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5. Novel numerical method for parameterising fretting contacts

Author

Wade, A, Copley, R, Alsheikh Omar, A, Clarke, B, Liskiewicz, T, Bryant, M, Wade, A, Copley, R, Alsheikh Omar, A, Clarke, B, Liskiewicz, T, and Bryant, M

Abstract

Fretting regime transition is traditionally achieved by qualitative assessment of the fretting loops (tangential force, vs tangential displacement ) and material response. Other studies used parameters in which thresholds are theoretically determined to exceed friction at the contact for regime transition identification. This study successfully developed a flexible loop analysis method based on simple vector principles that is able to quantify and characterise its constituent parts. In terms of fretting contact analysis the loop analysis method provided a complementary method of regime transition identification to those based on theoretically overcoming friction at the contact, with strong agreement between the two. This novel method provides an efficient way to correlate regime transition with other data sets, with additional insights into the mechanical response of the contact compared to other regime transition criteria. Possible applications of this method include enabling smart asset monitoring and in the development of engineering components that are subject to fretting. This is an extremely flexible technique that has applicability for other types of loop analysis.

Published
2020

6. Real-time fretting loop regime transition identification using acoustic emissions

Author

Wade, A, Copley, R, Clarke, B, Alsheikh Omar, A, Beadling, AR, Liskiewicz, T, Bryant, MG, Wade, A, Copley, R, Clarke, B, Alsheikh Omar, A, Beadling, AR, Liskiewicz, T, and Bryant, MG

Abstract

© 2020 Elsevier Ltd Acoustic emission (AE) has been successfully used to investigate the damage mechanisms of fretting contacts within different regimes. This study investigated the transition between fretting regimes using the relationship between AE and the mechanical response of a dry, steel-on-steel, ball-on-flat contact under different tangential displacements achieving the partial slip regime, mixed fretting regime and gross slip regime. Increased AE response occurred during gross-slip events and there was strong positive correlation between AE and fretting energy ratio. The relationship was strongest when gross sliding was experienced allowing identification of transition from the partial slip to the gross slip regime. This makes AE a good candidate to detect regime transition in-situ due to ease of integration and its non-destructive nature.

Published
2020

7. NOX1 loss-of-function genetic variants in patients with inflammatory bowel disease

Author

Schwerd, T., Bryant, R. V., Pandey, S., Capitani, M., Meran, L., Cazier, J. -B., Jung, J., Mondal, K., Parkes, M., Mathew, C. G., Fiedler, K., McCarthy, D. J., Sullivan, P. B., Rodrigues, A., Travis, S. P. L., Moore, C., Sambrook, J., Ouwehand, W. H., Roberts, D. J., Danesh, J., Russell, R. K., Wilson, D. C., Kelsen, J. R., Cornall, R., Denson, L. A., Kugathasan, S., Knaus, U. G., Serra, E. G., Anderson, C. A., Duerr, R. H., McGovern, D. P. B., Cho, J., Powrie, Fiona, Li, V. S. W., Muise, A. M., Uhlig, H. H., Donnelly, P., Bell, J., Bentley, D., McVean, G., Ratcliffe, P., Taylor, J., Wilkie, A. O. M., Broxholme, J., Buck, D., Gregory, L., Gregory, J., Lunter, G., Tomlinson, I., Allan, C., Attar, M., Green, A., Humphray, S., Kingsbury, Z., Lamble, S., Lonie, L., Pagnamenta, A., Piazza, P., Polanco, G., Trebes, A., Copley, R., Fiddy, S., Grocock, R., Hatton, E., Holmes, C., Hughes, L., Humburg, P., Kanapin, A., Lise, S., Martin, H., Murray, L., McCarthy, D., Rimmer, A., Sahgal, N., Wright, B., Yau, C., Arancibia, Carolina, Bailey, Adam, Barnes, Ellie, Bird-Lieberman, Beth, Brain, Oliver, Braden, Barbara, Collier, Jane, East, James, Geremia, Alessandra, Howarth, Lucy, Keshav, Satish, Klenerman, Paul, Leedham, Simon, Palmer, Rebecca, Rodrigues, Astor, Simmons, Alison, Sullivan, Peter B, Travis, Simon P L, Uhlig, Holm H, Heuschkel, Rob, Zilbauer, Matthias, Auth, Marcus K. H., Shah, Neil, Kammermeier, Jochen, Croft, Nick, Barakat, Farah, Russell, Richard K., Wilson, David C., Henderson, Paul, Braegger, Christian P., Posovszky, Carsten, Fyderek, Krzysztof, Wedrychowicz, Andrzej, Zurek, Marlen, Strisciuglio, Caterina, Elawad, Mamoun, Lo, Bernice, Parkes, Miles, Satsangi, Jack, Anderson, Carl A., Jostins, L., Kennedy, N. A., Lamb, C. A., Ahmad, T., Edwards, C., Hart, A., Hawkey, C., Mansfield, J. C., Mowat, C., Newman, W. G., Satsangi, J., Simmons, A., Tremelling, M., Lee, J. C., Prescott, N. J., Lees, C. W., Barrett, J. C., UK IBD Genetics Consortium, COLORS in IBD, Oxford IBD cohort study investigators, WGS500 Consortium, INTERVAL Study, Schwerd, T., Bryant, R. V., Pandey, S., Capitani, M., Meran, L., Cazier, J. -B., Jung, J., Mondal, K., Parkes, M., Mathew, C. G., Fiedler, K., Mccarthy, D. J., Sullivan, P. B., Rodrigues, A., Travis, S. P. L., Moore, C., Sambrook, J., Ouwehand, W. H., Roberts, D. J., Danesh, J., Russell, R. K., Wilson, D. C., Kelsen, J. R., Cornall, R., Denson, L. A., Kugathasan, S., Knaus, U. G., Serra, E. G., Anderson, C. A., Duerr, R. H., Mcgovern, D. P. B., Cho, J., Powrie, Fiona, Li, V. S. W., Muise, A. M., Uhlig, H. H., Donnelly, P., Bell, J., Bentley, D., Mcvean, G., Ratcliffe, P., Taylor, J., Wilkie, A. O. M., Broxholme, J., Buck, D., Gregory, L., Gregory, J., Lunter, G., Tomlinson, I., Allan, C., Attar, M., Green, A., Humphray, S., Kingsbury, Z., Lamble, S., Lonie, L., Pagnamenta, A., Piazza, P., Polanco, G., Trebes, A., Copley, R., Fiddy, S., Grocock, R., Hatton, E., Holmes, C., Hughes, L., Humburg, P., Kanapin, A., Lise, S., Martin, H., Murray, L., Mccarthy, D., Rimmer, A., Sahgal, N., Wright, B., Yau, C., Arancibia, Carolina, Bailey, Adam, Barnes, Ellie, Bird-Lieberman, Beth, Brain, Oliver, Braden, Barbara, Collier, Jane, East, Jame, Geremia, Alessandra, Howarth, Lucy, Keshav, Satish, Klenerman, Paul, Leedham, Simon, Palmer, Rebecca, Rodrigues, Astor, Simmons, Alison, Sullivan, Peter B, Travis, Simon P L, Uhlig, Holm H, Heuschkel, Rob, Zilbauer, Matthia, Auth, Marcus K. H., Shah, Neil, Kammermeier, Jochen, Croft, Nick, Barakat, Farah, Russell, Richard K., Wilson, David C., Henderson, Paul, Braegger, Christian P., Posovszky, Carsten, Fyderek, Krzysztof, Wedrychowicz, Andrzej, Zurek, Marlen, Strisciuglio, Caterina, Elawad, Mamoun, Lo, Bernice, Parkes, Mile, Satsangi, Jack, Anderson, Carl A., Jostins, L., Kennedy, N. A., Lamb, C. A., Ahmad, T., Edwards, C., Hart, A., Hawkey, C., Mansfield, J. C., Mowat, C., Newman, W. G., Satsangi, J., Simmons, A., Tremelling, M., Lee, J. C., Prescott, N. J., Lees, C. W., Barrett, J. C., UK IBD Genetics, Consortium, COLORS in, Ibd, Oxford IBD cohort study, Investigator, Wgs500, Consortium, and Interval, Study

Subjects
Male, Genotype, Colon, Immunology, Mutation, Missense, Genetic Association Studie, Polymorphism, Single Nucleotide, Article, Mice, Animals, Humans, Immunology and Allergy, Genetic Predisposition to Disease, Child, Genetic Association Studies, Genes, Modifier, Genome, Animal, Inflammatory Bowel Disease, High-Throughput Nucleotide Sequencing, Inflammatory Bowel Diseases, digestive system diseases, Host-Pathogen Interaction, Mice, Inbred C57BL, Child, Preschool, Host-Pathogen Interactions, NADPH Oxidase 1, Reactive Oxygen Species, Reactive Oxygen Specie, Human
Abstract

Genetic defects that affect intestinal epithelial barrier function can present with very early-onset inflammatory bowel disease (VEOIBD). Using whole-genome sequencing, a novel hemizygous defect in NOX1 encoding NAPDH oxidase 1 was identified in a patient with ulcerative colitis-like VEOIBD. Exome screening of 1,878 pediatric patients identified further seven male inflammatory bowel disease (IBD) patients with rare NOX1 mutations. Loss-of-function was validated in p.N122H and p.T497A, and to a lesser degree in p.Y470H, p.R287Q, p.I67M, p.Q293R as well as the previously described p.P330S, and the common NOX1 SNP p.D360N (rs34688635) variant. The missense mutation p.N122H abrogated reactive oxygen species (ROS) production in cell lines, ex vivo colonic explants, and patient-derived colonic organoid cultures. Within colonic crypts, NOX1 constitutively generates a high level of ROS in the crypt lumen. Analysis of 9,513 controls and 11,140 IBD patients of non-Jewish European ancestry did not reveal an association between p.D360N and IBD. Our data suggest that loss-of-function variants in NOX1 do not cause a Mendelian disorder of high penetrance but are a context-specific modifier. Our results implicate that variants in NOX1 change brush border ROS within colonic crypts at the interface between the epithelium and luminal microbes.

Published
2018

8. Pelagia noctiluca as a model to uncover scyphozoan developmental mechanisms

Author

Kraus, Y., Copley, R., Aury, J.M., Rentzsch, F., Lombard, F., Guidi, L, Leclere, L., Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Department for Molecular Evolution and Development, University of Vienna [Vienna], Laboratoire d'océanographie de Villefranche (LOV), Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de la Mer de Villefranche (IMEV), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie du Développement de Villefranche sur mer (LBDV), and Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de la Mer de Villefranche (IMEV)

Subjects
[SDU.STU.OC]Sciences of the Universe [physics]/Earth Sciences/Oceanography
Abstract

International audience

Published
2019

9. Real-time fretting loop regime transition identification using acoustic emissions

Author

Wade, A, Copley, R, Clarke, B, Alsheikh Omar, A, Beadling, AR, Liskiewicz, T, Bryant, MG, Wade, A, Copley, R, Clarke, B, Alsheikh Omar, A, Beadling, AR, Liskiewicz, T, and Bryant, MG

Abstract

© 2020 Elsevier Ltd Acoustic emission (AE) has been successfully used to investigate the damage mechanisms of fretting contacts within different regimes. This study investigated the transition between fretting regimes using the relationship between AE and the mechanical response of a dry, steel-on-steel, ball-on-flat contact under different tangential displacements achieving the partial slip regime, mixed fretting regime and gross slip regime. Increased AE response occurred during gross-slip events and there was strong positive correlation between AE and fretting energy ratio. The relationship was strongest when gross sliding was experienced allowing identification of transition from the partial slip to the gross slip regime. This makes AE a good candidate to detect regime transition in-situ due to ease of integration and its non-destructive nature.

Published
2019

10. MicroRNAs that contribute to coordinating the immune response in Drosophila melanogaster

Author

Atilano, M, Glittenberg, M, Monteiro, A, Copley, R, and Ligoxygakis, P

Abstract

Small noncoding RNAs called microRNAs (miRNAs) have emerged as post-transcriptional regulators of gene expression related to host defenses. Here, we have used Drosophila melanogaster to explore the contribution of individual or clusters of miRNAs in countering systemic Candida albicans infection. From a total of 72 tested, we identify 6 miRNA allelic mutant backgrounds that modulate the survival response to infection and the ability to control pathogen number. These mutants also exhibit dysregulation of the Toll pathway target transcripts Drosomycin (Drs) and Immune-Induced Molecule 1 (IM1). These are characteristics of defects in Toll signaling, and consistent with this, we demonstrate dependency for one of the miRNA mutants on the NF-κΒ homolog Dif. We also quantify changes in the miRNA expression profile over time in response to three pathogen types, and identify 13 mature miRNA forms affected by pathogens that stimulate Toll signaling. To complement this, we provide a genome-wide map of potential NF-κB sites in proximity to miRNA genes. Finally, we demonstrate that systemic C. albicans infection contributes to a reduction in the total amount of branch-chained amino acids, which is miRNA-regulated. Overall, our data reveal a new layer of miRNA complexity regulating the fly response to systemic fungal infection.

Published
2017

12. A structural analysis of phosphate and sulphate binding sites in proteins. Estimation of propensities for binding and conservation of phosphate binding sites

Author

Copley, R. R. and Geoffrey John Barton

Subjects
Structural Biology, Molecular Biology
Abstract

The high resolution X-ray structures of 38 proteins that bind phosphate containing groups and 36 proteins binding sulphate ions were analysed to characterise the structural features of anion binding sites in proteins. 34 of the 66 phosphates found were in close proximity to the amino terminus of an alpha-helix. 27% of phosphate groups bind to only one amino acid, but there is a wide distribution, with 3% of phosphates binding to seven residues. Similarly, there is a large variability in the number of contacts each phosphate group makes to the protein. This ranges from none (3% of phosphates) to nine (3% of phosphates). The most common number of contacts is two (23% of phosphates). The most commonly found residue at helix-type binding sites is glycine, followed by Arg, Thr, Ser and Lys. At non-helix binding sites, the most commonly found residue is Arg followed by Tyr, His, Lys and Ser. There is no typical phosphate binding site. There are marked differences between propensities for phosphate binding at helix and non-helix type binding sites. Non-helix binding sites show more discrimination between the types of residues involved in binding when compared to the helix set. The propensities for binding of the amino acids reveal the expected trend of positively charged and polar residues being good at binding (although that for lysine is unexpectedly low) with the bulky non-polar residues being poor at binding. Bulky residues are less likely to bind with the amide nitrogen. Sulphate binding sites show similar trends. Analysis of multiple sequence alignments that include phosphate and sulphate binding proteins reveals the degree of conservation at the binding site residues compared to the average conservation of residues in the protein. Phosphate binding site residues are more conserved than sulphate binding sites.

Published
2016

16. Adoption by clinicians of electronic order communications in NHS secondary care: a descriptive account.

Author

Coleman JJ, Atia J, Evison F, Wilson L, Gallier S, Sames R, Capewell A, Copley R, Gyves H, Ball S, and Pankhurst T

Subjects
Humans, Retrospective Studies, United Kingdom, Medical Order Entry Systems, Secondary Care, State Medicine
Abstract

Background: Due to the rapid advancement in information technology, changes to communication modalities are increasingly implemented in healthcare. One such modality is Computerised Provider Order Entry (CPOE) systems which replace paper, verbal or telephone orders with electronic booking of requests. We aimed to understand the uptake, and user acceptability, of CPOE in a large National Health Service hospital system., Methods: This retrospective single-centre study investigates the longitudinal uptake of communications through the Prescribing, Information and Communication System (PICS). The development and configuration of PICS are led by the doctors, nurses and allied health professionals that use it and requests for CPOE driven by clinical need have been described.Records of every request (imaging, specialty review, procedure, laboratory) made through PICS were collected between October 2008 and July 2019 and resulting counts were presented. An estimate of the proportion of completed requests made through the system has been provided for three example requests. User surveys were completed., Results: In the first 6 months of implementation, a total of 832 new request types (imaging types and specialty referrals) were added to the system. Subsequently, an average of 6.6 new request types were added monthly. In total, 8 035 132 orders were requested through PICS. In three example request types (imaging, endoscopy and full blood count), increases in the proportion of requests being made via PICS were seen. User feedback at 6 months reported improved communications using the electronic system., Conclusion: CPOE was popular, rapidly adopted and diversified across specialties encompassing wide-ranging requests., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2024
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17. Effect of Tart Cherry on Aromatase Inhibitor-Induced Arthralgia (AIA) in Nonmetastatic Hormone-Positive Breast Cancer Patients: A Randomized Double-Blind Placebo-Controlled Trial.

Author

Shenouda M, Copley R, Pacioles T, Lebowicz Y, Jamil M, Akpanudo S, and Tirona MT

Subjects
Adult, Arthralgia chemically induced, Breast Neoplasms pathology, Double-Blind Method, Female, Humans, Middle Aged, Musculoskeletal Pain prevention & control, Quality of Life, Antineoplastic Agents adverse effects, Aromatase Inhibitors adverse effects, Arthralgia prevention & control, Breast Neoplasms drug therapy, Prunus avium
Abstract

Background: Aromatase Inhibitor induced Arthralgia (AIA) can cause noncompliance leading to decreased breast-cancer survival. Effective interventions for AIA are limited. Tart cherry (TC) showed beneficial effect on musculoskeletal pain. 48 patients (Pts) randomized to TC versus placebo over 6 weeks, TC (23pts) had 34.7% mean pain decrease versus 1.4% in Placebo (25pts). TC can improve AIA in nonmetastatic breast-cancer patients., Methods: Randomized, placebo-controlled, double-blind trial. Eligible patients with NMHPBC on AI for at least 4 weeks were randomized to TC concentrate [50 tart cherries] vs. placebo (P) [syrup] in 1:1 model. Patients instructed to consume 1 Oz of concentrate in 8 Oz water daily for 6 weeks, and document their pain intensity at baseline, weekly and at study completion in a diary using Visual Analog Scale (VAS), with 0 mm indicating no pain, and 100 mm indicating highest pain., Results: Sixty patients were enrolled. Two patients did not complete the study due to diarrhea, and 10 patients were noncompliant. Forty-eight patients were included in the final analysis. TC group (23 pts) had 34.7% mean decrease in pain compared to 1.4% in P group (25 pts). This difference was statistically significant (Mann-Whitney U Test, P = .034)., Conclusions: Tart cherry can significantly improve AIA in nonmetastatic breast cancer patient., Competing Interests: Disclosure This clinical trial was supported by a grant from the Cherry Marketing Institute, Dewitt, Michigan. The authors otherwise declare that there is no conflict of interest., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2022
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