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2. Aerothermodynamic Analysis of Faceted Aeroshell at Hypersonic Speed

Author

Innocenzi, Pietro, Gramola, Michela, Fisher, Tom B., Quinn, Mark K., Bruce, Paul J. K., and Navarro-Martinez, Salvador

Subjects
Physics - Fluid Dynamics
Abstract

This study explores the aerothermal behaviour of a rigid mechanically deployable aeroshell developed at Imperial College London for high payload atmospheric entry missions. The multiphysics CFD software STAR-CCM+ is used to perform a Conjugate Heat Transfer analysis on the aeroshell's faceted geometry. Results are presented for four different geometry models tested in air at Mach 5 with angles of attack 0{\deg}, 5{\deg} and 10{\deg}. The predicted surface heat transfer reveals areas of elevated heat loads at the ribs between facets and at the aeroshell shoulder, due to local boundary layer thinning. The increase in heat transfer at the ribs depends on the sharpness of the rib: more rounded shapes result in lower heat fluxes. Comparison with high-speed wind tunnel tests shows good agreement with experimental data. Stanton number and temperature profiles agree within 8% and 2%, respectively. The discrepancies between experiments and simulations are largest at the sharp ribs of the aeroshell. The sources of error can be associated with three-dimensional effects neglected in the heat flux derivations from temperature measurements as well as experimental uncertainties., Comment: Conference paper presented at HiSST: 2nd International Coneference on High-Speed Vehicle Science Technology (Bruges, Belgium 2022)

Published
2023

3. Optimizing laser coupling, matter heating, and particle acceleration from solids using multiplexed ultraintense lasers

Author

Yao, Weipeng, Nakatsutsumi, Motoaki, Buffechoux, Sébastien, Antici, Patrizio, Borghesi, Macro, Ciardi, Andrea, Chen, Sophia N., d'Humières, Emmanuel, Gremillet, Laurent, Heathcote, Robert, Horný, Vojtěch, McKenna, Paul, Quinn, Mark N., Romagnani, Lorenzo, Royle, Ryan, Sarri, Gianluca, Sentoku, Yasuhiko, Schlenvoigt, Hans-Peter, Toncian, Toma, Tresca, Olivier, Vassura, Laura, Willi, Oswald, and Fuchs, Julien

Subjects
Physics - Plasma Physics
Abstract

Realizing the full potential of ultrahigh-intensity lasers for particle and radiation generation will require multi-beam arrangements due to technology limitations. Here, we investigate how to optimize their coupling with solid targets. Experimentally, we show that overlapping two intense lasers in a mirror-like configuration onto a solid with a large preplasma can greatly improve the generation of hot electrons at the target front and ion acceleration at the target backside. The underlying mechanisms are analyzed through multidimensional particle-in-cell simulations, revealing that the self-induced magnetic fields driven by the two laser beams at the target front are susceptible to reconnection, which is one possible mechanism to boost electron energization. In addition, the resistive magnetic field generated during the transport of the hot electrons in the target bulk tends to improve their collimation. Our simulations also indicate that such effects can be further enhanced by overlapping more than two laser beams.

Published
2022

6. A comprehensive characterisation of phaeochromocytoma and paraganglioma tumours through histone protein profiling, DNA methylation and transcriptomic analysis genome wide

Author

Chatzikyriakou, Prodromos, Brempou, Dimitria, Quinn, Mark, Fishbein, Lauren, Noberini, Roberta, Anastopoulos, Ioannis N., Tufton, Nicola, Lim, Eugenie S., Obholzer, Rupert, Hubbard, Johnathan G., Moonim, Mufaddal, Bonaldi, Tiziana, Nathanson, Katherine L., Izatt, Louise, and Oakey, Rebecca J.

Published
2023
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9. Unsteady and Transient applications of Pressure-Sensitive Paint

Author

Quinn, Mark, speaker

Abstract

Pressure-sensitive paint is a promising and ever growing aerodynamic measurement tool which is finding new applications in many different areas. Unsteady applications have yielded fantastic insights into spatially varying transient phenomenon such as buffet. This talk describes approaches for unsteady and transient applications of PSP from data processing and physical set up perspectives.

Published
2023
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12. Long-term outcomes in patients with COPD treated with non-invasive ventilation for acute hypercapnic respiratory failure.

Author

O'Brien, Shane, Gill, Cara, Cograve, Niall, Quinn, Mark, and Fahy, Ruairi J.

Abstract

Purpose: Chronic Obstructive Lung Disease (COPD) remains a major cause of morbidity and mortality across the world. We evaluated survival over 9 years in a cohort of patients with COPD requiring acute inpatient non-invasive ventilation (NIV). We analyzed prognostic indices to evaluate if they were associated with mortality. Patients and methods: We performed a retrospective chart review of all patients who were admitted to St. James's Hospital respiratory ward with COPD and acute hypercapnic respiratory failure who required NIV over a 12-month period and followed their outcomes over 9 years. We investigated the association between survival and potential prognostic variables using univariate analysis and multivariate Cox proportional hazards model. We evaluated the association between survival and the following parameters: age, gender, multiple admissions requiring NIV (> 1 admission in within 12 months of index presentation), home NIV use preadmission, initial arterial blood gas pH, days spent on NIV, serum albumin and serum albumin to serum CRP ratio at admission. Results: Ninety-nine patients with COPD and acute hypercapnic respiratory failure were identified over a 12-month period from January to December 2011. Survival at 1, 2, 5 and 9 years was 65% (n = 64), 42% (n = 42), 25% (n = 25) and 21% (n = 21), respectively. Increasing age (p value < 0.001) and a lower serum albumin (p value < 0.005) were associated with a higher mortality. There was a trend towards improved survival in the group who were treated with home NIV prior to admission compared to no NIV therapy at home but this did not reach statistical significance (Fig. 3, p value = 0.088). Conclusion: This study highlights the long-term mortality in patients with COPD admitted with hypercapnic respiratory failure requiring NIV and correlates with prior studies. Increasing age and lower serum albumin were associated with increased mortality. Home NIV may have a protective long-term survival benefit in patients with COPD who have been admitted for acute NIV. [ABSTRACT FROM AUTHOR]

Published
2024
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17. Optimizing laser coupling, matter heating, and particle acceleration from solids using multiplexed ultraintense lasers

Author

Yao, Weipeng, primary, Nakatsutsumi, Motoaki, additional, Buffechoux, Sébastien, additional, Antici, Patrizio, additional, Borghesi, Marco, additional, Ciardi, Andrea, additional, Chen, Sophia N., additional, d’Humières, Emmanuel, additional, Gremillet, Laurent, additional, Heathcote, Robert, additional, Horný, Vojtěch, additional, McKenna, Paul, additional, Quinn, Mark N., additional, Romagnani, Lorenzo, additional, Royle, Ryan, additional, Sarri, Gianluca, additional, Sentoku, Yasuhiko, additional, Schlenvoigt, Hans-Peter, additional, Toncian, Toma, additional, Tresca, Olivier, additional, Vassura, Laura, additional, Willi, Oswald, additional, and Fuchs, Julien, additional

Published
2024
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18. Phytochemical Composition and Biological Activity of the Essential Oil from Ericameria nauseosa Collected in Southwestern Montana, United States.

Author

Schepetkin, Igor A., Özek, Gulmira, Özek, Temel, Kirpotina, Liliya N., Khlebnikov, Andrei I., Ayçiçek, Kevser, Lavin, Matthew, and Quinn, Mark T.

Subjects
ESSENTIAL oils, PRINCIPAL components analysis, CLUSTER analysis (Statistics), POLYACETYLENES, TRADITIONAL medicine
Abstract

Ericameria nauseosa (Pall. ex Pursh) G.L. Nesom & G.I. Baird) is used in traditional medicine to treat various diseases; however, little is known about the immunomodulatory activity of essential oil from this plant. Thus, we isolated essential oil from the aerial parts of E. nauseosa and evaluated their chemical composition and biological activity. Compositional analysis of E. nauseosa essential oil revealed that the main (>2%) components were γ-decalactone (13.3%), cryptone (9.4%), terpinen-4-ol (9.3%), (E)-methyl cinnamate (6.0%), T-cadinol (4.7%), spathulenol (3.6%), 8Z-2,3-dihydromatricaria ester (3.1%), β-phellandrene (3.0%), p-cymen-8-ol (2.2%), 3-ethoxy-2-cycloocten-1-one (2.2%), and trans-p-menth-2-en-1-ol (2.1%). Distinctive features were the lactones (up to 15%) and polyacetylenes (up to 3.1%), including (2Z,8Z)-matricaria ester and 8Z-2,3-dihydromatricaria ester. A comparison with other reported E. nauseosa essential oil samples showed that our samples were distinct from those collected in other areas of the country; however, they did have the most similarity to one sample collected in North Central Utah. Pharmacological studies showed that E. nauseosa essential oil activated human neutrophil Ca2+ influx, which desensitized these cells to subsequent agonist-induced functional responses. Based on our previously reported data that nerolidol, β-pinene, spathulenol, sabinene, and γ-terpinene were active in human neutrophils, these compounds are the most likely constituents contributing to this immunomodulatory activity. However, the relatively high amount of polyacetylenes may also contribute, as these compounds have been characterized as potent immunomodulators. [ABSTRACT FROM AUTHOR]

Published
2024
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19. Most common movements preceding goal scoring situations in female professional soccer.

Author

Martínez-Hernández, David, Quinn, Mark, and Jones, Paul

Subjects
WOMEN'S soccer, HANDBALL players, MOVEMENT disorders, JOGGING, ACCELERATION (Mechanics), PROFESSIONAL athletes
Abstract

This study aimed to assess movements occurring during goal scoring situations in a female professional league. Data from all the goals on the Women's Super League 2018/2019 were collected through time-motion analysis using a modified version of the Bloomfield Movement Classification with differences analysed through chi-square. Analysis was performed on players (assistant, scorer [attackers], defender of assistant and defender of scorer [defenders]), movements, intensities and directions. Linear advancing motion (walking, jogging, running or sprint) (total percentage [95% CI] 37% attackers and 32.7% defenders) was the most common action preceding a goal, followed by deceleration (21.5% attackers; 18.4% defenders) and turn (19.2% attackers; 17.6% defenders). Other movements involved but with lower percentages were change in angle run (cut and arc run), ball blocking, lateral advancing motion (crossover and shuffle) and jumps. Players displayed similar tendencies but presented variations based on the role, with attackers performing more linear actions, subtle turns and cuts and defenders more ball blocking actions, lateral movements and high intensity linear actions and decelerations. Assistant performed the less percentage of involvements with at least 1 high intensity action (67.4%), scorer and defender of assistant showed similar values (86.3% and 87.1%), while defender of scorer had the highest percentage (97.3%). This study shows the importance of linear actions with other movements also being of high significance but with differentiated characteristics based on the role. This study could help practitioners design drills for the enhancement of physical capabilities related to movements occurring in goal scoring situations. [ABSTRACT FROM AUTHOR]

Published
2024
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21. Ebselen analogues with dual human neutrophil elastase (HNE) inhibitory and antiradical activity

Author

Crocetti, Letizia, primary, Catarzi, Francesca, additional, Giovannoni, Maria Paola, additional, Vergelli, Claudia, additional, Bartolucci, Gianluca, additional, Pallecchi, Marco, additional, Paoli, Paola, additional, Rossi, Patrizia, additional, Lippi, Martina, additional, Schepetkin, Igor A., additional, Quinn, Mark T., additional, and Guerrini, Gabriella, additional

Published
2024
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25. Volatile Composition, Antimicrobial Activity, and In Vitro Innate Immunomodulatory Activity of Echinacea purpurea (L.) Moench Essential Oils

Author

Dosoky, Noura S., primary, Kirpotina, Liliya N., additional, Schepetkin, Igor A., additional, Khlebnikov, Andrei I., additional, Lisonbee, Brent L., additional, Black, Jeffrey L., additional, Woolf, Hillary, additional, Thurgood, Trever L., additional, Graf, Brittany L., additional, Satyal, Prabodh, additional, and Quinn, Mark T., additional

Published
2023
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26. Immunomodulatory Activity of Polysaccharides Isolated from Saussurea salicifolia L. and Saussurea frolovii Ledeb

Author

Schepetkin, Igor A., primary, Danilets, Marina G., additional, Ligacheva, Anastasia A., additional, Trofimova, Evgenia S., additional, Selivanova, Natalia S., additional, Sherstoboev, Evgenii Yu., additional, Krivoshchekov, Sergei V., additional, Gulina, Ekaterina I., additional, Brazovskii, Konstantin S., additional, Kirpotina, Liliya N., additional, Quinn, Mark T., additional, and Belousov, Mikhail V., additional

Published
2023
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27. Neuroprotective Effects of Tryptanthrin-6-Oxime in a Rat Model of Transient Focal Cerebral Ischemia

Author

Plotnikov, Mark B., primary, Chernysheva, Galina A., additional, Smol’yakova, Vera I., additional, Aliev, Oleg I., additional, Anishchenko, Anna M., additional, Ulyakhina, Olga A., additional, Trofimova, Eugene S., additional, Ligacheva, Anastasia A., additional, Anfinogenova, Nina D., additional, Osipenko, Anton N., additional, Kovrizhina, Anastasia R., additional, Khlebnikov, Andrei I., additional, Schepetkin, Igor A., additional, Drozd, Anastasia G., additional, Plotnikov, Evgenii V., additional, Atochin, Dmitriy N., additional, and Quinn, Mark T., additional

Published
2023
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32. Inhibition of Acetylcholinesterase by Novel Lupinine Derivatives

Author

Schepetkin, Igor A., primary, Nurmaganbetov, Zhangeldy S., additional, Fazylov, Serik D., additional, Nurkenov, Oralgazy A., additional, Khlebnikov, Andrei I., additional, Seilkhanov, Tulegen M., additional, Kishkentaeva, Anarkul S., additional, Shults, Elvira E., additional, and Quinn, Mark T., additional

Published
2023
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33. The Concise Guide to PHARMACOLOGY 2023/24 : G protein-coupled receptors

Author

Alexander, Stephen P. H., Christopoulos, Arthur, Davenport, Anthony P., Kelly, Eamonn, Mathie, Alistair A., Peters, John A., Veale, Emma L., Armstrong, Jane F., Faccenda, Elena, Harding, Simon D., Davies, Jamie A., Abbracchio, Maria Pia, Abraham, George, Agoulnik, Alexander, Alexander, Wayne, Al-hosaini, Khaled, Baeck, Magnus, Baker, Jillian G., Barnes, Nicholas M., Bathgate, Ross, Beaulieu, Jean-Martin, Beck-Sickinger, Annette G., Behrens, Maik, Bernstein, Kenneth E., Bettler, Bernhard, Birdsall, Nigel J. M., Blaho, Victoria, Boulay, Francois, Bousquet, Corinne, Braeuner-Osborne, Hans, Burnstock, Geoffrey, Calo, Girolamo, Castano, Justo P., Catt, Kevin J., Ceruti, Stefania, Chazot, Paul, Chiang, Nan, Chini, Bice, Chun, Jerold, Cianciulli, Antonia, Civelli, Olivier, Clapp, Lucie H., Couture, Rejean, Cox, Helen M., Csaba, Zsolt, Dahlgren, Claes, Dent, Gordon, Douglas, Steven D., Dournaud, Pascal, Eguchi, Satoru, Escher, Emanuel, Filardo, Edward J., Fong, Tung, Fumagalli, Marta, Gainetdinov, Raul R., Garelja, Michael L., de Gasparo, Marc, Gerard, Craig, Gershengorn, Marvin, Gobeil, Fernand, Goodfriend, Theodore L., Goudet, Cyril, Graetz, Lukas, Gregory, Karen J., Gundlach, Andrew L., Hamann, Joerg, Hanson, Julien, Hauger, Richard L., Hay, Debbie L., Heinemann, Akos, Herr, Deron, Hollenberg, Morley D., Holliday, Nicholas D., Horiuchi, Mastgugu, Hoyer, Daniel, Hunyady, Laszlo, Husain, Ahsan, Ijzerman, Adriaan P., Inagami, Tadashi, Jacobson, Kenneth A., Jensen, Robert T., Jockers, Ralf, Jonnalagadda, Deepa, Karnik, Sadashiva, Kaupmann, Klemens, Kemp, Jacqueline, Kennedy, Charles, Kihara, Yasuyuki, Kitazawa, Takio, Kozielewicz, Pawel, Kreienkamp, Hans-Juergen, Kukkonen, Jyrki P., Langenhan, Tobias, Larhammar, Dan, Leach, Katie, Lecca, Davide, Lee, John D., Leeman, Susan E., Leprince, Jerome, Li, Xaria X., Lolait, Stephen J., Lupp, Amelie, Macrae, Robyn, Maguire, Janet, Malfacini, Davide, Mazella, Jean, Mcardle, Craig A., Melmed, Shlomo, Michel, Martin C., Miller, Laurence J., Mitolo, Vincenzo, Mouillac, Bernard, Mueller, Christa E., Murphy, Philip M., Nahon, Jean-Louis, Ngo, Tony, Norel, Xavier, Nyimanu, Duuamene, O'Carroll, Anne-Marie, Offermanns, Stefan, Panaro, Maria Antonietta, Parmentier, Marc, Pertwee, Roger G., Pin, Jean-Philippe, Prossnitz, Eric R., Quinn, Mark, Ramachandran, Rithwik, Ray, Manisha, Reinscheid, Rainer K., Rondard, Philippe, Rovati, G. Enrico, Ruzza, Chiara, Sanger, Gareth J., Schoeneberg, Torsten, Schulte, Gunnar, Schulz, Stefan, Segaloff, Deborah L., Serhan, Charles N., Singh, Khuraijam Dhanachandra, Smith, Craig M., Stoddart, Leigh A., Sugimoto, Yukihiko, Summers, Roger, Tan, Valerie P., Thal, David, Thomas, Walter ( Wally), Timmermans, Pieter B. M. W. M., Tirupula, Kalyan, Toll, Lawrence, Tulipano, Giovanni, Unal, Hamiyet, Unger, Thomas, Valant, Celine, Vanderheyden, Patrick, Vaudry, David, Vaudry, Hubert, Vilardaga, Jean-Pierre, Walker, Christopher S., Wang, Ji Ming, Ward, Donald T., Wester, Hans-Juergen, Willars, Gary B., Williams, Tom Lloyd, Woodruff, Trent M., Yao, Chengcan, Ye, Richard D., Alexander, Stephen P. H., Christopoulos, Arthur, Davenport, Anthony P., Kelly, Eamonn, Mathie, Alistair A., Peters, John A., Veale, Emma L., Armstrong, Jane F., Faccenda, Elena, Harding, Simon D., Davies, Jamie A., Abbracchio, Maria Pia, Abraham, George, Agoulnik, Alexander, Alexander, Wayne, Al-hosaini, Khaled, Baeck, Magnus, Baker, Jillian G., Barnes, Nicholas M., Bathgate, Ross, Beaulieu, Jean-Martin, Beck-Sickinger, Annette G., Behrens, Maik, Bernstein, Kenneth E., Bettler, Bernhard, Birdsall, Nigel J. M., Blaho, Victoria, Boulay, Francois, Bousquet, Corinne, Braeuner-Osborne, Hans, Burnstock, Geoffrey, Calo, Girolamo, Castano, Justo P., Catt, Kevin J., Ceruti, Stefania, Chazot, Paul, Chiang, Nan, Chini, Bice, Chun, Jerold, Cianciulli, Antonia, Civelli, Olivier, Clapp, Lucie H., Couture, Rejean, Cox, Helen M., Csaba, Zsolt, Dahlgren, Claes, Dent, Gordon, Douglas, Steven D., Dournaud, Pascal, Eguchi, Satoru, Escher, Emanuel, Filardo, Edward J., Fong, Tung, Fumagalli, Marta, Gainetdinov, Raul R., Garelja, Michael L., de Gasparo, Marc, Gerard, Craig, Gershengorn, Marvin, Gobeil, Fernand, Goodfriend, Theodore L., Goudet, Cyril, Graetz, Lukas, Gregory, Karen J., Gundlach, Andrew L., Hamann, Joerg, Hanson, Julien, Hauger, Richard L., Hay, Debbie L., Heinemann, Akos, Herr, Deron, Hollenberg, Morley D., Holliday, Nicholas D., Horiuchi, Mastgugu, Hoyer, Daniel, Hunyady, Laszlo, Husain, Ahsan, Ijzerman, Adriaan P., Inagami, Tadashi, Jacobson, Kenneth A., Jensen, Robert T., Jockers, Ralf, Jonnalagadda, Deepa, Karnik, Sadashiva, Kaupmann, Klemens, Kemp, Jacqueline, Kennedy, Charles, Kihara, Yasuyuki, Kitazawa, Takio, Kozielewicz, Pawel, Kreienkamp, Hans-Juergen, Kukkonen, Jyrki P., Langenhan, Tobias, Larhammar, Dan, Leach, Katie, Lecca, Davide, Lee, John D., Leeman, Susan E., Leprince, Jerome, Li, Xaria X., Lolait, Stephen J., Lupp, Amelie, Macrae, Robyn, Maguire, Janet, Malfacini, Davide, Mazella, Jean, Mcardle, Craig A., Melmed, Shlomo, Michel, Martin C., Miller, Laurence J., Mitolo, Vincenzo, Mouillac, Bernard, Mueller, Christa E., Murphy, Philip M., Nahon, Jean-Louis, Ngo, Tony, Norel, Xavier, Nyimanu, Duuamene, O'Carroll, Anne-Marie, Offermanns, Stefan, Panaro, Maria Antonietta, Parmentier, Marc, Pertwee, Roger G., Pin, Jean-Philippe, Prossnitz, Eric R., Quinn, Mark, Ramachandran, Rithwik, Ray, Manisha, Reinscheid, Rainer K., Rondard, Philippe, Rovati, G. Enrico, Ruzza, Chiara, Sanger, Gareth J., Schoeneberg, Torsten, Schulte, Gunnar, Schulz, Stefan, Segaloff, Deborah L., Serhan, Charles N., Singh, Khuraijam Dhanachandra, Smith, Craig M., Stoddart, Leigh A., Sugimoto, Yukihiko, Summers, Roger, Tan, Valerie P., Thal, David, Thomas, Walter ( Wally), Timmermans, Pieter B. M. W. M., Tirupula, Kalyan, Toll, Lawrence, Tulipano, Giovanni, Unal, Hamiyet, Unger, Thomas, Valant, Celine, Vanderheyden, Patrick, Vaudry, David, Vaudry, Hubert, Vilardaga, Jean-Pierre, Walker, Christopher S., Wang, Ji Ming, Ward, Donald T., Wester, Hans-Juergen, Willars, Gary B., Williams, Tom Lloyd, Woodruff, Trent M., Yao, Chengcan, and Ye, Richard D.

Abstract

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at . G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

Published
2023
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34. Estimating the Prevalence of AATD Patients in the UK to Identify Underdiagnosis and Determine the Eligibility for Potential Augmentation Therapy

Author

Newnham,Michael, Quinn,Mark, Turner,Alice M, Newnham,Michael, Quinn,Mark, and Turner,Alice M

Abstract

Michael Newnham,1,2 Mark Quinn,1 Alice M Turner1,2 1Institute of Applied Health Research, University of Birmingham, Birmingham, UK; 2University Hospitals Birmingham, Birmingham, UKCorrespondence: Alice M Turner, Institute of Applied Health Research, University of Birmingham, Birmingham, UK, Email a.m.turner@bham.ac.ukPurpose: Alpha 1 antitrypsin deficiency (AATD) is a genetic risk factor for chronic obstructive pulmonary disease (COPD). Whilst testing for the condition is relatively simple, there is a disconnect in published literature between genetic epidemiology and numbers of patients known to specialists. This makes planning services for patients difficult. We aimed to estimate the number of patients likely to have lung disease eligible for specific AATD therapy within the UK.Patients and Methods: The THIN database was used to determine the prevalence of AATD and symptomatic COPD. This, and published rates of AATD were used to extrapolate THIN data to the population size of the UK to give an indicative population size for symptomatic AATD patients who have lung disease. The Birmingham AATD registry was used to describe age at diagnosis, rate of lung disease and symptomatic lung disease for patients with PiZZ (or equivalent) AATD, together with the time from symptom onset to diagnosis, in order to aid interpretation of the THIN data and improve modeling.Results: THIN data showed COPD prevalence of 3%, and AATD prevalence of 0.005– 0.2%, depending on how stringently AATD diagnostic codes were applied. The majority of Birmingham AATD patients were diagnosed between the ages 46– 55, whilst patients recorded in THIN tended to be older. The rate of COPD was similar in the THIN and Birmingham patients diagnosed with AATD. Modelling to the size of the UK demonstrated a likely symptomatic AATD population of between 3016 and 9866 people.Conclusion: AATD is likely to be under-diagnosed in the UK. Based on projected patient numbers an expansion to specialist services is

Published
2023

35. The Concise Guide to PHARMACOLOGY 2023/24:G protein-coupled receptors

Author

Alexander, Stephen P H, Christopoulos, Arthur, Davenport, Anthony P, Kelly, Eamonn, Mathie, Alistair A, Peters, John A, Veale, Emma L, Armstrong, Jane F, Faccenda, Elena, Harding, Simon D, Davies, Jamie A, Abbracchio, Maria Pia, Abraham, George, Agoulnik, Alexander, Alexander, Wayne, Al-Hosaini, Khaled, Bäck, Magnus, Baker, Jillian G, Barnes, Nicholas M, Bathgate, Ross, Beaulieu, Jean-Martin, Beck-Sickinger, Annette G, Behrens, Maik, Bernstein, Kenneth E, Bettler, Bernhard, Birdsall, Nigel J M, Blaho, Victoria, Boulay, Francois, Bousquet, Corinne, Bräuner-Osborne, Hans, Burnstock, Geoffrey, Caló, Girolamo, Castaño, Justo P, Catt, Kevin J, Ceruti, Stefania, Chazot, Paul, Chiang, Nan, Chini, Bice, Chun, Jerold, Cianciulli, Antonia, Civelli, Olivier, Clapp, Lucie H, Couture, Réjean, Cox, Helen M, Csaba, Zsolt, Dahlgren, Claes, Dent, Gordon, Douglas, Steven D, Dournaud, Pascal, Eguchi, Satoru, Escher, Emanuel, Filardo, Edward J, Fong, Tung, Fumagalli, Marta, Gainetdinov, Raul R, Garelja, Michael L, de Gasparo, Marc, Gerard, Craig, Gershengorn, Marvin, Gobeil, Fernand, Goodfriend, Theodore L, Goudet, Cyril, Grätz, Lukas, Gregory, Karen J, Gundlach, Andrew L, Hamann, Jörg, Hanson, Julien, Hauger, Richard L, Hay, Debbie L, Heinemann, Akos, Herr, Deron, Hollenberg, Morley D, Holliday, Nicholas D, Horiuchi, Mastgugu, Hoyer, Daniel, Hunyady, László, Husain, Ahsan, IJzerman, Adriaan P, Inagami, Tadashi, Jacobson, Kenneth A, Jensen, Robert T, Jockers, Ralf, Jonnalagadda, Deepa, Karnik, Sadashiva, Kaupmann, Klemens, Kemp, Jacqueline, Kennedy, Charles, Kihara, Yasuyuki, Kitazawa, Takio, Kozielewicz, Pawel, Kreienkamp, Hans-Jürgen, Kukkonen, Jyrki P, Langenhan, Tobias, Larhammar, Dan, Leach, Katie, Lecca, Davide, Lee, John D, Leeman, Susan E, Leprince, Jérôme, Li, Xaria X, Lolait, Stephen J, Lupp, Amelie, Macrae, Robyn, Maguire, Janet, Malfacini, Davide, Mazella, Jean, McArdle, Craig A, Melmed, Shlomo, Michel, Martin C, Miller, Laurence J, Mitolo, Vincenzo, Mouillac, Bernard, Müller, Christa E, Murphy, Philip M, Nahon, Jean-Louis, Ngo, Tony, Norel, Xavier, Nyimanu, Duuamene, O'Carroll, Anne-Marie, Offermanns, Stefan, Panaro, Maria Antonietta, Parmentier, Marc, Pertwee, Roger G, Pin, Jean-Philippe, Prossnitz, Eric R, Quinn, Mark, Ramachandran, Rithwik, Ray, Manisha, Reinscheid, Rainer K, Rondard, Philippe, Rovati, G Enrico, Ruzza, Chiara, Sanger, Gareth J, Schöneberg, Torsten, Schulte, Gunnar, Schulz, Stefan, Segaloff, Deborah L, Serhan, Charles N, Singh, Khuraijam Dhanachandra, Smith, Craig M, Stoddart, Leigh A, Sugimoto, Yukihiko, Summers, Roger, Tan, Valerie P, Thal, David, Thomas, Walter Wally, Timmermans, Pieter B M W M, Tirupula, Kalyan, Toll, Lawrence, Tulipano, Giovanni, Unal, Hamiyet, Unger, Thomas, Valant, Celine, Vanderheyden, Patrick, Vaudry, David, Vaudry, Hubert, Vilardaga, Jean-Pierre, Walker, Christopher S, Wang, Ji Ming, Ward, Donald T, Wester, Hans-Jürgen, Willars, Gary B, Williams, Tom Lloyd, Woodruff, Trent M, Yao, Chengcan, Ye, Richard D, Alexander, Stephen P H, Christopoulos, Arthur, Davenport, Anthony P, Kelly, Eamonn, Mathie, Alistair A, Peters, John A, Veale, Emma L, Armstrong, Jane F, Faccenda, Elena, Harding, Simon D, Davies, Jamie A, Abbracchio, Maria Pia, Abraham, George, Agoulnik, Alexander, Alexander, Wayne, Al-Hosaini, Khaled, Bäck, Magnus, Baker, Jillian G, Barnes, Nicholas M, Bathgate, Ross, Beaulieu, Jean-Martin, Beck-Sickinger, Annette G, Behrens, Maik, Bernstein, Kenneth E, Bettler, Bernhard, Birdsall, Nigel J M, Blaho, Victoria, Boulay, Francois, Bousquet, Corinne, Bräuner-Osborne, Hans, Burnstock, Geoffrey, Caló, Girolamo, Castaño, Justo P, Catt, Kevin J, Ceruti, Stefania, Chazot, Paul, Chiang, Nan, Chini, Bice, Chun, Jerold, Cianciulli, Antonia, Civelli, Olivier, Clapp, Lucie H, Couture, Réjean, Cox, Helen M, Csaba, Zsolt, Dahlgren, Claes, Dent, Gordon, Douglas, Steven D, Dournaud, Pascal, Eguchi, Satoru, Escher, Emanuel, Filardo, Edward J, Fong, Tung, Fumagalli, Marta, Gainetdinov, Raul R, Garelja, Michael L, de Gasparo, Marc, Gerard, Craig, Gershengorn, Marvin, Gobeil, Fernand, Goodfriend, Theodore L, Goudet, Cyril, Grätz, Lukas, Gregory, Karen J, Gundlach, Andrew L, Hamann, Jörg, Hanson, Julien, Hauger, Richard L, Hay, Debbie L, Heinemann, Akos, Herr, Deron, Hollenberg, Morley D, Holliday, Nicholas D, Horiuchi, Mastgugu, Hoyer, Daniel, Hunyady, László, Husain, Ahsan, IJzerman, Adriaan P, Inagami, Tadashi, Jacobson, Kenneth A, Jensen, Robert T, Jockers, Ralf, Jonnalagadda, Deepa, Karnik, Sadashiva, Kaupmann, Klemens, Kemp, Jacqueline, Kennedy, Charles, Kihara, Yasuyuki, Kitazawa, Takio, Kozielewicz, Pawel, Kreienkamp, Hans-Jürgen, Kukkonen, Jyrki P, Langenhan, Tobias, Larhammar, Dan, Leach, Katie, Lecca, Davide, Lee, John D, Leeman, Susan E, Leprince, Jérôme, Li, Xaria X, Lolait, Stephen J, Lupp, Amelie, Macrae, Robyn, Maguire, Janet, Malfacini, Davide, Mazella, Jean, McArdle, Craig A, Melmed, Shlomo, Michel, Martin C, Miller, Laurence J, Mitolo, Vincenzo, Mouillac, Bernard, Müller, Christa E, Murphy, Philip M, Nahon, Jean-Louis, Ngo, Tony, Norel, Xavier, Nyimanu, Duuamene, O'Carroll, Anne-Marie, Offermanns, Stefan, Panaro, Maria Antonietta, Parmentier, Marc, Pertwee, Roger G, Pin, Jean-Philippe, Prossnitz, Eric R, Quinn, Mark, Ramachandran, Rithwik, Ray, Manisha, Reinscheid, Rainer K, Rondard, Philippe, Rovati, G Enrico, Ruzza, Chiara, Sanger, Gareth J, Schöneberg, Torsten, Schulte, Gunnar, Schulz, Stefan, Segaloff, Deborah L, Serhan, Charles N, Singh, Khuraijam Dhanachandra, Smith, Craig M, Stoddart, Leigh A, Sugimoto, Yukihiko, Summers, Roger, Tan, Valerie P, Thal, David, Thomas, Walter Wally, Timmermans, Pieter B M W M, Tirupula, Kalyan, Toll, Lawrence, Tulipano, Giovanni, Unal, Hamiyet, Unger, Thomas, Valant, Celine, Vanderheyden, Patrick, Vaudry, David, Vaudry, Hubert, Vilardaga, Jean-Pierre, Walker, Christopher S, Wang, Ji Ming, Ward, Donald T, Wester, Hans-Jürgen, Willars, Gary B, Williams, Tom Lloyd, Woodruff, Trent M, Yao, Chengcan, and Ye, Richard D

Abstract

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.16177. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

Published
2023

36. Ebselen analogues with dual human neutrophil elastase (HNE) inhibitory and antiradical activityElectronic supplementary information (ESI) available: 1H NMR, 13C NMR, 77Se NMR spectra of some representative final compounds; mass spectrometry spectra and purity; crystallographic data and refinement parameters of 4d. CCDC 2309404. For ESI and crystallographic data in CIF or other electronic format see DOI: https://doi.org/10.1039/d3md00736g

Author

Crocetti, Letizia, Catarzi, Francesca, Giovannoni, Maria Paola, Vergelli, Claudia, Bartolucci, Gianluca, Pallecchi, Marco, Paoli, Paola, Rossi, Patrizia, Lippi, Martina, Schepetkin, Igor A., Quinn, Mark T., and Guerrini, Gabriella

Abstract

Human neutrophil elastase (HNE) plays an essential role in host defense against bacteria but is also involved in several respiratory diseases. Recent reports suggest that compounds exhibiting a combination of HNE inhibitory activity with antiradical properties may be therapeutically beneficial for the treatment of respiratory diseases involving inflammation and oxidative stress. We report here the synthesis and biological evaluation of novel ebselen analogues exhibiting HNE inhibitory and antiradical activities. HNE inhibition was evaluated in an enzymatic system using human HNE, whereas antiradical activity was evaluated in a cell-based assay system using phorbol 12-myristate 13-acetate (PMA)-stimulated murine bone marrow leukocytes as the source of reactive oxygen species (ROS). HNE inhibition was due to the N–CO group targeting Ser195-OH at position 2 of the scaffold, while antiradical activity was due to the presence of the selenium atom. The most active compounds 4d, 4f, and 4jexhibited a good balance between anti-HNE (IC50= 0.9–1.4 μM) and antiradical activity (IC50= 0.05–0.7 μM). Additionally, the solid-state structure of 4dwas determined and compared to that of the similar compound N-propionyl-1,2-benzisoselenazol-3(2H)-one.

Published
2024
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37. Cardioprotective Effects of a Selective c-Jun N-terminal Kinase Inhibitor in a Rat Model of Myocardial Infarction

Author

Plotnikov, Mark B., primary, Chernysheva, Galina A., additional, Smol’yakova, Vera I., additional, Aliev, Oleg I., additional, Fomina, Tatyana I., additional, Sandrikina, Lyubov A., additional, Sukhodolo, Irina V., additional, Ivanova, Vera V., additional, Osipenko, Anton N., additional, Anfinogenova, Nina D., additional, Khlebnikov, Andrei I., additional, Atochin, Dmitriy N., additional, Schepetkin, Igor A., additional, and Quinn, Mark T., additional

Published
2023
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45. Optimizing the laser coupling, matter heating, and particle acceleration from solids by using multiplexed ultraintense lasers

Author

Yao, Weipeng, Nakatsutsumi, Motoaki, Buffechoux, Sébastien, Antici, Patrizio, Borghesi, Macro, Chen, Sophia N., d'Humières, Emmanuel, Gremillet, Laurent, Heathcote, Robert, Horný, Vojtěch, Quinn, Mark N., Romagnani, Lorenzo, Royle, Ryan, Sarri, Gianluca, Sentoku, Yasuhiko, Schlenvoigt, Hans-Peter, Toncian, Toma, Tresca, Olivier, Vassura, Laura, Willi, Oswald, and Fuchs, Julien

Subjects
Plasma Physics (physics.plasm-ph), FOS: Physical sciences, Physics - Plasma Physics
Abstract

The new generation of multi-petawatt (PW) class laser systems will generally combine several beamlines. We here investigate how to arrange their irradiation geometry in order to optimize their coupling with solid targets, as well as the yields and beam quality of the produced particles. We first report on a proof-of-principle experiment, performed at the Rutherford Appleton Laboratory Vulcan laser facility, where two intense laser beams were overlapped in a mirror-like configuration onto a solid target, preceded by a long preplasma. We show that when the laser beams were close enough to each other, the generation of hot electrons at the target front was much improved and so was the ion acceleration at the target backside, both in terms of their maximum energy and collimation. The underlying mechanism is pinpointed with multidimensional particle-in-cell simulations, which demonstrate that the magnetic fields self-induced by the electron currents driven by the two laser beams at the target front can reconnect, thereby enhancing the production of hot electrons, and favoring their subsequent magnetic guiding across the target. Our simulations also reveal that the laser coupling with the target can be further improved when overlapping more than two beamlines. This multi-beam scheme would obviously be highly beneficial to the multi-PW laser projects proposed now and in the near future worldwide.

Published
2022

47. Neuroprotective Effects of the Lithium Salt of a Novel JNK Inhibitor in an Animal Model of Cerebral Ischemia–Reperfusion

Author

Schepetkin, Igor A., primary, Chernysheva, Galina A., additional, Aliev, Oleg I., additional, Kirpotina, Liliya N., additional, Smol’yakova, Vera I., additional, Osipenko, Anton N., additional, Plotnikov, Mark B., additional, Kovrizhina, Anastasia R., additional, Khlebnikov, Andrei I., additional, Plotnikov, Evgenii V., additional, and Quinn, Mark T., additional

Published
2022
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50. Changes in Body Mass and Movement Strategy Maintain Jump Height Immediately after Soccer Match.

Author

Spencer, Ryan, Sindall, Paul, Hammond, Kelly M., Atkins, Steve J., Quinn, Mark, and McMahon, John J.

Subjects
SOCCER tournaments, SOCCER players, SOCCER
Abstract

A countermovement jump (CMJ) performed on a force plate is commonly applied in soccer to quantify acute neuromuscular fatigue (NMF), which may manifest immediately following soccer match play. Jump height (JH) is the main outcome variable reported for this purpose; however, it is sensitive to alterations in movement strategy, which may act to mask JH and, therefore, mask any presence of NMF. Acute reductions in body mass (BM) during match play could also lead to the maintenance of JH, but this is yet to be explored. This study sought to explore soccer-match-induced alterations to JH, movement strategy, and BM to inform future variable selection for the study of acute NMF. Fourteen male English National League soccer players performed three CMJs on a dual-force plate system immediately before and after a competitive soccer match. Differences in jump height were non-significant and trivial (p = 0.924, g = 0.03) before and after soccer match play, but there was a large post-match decrease in BM (g = 1.66). Furthermore, moderate decreases in jump momentum (g = 0.56) and countermovement depth (g = 0.72) were noted. As JH was determined by the take-off velocity, reduced BM could have augmented it (less mass to accelerate); however, reduced countermovement depth seemingly counteracted this (less distance to attain velocity). It may, therefore, be beneficial to report these variables when monitoring acute NMF via the CMJ. [ABSTRACT FROM AUTHOR]

Published
2023
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