business
Abstract: Objectives Our aim was to assess the vitamin B6 intake and biochemical status in a sample of children who have undergone renal transplantation. Methods A prospective observational study was performed in 10 pediatric renal transplant recipients to determine their vitamin B6 status through dietary assessment and serum Pyridoxal 5′-phosphate (PLP) measurement. Results Ten children (mean age of 11.9 years) had median serum PLP concentrations of 62.45 nmol/L (interquartile range ±83.40). Two children (20%) had values above the reference range, and none below. Mean vitamin B6 intake was 138.7% of reference nutrient intake (standard deviation ±35.2%). No children were in receipt of vitamin B6 supplementation. Conclusion There is no previous literature on vitamin B6 status in children who have undergone renal transplantation. In adult transplant recipients, elevated serum PLP concentrations have been described and ascribed to possible excessive intakes. In this sample, no children appeared biochemically deficient, but 20% had elevated concentrations. Dietary intakes were not excessive, and no children reported oral Vitamin B6 supplementation. Exploration of vitamin B6 metabolism in this population is required.
Published: 2019
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36. The Oscillatory Adsorption of Organosilane Films on Aluminium Oxide: Film Morphology using Auger Electron Spectromicroscopy

Author: Jamie S. Quinton, Ruby A. Sims, and Sarah L. Harmer-Bassell
Subjects: Auger Electron Spectromicroscopy, Materials science, General Physics and Astronomy, chemistry.chemical_element, 02 engineering and technology, Substrate (electronics), 010402 general chemistry, 01 natural sciences, chemistry.chemical_compound, Adsorption, Oscillatory adsorption, Aluminium, Desorption, Monolayer, Auger electron spectroscopy, Organosilane, Surfaces and Interfaces, General Chemistry, 021001 nanoscience & nanotechnology, Condensed Matter Physics, Silane, 0104 chemical sciences, Surfaces, Coatings and Films, Self-Assembly, Film morphology, Chemical engineering, chemistry, Aluminium oxide, 0210 nano-technology
Abstract: © 2019 Elsevier BV. This manuscript version is made available under the CC-BY-NC-ND 4.0 license: http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 24 month embargo from date of publication (January 2019) in accordance with the publisher’s archiving policy, The morphology of Propyltrimethoxysilane films during the oscillatory growth mechanism is shown using Auger Electron Spectromicroscopy. While the link between oligomerisation of silane molecules on the substrate and the oscillatory growth mechanism has been proposed previously, here for the first time we show the presence of silane film islands through Auger Electron Spectromicroscopy elemental mapping of the substrate. Monitoring the morphology of the film at key peaks and throughout along the oscillatory curve reveals the formation of a stable thin, homogenous film along with the presence of islands approximately 20μm in diameter, whose numbers vary collectively during the adsorption/desorption mechanism. The measurable oscillations in silane substrate coverage has been directly linked to the repeated adsorption and desorption of silane islands on the aluminium substrate. The consequence of this mechanism is such that Propyltrimethoxysilane films behave most like a monolayer during the early stages of film growth, prior to siloxane oligomerisation.
Published: 2019
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37. Trivalent copper stabilised by acetylacetone dithiocarbazate Schiff base ligands: structural, spectroscopic and electrochemical properties

Author: Jeffrey Harmer, Nicole V. Silajew, Paul V. Bernhardt, Graeme R. Hanson, and Jessica K. Bilyj
Subjects: chemistry.chemical_classification, Schiff base, Ketone, 010405 organic chemistry, Dimer, Acetylacetone, Pyrazoline, 010402 general chemistry, 01 natural sciences, Redox, 0104 chemical sciences, Coordination complex, Inorganic Chemistry, chemistry.chemical_compound, chemistry, Polymer chemistry, Moiety
Abstract: The copper coordination chemistry of N2S2 Schiff base ligands derived from acetylacetone and S-methyl or S-benzyl dithiocarbazate (H3acacsR, R = Me, Bn) reveals a rich variety of products depending on the reaction conditions. The free ligands spontaneously cyclise to their pyrazoline isomers but ring-open upon complexation with CuII. In the absence of oxygen, the ligands form CuIIN2S2 complexes ([CuII(HacacsR)]) that have been characterised electrochemically, spectroscopically and structurally. Intermediates in the complexation reaction are observed with time-resolved UV-Vis spectroscopy. Upon exposure to air, a number of different complexes are formed. Facile oxidation of [CuII(HacacsR)] to the trivalent analogue [CuIII(acacsR)] occurs in air. This compound is the precursor to two further oxidation reactions; one to the ketone [CuII(acacsRO)] where a carbonyl group has been installed at the apical C atom of the acetylacetone moiety and another to afford the novel dinuclear complex [(CuIII(acacsR))2]. The presence of excess base (Et3N) favours formation of the dimer.
Published: 2019
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38. Unraveling the Origin of Photocatalytic Deactivation in CeO 2 /Nb 2 O 5 Heterostructure Systems during Methanol Oxidation: Insight into the Role of Cerium Species

Author: Tomasz Grzyb, Kirill Kovnir, Colin P. Harmer, Hanen Abdelli, Mohamad El-Roz, Lukasz Wolski, Marco Daturi, Oleg I. Lebedev, Laboratoire catalyse et spectrochimie (LCS), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Laboratoire de cristallographie et sciences des matériaux (CRISMAT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche sur les Matériaux Avancés (IRMA), Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Iowa State University (ISU), and Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Photoluminescence, Materials science, chemistry.chemical_element, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Article, X-ray photoelectron spectroscopy, Physisorption, [CHIM]Chemical Sciences, Physical and Theoretical Chemistry, ComputingMilieux_MISCELLANEOUS, business.industry, Heterojunction, 021001 nanoscience & nanotechnology, 0104 chemical sciences, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, Cerium, General Energy, Semiconductor, chemistry, Chemical engineering, Photocatalysis, Charge carrier, 0210 nano-technology, business
Abstract: The study provides deep insight into the origin of photocatalytic deactivation of Nb2O5 after modification with ceria. Of particular interest was to fully understand the role of ceria species in diminishing the photocatalytic performance of CeO2/Nb2O5 heterostructures. For this purpose, ceria was loaded on niobia surfaces by wet impregnation. The as-prepared materials were characterized by powder X-ray diffraction, nitrogen physisorption, UV-visible spectroscopy, X-ray photoelectron spectroscopy, high-resolution transmission electron microscopy, and photoluminescence measurements. Photocatalytic activity of parent metal oxides (i.e., Nb2O5 and CeO2) and as-prepared CeO2/Nb2O5 heterostructures with different ceria loadings were tested in methanol photooxidation, a model gas-phase reaction. Deep insight into the photocatalytic process provided by operando-IR techniques combined with results of photoluminescence studies revealed that deactivation of CeO2/Nb2O5 heterostructures resulted from increased recombination of photo-excited electrons and holes. The main factor contributing to more efficient recombination of the charge carriers in the heterostructures was the ultrafine size of the ceria species. The presence of such highly dispersed ceria species on the niobia surface provided a strong interface between these two semiconductors, enabling efficient charge transfer from Nb2O5 to CeO2. However, the ceria species supported on niobia exhibited a high defect site concentration, which acted as highly active recombination centers for the photo-induced charge carriers.
Published: 2021
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39. XAP5 CIRCADIAN TIMEKEEPER Affects Both DNA Damage Responses and Immune Signaling in

Author: Clare L. Casteel, Hongtao Zhang, Cory T Ellison, Gitta Coaker, Stacey L. Harmer, Roderick W. Kumimoto, Aurélie Bak, and Tania Y. Toruño
Subjects: DNA damage, Mutant, Pseudomonas syringae, Plant Biology, Plant Science, DNA damage response, SB1-1110, chemistry.chemical_compound, Immune system, Arabidopsis, Genetics, Arabidopsis thaliana, 2.1 Biological and endogenous factors, phase, Aetiology, Original Research, biology, Inflammatory and immune system, Plant culture, biology.organism_classification, NPR1, Cell biology, Histone, circadian, chemistry, biology.protein, immune signaling, DNA
Abstract: Numerous links have been reported between immune response and DNA damage repair pathways in both plants and animals but the precise nature of the relationship between these fundamental processes is not entirely clear. Here, we report that XAP5 CIRCADIAN TIMEKEEPER (XCT), a protein highly conserved across eukaryotes, acts as a negative regulator of immunity in Arabidopsis thaliana and plays a positive role in responses to DNA damaging radiation. We find xct mutants have enhanced resistance to infection by a virulent bacterial pathogen, Pseudomonas syringae pv. tomato DC3000, and are hyper-responsive to the defense-activating hormone salicylic acid (SA) when compared to wild-type. Unlike most mutants with constitutive effector-triggered immunity (ETI), xct plants do not have increased levels of SA and retain enhanced immunity at elevated temperatures. Genetic analysis indicates XCT acts independently of NONEXPRESSOR OF PATHOGENESIS RELATED GENES1 (NPR1), which encodes a known SA receptor. Since DNA damage has been reported to potentiate immune responses, we next investigated the DNA damage response in our mutants. We found xct seedlings to be hypersensitive to UV-C and γ radiation and deficient in phosphorylation of the histone variant H2A.X, one of the earliest known responses to DNA damage. These data demonstrate that loss of XCT causes a defect in an early step of the DNA damage response pathway. Together, our data suggest that alterations in DNA damage response pathways may underlie the enhanced immunity seen in xct mutants.
Published: 2021

40. Co-targeting strategy for precise, scarless gene editing with CRISPR/Cas9 and donor ssODNs in Chlamydomonas

Author: Romana Bacova, Xinrong Ma, X. Wen, Martin H. Spalding, S. Akella, David A. Wright, Martina Kolackova, Z. Harmer, Heriberto Cerutti, and Donald P. Weeks
Subjects: Regular Issue, AcademicSubjects/SCI01280, Physiology, Mutant, Plant Science, Computational biology, Homology directed repair, chemistry.chemical_compound, Genome editing, Genetics, CRISPR, Gene, Selectable marker, Research Articles, Gene Editing, AcademicSubjects/SCI01270, biology, Cas9, AcademicSubjects/SCI02288, AcademicSubjects/SCI02287, Chlamydomonas, Algal Proteins, AcademicSubjects/SCI02286, Genes, Development and Evolution, biology.organism_classification, chemistry, Ribonucleoproteins, CRISPR-Cas Systems, DNA
Abstract: Programmable site-specific nucleases, such as the clustered regularly interspaced short palindromic repeat (CRISPR)/ CRISPR-associated protein 9 (Cas9) ribonucleoproteins (RNPs), have allowed creation of valuable knockout mutations and targeted gene modifications in Chlamydomonas (Chlamydomonas reinhardtii). However, in walled strains, present methods for editing genes lacking a selectable phenotype involve co-transfection of RNPs and exogenous double-stranded DNA (dsDNA) encoding a selectable marker gene. Repair of the dsDNA breaks induced by the RNPs is usually accompanied by genomic insertion of exogenous dsDNA fragments, hindering the recovery of precise, scarless mutations in target genes of interest. Here, we tested whether co-targeting two genes by electroporation of pairs of CRISPR/Cas9 RNPs and single-stranded oligodeoxynucleotides (ssODNs) would facilitate the recovery of precise edits in a gene of interest (lacking a selectable phenotype) by selection for precise editing of another gene (creating a selectable marker)—in a process completely lacking exogenous dsDNA. We used PPX1 (encoding protoporphyrinogen IX oxidase) as the generated selectable marker, conferring resistance to oxyfluorfen, and identified precise edits in the homolog of bacterial ftsY or the WD and TetratriCopeptide repeats protein 1 genes in ∼1% of the oxyfluorfen resistant colonies. Analysis of the target site sequences in edited mutants suggested that ssODNs were used as templates for DNA synthesis during homology directed repair, a process prone to replicative errors. The Chlamydomonas acetolactate synthase gene could also be efficiently edited to serve as an alternative selectable marker. This transgene-free strategy may allow creation of individual strains containing precise mutations in multiple target genes, to study complex cellular processes, pathways, or structures., A transgene-free strategy allows precise editing of genes lacking a selectable phenotype by electroporation of CRISPR/Cas9 ribonucleoproteins and single-stranded oligodeoxynucleotide templates.
Published: 2021

41. Parent and Metabolite Concentration-QT Modeling to Evaluate QT-Interval Prolongation at Savolitinib Therapeutic Doses

Author: Tarjinder Sahota, Stein Schalkwijk, Alexander R. Harmer, Remy B. Verheijen, and Ghada F. Ahmed
Subjects: biology, business.industry, Metabolite, hERG, QTcF Prolongation, Prolongation, Cmax, Pharmaceutical Science, Pharmacology, 030226 pharmacology & pharmacy, QT interval, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, chemistry, 030220 oncology & carcinogenesis, biology.protein, Medicine, business, IC50, EC50
Abstract: Savolitinib is an oral, potent, and highly selective MET-tyrosine kinase inhibitor under investigation in various tumor types. A thorough QT study evaluated effects on QT interval after a 600-mg single savolitinib dose in healthy subjects. We report exposure-response (E-R) modeling from this study to characterize the effects of savolitinib and its metabolites, M2 and M3, on QTc changes. In a novel application, in vitro potencies against hERG current provided mechanistic support to model the metabolites' effects. The hERG IC50 estimates (95% CI) were 25.8 (22.2-29.9) and 22.6 (14.7-34.6) μM for parent and M2, respectively. The E-R was described by both linear and Emax models, with exposure captured by an active moiety that consisted of savolitinib and M2 concentrations, weighted by the hERG IC50 ratio (1.14). The maximal increase in ΔΔQTcF and EC50 estimates (95% CI) was 18.5 (9.2-27.7) ms and 5709 (2889-8529) nM, respectively. Ignoring M2 contribution resulted in under prediction of QTcF prolongation in the hypothetical case of inhibited M2 clearance; at 300 mg Cmax, the mean (90% CI) of ∆∆QTcF was 9.0 (5.7-12.6) and 5.9 (2.9-8.9) ms using the hERG-informed and parent-only linear models, respectively. Simulations in normal setting confirmed modest QTcF prolongation with 600 mg, but not 300 mg. Using the linear model, the mean (90% CI) maximum ΔΔQTcF were 12.3 (8.6-16.2) and 5.5 (2.6-8.5) ms for 600 and 300 mg, respectively. Further clinical studies will monitor cardiac safety to assess the clinical significance of QT-interval prolongation with savolitinib.
Published: 2021
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42. Probing Molecular Mechanisms during the Oscillatory Adsorption of Propyl Chain Functionalized Organosilane Films with Sum Frequency Generation Spectroscopy

Author: Kohei Uosaki, Hidenori Noguchi, Ruby A. Sims, Sarah L. Harmer, and Jamie S. Quinton
Subjects: Silanes, Materials science, 010304 chemical physics, Bilayer, Substrate (chemistry), 010402 general chemistry, 01 natural sciences, 0104 chemical sciences, Surfaces, Coatings and Films, chemistry.chemical_compound, Adsorption, chemistry, Covalent bond, Chemical physics, 0103 physical sciences, Monolayer, Materials Chemistry, Physical and Theoretical Chemistry, Selectivity, Sum frequency generation spectroscopy
Abstract: The selectivity rules of sum frequency generation spectroscopy were exploited to determine propyl chain order during the time-dependent oscillatory adsorption of propyltrimethoxysilane (PTMS) and Langmuir-type growth of propyldimethylmethoxysilane (PDMMS). During the early stages of film growth, molecular packing density determines the extent of propyl chain defects within both films with high surface coverage resulting in a film with fewer defects. Following this, an ordered monolayer-like film stabilizes on the Al2O3 substrate for both silanes. Although this result is intuitive for the Langmuir-type growth of PDMMS, the stabilization of molecular ordering despite the continuing oscillation in PTMS surface coverage indicates the presence of a stable monolayer, while it is the oligomerized PTMS dendrimers which continue to desorb and readsorb to the substrate. We also reveal for the first time, the formation of a physisorbed bilayer during the self-assembly process of PTMS. The presence of this ordered, physisorbed bilayer on top of the covalently bound PTMS film plays a key role in the process of the molecular self-assembly mechanism and is proposed to enable further condensation of the covalently bound film.
Published: 2021

43. Azithromycin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Author: Eugenia Abaleke, Mustafa Abbas, Sadia Abbasi, Alfie Abbott, Ashraf Abdelaziz, Sherif Abdelbadiee, Mohamed Abdelfattah, Basir Abdul, Althaf Abdul Rasheed, Rezan Abdul-Kadir, Abdulfatahi Abdulmumeen, Niyaz Abdulshukkoor, Kula Abdusamad, Yazeed Abed El Khaleq, Mai Abedalla, Abeer UA Abeer Ul Amna, Adebanke Aboaba, Hani Abo-Leyah, Ahmed Abou-Haggar, Mahmoud Abouibrahim, Miriam Abraham, Tizzy Abraham, Abraheem Abraheem, Judith Abrams, Hyacinth-John Abu, Ahmad Abu-Arafeh, Syed M Abubacker, Akata Abung, Yaa Aceampong, Devikumar Acharya, Janet Acheson, Andres Acosta, Catherine Acton, Jacqueline Adabie-Ankrah, Fiona Adam, Matthew Adam, Huzaifa Adamali, Carol Adams, Kate Adams, Richard Adams, Tim Adams, Malgorzata Adamus, Kirsty Adcock, Aderonke Adebiyi, Ken Adegoke, Vicki Adell, Aldrin Adeni, Sherna Adenwalla, Oluwasegun A Adesemoye, Emmanuel O Adewunmi, Joyce Adeyemi, Elizabeth Adeyeye, Gabrielle Adkins, Adnan Adnan, John Aeron-Thomas, Lynn Afari, Debbie Affleck, Carmel Afnan, Deborah Afolabi, Muhammad Afridi, Rachel Agbeko, Chris Agbo, Sunil Aggarwal, Arameh Aghababaie, Judith Agwada-Akeru, Kwame A Agyapong, Shafana Ahamed Sadiq, Mohamed H Ahammed Nazeer, Jonathan Ah-Chuen, Mahin Ahmad, Ashar Ahmed, Bilal Ahmed, Forizuddin Ahmed, Iram Ahmed, Irshad Ahmed, Liban Ahmed, Maria C Ahmed, Muhammad S Ahmed, Naseer Ahmed, Nausheen Ahmed, Osama Ahmed, Rajia A Ahmed, Rizwan Ahmed, Saif Ahmed, Sammiya Ahmed, Sara Ahmed, Syed H Ahmed, Roa Ahmed Ali, Sana Ahmer, Dhiraj Ail, Adam Ainsley, Mark Ainsworth, Myriam Aissa, Lucy Aitchson, Lindianne Aitken, Bini Ajay, Abdulakeem Ajibode, Ayesha Ajmi, Muhammad N Akhtar, Nasim Akhtar, Suha Akili, Oludoyinsola Akindolie, Yinka Akinfenwa, Olugbenga Akinkugbe, Ibrahim Akinpelu, Umeh Akudo, Asma Al Balushi, Majd Al Dakhola, Narendra Aladangady, Sajid Alam, Abbas Al-Asadi, Kyriaki Alatzoglou, Lorraine Albon, Stephen Alcorn, Aggie Aldana, David Alderdice, Rayan Aldouri, Jonathan Aldridge, Nicolas Aldridge, Ana Alegria, Alison Alexander, John Alexander, Peter DG Alexander, Julyan Al-Fori, Bahij Al-Hakim, Shams Al-Hity, Ali Ali, Anyat Ali, Fawzia R Ali, Jawad Ali, Mariam Ali, Mohammad Ali, Oudai Ali, Sakina Ali, Syed Ali, Abid Alina, Katrin Alizaedeh, Maithem Al-Jibury, Moutaz Alkhusheh, Alison Allanson, Robert Allcock, Eireann Allen, Jonathan Allen, Kerry Allen, Louise Allen, Rebecca Allen, Sam Allen, Sharon Allen, Simon Allen, Kathryn Allison, Bethan Allman, Lynne Allsop, Christine Almadenboyle, Hassan Al-Moasseb, Magda Al-Obaidi, Lina Alomari, Akram Al-Rabahi, Bahar Al-Ramadhani, Zayneb Al-Saadi, Warkaq Al-Shamkhani, Bashar Al-Sheklly, Mary Alvarez, Maysaa Alzetani, Susan Amamou, Sakarai Ambalavanan, Sarah-Jayne Ambler, Robert Ambrogetti, Chris Ambrose, Amir Ameen, Maria R Amezaga, Allison Amin, Amina Amin, Kanish Amin, Amjad Amjad, Victoria Amosun, Khaled Amsha, Atul Anand, Samantha Anandappa, Julie Anderson, Laura Anderson, Michelle Anderson, Nicola Anderson, Rachel Anderson, Rory Anderson, Prematie Andreou, Angela Andrews, Jill Andrews, Kanayochukwu Aneke, Andrew Ang, Wan Wei Ang, Tammy Angel, Paola Angelini, Lazarus Anguvaa, Oleg Anichtchik, Millicent Anim-Somuah, Krishnan Aniruddhan, Alpha Anthony, Aaron Anthony-Pillai, Philip Antill, Zhelyazkova Antonina, Varghese Anu, Muhammad Anwar, Aristeidis Apostolopoulos, Sarah Appleby, Diane Appleyard, Bianca Araba, Angela Aramburo, Ann Archer, Denise Archer, Simon Archer, Christian Ardley, Ana-Maria Arias, Ryoki Arimoto, Charlotte Arkley, Charlotte Armah, Ilianna Armata, Adam Armitage, Ceri Armstrong, Maureen Armstrong, Sonia Armstrong, Philippa Armtrong, Heike Arndt, Clare Arnison-Newgass, David Arnold, Rachael Arnold, Dhawal Arora, Pardeep Arora, Rishi Arora, Arslam Arter, Ganesh Arunachalam, Rita Arya, Salma Asam, Denisa Asandei, Adeeba Asghar, Catherine Ashbrook-Raby, Helen Ashby, Jan Ashcroft, John Ashcroft, Ayesha Ashfaq, Abdul Ashish, Sally Ashman-Flavell, Sundar Ashok, Muhammad Z Ashraf, Saima Ashraf, Mohammad B Ashraq, Deborah Ashton, Susan Ashton, Andrew Ashworth, Rebecca Ashworth, Harshini Asogan, Julia Asplin, Atif Asrar, Omar Assaf, Raine Astin-Chamberlain, Deborah Athorne, Christopher Atkins, Stacey Atkins, John Atkinson, Vicki Atkinson, Ahmed Attiq, Paula Aubrey, Suzannah August, Aye CT Aung, Hnin Aung, Kyaw Thu Aung, Nini Aung, Zaw Myo Aung, Emily Austin, Karen Austin, Miriam Avery, Joanne Avis, Cristina Avram, Paula Avram, Gabriel Awadzi, Aszad Aya, Eman Ayaz, Amanda Ayers, Vivek Ayra, Jawwad Azam, Mohammed Azharuddin, Ghazala Aziz, Ashaari Azman Shah, Giada Azzopardi, Hocine Azzoug, Nasaruilla Babajan, Fiyinfoluwa Babatunde, Melvin Babi, Babiker Babiker, Gayna Babington, Matthew Babirecki, Adetona O Babs-Osibodu, Gina Bacon, Jenny Bacon, Bibi Badal, Gurpreet R Badhan, Shreya Badhrinarayanan, Joseph Bae, Alice Baggaley, Amy Baggott, Graham Bagley, Dinesh Bagmane, Kasra Bahadori, Gayathri Baijiu, Charles Bailey, Julie Bailey, Katie Bailey, Lindsey Bailey, Liz Bailey, Morgan Bailey, Peter Bailey, Hamish Baillie, Kenneth Baillie, Jennifer Bain, Karen Bain, Becky Bainton, David Baird, Yolanda Baird, Aiysha Bajandouh, Evelyn Baker, Johanne Baker, Kenneth Baker, Pearl Baker, Hugh Bakere, Nawar Bakerly, Michelle Baker-Moffatt, Panos Bakoulas, Abhijit Bal, Niranjan Balachandran, Irvin Balagosa, Andrea Balan, Theodosios Balaskas, Madhu Balasubramaniam, Alison Balcombe, Cheryl Baldwick, Alexander Baldwin, Ashley Baldwin, Danielle Baldwin, Lisa Baldwin, Rebekah Baldwin-Jones, James Balfour, Ceri Ball, Craig Balmforth, Gabby Bambridge, Alasdair Bamford, Amy Bamford, Peter Bamford, Adefunke Bamgboye, Kasun Bamunuarachchi, Elizabeth Bancroft, Hollie Bancroft, Joyce Banda, Srini Bandi, Nageswar Bandla, Somaditya Bandyopadhyam, Ritwik Banerjee, Sandip Banerjee, Harrison Banks, Luke Banks, Daniel Banner, Oliver Bannister, Christopher Bannon, Laura Banton, Mariamma Baptist, Tanya Baqai, Ananya M Baral, Desislava Baramova, Russell Barber, Emma Barbon, Monica Barbosa, Jamie Barbour, Alexander Barclay, Charlotte Barclay, Stephanie Bareford, Shahedal Bari, Amy Barker, Debbie Barker, Joseph B Barker, Leon Barker, Oliver Barker, Kerry Barker-Williams, Sinha Barkha, Juliana Barla, Gavin Barlow, Richard Barlow, James Barnacle, Alex Barnard, Debi Barnes, Nicky Barnes, Amy Barnett, Debra Barnett, Ashton Barnett-Vanes, William Barnsley, Andrew Barr, David Barr, Shaney Barratt, Manuella Barrera, Fiona Barrett, Jessica Barrett, Jazz Bartholomew, Sarah Bartholomew, Claire Bartlett, Georgina Bartlett, Greg Barton, Jill Barton, Rachael Barton, Rosaleen Baruah, Sonia Baryschpolec, Archana Bashyal, Betsy Basker, Ayten Basoglu, Amira Bassaly, G Bassett, Bengisu Bassoy, Anupam Basumatary, Adam Bataineh, Freddie Batalla, Tristan Bate, Harry John Bateman, Kathryn Bateman, Vhairi Bateman, Eleanor Bates, Hayley Bates, Michelle Bates, Rizvan Batha, Sally Batham, Ana Batista, Amit Batla, Dushyant Batra, Harry Batty, Thomas Batty, Miranda Baum, Carina Bautista, Fatima S Bawani, Simon Bax, Matt Baxter, Nicola Baxter, Hannah Bayes, Farid Bazari, Rohit Bazaz, Ahmad Bazli, Laura Beacham, Hannah Beadle, Wendy Beadles, Philip Beak, Andy Beale, Kathy Beardsal, Jack Bearpark, Karen Beaumont, Matthew Beaumont, Dawn Beaumont-Jewell, Theresa Beaver, Sarah Beavis, Christy Beazley, Sarah Beck, Virginia Beckett, Rosie Beckitt, Heidi Beddall, Seonaid Beddows, Deborah Beeby, Michelle Beecroft, Sally Beer, Jane Beety, Gabriela Bega, Alison Begg, Susan Begg, Sara Beghini, Ayesha Begum, Safia Begum, Teresa Behan, Roya Behrouzi, Jon Beishon, Claire Beith, James Belcher, Holly Belfield, Katherine Belfield, Ajay Belgaumkar, Dina Bell, Gareth Bell, Gillian Bell, Lauren Bell, Louise Bell, Nicholas Bell, Stephanie Bell, Jennifer L Bell, Mary Bellamy, Arianna Bellini, Amanda Bellis, Fionn Bellis, Lesley Bendall, Naveena Benesh, Nicola Benetti, Leonie Benham, Guy Benison-Horner, Ann Bennett, Caroline Bennett, Gillian Bennett, Kristopher Bennett, Lorraine Bennett, Sara Bennett, Vivienne Benson, Andrew Bentley, Ian Benton, Eva Beranova, Matthew Beresford, Colin Bergin, Malin Bergstrom, Jolanta Bernatoniene, Thomas Berriman, Zoe Berry, Kimberley Best, Yvonne Beuvink, Emily Bevan, Sarah Bevins, Tom Bewick, Helen Bexhell, Andrew Bexley, Sonay Beyatli, Fenella Beynon, Arjun Bhadi, Sanjay Bhagani, Shweta Bhagat, Shiv Bhakta, Rekha Bhalla, Mahesh Bhalme, Khushpreet Bhandal, Kulbinder Bhandal, Ravina Bhanot, Prashanth Bhat, Nikhil Bhatia, Rahul Bhatnagar, Janki Bhayani, Deepika Bhojwani, Salimuzzaman Bhuiyan, Anna Bibby, Naheeda Bibi, Salma Bibi, Tihana Bicanic, Julie Bigg, Sarah Biggs, Alphonsa Biju, Andras Bikov, Sophie Billingham, Jessica Billings, Alice Binns, Oliver Bintcliffe, Catherine Birch, Janine Birch, Jenny Birch, Katherine Birchall, Sam Bird, Sumedha Bird, Mark Birt, Kilanalei Bishop, Linda Bishop, Lisa Bishop, Nibedan Biswas, Sahar Biuk, Karen Blachford, Ethel Black, Helen Black, Karen Black, Mairead Black, Polly Black, Sabrina Black, Bethan Blackledge, Joanne Blackler, Samantha Blackley, Helen Blackman, Caroline Blackstock, Francesca Blakemore, Helen Blamey, Sujata Blane, Simon Blankley, Parry Blaxill, Jane Blazeby, Natalie Blencowe, Ben Bloom, Angela Bloss, Hannah Bloxham, Louise Blundell, Susara Blunden, Mark Blunt, Ian Blyth, Kevin Blyth, Andrew Blythe, Karen Bobruk, Pritesh Bodalia, Neena Bodasing, Gabriele Boehmer, Marta Boffito, Sumit Bokhandi, Maria Bokhar, Saba Bokhari, Sakina Bokhari, Syed Owais Bokhari, Ambrose Boles, Matthew Bolton, Helena Bond, Stuart Bond, Thomas Bond, Alice Bone, Georgia Boniface, Lizzy Bonney, Joanne Borbone, Stephanie Borg, Catherine Borra, Samuel Bosompem, Liam Botfield, Fiona Bottrill, Hannah Bouattia, Laura Bough, Hayley Boughton, Zoe Boult, Miriam Bourke, Karen Bourne, Michelle Bourne, Rachel Bousefield, Lucy Boustred, Alexandra Bowes, Amy Bowes, Philip Bowker, Louise Bowman, Simon Bowman, Angie Bowring, Geetha Boyapati, Jenny Boyd, Laura Boyd, Namoi Boyle, Pauline Boyle, Rosalind Boyle, Louise Boyles, Leanna Brace, Jodie Bradder, Clare J Bradley, Pamela Bradley, Patrick Bradley, Joanne Bradley-Potts, Lynne Bradshaw, Zena Bradshaw, Rebecca Brady, Shirin Brady, Marie Branch, Emily Brandl-Salutz, Christina Branfield, Jamie Brannigan, Louise Brassington, Fiona Bray, Nancy Bray, Manny Brazil, Lucy Brear, Tracy Brear, Stephen Brearey, Morwenna Brend, Andrew Brereton, Chris Brewer, Gavin Bridgwood, Sara Brigham, John Bright, Christopher Brightling, Elaine Brinkworth, Robin Brittain-Long, Vianne Britten, Lauren Broad, Sarah Broad, Rosie Broadhurst, Andrew Broadley, Marie Broadway, Christopher Brockelsby, Megan Brocken, Tomos Brockley, Fiona Brogan, Felicity Brokke, Jacob Brolly, David Bromley, Hannah Brooke-Ball, Verity Brooker, Matthew Brookes, Alison Brooks, Kate Brooks, Nicole Brooks, Rachel Brooks, Sophie Brooks, Natalie Broomhead, Chloe Broughton, Nathaniel Broughton, Matt Brouns, Alison Brown, Carly Brown, Catrin Brown, Ellen Brown, Heather Brown, Janet Brown, Louise Brown, Niall Brown, Pauline Brown, Richard Brown, Robert Brown, Steven Brown, Tom Brown, Charlotte Browne, Duncan Browne, Rachel Browne, Stephen Brownlee, David Bruce, Johanna Bruce, Michelle Bruce, Wojciech Brudlo, Nigel Brunskill, Luke Brunton, Margaret Brunton, Jade Bryant, Mark Bryce, Maya Buch, Ruaridh Buchanan, Amanda Buck, Elizabeth Buckingham, Laura Buckley, Philip Buckley, Sarah Buckley, Carol Buckman, George Bugg, Ramadan Bujazia, Shanzay Bukhari, Richard Bulbulia, Alex Bull, Damian Bull, Rhian Bull, Thomas Bull, Sam Bullard, Naomi Bulteel, Katherine Bunclark, Roneleeh Bungue-Tuble, Caroline Burchett, Christy Burden, Thomas G Burden, Sarah Burge, Mika Burgess, Sophia Burgess, Emma Burke, Sara Burnard, Caroline Burnett, Amy Burns, Collette Burns, James Burns, Karen Burns, Daniel Burrage, Kate Burrows, Claire Burston, Ben Burton, Fiona Burton, Angus Butchart, Aaron Butler, Jo Butler, Joanne Butler, Joshua Butler, Peter Butler, Susan Butler, Al-Tahoor Butt, Caryl Butterworth, Nicola Butterworth-Cowin, Robert Buttery, Heather Button, Daniel Buttress, Jane Byrne, Wendy Byrne, Victoria Byrne-Watts, Ruth Cade, Donna Cairney, Claire Calderwood, James Calderwood, Giorgio Calisti, Debbie Callaghan, Jennifer Callaghan, Claire Callens, Caroline Calver, Melissa Cambell-Kelly, Tracey Camburn, David R Cameron, Eleanor Cameron, Fraser Cameron, Sheena Cameron, Christian Camm, Renee FD Cammack, Alison Campbell, Amy Campbell, Barbara Campbell, Bridget Campbell, Debbie Campbell, Helen Campbell, Hilary Campbell, Jonathan Campbell, Mark Campbell, Robyn Campbell, Wynny Campbell, Quentin Campbell Hewson, Laura Camrasa, Julie Camsooksai, Shaula M Candido, Cielito Caneja, Johnathon Cann, Ruby Cannan, Emma Cannon, Michael Cannon, Petra Cannon, Vivienne Cannons, Jane Cantliff, Ben Caplin, Angelika Capp, Thomas Capstick, Simon Carley, Tammy Carlin, Samantha Carmichael, Margaret Carmody, Mandy Carnahan, Charlotte Caroline, Patrick Carr, Sharon Carr, Anna Carrasco, Zoe Carrington, Jonathan Carter, Paul Carter, Penny Carter, Douglas Cartwright, Claire Carty, Jaime Carungcong, Paula Carvelli, Aisling Cashell, Barbara Cassimon, Teresa Castiello, Gail Castle, Melanie Caswell, Ana Maria Catana, Heidi Cate, Susanne Cathcart, Katrina Cathie, Christine Catley, Laura Catlow, Kerry Causer, Luke Cave, Frianne Cawa, Kathryn Cawley, Philippa Cawley, Chloe Caws, Hankins Cendl, Jeva Cernova, Ed Cetti, Stephanie Chabane, Manish Chablani, Cathleen Chabo, David Chadwick, Julie Chadwick, Robert Chadwick, Ela Chakkarapani, Arup Chakraborty, Mallinath Chakraborty, Mollika Chakravorty, James Chalmers, Georgina Chamberlain, Sarah Chamberlain, Carol Chambers, Emma Chambers, Jonathan Chambers, Lucy Chambers, Naomi Chambers, Shreekant Champanerkar, Carmen Chan, Cheuk Chan, Evelyn Chan, Kimberley Chan, Ping Chan, Rebekah (Pui-Ching) Chan, Xin H Chan, Chris Chandler, Kim J Chandler, Zoe Chandler, Badrinathan Chandrasekaran, Josephine Chaplin, Graeme Chapman, John Chapman, Katie Chapman, Laura Chapman, Lianne Chapman, Polly Chapman, Timothy Chapman, Lucy Chappell, Amanda Charalambou, Bethan Charles, Dianne Charlton, Kevin Chatar, Calvin Chatha, Priyanka Chaturvedi, Muhammad YN Chaudhary, Iram Chaudhry, Zain Chaudhry, Nazia Chaudhuri, Muhammad Chaudhury, Anoop Chauhan, Milan Chauhan, Ruchi S Chauhan, Nicola Chavasse, James Cheaveau, Michelle Cheeseman, Fang Chen, Hui Min Chen, Terence Chen, Lok Y Cheng, Zhihang Cheng, Ashok Chengappa, Helen Chenoweth, Chun H Cheong, Shiney Cherian, Helen Cheshire, Sarah Chessell, Chee Kay Cheung, Elaine Cheung, Claire Cheyne, Swati Chhabra, Eric Chiang, Angela Chiapparino, Rosavic Chicano, Sam Chilcott, Phillipa Chimbo, KokWai Chin, Wen Jie Chin, Amol Chingale, Heather Chisem, Ben Chisnall, Sunder Chita, Nihil Chitalia, Chipo Chitsenga, Matthew Chiu, Brenda Chivima, Soha Choi, Willy Choon Kon Yune, Khayzer Choudhary, Vandana Choudhary, Gary Chow, Muhibbur Chowdhury, Alexander Christides, Alex Christie, Daniel Christmas, Thereza Christopherson, Mark Christy, Paris Chrysostomou, Yunli Chua, Dip Chudgar, Richard Chudleigh, Srikanth Chukkambotla, Izu Chukwulobelu, Favour Chukwunonyerem, Chi Y Chung, Jonathan Chung, Elaine Church, Sara R Church, David Churchill, Paola Cicconi, Zdenka Cipinova, Bessie Cipriano, Sarah Clamp, Melanie Clapham, Edel Clare, Sarbjit Clare, Andrew Clark, Charlotte Clark, Diane Clark, Felicity Clark, Gabrielle Clark, James Clark, Katherine Clark, Lucy Clark, Matthew Clark, Patricia Clark, Richard Clark, Thomas Clark, Zoe Clark, Andrea Clarke, Paul Clarke, Robert Clarke, Roseanne Clarke, Samantha Clarke, Sheron Clarke, Alleyna Claxton, Elizabeth Clayton, Olivia Clayton, Jill Clayton-Smith, Chris Cleaver, Jayne Clemens, Carlota Clemente de la Torre, Suzanne Clements, Sarah Clifford, Amelia Clive, Jonathan Clouston, Samantha Clueit, Andrea Clyne, Peter GL Coakley, Kathryn Cobain, Susan Coburn, Alexandra Cochrane, Patricia Cochrane, Samantha Cockburn, Helen Cockerill, Shirley Cocks, Rhodri Codd, Rachel Codling, Adam Coe, Samantha Coetzee, David Coey, Paul F Cofie, Danielle Cohen, Jonathan Cohen, Oliver Cohen, Mike Cohn, Louise Coke, Nicholas Colbeck, Roghan Colbert, Esther Cole, Jade Cole, Joby Cole, Nicholas Cole, Garry Coleman, Matt Coleman, Holly Coles, Julie Colley, Dawn Collier, Heather Collier, Paul Collini, Emma Collins, Jaimie Collins, Joanne Collins, Nicola Collins, Sally Collins, Vicky Collins, Andrew Collinson, Jennifer Collinson, Madeleine Colmar, Hayley E Colton, James Colton, Katie Colville, Carolyn Colvin, Edward Combes, David Comer, Dónal Concannon, Robin Condliffe, Lynne Connell, Natalie Connell, Gavin Connolly, Emma Connor, Antonia Conroy, Veronica Conteh, Rory Convery, Grainne Conway, Rhiannon Conway, Jo-Anna Conyngham, Eloise Cook, Gemma Cook, Helen Cook, Graham Cooke, Katrina Cooke, Catherine Coombs, Chris Cooper, Jamie Cooper, Joshua Cooper, Lauren Cooper, Rowena Cooper, Sophie Cooper, Thomas Cope, Carolyn Corbett, John Corcoran, Jessica Cordle, Alasdair Corfield, John Corless, Alison Corlett, Pamela Corlett, Michael Cornwell, Diana Corogeanu, Ruth Corrigan, Rita Corser, Jon Cort, Denise Cosgrove, Patricia Costa, Charlie Coston, Susannah Cotgrove, Zoe Coton, Lisa-Jayne Cottam, Rhiannon Cotter, Donna Cotterill, Caroline Cotton, James Coulson, David Counter, Cherry Coupland, Ellie Courtney, Julia Courtney, Elena Cowan, Louise Cowen, Steve Cowman, Amanda Cowton, Ellie Cox, Giles Cox, Karina Cox, Rebecca Cox, Karen Coy, Victoria Craig, Matthew Cramp, Emma Crawford, Isobel Crawford, Sarah Crawshaw, Ben Creagh-Brown, Andrew Creamer, Peter Creber, Joanne Cremona, Janet Cresswell, Mark Cribb, Charles Crichton, Declan Crilly, Lauren Crisp, Nikki Crisp, Dominic Crocombe, Maria Croft, Jennifer Crooks, Harriet Crosby, Tim Cross, Stephen Crotty, Susan Crouch, Madeleine Crow, Rory Crowder, Becky Crowe, Rebecca Croysdill, Irena Cruickshank, James Cruise, Carina Cruz, Trino Cruz Cervera, Dominic Cryans, Guanguo Cui, Gillian Cummings-Fosong, Victoria Cunliffe, Caroline Cunningham, Mishell Cunningham, Neil 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Dosanjh, Paula Dospinescu, Andrew Dougherty, Katie Douglas, Lucy Dowden, Michelle Dower, Sud Dowling, Hayley Downe, Nicola Downer, Charlotte Downes, Rob Downes, Thomas Downes, Damian Downey, Louise Downs, Simon Dowson, Cornel Dragan, Cristina Dragos, Chelsea Drake, Victoria Drew, Olivia Drewett, Celine Driscoll, Helena Drogan, Ronald Druyeh, Simon Drysdale, Hazel Dube, Judith Dube, Stephen Duberley, Simon Dubrey, Roger Duckitt, Hayley Duckles-Leech, Nicola Duff, Helen Duffy, Lionel Dufour, Annette Duggan, Parveen Dugh, Janice Duignan, Simon Dummer, Andrew Duncan, Barrie Duncan, Christopher Duncan, Fullerton Duncan, Alessia Dunn, Damian Dunn, Laura Dunn, Karen Dunne, Fiona Dunning, Aidan Dunphy, Venkat Duraiswamy, Beatriz Duran, Ingrid DuRand, Alison Durie, Emily Durie, Laura Durrans, Hannah Durrington, Akshay Dwarakanath, Laasya Dwarakanath, Ellen Dwyer, Claudia Dyball, Harvey Dymond, Tom Dymond, Chris Eades, Melissa Earwaker, Nicholas Easom, Clare East, Jack Easton, Ruth Eatough, Oluwadamilola Ebigbola, Martin Ebon, Sinan Eccles, Chloe Eddings, Michael Eddleston, Maureen Edgar, Katharine Edgerley, Mary Edmondson, Tracy Edmunds, Alexandra Edwards, Andrea Edwards, Catherine Edwards, Joy Edwards, Kennedy Edwards, Mandy Edwards, Steven Edwards, Jenny Eedle, Dawn Egginton, Sarah Eisen, Ugochukwu Ekeowa, Mohamed Ekoi, Ayomide Ekunola, Kate El Bouzidi, Ashley Elden, Jennifer Elder, Haifa Eldew, Diana Eleanor, Maysoon Elfadil, Eman Elfar, Mayy M Elgamal, Amr Elgohary, Stellios Elia, Jennifer Elias, Tania Elias, Nadia Elkaram, Amin Elkhawad, Andrew V Elkins, Julie Ellam, Nikki Ellard, Laura Nicola Ellerton, Amy Elliott, Fiona Elliott, Kerry Elliott, Valmai Elliott, Annie Ellis, Hayley Ellis, Kaytie Ellis, Tak-Yan Ellis, Yvette Ellis, Rahma Elmahdi, Einas Elmahi, Omer Elneima, Mohamed Elokl, Ahmed Elradi, Mohamed Elsaadany, Sally El-Sayeh, Hana El-Sbahi, Tarek Elsefi, Karim El-Shakankery, Sarah Elyoussfi, Jonathan Emberson, John Emberton, Julian Emmanuel, Ingrid 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Fenn, Isabelle Fenner, Ciara Fenton, Melisa Fenton, Cameron Ferguson, Jenny Ferguson, Kathryn Ferguson, Katie Ferguson, Lisa Ferguson, Susan Ferguson, Susie Ferguson, Victoria Ferguson, Denzil Fernandes, Candida Fernandez, Eduardo Fernandez, Sonia Fernandez Lopez, Ahmed Feroz, Pietro Ferranti, Thais Ferrari, Catarina Ferreira-De Almeida, Alexandra Ferrera, Emma Ferriman, Nicholas Fethers, Ben Field, Janet Field, Andra Fielding, Julie Fielding, Sarah Fielding, Asma Fikree, Sarah Ann Filson, Joanne Finch, Laurie Finch, Natalie Fineman, Adam Finn, Joanne Finn, Sofia Fiouni, Jo Fiquet, James Fisher, Neil Fisher, Daniel Fishman, Krystofer Fishwick, Marie Fisk, Jan Flaherty, Michael Flanagan, Charles Flanders, Julie Fleming, Lucy Fleming, Paul Fleming, William Flesher, Alison Fletcher, Lucy Fletcher, Sophie Fletcher, Christopher Flood, Jonathan Flor, Vincent Florence, Sharon Floyd, Adama Fofana, Georgina Fogarty, Linda Folkes, Aiwyne Foo, Andrew Foot, Jayne Foot, Jane Forbes, Kathryn Forcer, Jamie Ford, Jennifer Foreman, Caroline Fornolles, Adam Forrest, Ellie Forsey, Thomas Forshall, Elliot Forster, Julian Forton, Emily Foster, Joseph Foster, Rachel A Foster, Tracy Foster, Angela Foulds, Ian Foulds, Folakemi Fowe, Emily Fowler, Robert Fowler, Stephen Fowler, Caroline Fox, Claire Fox, Heather Fox, Jonathan Fox, Lauren Fox, Natalie Fox, Simon Fox, Sarah-Jane Foxton, Rebecca Frake, Alex Francioni, Olesya Francis, Rebecca Francis, Sarah Francis, Theodora Francis-Bacon, Victoria Francois, Sharon Frayling, Martyn Fredlund, Michael Freeborn, Carol Freeman, Elaine Freeman, Hannah Freeman, Nicola Freeman, Clare Freer, Eleanor French, Anastasia Fries, Matthew Frise, Renate Fromson, Claire Froneman, John Frost, Victoria Frost, Rachel Frowd, Arun Fryatt, Bridget Fuller, Elizabeth Fuller, Tracy Fuller, Duncan Fullerton, Sarah Funnell, John Furness, Hassina Furreed, Waqas Gaba, Elizabeth Gabbitas, Claire Gabriel, Joshua Gahir, Katarzyna Gajewska-Knapik, Christopher Gale, Hugo Gale, Swetha Gali, Bernadette Gallagher, Edith Gallagher, Jude Gallagher, William Gallagher, Catherine Galloway, Emma Galloway, Jacqui Galloway, James Galloway, Laura Gamble, Liz Gamble, Brian Gammon, Jaikumar Ganapathi, Ramesh Ganapathy, Kaminiben Gandhi, Sarah Gandhi, Usha Ganesh, Abrar Gani, Iris Garcia Deniz, Antoni D Gardener, Danielle Gardiner, Emma Gardiner, Kirsty Gardiner, Siobhan Gardiner, Caroline Gardiner-Hill, Jonathan Gardner, Mark Garfield, Atul Garg, Nathan Garlick, Lucie Garner, Zoe Garner, Rosaline Garr, Mark Garton, Florence Garty, Rachel Gascoyne, Hyeriju Gashau, Aoife Gatenby, Erin Gaughan, Alok Gaurav, Mariana Gavrila, Jane Gaylard, Emma Gaywood, Catherine Geddie, Sarah Gee, Gemma Genato, Neil Gent, Susan Gent, Natalie Geoghegan, Nithin George, Sam George, Tina George, Simon Georges, Domonique Georgiou, Leigh Gerdes, Louise Germain, Helen Gerrish, Abel Getachew, Hisham Ghanayem, Auns Ghazanfar, Anca Gherman, Alison Ghosh, Arjun Ghosh, Justin Ghosh, Sudhamay Ghosh, Sarra 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Julia Greig, Rebecca Grenfell, Teena Grenier, Susan Grevatt, Glaxy Grey, Andrew Gribbin, Ben Griffin, Denise Griffin, Mel Griffin, Sian Griffith, Andrew Griffiths, Daniel Griffiths, David Griffiths, Donna Griffiths, Isabel Griffiths, Nicola Griffiths, Oliver Griffiths, Sofia Grigoriadou, Steph Grigsby, Russell Gritton, Evelina Grobovaite, Clarissa Grondin, Rachel Groome, Liliana Grosu, Jenny Grounds, Jayne Groves, Neil Grubb, Julie Grundy, Francesca Guarino, Sharada Gudur, Shivang Gulati, Vikas Gulia, Pumali Gunasekera, Kirun Gunganah, Jessica Gunn, Emma Gunter, Alok Gupta, Atul Gupta, Rajeev Gupta, Richa Gupta, Tarun Gupta, Vineet Gupta, Ankur Gupta-Wright, Sambasivarao Gurram, Ishy Gurung, Shraddha Gurung, Hazel Guth, Ruth Habibi, Pamela Hackney, Christian Hacon, Aiman Haddad, Denise Hadfield, Michalis Hadjiandreou, Anna Haestier, Nauman Hafiz, Rana Hafiz-Ur-Rehman, Samantha Hagan, Jack W Hague, Rosemary Hague, Andrew Haigh, Kate Haigh, Christina Haines, Scott Hainey, Morton Hair, Brigid Hairsine, Juraj Hajnik, Anne Haldeos, Carmel Halevy, William Halford, Alistair Hall, Anthony Hall, Chloe Hall, Claire Hall, Emily Hall, Helen Hall, Jennifer Hall, Kathryn Hall, Toni Hall, Jan Hallas, Kyle Hallas, Charles Hallett, Heather Halls, Maryam Hamdollah-Zadeh, Bilal Hameed, Imran Hamid, Mohamad Hamie, Bethany Hamilton, Fergus Hamilton, Leigh Hamilton, Ruth Hamlin, Eleanor Hamlyn, Shirley Hammersley, Kate Hammerton, Bev Hammond, Leah Hammond, Rachel Hammond-Hall, Fiona Hammonds, Nidal Hammoud, Ibrahim Hamoodi, Karen Hampshire, Jude Hampson, Shi Han Lee, Ozan Hanci, James Hand, Soran Handrean, Georgina Hands, Sheharyar Hanif, Amy Hannington, Merhej Hannun, Aidan Hanrath, Jane Hanson, Kathryn Hanson, Mazhar U Haq, Ala Haqiqi, Monjurul Haque, Zoe Harding, Simon Hardman, Kumar Haresh, Rachel Harford, Beverley Hargadon, Carolyn Hargreaves, James Hargreaves, Alice Harin, Mohammed Haris, Helen Harizaj, Edward Harlock, Paula Harman, Tracy Harman, Mark Harmer, Muhammad A Haroon, Charlie H Harper, Heather Harper, Peter Harper, Rosemary Harper, Sarah Harrhy, Sian Harrington, Yasmin Harrington-Davies, Claire Harris, Jade Harris, Julie Harris, Laura Harris, Marie-Clare Harris, Nichola Harris, David Harrison, Laura Harrison, Melanie Harrison, Rowan Harrison, Susie Harrison, Tom Harrison, Wendy Harrison, Elizabeth Harrod, Ciaran Hart, Dominic Hart, Rosemary Hartley, Ruth Hartley, Tom Hartley, William Hartrey, Hans Hartung, Alice Harvey, Angela Harvey, Max Harvey, Catherine Harwood, Helen Harwood, Neda Hasan, Brigitte Haselden, Mohammed Hashimm, Imranullah Hashmi, Zena Haslam, Abdulhakim Hassan, Adil Hassan, Ali Hassan, Waqar Ul Hassan, Philip Hassell, Alex Hastings, Bethany Hastings, Jonathan Hatton, Jennifer Haugh, May Havinden-Williams, Stefan Havlik, Dan Hawcutt, Liz Hawes, Nicola Hawes, Annie Hawkins, Nancy Hawkins, Daniel Hawley, Edward Haworth, Cathy Hay, Jamal Hayat, Anne Hayes, Melony Hayes, Fiona Hayes, Antara Hayman, Melanie Hayman, Matthew Haynes, Richard Haynes, Rachel Hayre, Patrick Haywood, Tracy Hazelton, Phoebe Hazenberg, Zhengmai He, Elizabeth Headon, Carrie Heal, Brendan Healy, Amy Hearn, Angela Heath, Rowan Heath, Diane Heaton, Kerry Hebbron, Neil Hedger, Katrine Hedges, Cheryl Heeley, Elaine Heeney, Rajdeep Heire, David Helm, Ulla Hemmila, Scott Hemphill, Deborah Hemsley, Alistair Henderson, Jennifer Henderson, Steven Henderson, Joanne Henry, Karol Henry, Lavinia Henry, Margo Henry, David Henshall, Gillian Herdman, Rosaleen Herdmangrant, William Herrington, Emilia Heselden, Peta Heslop, Simon Hester, Emily Hetherington, Joseph Hetherington, Andrew Hetreed, Chamila Hettiarachchi, Gihan Hettiarachchi, Hayley Hewer, John Hewertson, Anna Hewetson, Sue Hewins, Claire Hewitt, Davina Hewitt, Richard Hewitt, Robert S Heyderman, Matthis Heydtmann, Joseph Heys, Jonathan Heywood, Meg Hibbert, Naomi Hickey, Alexander Hicks, Jenny Hicks, Scott R Hicks, Daniel Higbee, Jennifer Higgins, Lucy Higgins, Andrew Higham, Martin Highcock, Judith 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Nicola Hornby, Sophie Horrocks, Latoya Horsford, Megan Horsford, Valana Horsham, Alex Horsley, Ashley Horsley, Elizabeth Horsley, Sarah Horton, Jane Hosea, Toby Hoskins, Ejaz Hossain, Muhammad S Hossain, Rashed Hossain, Maxine Hough, Sarah Hough, Kathryn Houghton, Rebecca Houlihan, Gordon Houston, Hamish Houston, Eleanor Hoverd, Roseanna Hovvels, Lee How, Laura Howaniec, Laura Howard, Linda Howard, Lucy Howard, Sarah Howard, Richard Howard-Griffin, Serena Howe, Mark Howells, Lyn Howie, Alex Howlett, Sophie Howlett, Josh Hrycaiczuk, Desmond Hsu, Hein Htet, Zaw Htet, Naing Z Htoon, Su Htwe, Ying Hu, Abby Huckle, Shahzya Huda, Alison Hudak, Lisa Hudig, Heather Hudson, Alison Hufton, Conor Huggins, Alistair Hughes, Emma Hughes, Gareth Hughes, Heather Hughes, Luke Hughes, Rachel Hughes, Rhian Hughes, Samantha Hughes, Stephen Hughes, Vikki Hughes, Wesley Hughes, Lukas Huhn, Ching Hui, Ruth Hulbert, Diana Hull, Robert Hull, Amanda Hulme, Peter Hulme, Wendy Hulse, George Hulston, Ryan Hum, Charlotte Humphrey, Alasdair Humphries, Joanne Humphries, David Hunt, Fiona Hunt, Jane Hunt, Kristen Hunt, Luke Hunt, Karl Hunter, Neil Hunter, Elizabeth Hurditch, Cian Hurley, Katrina Hurley, Mohammed A Husain, Syeda Y Husaini, Coralie Huson, Ibraar Hussain, Mohammad Hussain, Muhammad Hussain, Reda Hussain, Sajid Hussain, Samia Hussain, Sanniah Hussain, Yasmin Hussain, Mohammed Hussam El-Din, Rebecca Hussey, Christopher Hutchcroft, Camille Hutchinson, Dorothy Hutchinson, Elizabeth Hutchinson, John Hutchinson, Claire Hutsby, Paula Hutton, Daniella Hydes, Jamie Hyde-Wyatt, Niamh Hynes, Megan Hyslop, Ahmed Ibrahim, Asil Ibrahim, Kamal Ibrahim, Mohamed Ibrahim, Wadah Ibrahim, Muhammad Idrees, Hina Iftikhar, Chukwuemeka Igwe, Mohammad Ijaz, Amaju Ikomi, Clare Iles, Stamatina Iliodromiti, Lorna Ilves, La'ali Imam-Gutierrez, Christopher Imray, Haider Imtiaz, Jack Ingham, Julie Ingham, Rory Ingham, Tejas Ingle, Anne Ingram, Luke Ingram, Peter Inns, Ken Inweregbu, Andreea A Ionescu, Ana 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Sabrina Jansz, Deepa Japp, Catherine Jardine, Ellie Jarvie, Rosina Jarvis, Patrycja Jastrzebska, Hafsa Javed, Lona Jawaheer, Dinakaran Jayachandran, Deepak Jayaram, Geeshath Jayasekera, Lalith Jayasekera, Saman Jeddi, Mohammad S Jeelani, Katie Jeffery, Rachel Jeffrey, Nathan Jeffreys, Benjamin Jeffs, Debbie Jegede, Taylor Jemima, Ifan Jenkin, Alison Jenkins, David Jenkins, Elinor Jenkins, Sarah Jenkins, Sian Jenkins, Stephen Jenkins, Edward Jenner, David Jennings, Jacqui Jennings, Louise Jennings, Virginia Jennings, Ellen Jerome, Douglas Jerry, Ellen Jessup-Dunton, Jorge A Jesus Silva, Kishan Jethwa, Abi Jeyabalan, Akhilesh Jha, Shaman Jhanji, Khoo Jian, Zhixin Jiao, Ana Jimenez Gil, Jithin Jith, Teishel Joefield, Navraj Johal, Karine Johannessen, Aisyah Johari, Annie John, Anu John, Emma Johns, Margaret Johns, Antoinette Johnson, Gillian Johnson, Kathryn Johnson, Luke Johnson, Mark Johnson, Claire Johnston, Janet Johnston, Susan Johnston, Victoria Johnston, Dawn Johnstone, Ed 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Muhammad U Khalid, Amir Khalil, Asma Khalil, Sijjad Khalil, Ali Khan, Al-Imran Khan, Asad Khan, Burhan Khan, Fatimah Khan, Kausik Khan, Lubna Khan, Malik A Khan, Marria Khan, Mohammad Khan, Mohammed R Khan, Nayeem Khan, Omar Khan, Rahila Khan, Shabana Khan, Shahul Khan, Tasaduksultan Khan, Waseem Khan, Usman F Khatana, Jibran Khatri, Jyoti Khatri, Sagira Khatun, Taslima Khatun, Chuen R Khaw, Htet HE Khin, Kiran Khokhar, Najaf Khota, Chloe Khurana, Shruti Khurana, Faith Kibutu, Andrew Kidd, Michelle Kidd, Joe Kidney, Shane Kidney, Will Kieffer, Caroline Kilby, Eliz Kilich, Jee Whang Kim, Sarah Kimber, Andy King, Barbara King, Jennifer King, Kirsten King, Rachel King, Sam King, Victoria King, Emily King-Oakley, Laura Kingsmore, Fiona Kinney, Jeremy Kirk, Amy Kirkby, Emily Kirkham, Gemma Kirkman, Ursula Kirwan, Toby Kitching, Laura Kitto, Lauren Kittridge, Sarah Klaczek, Susan Kmachia, Christopher Knapp, Lucy Knibbs, Alicia Knight, Fraser Knight, Marian Knight, Sarah Knight, Steven Knight, Tom Knight, Ellen Knights, Martin Knolle, Carol Knott, Karen Knowles, Laurence Knowles, Emily Knox, Lucy Knox, Oliver Koch, Ronan Kodituwakku, Gouri Koduri, Eirene Kolakaluri, Magdalena Kolodziej, Eirini Kolokouri, Samantha Kon, Mari Kononen, Athanasios Konstantinidis, Imogen Koopmans, Laura Korcierz, James Korolewicz, George Koshy, Chris Kosmidis, Jalpa Kotecha, Easwari Kothandaraman, Rukhsana Kousar, Margarita Kousteni, Alex Kozak Eskenazia, Kestutis Krasauskas, Zuzana Krejcarova, Raghu Krishnamurthy, Manju Krishnan, Suzanne Krizak, Sean Krupej, Agnieszka Kubisz-Pudelko, Soren Kudsk-Iversen, Aurimas Kudzinskas, Chirag Kukadiya, Nainesha Kulkarni, Aditi Kumar, Ramesh Kumar, Ravi Kumar, Rita Kumar, Ritesh Kumar, Rupa Kumar, Satish Kumar, Vimal Kumar, Arun Kundu, Heinke Kunst, Amit Kurani, Mohammed Kurdy, Vimal Kurmars, Cameron Kuronen-Stewart, Ranganai S Kusangaya, Vlad Kushakovsky, Apexa Kuverji, Adriel JW Kwek, Amma Kyei-Mensah, Thyra Kyere-Diabour, Lynsey Kyeremeh, Moe Kyi, Nyan M Kyi, Laura Kyle, Stuart Kyle, Karali-Tsilimpari Kyriaki, Julius Labao, Louise Lacey, Nikki Lack, Emma Ladlow, Heather Lafferty, Shondipon Laha, Sushil Lahane, Clement Lai, James Lai, Robert Laing, Inez Laing-Faiers, Emily Laity, Nicki Lakeman, David Lalloo, Fiona Lalloo, Sarah-Jane Lam, Fiona Lamb, Thomas Lamb, Pauline Lambert, Claudia Lameirinhas, Mohammed KG Lami, Michal Lamparski, Christine Lanaghan, Geraldine Landers, Martin J Landray, Matthew Lane, Nicholas Lane, Matilda Lang, Stephen Lang, Daniel Langer, Maggie Langley, Charles Langoya, Emily Langthorne, Helen Langton, Scott Latham, John Latham-Mollart, Afzal Latheef, Nang Latt, Dawn Lau, Eva Lau, Myra Laurenson, Hou Law, Jessica Law, Penny Law, Richard Law, Emma Lawrence, Ryan Lawrie, Michael Lay, Stephen Laybourne, Christine Laycock, Reina Layug, Maria Lazo, Amelia Lea, William Lea, Ian Leadbitter, Samuel Leafe, Thomas Leahy, Richard Lean, Lorna Leandro, Darren Leaning, Todd Leckie, Marie Anne Ledingham, Emma Lee, Hannah Lee, Irish Lee, Sam Lee, Sindy Lee, Stephanie Lee, Tracey Lee, Xiang Lee, Diana Lees, Helen Legge, Julian Leggett, Katie Leigh-Ellis, Nicky Leitch, Eleni Lekoudis, Nicholas Lemoine, Liz Lennon, Daniel Lenton, Kelly Leonard, Wen Leong, Nicky Leopold, Isla Leslie, Emma Levell, Chris Levett, Alice Lewin, Alison Lewis, David Lewis, Dee Lewis, Joanne Lewis, Joseph Lewis, Kathryn Lewis, Keir Lewis, Leon Lewis, Marie Lewis, Marissa Lewis, Megan Lewis, Rob Lewis, Catherine Lewis-Clarke, Katherine Lewiston, Adam Lewszuk, Penny Lewthwaite, Samantha Ley, Anastasia Liaretidou, Victoria Licence, David Lieberman, Susan Liebeschuetz, Patrick Lillie, Ben Lim, Carys Lim, Ee T Lim, Ivy Lim, Terence Lim, Wei Shen Lim, Wilson Lim, James Limb, Usha Limbu, Dermot Linden, Lotte Lindenbaum, Gabriella Lindergard, Kate Lindley, Emily Lindsay, Mirella Ling, Claire Lingam, Mike Linney, Louise Linsell, Karen Lipscomb, Laura Lipskis, Ana Lisboa, Evangeline Lister, Sam Little, Xuedi Liu, Daniel K Llanera, Martin Llewelyn, Adam Lloyd, Aimee Lloyd, Arwel Lloyd, Charlotte Lloyd, Oliver Lloyd, Richard Lloyd, Lydianne Lock, Sara Lock, Stephen Lock, Jacqueline Locke, Thomas Locke, Teresa Lockett, Gary Lockley-Ault, Heather Loftus, Meg Logan, Chloe Logue, Sook Yin Loh, Siddharth Lokanathan, Tuck-Kay Loke, John-Paul Lomas, Kaatje Lomme, Emily London, Charlotte Long, Gabriella Long, Natalie Long, Bev Longhurst, Jennifer Lonnen, Laura Looby, Ronda Loosley, Pada Lopez, Paula Lopez, Robert W Lord, Claire Lorimer, Francesco Loro, Rachel Lorusso, Robert Loveless, Maxine Lovell, Angeliki Loverdou, Andrew Low, Jen Mae Low, Alastair Lowe, Catherine Lowe, Emily Lowe, Faye Lowe, Michael Lowe, Richard Lowsby, Alexandra Lubina Solomon, Georgia Lucas, Alice Lucey, Suzanne Luck, Jane Luke, Muriel Lunn, Ji Luo, Cindy N Luximon, Barrie Lyell, Ceri Lynch, Daniel Lynch, Daniella Lynch, Stephen Lynch, Claire Ma, Louise Ma, Hannah Mabb, Louies Andrew Mabelin, Jessica Macaro, Kateryna Macconaill, Jill MacCormac, Chloe MacDonald, Sheila MacFadyen, James G MacFarlane, Jill Macfarlane, Laura Macfarlane, Lisa MacInnes, Jill MacIntyre, Kirsten Mack, Callum Mackay, Euan Mackay, Alexander Mackenzie, Matt Mackenzie, Robert MacKenzie Ross, Ami Mackey, Fiona Mackie, Robert Mackie, Carolyn Mackinlay, Claire Mackintosh, Katherine Mackintosh, Colin MacLeod, Mary J MacLeod, Michael Macmahon, Andrew MacNair, Catherine Macphee, Iain Macpherson, Allan MacRaild, Alannah Madden, Mary Madden, Norman Madeja, Paula Madgwick, Madhavi Madhusudhana, Alpha Madu, Lorraine Madziva, Marion Mafham, Emma Magavern, Negar Maghsoodi, Christopher Magier, Marios Magriplis, Natasha Mahabir, Subramanian Mahadevan-Bava, Anjanie Maharajh, Ajit Mahaveer, Bal Mahay, Hibo Mahdi, Thushika Mahendiran, Siva Mahendran, Sarah Maher, Shameera Maheswaran, Parisa Mahjoob-Afag, Ahmed Mahmood, Farhana Mahmood, Hager Mahmoud, Mian Mahmood, Waheed Mahmood, Ewan Mahony, Luke Mair, James Maitland, Rupert Major, Jaydip Majumdar, Mohammad KH Majumder, Stephen Makin, Marius Malanca, Hannah Malcolm, Neeraj Malhan, Gulshan Malik, Mohammed Maljk, Petrina Mallinder, Louise Mallon, Edward Malone, Gracie Maloney, Madhu Mamman, Irene Man, Marco Mancuso-Marcello, Aritri Mandal, Tracy Manders, Lauren Manderson, Justin Mandeville, Roope Manhas, Carmen Maniero, Bobby Mann, Baranitharan Manoharan, Katherine Mansi, Dina Mansour, Isheunesu T Mapfunde, Predeesh Mappa, Hemant Maraj, Gemma Marayan, Clare Marchand, Neil Marcus, Maria Marecka, Gomathi Margabanthu, Jordi Margalef, Lavinia Margarit, Georgios Margaritopoulos, Mike Margarson, Fernandez M Maria del Rocio, Victor Mariano, Ashleigh Maric, Arran Marriott, Nemonie Marriott, Karen Marsden, Paul Marsden, Tracy Marsden, Robyn Marsh, Adam Marshall, Andrew Marshall, Gail Marshall, Henry Marshall, Jaimie Marshall, Jenna Marshall, Nicola Marshall, Emmeline Martin, Hayley Martin, Hope Martin, Jane Martin, Karen Martin, Laila Martin, Michael Martin, Sarah Martin, Winston Martin, Tim Martindale, Marcus Martineau, Anthony Martinelli, Lauren Martinez, Jose Carlos Martinez Garrido, Vijay K Maruthamuthu, Roman Mary-Genetu, Sam Maryosh, Vidan Masani, Diego Maseda, Sheila Mashate, Yasaman Mashhoudi, Sanna Masih, Nick Maskell, Perry Maskell, Jon Maskill, Matthew Masoli, Richard Mason, Ruth Mason, Mohammad Masood, Mohammad T Masood, Syed Masood, Syed SME Masood, Lear Matapure, Cristina Matei, Manraj Matharu, Stephy Mathen, Nicole Mather, Jonathan Mathers, Joanna Matheson, Anna Mathew, Verghese Mathew, Jesha Mathews, Kate Mathias, Wadzanai Matimba-Mupaya, Nashaba Matin, Elina Matisa, Max Matonhodze, Elijah Matovu, Szeto Matthew, Alison Jane Matthews, Edgar Maureen, Maria-Emanuela Maxan, Adam Maxwell, Veronica Maxwell, James May, Joanne May, Peter May, Philippa May, Matthew Maycock, Shelley Mayor, Paul McAlinden, Audrey McAlpine, Graeme McAlpine, Jonathan McAndrew, Hamish McAuley, Sarah McAuliffe, James McBurney, Amanda McCairn, Jake McCammon, Conor McCann, Alexandra McCarrick, Brendan 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Xia, Masseh Yakubi, May Yan, Michael Yanney, Salima Yasmin, Bryan Yates, David Yates, Edward Yates, Helen Yates, Mark Yates, Charlotte Yearwood Martin, Khin Yein, Robert Yellon, Fiona Yelnoorkar, Peter Yew, Kawai Yip, Laura Ylquimiche Melly, Inez Ynter, Cissy Yong, Jemma Yorke, Abdel Younes Ibrahim, Gail Young, Louise Young, Sajeda Youssouf, Ahmed Yousuf, Chrissie Yu, Bernard Yung, Daniel Yusef, Anna-Sophia Zafar, Silvia Zagalo, Su Zaher, Kareem Zaki, Nabhan Zakir, Kasia Zalewska, Ane Zamalloa, Mohsin Zaman, Shakir Zaman, Julie Zamikula, Louise Zammit, Marie Zammit-Mangion, Ausra Zdanaviciene, Esther Zebracki, Daniel Zehnder, Lisa Zeidan, Xiaobei Zhao, Dongling Zheng, Jane Zhixin, Doreen Zhu, Madiha Zia, Omar Zibdeh, Rabia Zill-E-Huma, Ei T Zin, Vivian Zinyemba, Christos Zipitis, Arkadiusz Zmierczak, Azam Zubir, Naz Zuhra, Rasha Zulaikha, Carol Zullo, Ana Zuriaga-Alvaro, National Institute for Health Research, UK Research and Innovation, University of St Andrews. School of Medicine, Horby, PW, Roddick, A, Spata, E, Staplin, N, Emberson, JR, Pessoa-Amorim, G, Peto, L, Day, J, Thwaites, G, Mafham, M, Haynes, R, and Landray, MJ
Subjects: Male, medicine.medical_treatment, 030204 cardiovascular system & hematology, Azithromycin, ResearchInstitutes_Networks_Beacons/humanitarian_conflict_response_institute, Rate ratio, chemistry.chemical_compound, 0302 clinical medicine, RA0421, Oxygen therapy, RA0421 Public health. Hygiene. Preventive Medicine, 030212 general & internal medicine, Hospital Mortality, 11 Medical and Health Sciences, azithromycin, education.field_of_study, Covid19, clinical trial, General Medicine, 3rd-DAS, Middle Aged, Hospitalization, Survival Rate, Treatment Outcome, Humanitarian and Conflict Response Institute, Female, Life Sciences & Biomedicine, medicine.medical_specialty, RM, Population, COVID-19/drug therapy, Azithromycin/therapeutic use, 03 medical and health sciences, Pharmacotherapy, Tocilizumab, Medicine, General & Internal, SDG 3 - Good Health and Well-being, Internal medicine, General & Internal Medicine, medicine, Humans, education, Survival rate, Mechanical ventilation, Science & Technology, business.industry, COVID-19, NIS, Length of Stay, R1, United Kingdom, COVID-19 Drug Treatment, RM Therapeutics. Pharmacology, RECOVERY Collaborative Group, chemistry, Relative risk, business, RA, Anaesthesia Pain and Critical Care
Abstract: The RECOVERY trial is supported by a grant to the University of Oxford from UK Research and Innovation (Medical Research Council) and NIHR (MC_PC_19056) and by core funding provided by NIHR Oxford Biomedical Research Centre, Wellcome, the Bill & Melinda Gates Foundation, the Department for International Development, Health Data Research UK, the Medical Research Council Population Health Research Unit, the NIHR Health Protection Unit in Emerging and Zoonotic Infections, and NIHR Clinical Trials Unit Support Funding. TJ is supported by a grant from UK Medical Research Council (MC_UU_0002/14) and an NIHR Senior Research Fellowship (NIHR-SRF-2015-08-001). WSL is supported by core funding provided by NIHR Nottingham Biomedical Research Centre. Background: Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatory actions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19. Methods: In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospital with COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients were randomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once per day by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatment groups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment and were twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants and local study staff were not masked to the allocated treatment, but all others involved in the trial were masked to the outcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) were eligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was 65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomly allocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall, 561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days (rate ratio 0·97, 95% CI 0·87-1·07; p=0·50). No significant difference was seen in duration of hospital stay (median 10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days (rate ratio 1·04, 95% CI 0·98-1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, no significant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilation or death (risk ratio 0·95, 95% CI 0·87-1·03; p=0·24). Interpretation: In patients admitted to hospital with COVID-19, azithromycin did not improve survival or other prespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restricted to patients in whom there is a clear antimicrobial indication. Publisher PDF
Published: 2021
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44. Targeted Conservative Cointegrate Formation Mediated by IS 26 Family Members Requires Sequence Identity at the Reacting End

Author: Christopher J. Harmer and Ruth M. Hall
Subjects: insertion sequence, cointegrate, IS26, Cointegrate, Inverted repeat, transposase, Biology, Microbiology, DNA sequencing, 03 medical and health sciences, chemistry.chemical_compound, Escherichia coli, Holliday junction, strand transfer, Insertion sequence, Molecular Biology, Gene, Transposase, 030304 developmental biology, Genetics, 0303 health sciences, Base Sequence, Applied and Environmental Science, 030306 microbiology, mobile genetic element, QR1-502, chemistry, DNA Transposable Elements, DNA, Research Article
Abstract: The IS26 family includes the ISs that are commonly found associated with antibiotic resistance genes in multiply resistant Gram-negative and Gram-positive bacteria. IS26 is most prevalent in Gram-negative species and can generate the clusters of antibiotic resistance genes interspersed with directly oriented IS26 seen in multiply resistant pathogens., IS26 forms cointegrates using two distinct routes, a copy-in mechanism involving one insertion sequence (IS) and a target and a targeted conservative mechanism involving two ISs in different DNA molecules. In this study, the ability of IS26 and some close relatives, IS1006, IS1008, and a natural hybrid, IS1006/IS1008, which are found predominantly in Acinetobacter spp., to interact was examined. IS1006/1008 consists of 175 bp from IS1006 at the left end, with the remainder from IS1008. These ISs all have the same 14-bp terminal inverted repeats, and the Tnp26, Tnp1006, and Tnp1008 transposases, with pairwise identities of 83.7% to 93.1%, should be able to recognize each other’s ends. In a recA-negative Escherichia coli strain, IS1006, IS1008, and IS1006/1008 each formed cointegrates via the copy-in route and via the targeted conservative route, albeit at frequencies for the targeted reaction at least 10-fold lower than for IS26. However, using mixed pairs, targeted cointegration was detected only when IS1008 was paired with the IS1006/1008 hybrid, which also encodes Tnp1008, and the targeted cointegrates formed all arose from a reaction occurring at the end where the DNA sequences are identical. The reaction also occurred at the end with extended DNA identity using IS26 paired with IS26::catA1, an artificially constructed IS26 derivative that includes the catA1 gene. Thus, both identical transposases and identical DNA sequences at the reacting end were required. These features indicate that the targeted conservative pathway proceeds via a single transposase-catalyzed strand transfer, followed by migration and resolution of the Holliday junction formed. IMPORTANCE The IS26 family includes the ISs that are commonly found associated with antibiotic resistance genes in multiply resistant Gram-negative and Gram-positive bacteria. IS26 is most prevalent in Gram-negative species and can generate the clusters of antibiotic resistance genes interspersed with directly oriented IS26 seen in multiply resistant pathogens. This ability relies on the novel dual mechanistic capabilities of IS26 family members. However, the mechanism underlying the recently discovered targeted conservative mode of cointegrate formation mediated by IS26, IS257/IS431, and IS1216, which is unlike any previously studied IS movement mechanism, is not well understood. An important question is what features of the IS and the transposase are key to allowing IS26 family members to undertake targeted conservative reaction. In this study, this question was addressed using mixed-partner crosses involving IS26 and naturally occurring close relatives of IS26 that are found near resistance genes in Acinetobacter baumannii and are widespread in Acinetobacter species.
Published: 2021
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45. Lithium modulates striatal reward anticipation and prediction error coding in healthy volunteers

Author: Phil J. Cowen, Catherine J. Harmer, Lennart Verhagen, A. Pringle, Michael Browning, and Inge Volman
Subjects: Male, Mean squared prediction error, Striatum, Lithium, Nucleus accumbens, Placebo, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Double-Blind Method, Reward, medicine, Humans, Bipolar disorder, Pharmacology, Motivation, Action, intention, and motor control, Lithium carbonate, Reproducibility of Results, Anticipation, Psychological, medicine.disease, Magnetic Resonance Imaging, Healthy Volunteers, 030227 psychiatry, Psychiatry and Mental health, Mood, chemistry, Psychology, Neuroscience, 030217 neurology & neurosurgery, psychological phenomena and processes, Coding (social sciences)
Abstract: Contains fulltext : 226107.pdf (Publisher’s version ) (Closed access) Lithium is one of the most effective mood-stabilizing medications in bipolar disorder. This study was designed to test whether lithium administration may stabilize mood via effects on reward processing. It was hypothesized that lithium administration would modulate reward processing in the striatum and affect both anticipation and outcome computations. Thirty-seven healthy human participants (18 males, 33 with suitable fMRI data) received 11 (±1) days of lithium carbonate or placebo intervention (double-blind), after which they completed the monetary incentive delay task while fMRI data were collected. The monetary incentive delay task is a robust task with excellent test-retest reliability and is well suited to investigate different phases of reward processing within the caudate and nucleus accumbens. To test for correlations with prediction error signals a Rescorla–Wagner reinforcement-learning model was applied. Lithium administration enhanced activity in the caudate during reward anticipation compared to placebo. In contrast, lithium administration reduced caudate and nucleus accumbens activity during reward outcome. This latter effect seems related to learning as reward prediction errors showed a positive correlation with caudate and nucleus accumbens activity during placebo, which was absent after lithium administration. Lithium differentially modulates the anticipation relative to the learning of rewards. This suggests that lithium might reverse dampened reward anticipation while reducing overactive reward updating in patients with bipolar disorder. This specific effect of lithium suggests that a targeted modulation of reward learning may be a viable approach for novel interventions in bipolar disorder. 8 p.
Published: 2021

46. Preparation and synthetic applications of aryl tetraflates (ArOS[O.sub.2]C[F.sub.2]C[F.sub.2]H)

Author: Rostovtsev, Vsevolod V., Bryman, Lois M., Junk, Christopher P., Harmer, Mark A., and Carcani, Liane G.
Subjects: Catalysis -- Research, Biological sciences, Chemistry
Abstract: The preparation of aryl esters of 1,1,2,2-tetrafluoroethanesulfonic acid (aryl tetraflates) that could be used in a number of palladium-catalyzed coupling reactions is described.
Published: 2008

47. TOAC spin-labeled peptides tailored for DNP-NMR studies in lipid membrane environments

Author: Frances Separovic, Shiying Zhu, Marc-Antoine Sani, Louise J. Brown, Ehsan Kachooei, and Jeffrey Harmer
Subjects: Circular dichroism, Antimicrobial peptides, Biophysics, Phospholipid, Peptide, 010402 general chemistry, 01 natural sciences, Micelle, law.invention, Cyclic N-Oxides, 03 medical and health sciences, chemistry.chemical_compound, law, Electron paramagnetic resonance, Lipid bilayer, Phospholipids, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Spin–lattice relaxation, Articles, 0104 chemical sciences, chemistry, Spin Labels, Peptides
Abstract: The benefit of combining in-cell solid-state dynamic nuclear polarization (DNP) NMR and cryogenic temperatures is providing sufficient signal/noise and preservation of bacterial integrity via cryoprotection to enable in situ biophysical studies of antimicrobial peptides. The radical source required for DNP was delivered into cells by adding a nitroxide-tagged peptide based on the antimicrobial peptide maculatin 1.1 (Mac1). In this study, the structure, localization, and signal enhancement properties of a single (T-MacW) and double (T-T-MacW) TOAC (2,2,6,6-tetramethylpiperidine-N-oxyl-4-amino-4-carboxylic acid) spin-labeled Mac1 analogs were determined within micelles or lipid vesicles. The solution NMR and circular dichroism results showed that the spin-labeled peptides adopted helical structures in contact with micelles. The peptides behaved as an isolated radical source in the presence of multilamellar vesicles, and the electron paramagnetic resonance (EPR) electron-electron distance for the doubly spin-labeled peptide was ∼1 nm. The strongest paramagnetic relaxation enhancement (PRE) was observed for the lipid NMR signals near the glycerol-carbonyl backbone and was stronger for the doubly spin-labeled peptide. Molecular dynamics simulation of the T-T-MacW radical source in phospholipid bilayers supported the EPR and PRE observations while providing further structural insights. Overall, the T-T-MacW peptide achieved better (13)C and (15)N signal NMR enhancements and (1)H spin-lattice T(1) relaxation than T-MacW.
Published: 2020

48. Synthesis and Properties of Perylene-Bridge-Anchor Chromophoric Compounds

Author: Elena Galoppini, Samantha Doble, Joseph P. Avenoso, Ryan Harmer, Katherine Lloyd, Hao Fan, Han Yan, Lars Gundlach, and Luis G. C. Rego
Subjects: 010304 chemical physics, Chromophore, 010402 general chemistry, 01 natural sciences, Borylation, 0104 chemical sciences, chemistry.chemical_compound, chemistry, Atomic orbital, Computational chemistry, 0103 physical sciences, Charge carrier, Density functional theory, Physical and Theoretical Chemistry, HOMO/LUMO, Linker, Perylene
Abstract: The quest to control chromophore/semiconductor properties to enable new technologies in energy and information science requires detailed understanding of charge carrier dynamics at the atomistic level, which can often be attained through the use of model systems. Perylene-bridge-anchor compounds are successful models for studying fundamental charge transfer processes on TiO2, which remains among the most commonly investigated and technologically important interfaces, mostly because of perylene's advantageous electronic and optical properties. Nonetheless, the ability to fully exploit synthetically the substitution pattern of perylene with linker (= bridge-anchor) units remains little explored. Here we developed 2,5-di-tert-butylperylene (DtBuPe)-bridge-anchor compounds with t-Bu group substituents to prevent π-stacking and one or two linker units in both the peri and ortho positions, by employing a combination of Friedel-Crafts alkylations, bromination, iridium-catalyzed borylation, and palladium-catalyzed cross-coupling reactions. Photophysical characterization and computational analysis by density functional theory (DFT) and time-dependent DFT (TD-DFT) were carried out on four DtBuPe acrylic acid derivatives with a single or a double linker in peri (12b), ortho (15b), peri,peri (18b), and ortho,ortho (21b). The energies of the unoccupied orbitals {LUMO, LUMO + 1, LUMO + 2} are strongly affected by the presence of a π-conjugated linker, resulting in a stabilization of these states and a red shift of their absorption and emission spectra, as well as the loss of vibronic structure in the spectrum of the peri,peri compound, consistent with the strong bonding character of this substitution pattern.
Published: 2020

49. Automated segmentation and analysis of retinal microglia within ImageJ

Author: Lindsey Harmer, Neil F. Ash, Alfred S. Lewin, Ahmed Jafri, and Michael T. Massengill
Subjects: 0301 basic medicine, Retinal degeneration, Morphological gradient, Light, Image processing, Cell Count, Biology, Retina, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Mice, 0302 clinical medicine, Imaging, Three-Dimensional, medicine, Image Processing, Computer-Assisted, Animals, Segmentation, Mice, Inbred BALB C, Microglia, Retinal Degeneration, Retinal Vessels, Retinal, medicine.disease, Immunohistochemistry, Sensory Systems, Mice, Inbred C57BL, Ophthalmology, Disease Models, Animal, Radiation Injuries, Experimental, 030104 developmental biology, medicine.anatomical_structure, chemistry, Morphological analysis, 030221 ophthalmology & optometry, Neuroscience, Algorithms
Abstract: Microglia are immune cells of the central nervous system capable of distinct phenotypic changes and migration in response to injury. These changes most notably include the retraction of fine dendritic structures and adoption of a globular, phagocytic morphology. Due to their characteristic responses, microglia frequently act as histological indicators of injury progression. While algorithms seeking to automate microglia counts and morphological analysis are becoming increasingly popular, few exist that are adequate for use within the retina and manual analysis remains prevalent. To address this, we propose a novel segmentation routine, implemented within FIJI-ImageJ, to perform automated segmentation and cell counting of retinal microglia. We show that our routine could perform cell counts with accuracy similar to manual observers using the I307N Rho model. Tracking cell position relative to retinal vasculature, we observed population migration towards the photoreceptor layer beginning 12 h post light damage. Using feature selection with Chi2 and principal component analysis, we resolved cells along a morphological gradient, demonstrating that extracted features were sufficiently descriptive to capture subtle morphological changes within cell populations in I307N Rho and Balb/c TLR2−/− retinal degeneration models. Taken together, we introduce a novel automated routine capable of efficient image processing and segmentation. Using data retrieved following segmentation, we perform morphological analysis simultaneously on whole populations of cells, rather than individually. Our algorithm was built entirely with open-source software, for use on retinal microglia.
Published: 2020

50. Serine mutation of a conserved threonine in the hERG K+ channel S6-pore region leads to loss-of-function through trafﬁcking impairment

Author: Yihong Zhang, Jules C. Hancox, Stephen C Harmer, Henggui Zhang, Christopher E. Dempsey, and Ehab Al-Moubarak
Subjects: 0301 basic medicine, congenital, hereditary, and neonatal diseases and abnormalities, IKr, Long QT syndrome, Voltage clamp, Mutant, hERG, Biophysics, medicine.disease_cause, arrhythmia, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, trafficking, medicine, long QT syndrome, Repolarization, cardiovascular diseases, Molecular Biology, rapid delayed rectifier, Mutation, biology, Chemistry, HEK 293 cells, Cell Biology, medicine.disease, Potassium channel, Cell biology, 030104 developmental biology, 030220 oncology & carcinogenesis, biology.protein, LQTS
Abstract: The human Ether-a-go-go Related Gene (hERG) encodes a potassium channel responsible for the cardiac rapid delayed rectifier K+ current, IKr, which regulates ventricular repolarization. Loss-of-function hERG mutations underpin the LQT2 form of congenital long QT syndrome. This study was undertaken to elucidate the functional consequences of a variant of uncertain significance, T634S, located at a highly conserved position at the top of the S6 helix of the hERG channel. Whole-cell patch-clamp recordings were made at 37 °C of hERG current (IhERG) from HEK 293 cells expressing wild-type (WT) hERG, WT+T634S and hERG-T634S alone. When the T634S mutation was expressed alone little or no IhERG could be recorded. Co-expressing WT and hERG-T634S suppressed IhERG tails by ∼57% compared to WT alone, without significant alteration of voltage dependent activation of IhERG. A similar suppression of IhERG was observed under action potential voltage clamp. Comparable reduction of IKr in a ventricular AP model delayed repolarization and led to action potential prolongation. A LI-COR® based On/In-Cell Western assay showed that cell surface expression of hERG channels in HEK 293 cells was markedly reduced by the T634S mutation, whilst total cellular hERG expression was unaffected, demonstrating impaired trafficking of the hERG-T634S mutant. Incubation with E−4031, but not lumacaftor, rescued defective hERG-T634S channel trafficking and IhERG density. In conclusion, these data identify hERG-T634S as a rescuable trafficking defective mutation that reduces IKr sufficiently to delay repolarization and, thereby, potentially produce a LQT2 phenotype.
Published: 2020
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