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6. Lens Free Holographic Imaging for Urinary Tract Infection Screening

Author

Gregory N. McKay, Anisha Oommen, Carolina Pacheco, Mason T. Chen, Stuart C. Ray, Rene Vidal, Benjamin D. Haeffele, and Nicholas J. Durr

Subjects
Biomedical Engineering, FOS: Physical sciences, Medical Physics (physics.med-ph), Physics - Medical Physics, Article
Abstract

OBJECTIVE: The diagnosis of urinary tract infection (UTI) currently requires precise specimen collection, handling infectious human waste, controlled urine storage, and timely transportation to modern laboratory equipment for analysis. Here we investigate holographic lens free imaging (LFI) to show its promise for enabling automatic urine analysis at the patient bedside. METHODS: We introduce an LFI system capable of resolving important urine clinical biomarkers such as red blood cells, white blood cells, crystals, and casts in 2 mm thick urine phantoms. RESULTS: This approach is sensitive to the particulate concentrations relevant for detecting several clinical urine abnormalities such as hematuria and pyuria, linearly correlating to ground truth hemacytometer measurements with R(2) = 0.9941 and R(2) = 0.9973, respectively. We show that LFI can estimate E. coli concentrations of 10(3) to 10(5) cells/mL by counting individual cells, and is sensitive to concentrations of 10(5) cells/mL to 10(8) cells/mL by analyzing hologram texture. Further, LFI measurements of blood cell concentrations are relatively insensitive to changes in bacteria concentrations of over seven orders of magnitude. Lastly, LFI reveals clear differences between UTI-positive and UTI-negative urine from human patients. CONCLUSION: LFI is sensitive to clinically-relevant concentrations of bacteria, blood cells, and other sediment in large urine volumes. SIGNIFICANCE: Together, these results show promise for LFI as a tool for urine screening, potentially offering early, point-of-care detection of UTI and other pathological processes.

Published
2023
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7. Combined Impact of Asymmetric Critical Current and Flux Diverters on AC Loss of a 6.5 MVA/25 kV HTS Traction Transformer

Author

Yue Wu, Wenjuan Song, Stuart C. Wimbush, Jin Fang, Rodney A. Badcock, Nicholas J. Long, and Zhenan Jiang

Subjects
90699 Electrical and Electronic Engineering not elsewhere classified, Automotive Engineering, FOS: Electrical engineering, electronic engineering, information engineering, Energy Engineering and Power Technology, Transportation, Electrical and Electronic Engineering
Abstract

A 6.5 MVA/25 kV high temperature superconducting (HTS) transformer for the Chinese Fuxing high-speed train has been proposed to replace the oil-based transformers while achieving higher efficiency, lighter weight, and minimized volume. The high targeted efficiency (> 99%) makes AC loss reduction a vital issue. HTS coated conductors generally exhibit asymmetric critical current characteristics as a function of magnetic field angle Ic(B, θ), leading to a non-trivial influence on the AC loss of coil windings. The fast-computing T-A homogenization method is proposed to calculate the AC loss of the 6.5 MVA/25 kV traction transformer with large turn numbers. The variables, T and A, are the current and magnetic vector potentials, respectively. The AC loss of the transformer windings is analyzed for various coil configurations with and without flux diverters considering Ic(B, θ). At the rated current and 65 K, employing the flux diverters with a square-shape cross-section, the total AC loss is decreased by 73.7% and an extra 150 W loss reduction was also obtained. Moreover, an additional reduction of 37 W is realized upon utilizing the asymmetric Ic(B, θ) characteristic. The reduced 187 W in AC loss at 65 K corresponds to a reduction in ambient power requirement of over 5.6 kW. Therefore, considering asymmetric Ic(B, θ), can lead to a non-trivial reduction in AC loss, even incorporating flux diverters.

Published
2023
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11. Visualization of translation and protein biogenesis at the ER membrane

Author

Max Gemmer, Marten L. Chaillet, Joyce van Loenhout, Rodrigo Cuevas Arenas, Dimitrios Vismpas, Mariska Gröllers-Mulderij, Fujiet A. Koh, Pascal Albanese, Richard A. Scheltema, Stuart C. Howes, Abhay Kotecha, Juliette Fedry, and Friedrich Förster

Subjects
Multidisciplinary
Abstract

The dynamic ribosome–translocon complex, which resides at the endoplasmic reticulum (ER) membrane, produces a major fraction of the human proteome1,2. It governs the synthesis, translocation, membrane insertion, N-glycosylation, folding and disulfide-bond formation of nascent proteins. Although individual components of this machinery have been studied at high resolution in isolation3–7, insights into their interplay in the native membrane remain limited. Here we use cryo-electron tomography, extensive classification and molecular modelling to capture snapshots of mRNA translation and protein maturation at the ER membrane at molecular resolution. We identify a highly abundant classical pre-translocation intermediate with eukaryotic elongation factor 1a (eEF1a) in an extended conformation, suggesting that eEF1a may remain associated with the ribosome after GTP hydrolysis during proofreading. At the ER membrane, distinct polysomes bind to different ER translocons specialized in the synthesis of proteins with signal peptides or multipass transmembrane proteins with the translocon-associated protein complex (TRAP) present in both. The near-complete atomic model of the most abundant ER translocon variant comprising the protein-conducting channel SEC61, TRAP and the oligosaccharyltransferase complex A (OSTA) reveals specific interactions of TRAP with other translocon components. We observe stoichiometric and sub-stoichiometric cofactors associated with OSTA, which are likely to include protein isomerases. In sum, we visualize ER-bound polysomes with their coordinated downstream machinery.

Published
2023
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12. Clinical and patient‐reported outcome profile of patients with hepatitis B viral infection from the Global Liver Registry™

Author

Zobair M. Younossi, Ming‐Lung Yu, Yusuf Yilmaz, Khalid Aida Alswat, Maria Buti, Marlen Ivon Castellanos Fernandez, Georgios Papatheodoridis, Saeed S. Hamid, Mohamed El‐Kassas, Wah Kheong Chan, Ajay K. Duseja, Stuart C. Gordon, Yuichiro Eguchi, Vasily A. Isakov, Stuart K. Roberts, Jian‐Gao Fan, Ashwani K. Singal, Manuel Romero‐Gómez, Aijaz Ahmed, Janus Ong, Brian P. Lam, Issah Younossi, Fatema Nader, Andrei Racila, Maria Stepanova, and Saleh Alqahtani

Subjects
Infectious Diseases, Hepatology, Virology
Abstract

Chronic hepatitis B (CHB) infection is one of the most common causes of cirrhosis and liver cancer worldwide. Our aim was to assess clinical and patient-reported outcome (PRO) profile of CHB patients from different regions of the world using the Global Liver Registry. The CHB patients seen in real-world practices are being enrolled in the Global Liver Registry. Clinical and PRO (FACIT-F, CLDQ, WPAI) data were collected and compared to baseline data from CHB controls from clinical trials. The study included 1818 HBV subjects (48±13 years, 58% male, 14% advanced fibrosis, 7% cirrhosis) from 15 countries in 6/7 Global Burden of Disease super-regions. The rates of advanced fibrosis varied (3-24%). The lowest PRO scores across multiple domains were in HBV subjects from the Middle East/North Africa (MENA), the highest - Southeast/East and South Asia. Subjects with advanced fibrosis had PRO impairment in 3 CLDQ domains, Activity of WPAI (p0.05). HBV subjects with superimposed fatty liver had more PRO impairments. In multivariate analysis adjusted for location, predictors of PRO impairment in CHB included female sex, advanced fibrosis, and non-hepatic comorbidities (p0.05). In comparison to Global Liver Registry patients, 242 controls from clinical trials had better PRO scores (Abdominal, Emotional, and Systemic scores of CLDQ, all domains of WPAI) (p0.05). In multivariate analysis with adjustment for location and clinicodemographic parameters, the associations of PROs with the enrollment setting (real-life Global Liver Registry vs. clinical trials) were no longer significant (all p0.10). The clinico-demographic portrait of CHB patients varies across regions of the world and enrollment settings. Advanced fibrosis and non-hepatic comorbidities are independently associated with PRO impairment in CHB patients.

Published
2023
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13. Development of the Auburn Induction Scale for evaluating induction quality in dogs

Author

Kathryn L, Wolfe, Erik H, Hofmeister, Stuart C, Clark-Price, Rachel, Reed, and Jane, Quandt

Subjects
Dogs, Cross-Sectional Studies, Visual Analog Scale, General Veterinary, Anesthesiology, Animals, Reproducibility of Results, Pain Measurement
Abstract

To develop and begin establishing evidence for validity of an instrument to assess the quality of induction in dogs.Cross-sectional survey and video scoring.A total of 51 veterinary anesthesia personnel, four board-certified anesthesiologists and videos of induction of anesthesia in 18 dogs.In Part 1, an online survey was sent to veterinary anesthesia personnel to solicit expressions and words that they associate with induction of anesthesia. These expressions were evaluated by four anesthesiologists to create a composite scale (Auburn Induction Scale). In Part 2, 18 videos were reviewed by the same four anesthesiologists on two separate occasions. The videos were scored using the Auburn Induction Scale, a simple descriptive scale (SDS) and a visual analog scale (VAS). Intra-rater and inter-rater reliability was measured using an intraclass correlation coefficient (ICC). Significance was set at p0.05.The survey yielded 51 responses that were condensed into 133 expressions. The four anesthesiologists created 18 items incorporating the 133 expressions. The mean ± standard deviation intra-rater reliability ICC was 0.81 ± 0.08 for the Auburn Induction Scale, 0.71 ± 0.02 for the SDS and 0.71 ± 0.08 for the VAS for all raters. The mean ± standard deviation inter-rater reliability ICC was 0.69 ± 0.04 for the Auburn Induction Scale, 0.61 ± 0.05 for the SDS and 0.60 ± 0.06 for the VAS.In a research setting, widespread use of this scale may be helpful in increasing the accuracy of data and improving agreement between studies assessing induction of anesthesia in dogs. The results of this study have yielded a composite scale that is more reliable between and among raters than a unidimensional scale.

Published
2022
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14. Enhanced performance in fusion plasmas through turbulence suppression by megaelectronvolt ions

Author

Mazzi, S., Garcia, J., Zarzoso, D., Kazakov, Y., Ongena, J., Dreval, M., Nocente, M., Stancar, Z., Szepesi, G., Eriksson, J., Sahlberg, A., Benkadda, S., Abid, N., Abraham, K., Abreu, P., Adabonyan, O., Adrich, P., Afanasev, V., Afzal, M., Ahlgren, T., Aho-Mantila, L., Aiba, N., Airila, M., Akhtar, M., Albanese, R., Alderson-Martin, M., Alegre, D., Aleiferis, S., Aleksa, A., Alekseev, A., Alessi, E., Aleynikov, P., Algualcil, J., Ali, M., Allinson, M., Alper, B., Alves, E., Ambrosino, G., Ambrosino, R., Amosov, V., Andersson Sunden, E., Andrew, P., Angelini, B., Angioni, C., Antoniou, I., Appel, L., Appelbee, C., Aria, S., Ariola, M., Artaserse, G., Arter, W., Artigues, V., Asakura, N., Ash, A., Ashikawa, N., Aslanyan, V., Astrain, M., Asztalos, O., Auld, D., Auriemma, F., Austin, Y., Avotina, L., Aymerich, E., Baciero, A., Bairaktaris, F., Balbin, J., Balbinot, L., Balboa, I., Balden, M., Balshaw, C., Balshaw, N., Bandaru, V., Banks, J., Baranov, Y., Barcellona, C., Barnard, A., Barnard, M., Barnsley, R., Barth, A., Baruzzo, M., Barwell, S., Bassan, M., Batista, A., Batistoni, P., Baumane, L., Bauvir, B., Baylor, L., Beaumont, P., Beckett, D., Begolli, A., Beidler, M., Bekris, N., Beldishevski, M., Belli, E., Belli, F., Belonohy, E., Ben Yaala, M., Benayas, J., Bentley, J., Bergsaker, H., Bernardo, J., Bernert, M., Berry, M., Bertalot, L., Betar, H., Beurskens, M., Bickerton, S., Bieg, B., Bielecki, J., Bierwage, A., Biewer, T., Bilato, R., Bílkova, P., Birkenmeier, G., Bishop, H., Bizarro, J., Blackburn, J., Blanchard, P., Blatchford, P., Bobkov, V., Boboc, A., Bohm, P., Bohm, T., Bolshakova, I., Bolzonella, T., Bonanomi, N., Bonfiglio, D., Bonnin, X., Bonofiglo, P., Boocock, S., Booth, A., Booth, J., Borba, D., Borodin, D., Borodkina, I., Boulbe, C., Bourdelle, C., Bowden, M., Boyd, K., Bozicevic Mihalic, I., Bradnam, S., Braic, V., Brandt, L., Bravanec, R., Breizman, B., Brett, A., Brezinsek, S., Brix, M., Bromley, K., Brown, B., Brunetti, D., Buckingham, R., Buckley, M., Budny, R., Buermans, J., Bufferand, H., Buratti, P., Burgess, A., Buscarino, A., Busse, A., Butcher, D., Cal, E., Calabro, G., Calacci, L., Calado, R., Camenen, Y., Canal, G., Cannas, B., Cappelli, M., Carcangiu, S., Card, P., Cardinali, A., Carman, P., Carnevale, D., Carr, M., Carralero, D., Carraro, L., Carvalho, I., Carvalho, P., Casiraghi, I., Casson, F., Castaldo, C., Catalan, J., Catarino, N., Causa, F., Cavedon, M., Cecconello, M., Challis, C., Chamberlain, B., Chang, C., Chankin, A., Chapman, B., Chernyshova, M., Chiariello, A., Chmielewski, P., Chomiczewska, A., Chone, L., Ciraolo, G., Ciric, D., Citrin, J., Ciupinski, t., Clark, M., Clarkson, R., Clements, C., Cleverly, M., Coad, J., Coates, P., Cobalt, A., Coccorese, V., Coelho, R., Coenen, J., Coffey, I., Colangeli, A., Colas, L., Collins, C., Collins, J., Collins, S., Conka, D., Conroy, S., Conway, B., Conway, N., Coombs, D., Cooper, P., Cooper, S., Corradino, C., Corrigan, G., Coster, D., Cox, P., Craciunescu, T., Cramp, S., Crapper, C., Craven, D., Craven, R., Crialesi Esposito, M., Croci, G., Croft, D., Croitoru, A., Crombe, K., Cronin, T., Cruz, N., Crystal, C., Cseh, G., Cufar, A., Cullen, A., Curuia, M., Czarski, T., Dabirikhah, H., Dal Molin, A., Dale, E., Dalgliesh, P., Dalley, S., Dankowski, J., David, P., Davies, A., Davies, S., Davis, G., Dawson, K., Dawson, S., Day, I., De Bock, M., De Temmerman, G., De Tommasi, G., Deakin, K., Deane, J., Dejarnac, R., Del Sarto, D., Delabie, E., Del-Castillo-Negrete, D., Dempsey, A., Dendy, R., Devynck, P., Di Siena, A., Di Troia, C., Dickson, T., Dinca, P., Dittmar, T., Dobrashian, J., Doerner, R., Donne, A., Dorling, S., Dormido-Canto, S., Douai, D., Dowson, S., Doyle, R., Drewelow, P., Drews, P., Drummond, G., Duckworth, P., Dudding, H., Dumont, R., Dumortier, P., Dunai, D., Dunatov, T., Dunne, M., Duran, I., Durodie, F., Dux, R., Dvornova, A., Eastham, R., Edwards, J., Eich, T., Eichorn, A., Eidietis, N., Eksaeva, A., Haroun, H., Ellwood, G., Elsmore, C., Embreus, O., Emery, S., Ericsson, G., Eriksson, B., Eriksson, F., Eriksson, L., Ertmer, S., Esquembri, S., Esquisabel, A., Estrada, T., Evans, G., Evans, S., Fable, E., Fagan, D., Faitsch, M., Falessi, M., Fanni, A., Farahani, A., Farquhar, I., Fasoli, A., Faugeras, B., Fazinie, S., Felici, F., Felton, R., Fernandes, A., Fernandes, H., Ferrand, J., Ferreira, D., Ferreira, J., Ferro, G., Fessey, J., Ficker, O., Field, A., Figueiredo, A., Figueiredo, J., Fil, A., Fil, N., Finburg, P., Fiorucci, D., Fischer, U., Fishpool, G., Fittill, L., Fitzgerald, M., Flammini, D., Flanagan, J., Flinders, K., Foley, S., Fonnesu, N., Fontana, M., Fontdecaba, J., Forbes, S., Formisano, A., Fornal, T., Fortuna, L., Fortuna-Zalesna, E., Fortune, M., Fowler, C., Fransson, E., Frassinetti, L., Freisinger, M., Fresa, R., Fridstrom, R., Frigione, D., Fülop, T., Furseman, M., Fusco, V., Futatani, S., Gadariya, D., Gal, K., Galassi, D., Gafezka, K., Galeani, S., Gallart, D., Galvao, R., Gao, Y., Garcia-Munoz, M., Gardener, M., Garzotti, L., Gaspar, J., Gatto, R., Gaudio, P., Gear, D., Gebhart, T., Gee, S., Gelfusa, M., George, R., Gerasimov, S., Gervasini, G., Gethins, M., Ghani, Z., Gherendi, M., Ghezzi, F., Giacalone, J., Giacomelli, L., Giacometti, G., Gibson, C., Gibson, K., Gil, L., Gillgren, A., Gin, D., Giovannozzi, E., Giroud, C., Glen, R., Gloggler, S., Goff, J., Gohil, P., Goloborodko, V., Gomes, R., Goncalves, B., Goniche, M., Goodyear, A., Gore, S., Gorini, G., Görler, T., Gotts, N., Goulding, R., Gow, E., Graham, B., Graves, J., Greuner, H., Grierson, B., Griffiths, J., Griph, S., Grist, D., Gromelski, W., Groth, M., Grove, R., Gruca, M., Guard, D., Gupta, N., Gurl, C., Gusarov, A., Hackett, L., Hacquin, S., Hager, R., Hagg, L., Hakola, A., Halitovs, M., Hall, S., Hallworth-Cook, S., Ham, C., Hamaguchi, D., Hamed, M., Hamlyn-Harris, C., Hammond, K., Harford, E., Harrison, J., Harting, D., Hatano, Y., Hatch, D., Haupt, T., Hawes, J., Hawkes, N., Hawkins, J., Hayashi, T., Hazael, S., Hazel, S., Heesterman, P., Heidbrink, B., Helou, W., Hemming, O., Henderson, S., Henriques, R., Hepple, D., Herfindal, J., Hermon, G., Hill, J., Hillesheim, J., Hizanidis, K., Hjalmarsson, A., Ho, A., Hobirk, J., Hoenen, O., Hogben, C., Hollingsworth, A., Hollis, S., Hollmann, E., Hoelzl, M., Homan, B., Hook, M., Hopley, D., Horacek, J., Horsley, D., Horsten, N., Horton, A., Horton, L., Horvath, L., Hotchin, S., Howell, R., Hu, Z., Huber, A., Huber, V., Huddleston, T., Huijsmans, G., Huynh, P., Hynes, A., Iliasova, M., lmrie, D., lmrísek, M., lngleby, J., Innocente, P., Insulander Björk, K., Isernia, N., lvanova-Stanik, I., lvings, E., Jablonski, S., Jachmich, S., Jackson, T., Jacquet, P., Järleblad, H., Jaulmes, F., Jenaro Rodriguez, J., Jepu, I., Joffrin, E., Johnson, R., Johnson, T., Johnston, J., Jones, C., Jones, G., Jones, L., Jones, N., Jones, T., Joyce, A., Juarez, R., Juvonen, M., Kalnina, P., Kaltiaisenaho, T., Kaniewski, J., Kantor, A., Kappatou, A., Karhunen, J., Karkinsky, D., Kashchuk, Y., Kaufman, M., Kaveney, G., Kazantzidis, V., Keeling, D., Kelly, R., Kempenaars, M., Kennedy, C., Kennedy, D., Kent, J., Khan, K., Khilkevich, E., Kiefer, C., Kilpeläinen, J., Kim, C., Kim, H., Kim, S., King, D., King, R., Kinna, D., Kiptily, V., Kirjasuo, A., Kirov, K., Kirschner, A., kiviniemi, T., Kizane, G., Klas, M., Klepper, C., Klix, A., Kneale, G., Knight, M., Knight, P., Knights, R., Knipe, S., Knolker, M., Knott, S., Kocan, M., Kochl, F., Kodeli, I., Kolesnichenko, Y., Kominis, Y., Kong, M., Korovin, V., Kos, B., Kos, D., Koslowski, H., Kotschenreuther, M., Koubiti, M., Kowalska-Strzeciwilk, E., Koziol, K., Krasilnikov, A., Krasilnikov, V., Kresina, M., Krieger, K., Krishnan, N., Krivska, A., Kruezi, U., Ksiezek, I., Kukushkin, A., Kumpulainen, H., Kurki-Suonio, T., Kurotaki, H., Kwak, S., Kwon, O., Laguardia, L., Lagzdina, E., Lahtinen, A., Laing, A., Lam, N., Lambertz, H., Lane, B., Lane, C., Lascas Neto, E., Laszyriska, E., Lawson, K., Lazaros, A., Lazzaro, E., Learoyd, G., Lee, C., Lee, S., Leerink, S., Leeson, T., Lefebvre, X., Leggate, H., Lehmann, J., Lehnen, M., Leichtle, D., Leipold, F., Lengar, I., Lennholm, M., Leon Gutierrez, E., Lepiavko, B., Leppanen, J., Lerche, E., Lescinskis, A., Lewis, J., Leysen, W., Li, L., Li, Y., Likonen, J., Linsmeier, C., Lipschultz, B., Litaudon, X., Litherland-Smith, E., Liu, F., Loarer, T., Loarte, A., Lobel, R., Lomanowski, B., Lomas, P., Lopez, J., Lorenzini, R., Loreti, S., Losada, U., Loschiavo, V., Loughlin, M., Louka, Z., Lovell, J., Lowe, T., Lowry, C., Lubbad, S., Luce, T., Lucock, R., Lukin, A., Luna, C., Luna, E., Lungaroni, M., Lungu, C., Lunt, T., Lutsenko, V., Lyons, B., Lyssoivan, A., Machielsen, M., Macusova, E., Mäenpää, R., Maggi, C., Maggiora, R., Magness, M., Mahesan, S., Maier, H., Maingi, R., Malinowski, K., Manas, P., Mantica, P., Mantsinen, M., Manyer, J., Manzanares, A., Maquet, P., Marceca, G., Marcenko, N., Marchetto, C., Marchuk, O., Mariani, A., Mariano, G., Marin, M., Marinelli, M., Markovic, T., Marocco, D., Marot, L., Marsden, S., Marsh, J., Marshall, R., Martellucci, L., Martin, A., Martone, R., Maruyama, S., Maslov, M., Masuzaki, S., Matejcik, S., Mattei, M., Matthews, G., Matveev, D., Matveeva, E., Mauriya, A., Maviglia, F., Mayer, M., Mayoral, M., Mazzotta, C., McAdams, R., McCarthy, P., McClements, K., McClenaghan, J., McCullen, P., McDonald, D., McGuckin, D., McHugh, D., Mclntyre, G., McKean, R., McKehon, J., McMillan, B., McNamee, L., McShee, A., Meakins, A., Medley, S., Meekes, C., Meghani, K., Meigs, A., Meisl, G., Meitner, S., Menmuir, S., Mergia, K., Merriman, S., Mertens, P., Meshchaninov, S., Messiaen, A., Michling, R., Middleton, P., Middleton-Gear, D., Mietelski, J., Milanesio, D., Milani, E., Militello, F., Militello Asp, A., Milnes, J., Milocco, A., Miloshevsky, G., Minghao, C., Minucci, S., Miron, I., Miyamoto, M., Mlynar, J., Moiseenko, V., Monaghan, P., Monakhov, I., Moody, T., Moon, S., Mooney, R., Moradi, S., Morales, J., Morales, R., Mordijck, S., Moreira, L., Morgan, L., Moro, F., Morris, J., Morrison, K., Moser, L., Moulton, D., Mrowetz, T., Mundy, T., Muraglia, M., Murari, A., Muraro, A., Muthusonai, N., N'Konga, B., Na, Y., Nabais, F., Naden, M., Naish, J., Naish, R., Napoli, F., Nardon, E., Naulin, V., Nave, M., Nedzelskiy, I., Nemtsev, G., Nesenevich, V., Nestoras, I., Neu, R., Neverov, V., Ng, S., Nicassio, M., Nielsen, A., Nina, D., Nishijima, D., Noble, C., Nobs, C., Nodwell, D., Nordlund, K., Nordman, H., Normanton, R., Noterdaeme, J., Nowak, S., Nunn, E., Nystrom, H., Oberparleiter, M., Obryk, B., O'Callaghan, J., Odupitan, T., Oliver, H., Olney, R., O'Mullane, M., Organ, E., Orsitto, F., Orszagh, J., Osborne, T., Otin, R., Otsuka, T., Owen, A., Oya, Y., Oyaizu, M., Paccagnella, R., Pace, N., Packer, L., Paige, S., Pajuste, E., Palade, D., Pamela, S., Panadero, N., Panontin, E., Papadopoulos, A., Papp, G., Papp, P., Parail, V., Pardanaud, C., Parisi, J., Parra Diaz, F., Parsloe, A., Parsons, M., Parsons, N., Passeri, M., Patel, A., Pau, A., Pautasso, G., Pavlichenko, R., Pavone, A., Pawelec, E., Paz Soldan, C., Peacock, A., Pearce, M., Peluso, E., Penot, C., Pepperell, K., Pereira, R., Pereira, T., Perelli Cippo, E., Pereslavtsev, P., Perez von Thun, C., Pericoli, V., Perry, D., Peterka, M., Petersson, P., Petravich, G., Petrella, N., Peyman, M., Pillon, M., Pinches, S., Pintsuk, G., Pires de Sa, W., Pires dos Reis, A., Piron, C., Piron, L., Pironti, A., Pitts, R., Plassche, K., Platt, N., Plyusnin, V., Podesta, M., Pokol, G., Poli, F., Pompilian, O., Popovichev, S., Poradzinski, M., Porfiri, M., Porkolab, M., Porosnicu, C., Porton, M., Poulipoulis, G., Predebon, I., Prestopino, G., Price, C., Price, D., Price, M., Primetzhofer, D., Prior, P., Provatas, G., Pucella, G., Puglia, P., Purahoo, K., Pusztai, I., Putignano, O., Pütterich, T., Quercia, A., Rachlew, E., Radulescu, G., Radulovic, V., Rainford, M., Raj, P., Ralph, G., Ramogida, G., Rasmussen, D., Rasmussen, J., Ratta, G., Ratynskaia, S., Rebai, M., Refy, D., Reichle, R., Reinke, M., Reiser, D., Reux, C., Reynolds, S., Richiusa, M., Richyal, S., Rigamonti, D., Rimini, F., Risner, J., Riva, M., Rivero-Rodriguez, J., Roach, C., Robins, R., Robinson, S., Robson, D., Rodionov, R., Rodrigues, P., Rodriguez Ramos, M., Rodriguez-Fernandez, P., Romanelli, F., Romanelli, M., Romanelli, S., Romazanov, J., Rossi, R., Rowe, S., Rowlands, D., Rubel, M., Rubinacci, G., Rubino, G., Ruchko, L., Ruiz, M., Ruiz Ruiz, J., Ruset, C., Rzadkiewicz, J., Saarelma, S., Safi, E., Salewski, M., Salmi, A., Salmon, R., Salzedas, F., Sanders, I., Sandiford, D., Santos, B., Santucci, A., Sarkimaki, K., Sarwar, R., Sarychev, I., Sauter, O., Sauwan, P., Scapin, N., Schluck, F., Schmid, K., Schmuck, S., Schneider, M., Schneider, P., Schworer, D., Scott, G., Scott, M., Scraggs, D., Scully, S., Segato, M., Seo, J., Sergienko, G., Sertoli, M., Sharapov, S., Shaw, A., Sheikh, H., Sheikh, U., Shepherd, A., Shevelev, A., Shigin, P., Shinohara, K., Shiraiwa, S., Shiraki, D., Short, M., Sias, G., Silburn, S., Silva, A., Silva, C., Silva, J., Silvagni, D., Simfukwe, D., Simpson, J., Sinclair, D., Sipilä, S., Sips, A., Siren, P., Sirinelli, A., Sjöstrand, H., Skinner, N., Slater, J., Smith, N., Smith, P., Snell, J., Snoep, G., Snoj, L., Snyder, P., Soare, S., Solano, E., Solokha, V., Somers, A., Sommariva, C., Soni, K., Sorokovoy, E., Sos, M., Sousa, J., Sozzi, C., Spagnolo, S., Spelzini, T., Spineanu, F., Spong, D., Sprada, D., Sridhar, S., Srinivasan, C., Stables, G., Staebler, G., Stamatelatos, I., Staniec, P., Stankunas, G., Stead, M., Stefanikova, E., Stephen, A., Stephens, J., Stevenson, P., Stojanov, M., Strand, P., Strauss, H., Strikwerda, S., Ström, P., Stuart, C., Studholme, W., Subramani, M., Suchkov, E., Sumida, S., Sun, H., Susts, T., Svensson, J., Svoboda, J., Sweeney, R., Sytnykov, D., Szabolics, T., Tabia, B., Tadic, T., Tal, B., Tala, T., Tallargio, A., Tamain, P., Tan, H., Tanaka, K., Tang, W., Tardocchi, M., Taylor, D., Teimane, A., Telesca, G., Teplova, N., Teplukhina, A., Terentyev, D., Terra, A., Terranova, D., Terranova, N., Testa, D., Tholerus, E., Thomas, J., Thoren, E., Thorman, A., Tierens, W., Tinguely, R., Tipton, A., Todd, H., Tokitani, M., Tolias, P., Tomes, M., Tookey, A., Torikai, Y., Toussaint, U., Tsavalas, P., Tskhakaya, D., Turner, I., Turner, M., Turnyanskiy, M., Tvalashvili, G., Tyrrell, S., Tyshchenko, M., Uccello, A., Udintsev, V., Urbanczyk, G., Vadgama, A., Valcarcel, D., Valisa, M., Vallejos Olivares, P., Vallhagen, O., Valovic, M., Van Eester, D., Varje, J., Vartanian, S., Vasilopoulou, T., Vayakis, G., Vecsei, M., Vega, J., Ventre, S., Verdoolaege, G., Verona, C., Verona Rinati, G., Veshchev, E., Vianello, N., Viezzer, E., Vignitchouk, L., Vila, R., Villari, R., Villone, F., Vincenzi, P., Vinyar, I., Viola, B., Virtanen, A., Vitins, A., Vizvary, Z., Vlad, G., Vlad, M., Vondracek, P., de Vries, P., Wakeling, B., Walkden, N., Walker, M., Walker, R., Walsh, M., Wang, E., Wang, N., Warder, S., Warren, R., Waterhouse, J., Watts, C., Wauters, T., Weckmann, A., Wedderburn Maxwell, H., Weiland, M., Weisen, H., Weiszflog, M., Welch, P., Wendler, N., West, A., Wheatley, M., Wheeler, S., Whitehead, A., Whittaker, D., Widdowson, A., Wiesen, S., Wilkinson, J., Williams, J., Willoughby, D., Wilson, I., Wilson, J., Wilson, T., Wischmeier, M., Wise, P., Withenshaw, G., Withycombe, A., Witts, D., Wojcik-Gargula, A., Wolfrum, E., Wood, R., Woodley, C., Woodley, R., Woods, B., Wright, J., Xu, T., Yadikin, D., Yajima, M., Yakovenko, Y., Yang, Y., Yanling, W., Yanovskiy, V., Young, I., Young, R., Zabolockis, R., Zacks, J., Zagorski, R., Zaitsev, F., Zakharov, L., Zarins, A., Zarzoso Fernandez, D., Zastrow, K., Zayachuk, Y., Zerbini, M., Zhang, W., Zhou, Y., Zlobinski, M., Zocco, A., Zohar, A., Zoita, V., Zoletnik, S., Zotta, V., Zoulias, I., Zwingmann, W., Zychor, I., Physique des interactions ioniques et moléculaires (PIIM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche sur la Fusion par confinement Magnétique (IRFM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Swiss Plasma Center (SPC), Ecole Polytechnique Fédérale de Lausanne (EPFL), Laboratory for Plasma Physics (LPP), Ecole Royale Militaire / Koninklijke Militaire School (ERM KMS), Kharkiv Institute of Physics and Technology (Ukraine), V.N. Karazin Kharkiv National University (KhNU), Dipartimento di Fisica (Milano), Università degli Studi di Milano = University of Milan (UNIMI), Consiglio Nazionale delle Ricerche [Milano] (CNR), Jozef Stefan Institute [Ljubljana] (IJS), Culham Centre for Fusion Energy (CCFE), Department of Physics and Astronomy [Uppsala], Uppsala University, This work has been carried out within the framework of the EUROfusion Consortium and has received funding from the Euratom research and training programme 2014–2018 and 2019–2020 under Grant agreement No 633053., Mazzi, S, Garcia, J, Zarzoso, D, Kazakov, Y, Ongena, J, Dreval, M, Nocente, M, Stancar, Z, Szepesi, G, Eriksson, J, Sahlberg, A, Benkadda, S, Abid, N, Abraham, K, Abreu, P, Adabonyan, O, Adrich, P, Afzal, M, Ahlgren, T, Aho-Mantila, L, Aiba, N, Airila, M, Akhtar, M, Albanese, R, Alderson-Martin, M, Alegre, D, Aleiferis, S, Aleksa, A, Alessi, E, Aleynikov, P, Algualcil, J, Ali, M, Allinson, M, Alper, B, Alves, E, Ambrosino, G, Ambrosino, R, Andersson Sunden, E, Andrew, P, Angelini, B, Angioni, C, Antoniou, I, Appel, L, Appelbee, C, Aria, S, Ariola, M, Artaserse, G, Arter, W, Artigues, V, Asakura, N, Ash, A, Ashikawa, N, Aslanyan, V, Astrain, M, Asztalos, O, Auld, D, Auriemma, F, Austin, Y, Avotina, L, Aymerich, E, Baciero, A, Bairaktaris, F, Balbin, J, Balbinot, L, Balboa, I, Balden, M, Balshaw, C, Balshaw, N, Bandaru, V, Banks, J, Baranov, Y, Barcellona, C, Barnard, A, Barnard, M, Barnsley, R, Barth, A, Baruzzo, M, Barwell, S, Bassan, M, Batista, A, Batistoni, P, Baumane, L, Bauvir, B, Baylor, L, Beaumont, P, Beckett, D, Begolli, A, Beidler, M, Bekris, N, Beldishevski, M, Belli, E, Belli, F, Belonohy, E, Ben Yaala, M, Benayas, J, Bentley, J, Bergsaker, H, Bernardo, J, Bernert, M, Berry, M, Bertalot, L, Betar, H, Beurskens, M, Bickerton, S, Bieg, B, Bielecki, J, Bierwage, A, Biewer, T, Bilato, R, Bilkova, P, Birkenmeier, G, Bishop, H, Bizarro, J, Blackburn, J, Blanchard, P, Blatchford, P, Bobkov, V, Boboc, A, Bohm, P, Bohm, T, Bolshakova, I, Bolzonella, T, Bonanomi, N, Bonfiglio, D, Bonnin, X, Bonofiglo, P, Boocock, S, Booth, A, Booth, J, Borba, D, Borodin, D, Borodkina, I, Boulbe, C, Bourdelle, C, Bowden, M, Boyd, K, Bozicevic Mihalic, I, Bradnam, S, Braic, V, Brandt, L, Bravanec, R, Breizman, B, Brett, A, Brezinsek, S, Brix, M, Bromley, K, Brown, B, Brunetti, D, Buckingham, R, Buckley, M, Budny, R, Buermans, J, Bufferand, H, Buratti, P, Burgess, A, Buscarino, A, Busse, A, Butcher, D, de la Cal, E, Calabro, G, Calacci, L, Calado, R, Camenen, Y, Canal, G, Cannas, B, Cappelli, M, Carcangiu, S, Card, P, Cardinali, A, Carman, P, Carnevale, D, Carr, M, Carralero, D, Carraro, L, Carvalho, I, Carvalho, P, Casiraghi, I, Casson, F, Castaldo, C, Catalan, J, Catarino, N, Causa, F, Cavedon, M, Cecconello, M, Challis, C, Chamberlain, B, Chang, C, Chankin, A, Chapman, B, Chernyshova, M, Chiariello, A, Chmielewski, P, Chomiczewska, A, Chone, L, Ciraolo, G, Ciric, D, Citrin, J, Ciupinski, L, Clark, M, Clarkson, R, Clements, C, Cleverly, M, Coad, J, Coates, P, Cobalt, A, Coccorese, V, Coelho, R, Coenen, J, Coffey, I, Colangeli, A, Colas, L, Collins, C, Collins, J, Collins, S, Conka, D, Conroy, S, Conway, B, Conway, N, Coombs, D, Cooper, P, Cooper, S, Corradino, C, Corrigan, G, Coster, D, Cox, P, Craciunescu, T, Cramp, S, Crapper, C, Craven, D, Craven, R, Crialesi Esposito, M, Croci, G, Croft, D, Croitoru, A, Crombe, K, Cronin, T, Cruz, N, Crystal, C, Cseh, G, Cufar, A, Cullen, A, Curuia, M, Czarski, T, Dabirikhah, H, Molin, A, Dale, E, Dalgliesh, P, Dalley, S, Dankowski, J, David, P, Davies, A, Davies, S, Davis, G, Dawson, K, Dawson, S, Day, I, De Bock, M, De Temmerman, G, De Tommasi, G, Deakin, K, Deane, J, Dejarnac, R, Del Sarto, D, Delabie, E, Del-Castillo-Negrete, D, Dempsey, A, Dendy, R, Devynck, P, Di Siena, A, Di Troia, C, Dickson, T, Dinca, P, Dittmar, T, Dobrashian, J, Doerner, R, Donne, A, Dorling, S, Dormido-Canto, S, Douai, D, Dowson, S, Doyle, R, Drewelow, P, Drews, P, Drummond, G, Duckworth, P, Dudding, H, Dumont, R, Dumortier, P, Dunai, D, Dunatov, T, Dunne, M, Duran, I, Durodie, F, Dux, R, Dvornova, A, Eastham, R, Edwards, J, Eich, T, Eichorn, A, Eidietis, N, Eksaeva, A, El Haroun, H, Ellwood, G, Elsmore, C, Embreus, O, Emery, S, Ericsson, G, Eriksson, B, Eriksson, F, Eriksson, L, Ertmer, S, Esquembri, S, Esquisabel, A, Estrada, T, Evans, G, Evans, S, Fable, E, Fagan, D, Faitsch, M, Falessi, M, Fanni, A, Farahani, A, Farquhar, I, Fasoli, A, Faugeras, B, Fazinic, S, Felici, F, Felton, R, Fernandes, A, Fernandes, H, Ferrand, J, Ferreira, D, Ferreira, J, Ferro, G, Fessey, J, Ficker, O, Field, A, Figueiredo, A, Figueiredo, J, Fil, A, Fil, N, Finburg, P, Fiorucci, D, Fischer, U, Fishpool, G, Fittill, L, Fitzgerald, M, Flammini, D, Flanagan, J, Flinders, K, Foley, S, Fonnesu, N, Fontana, M, Fontdecaba, J, Forbes, S, Formisano, A, Fornal, T, Fortuna, L, Fortuna-Zalesna, E, Fortune, M, Fowler, C, Fransson, E, Frassinetti, L, Freisinger, M, Fresa, R, Fridstrom, R, Frigione, D, Fulop, T, Furseman, M, Fusco, V, Futatani, S, Gadariya, D, Gal, K, Galassi, D, Galazka, K, Galeani, S, Gallart, D, Galvao, R, Gao, Y, Garcia-Munoz, M, Gardener, M, Garzotti, L, Gaspar, J, Gatto, R, Gaudio, P, Gear, D, Gebhart, T, Gee, S, Gelfusa, M, George, R, Gerasimov, S, Gervasini, G, Gethins, M, Ghani, Z, Gherendi, M, Ghezzi, F, Giacalone, J, Giacomelli, L, Giacometti, G, Gibson, C, Gibson, K, Gil, L, Gillgren, A, Giovannozzi, E, Giroud, C, Glen, R, Gloggler, S, Goff, J, Gohil, P, Goloborodko, V, Gomes, R, Goncalves, B, Goniche, M, Goodyear, A, Gore, S, Gorini, G, Gorler, T, Gotts, N, Goulding, R, Gow, E, Graham, B, Graves, J, Greuner, H, Grierson, B, Griffiths, J, Griph, S, Grist, D, Gromelski, W, Groth, M, Grove, R, Gruca, M, Guard, D, Gupta, N, Gurl, C, Gusarov, A, Hackett, L, Hacquin, S, Hager, R, Hagg, L, Hakola, A, Halitovs, M, Hall, S, Hallworth-Cook, S, Ham, C, Hamaguchi, D, Hamed, M, Hamlyn-Harris, C, Hammond, K, Harford, E, Harrison, J, Harting, D, Hatano, Y, Hatch, D, Haupt, T, Hawes, J, Hawkes, N, Hawkins, J, Hayashi, T, Hazael, S, Hazel, S, Heesterman, P, Heidbrink, B, Helou, W, Hemming, O, Henderson, S, Henriques, R, Hepple, D, Herfindal, J, Hermon, G, Hill, J, Hillesheim, J, Hizanidis, K, Hjalmarsson, A, Ho, A, Hobirk, J, Hoenen, O, Hogben, C, Hollingsworth, A, Hollis, S, Hollmann, E, Holzl, M, Homan, B, Hook, M, Hopley, D, Horacek, J, Horsley, D, Horsten, N, Horton, A, Horton, L, Horvath, L, Hotchin, S, Howell, R, Hu, Z, Huber, A, Huber, V, Huddleston, T, Huijsmans, G, Huynh, P, Hynes, A, Imrie, D, Imrisek, M, Ingleby, J, Innocente, P, Insulander Bjork, K, Isernia, N, Ivanova-Stanik, I, Ivings, E, Jablonski, S, Jachmich, S, Jackson, T, Jacquet, P, Jarleblad, H, Jaulmes, F, Rodriguez, J, Jepu, I, Joffrin, E, Johnson, R, Johnson, T, Johnston, J, Jones, C, Jones, G, Jones, L, Jones, N, Jones, T, Joyce, A, Juarez, R, Juvonen, M, Kalnina, P, Kaltiaisenaho, T, Kaniewski, J, Kantor, A, Kappatou, A, Karhunen, J, Karkinsky, D, Kaufman, M, Kaveney, G, Kazantzidis, V, Keeling, D, Kelly, R, Kempenaars, M, Kennedy, C, Kennedy, D, Kent, J, Khan, K, Kiefer, C, Kilpelainen, J, Kim, C, Kim, H, Kim, S, King, D, King, R, Kinna, D, Kiptily, V, Kirjasuo, A, Kirov, K, Kirschner, A, Kiviniemi, T, Kizane, G, Klas, M, Klepper, C, Klix, A, Kneale, G, Knight, M, Knight, P, Knights, R, Knipe, S, Knolker, M, Knott, S, Kocan, M, Kochl, F, Kodeli, I, Kolesnichenko, Y, Kominis, Y, Kong, M, Korovin, V, Kos, B, Kos, D, Koslowski, H, Kotschenreuther, M, Koubiti, M, Kowalska-Strzeciwilk, E, Koziol, K, Krasilnikov, V, Kresina, M, Krieger, K, Krishnan, N, Krivska, A, Kruezi, U, Ksiazek, I, Kukushkin, A, Kumpulainen, H, Kurki-Suonio, T, Kurotaki, H, Kwak, S, Kwon, O, Laguardia, L, Lagzdina, E, Lahtinen, A, Laing, A, Lam, N, Lambertz, H, Lane, B, Lane, C, Lascas Neto, E, Laszynska, E, Lawson, K, Lazaros, A, Lazzaro, E, Learoyd, G, Lee, C, Lee, S, Leerink, S, Leeson, T, Lefebvre, X, Leggate, H, Lehmann, J, Lehnen, M, Leichtle, D, Leipold, F, Lengar, I, Lennholm, M, Leon Gutierrez, E, Lepiavko, B, Leppanen, J, Lerche, E, Lescinskis, A, Lewis, J, Leysen, W, Li, L, Li, Y, Likonen, J, Linsmeier, C, Lipschultz, B, Litaudon, X, Litherland-Smith, E, Liu, F, Loarer, T, Loarte, A, Lobel, R, Lomanowski, B, Lomas, P, Lopez, J, Lorenzini, R, Loreti, S, Losada, U, Loschiavo, V, Loughlin, M, Louka, Z, Lovell, J, Lowe, T, Lowry, C, Lubbad, S, Luce, T, Lucock, R, Luna, C, de la Luna, E, Lungaroni, M, Lungu, C, Lunt, T, Lutsenko, V, Lyons, B, Lyssoivan, A, Machielsen, M, Macusova, E, Maenpaa, R, Maggi, C, Maggiora, R, Magness, M, Mahesan, S, Maier, H, Mailloux, J, Maingi, R, Malinowski, K, Manas, P, Mantica, P, Mantsinen, M, Manyer, J, Manzanares, A, Maquet, P, Marceca, G, Marchetto, C, Marchuk, O, Mariani, A, Mariano, G, Marin, M, Marinelli, M, Markovic, T, Marocco, D, Marot, L, Marsden, S, Marsh, J, Marshall, R, Martellucci, L, Martin, A, Martone, R, Maruyama, S, Maslov, M, Masuzaki, S, Matejcik, S, Mattei, M, Matthews, G, Matveev, D, Matveeva, E, Mauriya, A, Maviglia, F, Mayer, M, Mayoral, M, Mazzotta, C, Mcadams, R, Mccarthy, P, Mcclements, K, Mcclenaghan, J, Mccullen, P, Mcdonald, D, Mcguckin, D, Mchugh, D, Mcintyre, G, Mckean, R, Mckehon, J, Mcmillan, B, Mcnamee, L, Mcshee, A, Meakins, A, Medley, S, Meekes, C, Meghani, K, Meigs, A, Meisl, G, Meitner, S, Menmuir, S, Mergia, K, Merriman, S, Mertens, P, Messiaen, A, Michling, R, Middleton, P, Middleton-Gear, D, Mietelski, J, Milanesio, D, Milani, E, Militello, F, Militello Asp, A, Milnes, J, Milocco, A, Miloshevsky, G, Minghao, C, Minucci, S, Miron, I, Miyamoto, M, Mlynar, J, Moiseenko, V, Monaghan, P, Monakhov, I, Moody, T, Moon, S, Mooney, R, Moradi, S, Morales, J, Morales, R, Mordijck, S, Moreira, L, Morgan, L, Moro, F, Morris, J, Morrison, K, Moser, L, Moulton, D, Mrowetz, T, Mundy, T, Muraglia, M, Murari, A, Muraro, A, Muthusonai, N, N'Konga, B, Na, Y, Nabais, F, Naden, M, Naish, J, Naish, R, Napoli, F, Nardon, E, Naulin, V, Nave, M, Nedzelskiy, I, Nestoras, I, Neu, R, Ng, S, Nicassio, M, Nielsen, A, Nina, D, Nishijima, D, Noble, C, Nobs, C, Nodwell, D, Nordlund, K, Nordman, H, Normanton, R, Noterdaeme, J, Nowak, S, Nunn, E, Nystrom, H, Oberparleiter, M, Obryk, B, O'Callaghan, J, Odupitan, T, Oliver, H, Olney, R, O'Mullane, M, Organ, E, Orsitto, F, Orszagh, J, Osborne, T, Otin, R, Otsuka, T, Owen, A, Oya, Y, Oyaizu, M, Paccagnella, R, Pace, N, Packer, L, Paige, S, Pajuste, E, Palade, D, Pamela, S, Panadero, N, Panontin, E, Papadopoulos, A, Papp, G, Papp, P, Parail, V, Pardanaud, C, Parisi, J, Parra Diaz, F, Parsloe, A, Parsons, M, Parsons, N, Passeri, M, Patel, A, Pau, A, Pautasso, G, Pavlichenko, R, Pavone, A, Pawelec, E, Soldan, C, Peacock, A, Pearce, M, Peluso, E, Penot, C, Pepperell, K, Pereira, R, Pereira, T, Cippo, E, Pereslavtsev, P, von Thun, C, Pericoli, V, Perry, D, Peterka, M, Petersson, P, Petravich, G, Petrella, N, Peyman, M, Pillon, M, Pinches, S, Pintsuk, G, de Sa, W, dos Reis, A, Piron, C, Piron, L, Pironti, A, Pitts, R, van de Plassche, K, Platt, N, Plyusnin, V, Podesta, M, Pokol, G, Poli, F, Pompilian, O, Popovichev, S, Poradzinski, M, Porfiri, M, Porkolab, M, Porosnicu, C, Porton, M, Poulipoulis, G, Predebon, I, Prestopino, G, Price, C, Price, D, Price, M, Primetzhofer, D, Prior, P, Provatas, G, Pucella, G, Puglia, P, Purahoo, K, Pusztai, I, Putignano, O, Putterich, T, Quercia, A, Rachlew, E, Radulescu, G, Radulovic, V, Rainford, M, Raj, P, Ralph, G, Ramogida, G, Rasmussen, D, Rasmussen, J, Ratta, G, Ratynskaia, S, Rebai, M, Refy, D, Reichle, R, Reinke, M, Reiser, D, Reux, C, Reynolds, S, Richiusa, M, Richyal, S, Rigamonti, D, Rimini, F, Risner, J, Riva, M, Rivero-Rodriguez, J, Roach, C, Robins, R, Robinson, S, Robson, D, Rodrigues, P, Rodriguez Ramos, M, Rodriguez-Fernandez, P, Romanelli, F, Romanelli, M, Romanelli, S, Romazanov, J, Rossi, R, Rowe, S, Rowlands, D, Rubel, M, Rubinacci, G, Rubino, G, Ruchko, L, Ruiz, M, Ruiz, J, Ruset, C, Rzadkiewicz, J, Saarelma, S, Safi, E, Salewski, M, Salmi, A, Salmon, R, Salzedas, F, Sanders, I, Sandiford, D, Santos, B, Santucci, A, Sarkimaki, K, Sarwar, R, Sarychev, I, Sauter, O, Sauwan, P, Scapin, N, Schluck, F, Schmid, K, Schmuck, S, Schneider, M, Schneider, P, Schworer, D, Scott, G, Scott, M, Scraggs, D, Scully, S, Segato, M, Seo, J, Sergienko, G, Sertoli, M, Sharapov, S, Shaw, A, Sheikh, H, Sheikh, U, Shepherd, A, Shigin, P, Shinohara, K, Shiraiwa, S, Shiraki, D, Short, M, Sias, G, Silburn, S, Silva, A, Silva, C, Silva, J, Silvagni, D, Simfukwe, D, Simpson, J, Sinclair, D, Sipila, S, Sips, A, Siren, P, Sirinelli, A, Sjostrand, H, Skinner, N, Slater, J, Smith, N, Smith, P, Snell, J, Snoep, G, Snoj, L, Snyder, P, Soare, S, Solano, E, Solokha, V, Somers, A, Sommariva, C, Soni, K, Sorokovoy, E, Sos, M, Sousa, J, Sozzi, C, Spagnolo, S, Spelzini, T, Spineanu, F, Spong, D, Sprada, D, Sridhar, S, Srinivasan, C, Stables, G, Staebler, G, Stamatelatos, I, Staniec, P, Stankunas, G, Stead, M, Stefanikova, E, Stephen, A, Stephens, J, Stevenson, P, Stojanov, M, Strand, P, Strauss, H, Strikwerda, S, Strom, P, Stuart, C, Studholme, W, Subramani, M, Suchkov, E, Sumida, S, Sun, H, Susts, T, Svensson, J, Svoboda, J, Sweeney, R, Sytnykov, D, Szabolics, T, Tabia, B, Tadic, T, Tal, B, Tala, T, Tallargio, A, Tamain, P, Tan, H, Tanaka, K, Tang, W, Tardocchi, M, Taylor, D, Teimane, A, Telesca, G, Teplukhina, A, Terentyev, D, Terra, A, Terranova, D, Terranova, N, Testa, D, Tholerus, E, Thomas, J, Thoren, E, Thorman, A, Tierens, W, Tinguely, R, Tipton, A, Todd, H, Tokitani, M, Tolias, P, Tomes, M, Tookey, A, Torikai, Y, von Toussaint, U, Tsavalas, P, Tskhakaya, D, Turner, I, Turner, M, Turnyanskiy, M, Tvalashvili, G, Tyrrell, S, Tyshchenko, M, Uccello, A, Udintsev, V, Urbanczyk, G, Vadgama, A, Valcarcel, D, Valisa, M, Vallejos Olivares, P, Vallhagen, O, Valovic, M, Van Eester, D, Varje, J, Vartanian, S, Vasilopoulou, T, Vayakis, G, Vecsei, M, Vega, J, Ventre, S, Verdoolaege, G, Verona, C, Rinati, G, Veshchev, E, Vianello, N, Viezzer, E, Vignitchouk, L, Vila, R, Villari, R, Villone, F, Vincenzi, P, Viola, B, Virtanen, A, Vitins, A, Vizvary, Z, Vlad, G, Vlad, M, Vondracek, P, de Vries, P, Wakeling, B, Walkden, N, Walker, M, Walker, R, Walsh, M, Wang, E, Wang, N, Warder, S, Warren, R, Waterhouse, J, Watts, C, Wauters, T, Weckmann, A, Wedderburn Maxwell, H, Weiland, M, Weisen, H, Weiszflog, M, Welch, P, Wendler, N, West, A, Wheatley, M, Wheeler, S, Whitehead, A, Whittaker, D, Widdowson, A, Wiesen, S, Wilkinson, J, Williams, J, Willoughby, D, Wilson, I, Wilson, J, Wilson, T, Wischmeier, M, Wise, P, Withenshaw, G, Withycombe, A, Witts, D, Wojcik-Gargula, A, Wolfrum, E, Wood, R, Woodley, C, Woodley, R, Woods, B, Wright, J, Xu, T, Yadikin, D, Yajima, M, Yakovenko, Y, Yang, Y, Yanling, W, Yanovskiy, V, Young, I, Young, R, Zabolockis, R, Zacks, J, Zagorski, R, Zaitsev, F, Zakharov, L, Zarins, A, Zastrow, K, Zayachuk, Y, Zerbini, M, Zhang, W, Zhou, Y, Zlobinski, M, Zocco, A, Zohar, A, Zoita, V, Zoletnik, S, Zotta, V, Zoulias, I, Zwingmann, W, Zychor, I, Mazzi, S., Garcia, J., Zarzoso, D., Kazakov, Y. O., Ongena, J., Dreval, M., Nocente, M., Stancar, Z., Szepesi, G., Eriksson, J., Sahlberg, A., Benkadda, S., Abid, N., Abraham, K., Abreu, P., Adabonyan, O., Adrich, P., Afzal, M., Ahlgren, T., Aho-Mantila, L., Aiba, N., Airila, M., Akhtar, M., Albanese, R., Alderson-Martin, M., Alegre, D., Aleiferis, S., Aleksa, A., Alessi, E., Aleynikov, P., Algualcil, J., Ali, M., Allinson, M., Alper, B., Alves, E., Ambrosino, G., Ambrosino, R., Andersson Sunden, E., Andrew, P., Angelini, B. M., Angioni, C., Antoniou, I., Appel, L. C., Appelbee, C., Aria, S., Ariola, M., Artaserse, G., Arter, W., Artigues, V., Asakura, N., Ash, A., Ashikawa, N., Aslanyan, V., Astrain, M., Asztalos, O., Auld, D., Auriemma, F., Austin, Y., Avotina, L., Aymerich, E., Baciero, A., Bairaktaris, F., Balbin, J., Balbinot, L., Balboa, I., Balden, M., Balshaw, C., Balshaw, N., Bandaru, V. K., Banks, J., Baranov, Y. F., Barcellona, C., Barnard, A., Barnard, M., Barnsley, R., Barth, A., Baruzzo, M., Barwell, S., Bassan, M., Batista, A., Batistoni, P., Baumane, L., Bauvir, B., Baylor, L., Beaumont, P. S., Beckett, D., Begolli, A., Beidler, M., Bekris, N., Beldishevski, M., Belli, E., Belli, F., Belonohy, E., Ben Yaala, M., Benayas, J., Bentley, J., Bergsaker, H., Bernardo, J., Bernert, M., Berry, M., Bertalot, L., Betar, H., Beurskens, M., Bickerton, S., Bieg, B., Bielecki, J., Bierwage, A., Biewer, T., Bilato, R., Bilkova, P., Birkenmeier, G., Bishop, H., Bizarro, J. P. S., Blackburn, J., Blanchard, P., Blatchford, P., Bobkov, V., Boboc, A., Bohm, P., Bohm, T., Bolshakova, I., Bolzonella, T., Bonanomi, N., Bonfiglio, D., Bonnin, X., Bonofiglo, P., Boocock, S., Booth, A., Booth, J., Borba, D., Borodin, D., Borodkina, I., Boulbe, C., Bourdelle, C., Bowden, M., Boyd, K., Bozicevic Mihalic, I., Bradnam, S. C., Braic, V., Brandt, L., Bravanec, R., Breizman, B., Brett, A., Brezinsek, S., Brix, M., Bromley, K., Brown, B., Brunetti, D., Buckingham, R., Buckley, M., Budny, R., Buermans, J., Bufferand, H., Buratti, P., Burgess, A., Buscarino, A., Busse, A., Butcher, D., de la Cal, E., Calabro, G., Calacci, L., Calado, R., Camenen, Y., Canal, G., Cannas, B., Cappelli, M., Carcangiu, S., Card, P., Cardinali, A., Carman, P., Carnevale, D., Carr, M., Carralero, D., Carraro, L., Carvalho, I. S., Carvalho, P., Casiraghi, I., Casson, F. J., Castaldo, C., Catalan, J. P., Catarino, N., Causa, F., Cavedon, M., Cecconello, M., Challis, C. D., Chamberlain, B., Chang, C. S., Chankin, A., Chapman, B., Chernyshova, M., Chiariello, A., Chmielewski, P., Chomiczewska, A., Chone, L., Ciraolo, G., Ciric, D., Citrin, J., Ciupinski, L., Clark, M., Clarkson, R., Clements, C., Cleverly, M., Coad, J. P., Coates, P., Cobalt, A., Coccorese, V., Coelho, R., Coenen, J. W., Coffey, I. H., Colangeli, A., Colas, L., Collins, C., Collins, J., Collins, S., Conka, D., Conroy, S., Conway, B., Conway, N. J., Coombs, D., Cooper, P., Cooper, S., Corradino, C., Corrigan, G., Coster, D., Cox, P., Craciunescu, T., Cramp, S., Crapper, C., Craven, D., Craven, R., Crialesi Esposito, M., Croci, G., Croft, D., Croitoru, A., Crombe, K., Cronin, T., Cruz, N., Crystal, C., Cseh, G., Cufar, A., Cullen, A., Curuia, M., Czarski, T., Dabirikhah, H., Molin, A. D., Dale, E., Dalgliesh, P., Dalley, S., Dankowski, J., David, P., Davies, A., Davies, S., Davis, G., Dawson, K., Dawson, S., Day, I. E., De Bock, M., De Temmerman, G., De Tommasi, G., Deakin, K., Deane, J., Dejarnac, R., Del Sarto, D., Delabie, E., Del-Castillo-Negrete, D., Dempsey, A., Dendy, R. O., Devynck, P., Di Siena, A., Di Troia, C., Dickson, T., Dinca, P., Dittmar, T., Dobrashian, J., Doerner, R. P., Donne, A. J. H., Dorling, S., Dormido-Canto, S., Douai, D., Dowson, S., Doyle, R., Drewelow, P., Drews, P., Drummond, G., Duckworth, P., Dudding, H., Dumont, R., Dumortier, P., Dunai, D., Dunatov, T., Dunne, M., Duran, I., Durodie, F., Dux, R., Dvornova, A., Eastham, R., Edwards, J., Eich, T., Eichorn, A., Eidietis, N., Eksaeva, A., El Haroun, H., Ellwood, G., Elsmore, C., Embreus, O., Emery, S., Ericsson, G., Eriksson, B., Eriksson, F., Eriksson, L. G., Ertmer, S., Esquembri, S., Esquisabel, A. L., Estrada, T., Evans, G., Evans, S., Fable, E., Fagan, D., Faitsch, M., Falessi, M., Fanni, A., Farahani, A., Farquhar, I., Fasoli, A., Faugeras, B., Fazinic, S., Felici, F., Felton, R., Fernandes, A., Fernandes, H., Ferrand, J., Ferreira, D. R., Ferreira, J., Ferro, G., Fessey, J., Ficker, O., Field, A. R., Figueiredo, A., Figueiredo, J., Fil, A., Fil, N., Finburg, P., Fiorucci, D., Fischer, U., Fishpool, G., Fittill, L., Fitzgerald, M., Flammini, D., Flanagan, J., Flinders, K., Foley, S., Fonnesu, N., Fontana, M., Fontdecaba, J. M., Forbes, S., Formisano, A., Fornal, T., Fortuna, L., Fortuna-Zalesna, E., Fortune, M., Fowler, C., Fransson, E., Frassinetti, L., Freisinger, M., Fresa, R., Fridstrom, R., Frigione, D., Fulop, T., Furseman, M., Fusco, V., Futatani, S., Gadariya, D., Gal, K., Galassi, D., Galazka, K., Galeani, S., Gallart, D., Galvao, R., Gao, Y., Garcia-Munoz, M., Gardener, M., Garzotti, L., Gaspar, J., Gatto, R., Gaudio, P., Gear, D., Gebhart, T., Gee, S., Gelfusa, M., George, R., Gerasimov, S. N., Gervasini, G., Gethins, M., Ghani, Z., Gherendi, M., Ghezzi, F., Giacalone, J. C., Giacomelli, L., Giacometti, G., Gibson, C., Gibson, K. J., Gil, L., Gillgren, A., Giovannozzi, E., Giroud, C., Glen, R., Gloggler, S., Goff, J., Gohil, P., Goloborodko, V., Gomes, R., Goncalves, B., Goniche, M., Goodyear, A., Gore, S., Gorini, G., Gorler, T., Gotts, N., Goulding, R., Gow, E., Graham, B., Graves, J. P., Greuner, H., Grierson, B., Griffiths, J., Griph, S., Grist, D., Gromelski, W., Groth, M., Grove, R., Gruca, M., Guard, D., Gupta, N., Gurl, C., Gusarov, A., Hackett, L., Hacquin, S., Hager, R., Hagg, L., Hakola, A., Halitovs, M., Hall, S., Hall, S. A., Hallworth-Cook, S., Ham, C. J., Hamaguchi, D., Hamed, M., Hamlyn-Harris, C., Hammond, K., Harford, E., Harrison, J. R., Harting, D., Hatano, Y., Hatch, D. R., Haupt, T., Hawes, J., Hawkes, N. C., Hawkins, J., Hayashi, T., Hazael, S., Hazel, S., Heesterman, P., Heidbrink, B., Helou, W., Hemming, O., Henderson, S. S., Henriques, R. B., Hepple, D., Herfindal, J., Hermon, G., Hill, J., Hillesheim, J. C., Hizanidis, K., Hjalmarsson, A., Ho, A., Hobirk, J., Hoenen, O., Hogben, C., Hollingsworth, A., Hollis, S., Hollmann, E., Holzl, M., Homan, B., Hook, M., Hopley, D., Horacek, J., Horsley, D., Horsten, N., Horton, A., Horton, L. D., Horvath, L., Hotchin, S., Howell, R., Hu, Z., Huber, A., Huber, V., Huddleston, T., Huijsmans, G. T. A., Huynh, P., Hynes, A., Imrie, D., Imrisek, M., Ingleby, J., Innocente, P., Insulander Bjork, K., Isernia, N., Ivanova-Stanik, I., Ivings, E., Jablonski, S., Jachmich, S., Jackson, T., Jacquet, P., Jarleblad, H., Jaulmes, F., Rodriguez, J. J., Jepu, I., Joffrin, E., Johnson, R., Johnson, T., Johnston, J., Jones, C., Jones, G., Jones, L., Jones, N., Jones, T., Joyce, A., Juarez, R., Juvonen, M., Kalnina, P., Kaltiaisenaho, T., Kaniewski, J., Kantor, A., Kappatou, A., Karhunen, J., Karkinsky, D., Kaufman, M., Kaveney, G., Kazantzidis, V., Keeling, D. L., Kelly, R., Kempenaars, M., Kennedy, C., Kennedy, D., Kent, J., Khan, K., Kiefer, C., Kilpelainen, J., Kim, C., Kim, H. -T., Kim, S. H., King, D. B., King, R., Kinna, D., Kiptily, V. G., Kirjasuo, A., Kirov, K. K., Kirschner, A., Kiviniemi, T., Kizane, G., Klas, M., Klepper, C., Klix, A., Kneale, G., Knight, M., Knight, P., Knights, R., Knipe, S., Knolker, M., Knott, S., Kocan, M., Kochl, F., Kodeli, I., Kolesnichenko, Y., Kominis, Y., Kong, M., Korovin, V., Kos, B., Kos, D., Koslowski, H. R., Kotschenreuther, M., Koubiti, M., Kowalska-Strzeciwilk, E., Koziol, K., Krasilnikov, V., Kresina, M., Krieger, K., Krishnan, N., Krivska, A., Kruezi, U., Ksiazek, I., Kukushkin, A. B., Kumpulainen, H., Kurki-Suonio, T., Kurotaki, H., Kwak, S., Kwon, O. J., Laguardia, L., Lagzdina, E., Lahtinen, A., Laing, A., Lam, N., Lambertz, H. T., Lane, B., Lane, C., Lascas Neto, E., Laszynska, E., Lawson, K. D., Lazaros, A., Lazzaro, E., Learoyd, G., Lee, C., Lee, S. E., Leerink, S., Leeson, T., Lefebvre, X., Leggate, H. J., Lehmann, J., Lehnen, M., Leichtle, D., Leipold, F., Lengar, I., Lennholm, M., Leon Gutierrez, E., Lepiavko, B., Leppanen, J., Lerche, E., Lescinskis, A., Lewis, J., Leysen, W., Li, L., Li, Y., Likonen, J., Linsmeier, C., Lipschultz, B., Litaudon, X., Litherland-Smith, E., Liu, F., Loarer, T., Loarte, A., Lobel, R., Lomanowski, B., Lomas, P. J., Lopez, J. M., Lorenzini, R., Loreti, S., Losada, U., Loschiavo, V. P., Loughlin, M., Louka, Z., Lovell, J., Lowe, T., Lowry, C., Lubbad, S., Luce, T., Lucock, R., Luna, C., de la Luna, E., Lungaroni, M., Lungu, C. P., Lunt, T., Lutsenko, V., Lyons, B., Lyssoivan, A., Machielsen, M., Macusova, E., Maenpaa, R., Maggi, C. F., Maggiora, R., Magness, M., Mahesan, S., Maier, H., Mailloux, J., Maingi, R., Malinowski, K., Manas, P., Mantica, P., Mantsinen, M. J., Manyer, J., Manzanares, A., Maquet, P., Marceca, G., Marchetto, C., Marchuk, O., Mariani, A., Mariano, G., Marin, M., Marinelli, M., Markovic, T., Marocco, D., Marot, L., Marsden, S., Marsh, J., Marshall, R., Martellucci, L., Martin, A., Martin, A. J., Martone, R., Maruyama, S., Maslov, M., Masuzaki, S., Matejcik, S., Mattei, M., Matthews, G. F., Matveev, D., Matveeva, E., Mauriya, A., Maviglia, F., Mayer, M., Mayoral, M. -L., Mazzotta, C., Mcadams, R., Mccarthy, P. J., Mcclements, K. G., Mcclenaghan, J., Mccullen, P., Mcdonald, D. C., Mcguckin, D., Mchugh, D., Mcintyre, G., Mckean, R., Mckehon, J., Mcmillan, B., Mcnamee, L., Mcshee, A., Meakins, A., Medley, S., Meekes, C. J., Meghani, K., Meigs, A. G., Meisl, G., Meitner, S., Menmuir, S., Mergia, K., Merriman, S., Mertens, P., Messiaen, A., Michling, R., Middleton, P., Middleton-Gear, D., Mietelski, J., Milanesio, D., Milani, E., Militello, F., Militello Asp, A., Milnes, J., Milocco, A., Miloshevsky, G., Minghao, C., Minucci, S., Miron, I., Miyamoto, M., Mlynar, J., Moiseenko, V., Monaghan, P., Monakhov, I., Moody, T., Moon, S., Mooney, R., Moradi, S., Morales, J., Morales, R. B., Mordijck, S., Moreira, L., Morgan, L., Moro, F., Morris, J., Morrison, K. -M., Moser, L., Moulton, D., Mrowetz, T., Mundy, T., Muraglia, M., Murari, A., Muraro, A., Muthusonai, N., N'Konga, B., Na, Y. -S., Nabais, F., Naden, M., Naish, J., Naish, R., Napoli, F., Nardon, E., Naulin, V., Nave, M. F. F., Nedzelskiy, I., Nestoras, I., Neu, R., Ng, S., Nicassio, M., Nielsen, A. H., Nina, D., Nishijima, D., Noble, C., Nobs, C. R., Nodwell, D., Nordlund, K., Nordman, H., Normanton, R., Noterdaeme, J. -M., Nowak, S., Nunn, E., Nystrom, H., Oberparleiter, M., Obryk, B., O'Callaghan, J., Odupitan, T., Oliver, H. J. C., Olney, R., O'Mullane, M., Organ, E., Orsitto, F., Orszagh, J., Osborne, T., Otin, R., Otsuka, T., Owen, A., Oya, Y., Oyaizu, M., Paccagnella, R., Pace, N., Packer, L. W., Paige, S., Pajuste, E., Palade, D., Pamela, S. J. P., Panadero, N., Panontin, E., Papadopoulos, A., Papp, G., Papp, P., Parail, V. V., Pardanaud, C., Parisi, J., Parra Diaz, F., Parsloe, A., Parsons, M., Parsons, N., Passeri, M., Patel, A., Pau, A., Pautasso, G., Pavlichenko, R., Pavone, A., Pawelec, E., Soldan, C. P., Peacock, A., Pearce, M., Peluso, E., Penot, C., Pepperell, K., Pereira, R., Pereira, T., Cippo, E. P., Pereslavtsev, P., von Thun, C. P., Pericoli, V., Perry, D., Peterka, M., Petersson, P., Petravich, G., Petrella, N., Peyman, M., Pillon, M., Pinches, S., Pintsuk, G., de Sa, W. P., dos Reis, A. P., Piron, C., Piron, L., Pironti, A., Pitts, R., van de Plassche, K. L., Platt, N., Plyusnin, V., Podesta, M., Pokol, G., Poli, F. M., Pompilian, O. G., Popovichev, S., Poradzinski, M., Porfiri, M. T., Porkolab, M., Porosnicu, C., Porton, M., Poulipoulis, G., Predebon, I., Prestopino, G., Price, C., Price, D., Price, M., Primetzhofer, D., Prior, P., Provatas, G., Pucella, G., Puglia, P., Purahoo, K., Pusztai, I., Putignano, O., Putterich, T., Quercia, A., Rachlew, E., Radulescu, G., Radulovic, V., Rainford, M., Raj, P., Ralph, G., Ramogida, G., Rasmussen, D., Rasmussen, J. J., Ratta, G., Ratynskaia, S., Rebai, M., Refy, D., Reichle, R., Reinke, M., Reiser, D., Reux, C., Reynolds, S., Richiusa, M. L., Richyal, S., Rigamonti, D., Rimini, F. G., Risner, J., Riva, M., Rivero-Rodriguez, J., Roach, C. M., Robins, R., Robinson, S., Robson, D., Rodrigues, P., Rodriguez Ramos, M., Rodriguez-Fernandez, P., Romanelli, F., Romanelli, M., Romanelli, S., Romazanov, J., Rossi, R., Rowe, S., Rowlands, D., Rubel, M., Rubinacci, G., Rubino, G., Ruchko, L., Ruiz, M., Ruiz, J. R., Ruset, C., Rzadkiewicz, J., Saarelma, S., Safi, E., Salewski, M., Salmi, A., Salmon, R., Salzedas, F., Sanders, I., Sandiford, D., Santos, B., Santucci, A., Sarkimaki, K., Sarwar, R., Sarychev, I., Sauter, O., Sauwan, P., Scapin, N., Schluck, F., Schmid, K., Schmuck, S., Schneider, M., Schneider, P. A., Schworer, D., Scott, G., Scott, M., Scraggs, D., Scully, S., Segato, M., Seo, J., Sergienko, G., Sertoli, M., Sharapov, S. E., Shaw, A., Sheikh, H., Sheikh, U., Shepherd, A., Shigin, P., Shinohara, K., Shiraiwa, S., Shiraki, D., Short, M., Sias, G., Silburn, S. A., Silva, A., Silva, C., Silva, J., Silvagni, D., Simfukwe, D., Simpson, J., Sinclair, D., Sipila, S. K., Sips, A. C. C., Siren, P., Sirinelli, A., Sjostrand, H., Skinner, N., Slater, J., Smith, N., Smith, P., Snell, J., Snoep, G., Snoj, L., Snyder, P., Soare, S., Solano, E. R., Solokha, V., Somers, A., Sommariva, C., Soni, K., Sorokovoy, E., Sos, M., Sousa, J., Sozzi, C., Spagnolo, S., Spelzini, T., Spineanu, F., Spong, D., Sprada, D., Sridhar, S., Srinivasan, C., Stables, G., Staebler, G., Stamatelatos, I., Staniec, P., Stankunas, G., Stead, M., Stefanikova, E., Stephen, A., Stephens, J., Stevenson, P., Stojanov, M., Strand, P., Strauss, H. R., Strikwerda, S., Strom, P., Stuart, C. I., Studholme, W., Subramani, M., Suchkov, E., Sumida, S., Sun, H. J., Susts, T. E., Svensson, J., Svoboda, J., Sweeney, R., Sytnykov, D., Szabolics, T., Tabia, B., Tadic, T., Tal, B., Tala, T., Tallargio, A., Tamain, P., Tan, H., Tanaka, K., Tang, W., Tardocchi, M., Taylor, D., Teimane, A. S., Telesca, G., Teplukhina, A., Terentyev, D., Terra, A., Terranova, D., Terranova, N., Testa, D., Tholerus, E., Thomas, J., Thoren, E., Thorman, A., Tierens, W., Tinguely, R. A., Tipton, A., Todd, H., Tokitani, M., Tolias, P., Tomes, M., Tookey, A., Torikai, Y., von Toussaint, U., Tsavalas, P., Tskhakaya, D., Turner, I., Turner, M., Turner, M. M., Turnyanskiy, M., Tvalashvili, G., Tyrrell, S., Tyshchenko, M., Uccello, A., Udintsev, V., Urbanczyk, G., Vadgama, A., Valcarcel, D., Valisa, M., Vallejos Olivares, P., Vallhagen, O., Valovic, M., Van Eester, D., Varje, J., Vartanian, S., Vasilopoulou, T., Vayakis, G., Vecsei, M., Vega, J., Ventre, S., Verdoolaege, G., Verona, C., Rinati, G. V., Veshchev, E., Vianello, N., Viezzer, E., Vignitchouk, L., Vila, R., Villari, R., Villone, F., Vincenzi, P., Viola, B., Virtanen, A. J., Vitins, A., Vizvary, Z., Vlad, G., Vlad, M., Vondracek, P., de Vries, P., Wakeling, B., Walkden, N. R., Walker, M., Walker, R., Walsh, M., Wang, E., Wang, N., Warder, S., Warren, R., Waterhouse, J., Watts, C., Wauters, T., Weckmann, A., Wedderburn Maxwell, H., Weiland, M., Weisen, H., Weiszflog, M., Welch, P., Wendler, N., West, A., Wheatley, M., Wheeler, S., Whitehead, A., Whittaker, D., Widdowson, A., Wiesen, S., Wilkinson, J., Williams, J. C., Willoughby, D., Wilson, I., Wilson, J., Wilson, T., Wischmeier, M., Wise, P., Withenshaw, G., Withycombe, A., Witts, D., Wojcik-Gargula, A., Wolfrum, E., Wood, R., Woodley, C., Woodley, R., Woods, B., Wright, J., Wright, J. C., Xu, T., Yadikin, D., Yajima, M., Yakovenko, Y., Yang, Y., Yanling, W., Yanovskiy, V., Young, I., Young, R., Zabolockis, R. J., Zacks, J., Zagorski, R., Zaitsev, F. S., Zakharov, L., Zarins, A., Zastrow, K. -D., Zayachuk, Y., Zerbini, M., Zhang, W., Zhou, Y., Zlobinski, M., Zocco, A., Zohar, A., Zoita, V., Zoletnik, S., Zotta, V. K., Zoulias, I., Zwingmann, W., Zychor, I., JET Contributors, Science and Technology of Nuclear Fusion, EIRES Eng. for Sustainable Energy Systems, Magneto-Hydro-Dynamic Stability of Fusion Plasmas, Applied Physics and Science Education, Kazakov, Yo, VTT Technical Research Centre of Finland, Culham Science Centre, Princeton Plasma Physics Laboratory, Department of Applied Physics, European Commission, Forschungszentrum Jülich, Universidade Lisboa, Fusion and Plasma Physics, University of Milan - Bicocca, Aalto University, General Atomics, ITER, University of Toyama, CEA, Oak Ridge National Laboratory, Technical University of Madrid, Swiss Federal Institute of Technology Lausanne, Dutch Institute for Fundamental Energy Research, Royal Military Academy, Seoul National University, Chalmers University of Technology, Max Planck Institute for Plasma Physics, KTH Royal Institute of Technology, and Aalto-yliopisto

Subjects
[PHYS]Physics [physics], Settore FIS/01, Settore ING-IND/18 - Fisica dei Reattori Nucleari, General Physics and Astronomy, simulation, magnetically confined plasma, nuclear fusion, tokamaks, turbulence suppression, Plasma, [PHYS.PHYS.PHYS-PLASM-PH]Physics [physics]/Physics [physics]/Plasma Physics [physics.plasm-ph], confinement, transport, Alpha particles, Fusion reactors, Turbulence, physics
Abstract

openaire: EC/H2020/633053/EU//EUROfusion Funding Information: We thank M. Baruzzo and F. Nave for the preparation and execution of JET experiments discussed in this paper; E. de la Luna for support in detailing the experimental diagnostics of JET; A. Ho for assistance in processing the experimental data; T. Görler for providing essential advice to ensure the correct numerical setup for the GENE modelling reported in this paper; Y. Camenen, X. Garbet and A. Bierwage for fruitful discussions about the gyrokinetic analyses; G. Giruzzi for valuable suggestions on the article strategy. The simulations were performed on the IRENE Joliot-Curie HPC system, in the framework of the PRACE projects IONFAST and AFIETC, led by J. Garcia, and on the CINECA Marconi HPC within the project GENE4EP, led by D. Zarzoso. This work has been carried out within the framework of the EUROfusion Consortium and has received funding from the Euratom research and training programme 2014-2018 and 2019-2020 under grant agreement no. 633053. The views and opinions express herein do not necessarily reflect those of the European Commission. Part of the work by Ye. O. Kazakov and J.Ongena was also carried out in the framework of projects done for the ITER Scientist Fellow Network (ISFN). Funding Information: We thank M. Baruzzo and F. Nave for the preparation and execution of JET experiments discussed in this paper; E. de la Luna for support in detailing the experimental diagnostics of JET; A. Ho for assistance in processing the experimental data; T. Görler for providing essential advice to ensure the correct numerical setup for the GENE modelling reported in this paper; Y. Camenen, X. Garbet and A. Bierwage for fruitful discussions about the gyrokinetic analyses; G. Giruzzi for valuable suggestions on the article strategy. The simulations were performed on the IRENE Joliot-Curie HPC system, in the framework of the PRACE projects IONFAST and AFIETC, led by J. Garcia, and on the CINECA Marconi HPC within the project GENE4EP, led by D. Zarzoso. This work has been carried out within the framework of the EUROfusion Consortium and has received funding from the Euratom research and training programme 2014-2018 and 2019-2020 under grant agreement no. 633053. The views and opinions express herein do not necessarily reflect those of the European Commission. Part of the work by Ye. O. Kazakov and J.Ongena was also carried out in the framework of projects done for the ITER Scientist Fellow Network (ISFN). Publisher Copyright: © 2022, The Author(s), under exclusive licence to Springer Nature Limited. Alpha particles with energies on the order of megaelectronvolts will be the main source of plasma heating in future magnetic confinement fusion reactors. Instead of heating fuel ions, most of the energy of alpha particles is transferred to electrons in the plasma. Furthermore, alpha particles can also excite Alfvénic instabilities, which were previously considered to be detrimental to the performance of the fusion device. Here we report improved thermal ion confinement in the presence of megaelectronvolts ions and strong fast ion-driven Alfvénic instabilities in recent experiments on the Joint European Torus. Detailed transport analysis of these experiments reveals turbulence suppression through a complex multi-scale mechanism that generates large-scale zonal flows. This holds promise for more economical operation of fusion reactors with dominant alpha particle heating and ultimately cheaper fusion electricity.

Published
2022
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15. Severe impairment of <scp>patient‐reported</scp> outcomes in patients with chronic hepatitis C virus infection seen in <scp>real‐world</scp> practices across the world: Data from the global liver registry

Author

Zobair M, Younossi, Ming-Lung, Yu, Mohamed, El-Kassas, Gamal, Esmat, Marlen I, Castellanos Fernández, Maria, Buti, Georgios, Papatheodoridis, Yusuf, Yilmaz, Vasily, Isakov, Ajay, Duseja, Nahum, Méndez-Sánchez, Saeed, Hamid, Stuart C, Gordon, Manuel, Romero-Gómez, Wah-Kheong, Chan, Janus P, Ong, Issah, Younossi, Brain, Lam, Mariam, Ziayee, Fatema, Nader, Andrei, Racila, Linda, Henry, and Maria, Stepanova

Subjects
Work productivity, Hepatology, Disease burden, Hepacivirus, Hepatitis C, Chronic, Direct-acting antivirals, Antiviral Agents, Hepatitis C, Infectious Diseases, Diabetes Mellitus, Type 2, Virology, Quality of Life, Humans, Drug Therapy, Combination, Female, Patient Reported Outcome Measures, Registries, Viral hepatitis, Sofosbuvir, Fatigue
Abstract

Cure of chronic hepatitis C (CHC) can lead to improvement of health-related quality of life and other patient-reported outcomes (PROs). While extensive PRO data for CHC patients who were enrolled in clinical trials are available, similar data for patients seen in real-world practices are scarce. Our aim was to assess PROs of CHC patients enrolled from real-world practices from different regions and to compare them with those enrolled in clinical trials. CHC patients seen in clinical practices and not receiving treatment were enrolled in the Global Liver Registry (GLR). Clinical and PRO (FACIT-F, CLDQ-HCV, WPAI) data were collected and compared with the baseline data from CHC patients enrolled in clinical trials. N = 12,171 CHC patients were included (GLR n = 3146, clinical trial subjects n = 9025). Patients were from 30 countries from 6 out of 7 Global Burden of Disease (GBD) super-regions. Compared with clinical trial enrollees, patients from GLR were less commonly enrolled from High-Income GBD super-region, older, more commonly female, less employed, had more type 2 diabetes, anxiety and clinically overt fatigue but less cirrhosis (all p 0.05). In conclusion, hepatitis C patients seen in the real-world practices have PRO impairment driven by fatigue and psychiatric comorbidities.

Published
2022
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16. Spatiotemporal influences of climate and humans on muskox range dynamics over multiple millennia

Author

Elisabetta Canteri, Stuart C. Brown, Niels Martin Schmidt, Rasmus Heller, David Nogués‐Bravo, and Damien A. Fordham

Subjects
Global and Planetary Change, range dynamics, Ecology, Arctic Regions, Fossils, mechanistic model, Climate Change, extinction dynamics, Ruminants, Arctic, climate change, megafauna, spatially explicit population model, Animals, Humans, Environmental Chemistry, DNA, Ancient, exploitation, General Environmental Science
Abstract

Processes leading to range contractions and population declines of Arctic megafauna during the late Pleistocene and early Holocene are uncertain, with intense debate on the roles of human hunting, climatic change, and their synergy. Obstacles to a resolution have included an overreliance on correlative rather than process-explicit approaches for inferring drivers of distributional and demographic change. Here, we disentangle the ecological mechanisms and threats that were integral in the decline and extinction of the muskox (Ovibos moschatus) in Eurasia and in its expansion in North America using process-explicit macroecological models. The approach integrates modern and fossil occurrence records, ancient DNA, spatiotemporal reconstructions of past climatic change, species-specific population ecology, and the growth and spread of anatomically modern humans. We show that accurately reconstructing inferences of past demographic changes for muskox over the last 21,000 years require high dispersal abilities, large maximum densities, and a small Allee effect. Analyses of validated process-explicit projections indicate that climatic change was the primary driver of muskox distribution shifts and demographic changes across its previously extensive (circumpolar) range, with populations responding negatively to rapid warming events. Regional analyses show that the range collapse and extinction of the muskox in Europe (~13,000 years ago) was likely caused by humans operating in synergy with climatic warming. In Canada and Greenland, climatic change and human activities probably combined to drive recent population sizes. The impact of past climatic change on the range and extinction dynamics of muskox during the Pleistocene–Holocene transition signals a vulnerability of this species to future increased warming. By better establishing the ecological processes that shaped the distribution of the muskox through space and time, we show that process-explicit macroecological models have important applications for the future conservation and management of this iconic species in a warming Arctic.

Published
2022
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17. Stable organic radicals and their untapped potential in ionic liquids

Author

Theo A. Ellingsen, Natasha Hoffmann, Wesley J. Olivier, Stuart C. Thickett, Debbie S. Silvester, and Rebecca O. Fuller

Subjects
General Chemistry
Abstract

Stable organic radicals have an open shell structure that makes them suitable for use in a diverse set of applications. Specifically, it is the reversible one-electron redox behaviour that makes these species suitable for energy storage and in molecular electronics. Maintaining chemical stability, low redox potential and charge transfer capabilities, are key to the further development of these materials. To date, researchers have largely focused on the the preparation of new molecules with improved redox capabilities for use in traditional solvents. More recently exploration into the use of ionic liquids to stabilise charged species and reduce side reactions has shown promise. Computational and preliminary experimental studies have explored the impact of ionic liquids on radical stabilisation, and notable improvements have been observed for nitroxide-based materials when traditional solvents are replaced by ionic liquids. However, these gains require significant refinement based on the identity of the radical species and the ionic liquid. In this highlight, we focus on the current state of using ionic liquids as solvents to stabilise organic radicals and suggestions on the future direction of the field.

Published
2022
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19. SARS-CoV-2 Outbreak Dynamics in an Isolated US Military Recruit Training Center With Rigorous Prevention Measures

Author

Rhonda A. Lizewski, Rachel S. G. Sealfon, Sang Woo Park, Gregory R. Smith, Chad K. Porter, Ana S. Gonzalez-Reiche, Yongchao Ge, Clare M. Miller, Carl W. Goforth, Hanna Pincas, Michael S. Termini, Irene Ramos, Venugopalan D. Nair, Stephen E. Lizewski, Hala Alshammary, Regina Z. Cer, Hua Wei Chen, Mary-Catherine George, Catherine E. Arnold, Lindsay A. Glang, Kyle A. Long, Francisco Malagon, Jan J. Marayag, Edgar Nunez, Gregory K. Rice, Ernesto Santa Ana, Megan A. Schilling, Darci R. Smith, Victor A. Sugiharto, Peifang Sun, Adriana van de Guchte, Zenab Khan, Jayeeta Dutta, Sindhu Vangeti, Logan J. Voegtly, Dawn L. Weir, C. Jessica E. Metcalf, Olga G. Troyanskaya, Kimberly A. Bishop-Lilly, Bryan T. Grenfell, Harm van Bakel, Andrew G. Letizia, and Stuart C. Sealfon

Subjects
Male, Military Personnel, SARS-CoV-2, Epidemiology, COVID-19, Humans, Female, Phylogeny, United States, Disease Outbreaks
Abstract

Marine recruits training at Parris Island experienced an unexpectedly high rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, despite preventive measures including a supervised, 2-week, pre-entry quarantine. We characterize SARS-CoV-2 transmission in this cohort.Between May and November 2020, we monitored 2,469 unvaccinated, mostly male, Marine recruits prospectively during basic training. If participants tested negative for SARS-CoV-2 by quantitative polymerase chain reaction (qPCR) at the end of quarantine, they were transferred to the training site in segregated companies and underwent biweekly testing for 6 weeks. We assessed the effects of coronavirus disease 2019 (COVID-19) prevention measures on other respiratory infections with passive surveillance data, performed phylogenetic analysis, and modeled transmission dynamics and testing regimens.Preventive measures were associated with drastically lower rates of other respiratory illnesses. However, among the trainees, 1,107 (44.8%) tested SARS-CoV-2-positive, with either mild or no symptoms. Phylogenetic analysis of viral genomes from 580 participants revealed that all cases but one were linked to five independent introductions, each characterized by accumulation of mutations across and within companies, and similar viral isolates in individuals from the same company. Variation in company transmission rates (mean reproduction number R 0 ; 5.5 [95% confidence interval [CI], 5.0, 6.1]) could be accounted for by multiple initial cases within a company and superspreader events. Simulations indicate that frequent rapid-report testing with case isolation may minimize outbreaks.Transmission of wild-type SARS-CoV-2 among Marine recruits was approximately twice that seen in the community. Insights from SARS-CoV-2 outbreak dynamics and mutations spread in a remote, congregate setting may inform effective mitigation strategies.

Published
2022
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20. A phase II, randomized, open-label, 52-week study of seladelpar in patients with primary biliary cholangitis

Author

Christopher L. Bowlus, Michael R. Galambos, Richard J. Aspinall, Gideon M. Hirschfield, David E.J. Jones, Yvonne Dörffel, Stuart C. Gordon, Stephen A. Harrison, Andreas E. Kremer, Marlyn J. Mayo, Paul J. Thuluvath, Cynthia Levy, Mark G. Swain, Guy W. Neff, David A. Sheridan, Carmen M. Stanca, Christoph P. Berg, Aparna Goel, Mitchell L. Shiffman, John M. Vierling, Pol Boudes, Alexandra Steinberg, Yun-Jung Choi, and Charles A. McWherter

Subjects
Hepatology
Published
2022
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24. Deep Phenotyping of the Lipidomic Response in COVID and non-COVID Sepsis

Author

Meng, Hu, Sengupta, Arjun, Ricciotti, Emanuela, Mrčela, Antonijo, Mathew, Divij, Mazaleuskaya, Liudmila L., Ghosh, Soumita, Brooks, Thomas G., Turner, Alexandra P., Schanoski, Alessa Soares, Lahens, Nicholas F., Tan, Ai Wen, Woolfork, Ashley, Grant, Greg, Susztak, Katalin, Letizia, Andrew G., Sealfon, Stuart C., Wherry, E. John, Laudanski, Krzysztof, Weljie, Aalim M., Meyer, Nuala B., and FitzGerald, Garret A.

Subjects
Article
Abstract

Lipids may influence cellular penetrance by pathogens and the immune response that they evoke. Here we find a broad based lipidomic storm driven predominantly by secretory (s) phospholipase A (2) (sPLA (2) ) dependent eicosanoid production occurs in patients with sepsis of viral and bacterial origin and relates to disease severity in COVID-19. Elevations in the cyclooxygenase (COX) products of arachidonic acid (AA), PGD (2) and PGI (2) , and the AA lipoxygenase (LOX) product, 12-HETE, and a reduction in the high abundance lipids, ChoE 18:3, LPC-O-16:0 and PC-O-30:0 exhibit relative specificity for COVID-19 amongst such patients, correlate with the inflammatory response and link to disease severity. Linoleic acid (LA) binds directly to SARS-CoV-2 and both LA and its di-HOME products reflect disease severity in COVID-19. AA and LA metabolites and LPC-O-16:0 linked variably to the immune response. These studies yield prognostic biomarkers and therapeutic targets for patients with sepsis, including COVID-19. An interactive purpose built interactive network analysis tool was developed, allowing the community to interrogate connections across these multiomic data and generate novel hypotheses.

Published
2023

25. Differential developmental rates and demographics in Red Kangaroo (Osphranter rufus) populations separated by the dingo barrier fence

Author

D Rex Mitchell, Stuart C Cairns, Gerhard Körtner, Corey J A Bradshaw, Frédérik Saltré, and Vera Weisbecker

Subjects
Ecology, Genetics, Animal Science and Zoology, Ecology, Evolution, Behavior and Systematics, Nature and Landscape Conservation
Abstract

Decommissioning the dingo barrier fence has been suggested to reduce destructive dingo control and encourage a free transfer of biota between environments in Australia. Yet the potential impacts that over a century of predator exclusion might have had on the population dynamics and developmental biology of prey populations has not been assessed. We here combine demographic data and both linear and geometric morphometrics to assess differences in populations among 166 red kangaroos (Osphranter rufus)—a primary prey species of the dingo—from two isolated populations on either side of the fence. We also quantified the differences in aboveground vegetation biomass for the last 10 years on either side of the fence. We found that the age structure and growth patterns, but not cranial shape, differed between the two kangaroo populations. In the population living with a higher density of dingoes, there were relatively fewer females and juveniles. These individuals were larger for a given age, despite what seems to be lower vegetation biomass. However, how much of this biomass represented kangaroo forage is uncertain and requires further on-site assessments. We also identified unexpected differences in the ontogenetic trajectories in relative pes length between the sexes for the whole sample, possibly associated with male competition or differential weight-bearing mechanics. We discuss potential mechanisms behind our findings and suggest that the impacts of contrasting predation pressures across the fence, for red kangaroos and other species, merit further investigation.

Published
2023
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26. Anthropogenic nitrogen pollution threats and challenges to the health of South Asian coral reefs

Author

Painter, Stuart C., Artioli, Yuri, Amir, Fathimath Hana, Arnull, Jessica, Ganeshram, Raja S., Ibrahim, Nizam, Samuel, V. Deepak, Robin, R.s., Raghuraman, R., Purvaja, R., Ramesh, R., Rajasuriya, Arjan, Rendon, Olivia R., Shazly, Aminath, Wilson, A. Meriwether W., and Tudhope, Alexander W.

Subjects
Global and Planetary Change, Ocean Engineering, Aquatic Science, Oceanography, Water Science and Technology
Abstract

Nitrogen pollution is a widespread and growing problem in the coastal waters of South Asia yet the ecological impacts on the region’s coral ecosystems are currently poorly known and understood. South Asia hosts just under 7% of global coral reef coverage but has experienced significant and widespread coral loss in recent decades. The extent to which this coral ecosystem decline at the regional scale can be attributed to the multiple threats posed by nitrogen pollution has been largely overlooked in the literature. Here, we assess the evidence for nitrogen pollution impacts on corals in the central Indian Ocean waters of India, Sri Lanka and the Maldives. We find that there is currently limited evidence with which to clearly demonstrate widespread impacts on coral reefs from nitrogen pollution, including from its interactions with other stressors such as seawater warming. However, this does not prove there are no significant impacts, but rather it reflects the paucity of appropriate observations and related understanding of the range of potential impacts of nitrogen pollution at individual, species and ecosystem levels. This situation presents significant research, management and conservation challenges given the wide acceptance that such pollution is problematic. Following from this, we recommend more systematic collection and sharing of robust observations, modelling and experimentation to provide the baseline on which to base prescient pollution control action.

Published
2023
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27. Investigation of Upper Respiratory Carriage of Bacterial Pathogens among University Students in Kampar, Malaysia

Author

Hing Huat Ong, Wai Keat Toh, Li Ying Thong, Lee Quen Phoon, Stuart C. Clarke, and Eddy Seong Guan Cheah

Subjects
Infectious Diseases, upper respiratory tract, Malaysia, carriage study, Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, General Immunology and Microbiology, Public Health, Environmental and Occupational Health
Abstract

The carriage of bacterial pathogens in the human upper respiratory tract (URT) is associated with a risk of invasive respiratory tract infections, but the related epidemiological information on this at the population level is scarce in Malaysia. This study aimed to investigate the URT carriage of Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa among 100 university students by nasal and oropharyngeal swabbing. The presence of S. aureus, K. pneumoniae and P. aeruginosa was assessed via swab culture on selective media and PCR on the resulting isolates. For S. pneumoniae, H. influenzae and N. meningitidis, their presence was assessed via multiplex PCR on the total DNA extracts from chocolate agar cultures. The carriage prevalence of H. influenzae, S. aureus, S. pneumoniae, K. pneumoniae, N. meningitidis and P. aeruginosa among the subjects was 36%, 27%, 15%, 11%, 5% and 1%, respectively, by these approaches. Their carriage was significantly higher in males compared to females overall. The S. aureus, K. pneumoniae and P. aeruginosa isolates were also screened by the Kirby-Bauer assay, in which 51.6% of S. aureus were penicillin-resistant. The outcomes from carriage studies are expected to contribute to informing infectious disease control policies and guidelines.

Published
2023
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28. Modelling Climate Using Leaves of Nothofagus cunninghamii—Overcoming Confounding Factors

Author

Kathryn E. Hill, Stuart C. Brown, Alice Jones, Damien Fordham, and Robert S. Hill

Subjects
Renewable Energy, Sustainability and the Environment, Nothofagus cunninghamii, sun and shade leaves, cuticular anatomy, climate change, Geography, Planning and Development, Building and Construction, Management, Monitoring, Policy and Law
Abstract

Fossil leaf anatomy has previously been used as a proxy for paleoclimate. However, the exposure of leaves to sun or shade during their growth can lead to morphotype differences that confound the interpretation of fossil leaf anatomy in relation to climate and prevent reliable paleoclimate reconstruction. This work aims to model the differences in leaf anatomy that are due to various climatic drivers and differences attributable to sun or shade positions, using Nothofagus cunninghamii as the model species. Leaves from the sun and shade parts of three trees have been sampled from each of 11 sites in Victoria and Tasmania, Australia. The gross morphological and cuticular features have been scored and modelled with climate data from the sites. Random forest models can accurately predict Nothofagus cunninghamii contemporary climatic conditions of the spring temperature and summer rainfall based on leaf anatomical measurements. Leaf area, stomatal density and epidermal cell density are the most accurate predictors of whether a leaf grew in the sun or shade. Leaf area is also the strongest predictor of the maximum and minimum spring temperatures and rainfall. The models have implications for the use of fossilised leaves in paleoclimate reconstruction. The models we have built can be used to effectively predict whether a fossil leaf was from a sun or shade position on the tree and thus enable more reliable inference of paleoclimate by removing the confounding issues of variable leaf anatomy due to sun exposure during growth. Finally, these models could conceivably be used to make predictions of past paleoclimatic conditions provided suitable training and validation data on climatic conditions are available.

Published
2023
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31. Thermal quenching of classical and semiclassical chaos

Author

Sadhasivam, Vijay Ganesh, Meuser, Lars, and Althorpe, Stuart C.

Subjects
FOS: Physical sciences, Chaotic Dynamics (nlin.CD), Nonlinear Sciences - Chaotic Dynamics
Abstract

The growth rate of out-of-time ordered correlators (OTOCs) provide for the notion of a quantum Lyapunov exponent, which quantifies chaos and information scrambling in quantum systems. In thermal ensembles, this growth rate is reduced from its corresponding value in the microcanonical distribution, and a temperature-dependent bound on has been conjectured to exist for the quantum Lyapunov exponent. We detail a two-fold mechanism which is responsible for the reduction of the Lyapunov exponents in thermal quantum systems.

Published
2023

32. Supplementary Figures 1 - 6 from Effector CD8+ T-cell Engraftment and Antitumor Immunity in Lymphodepleted Hosts Is IL7Rα Dependent

Author

Mark P. Rubinstein, David J. Cole, Shikhar Mehrotra, Elizabeth Garrett-Mayer, Kevin F. Staveley-O'Carroll, Guangfu Li, Stuart C. Gilreath, Bennett R. May, Brian P. Riesenberg, and C. Bryce Johnson

Abstract

Figure S1. Blockade of IL-7 but not IL-2 reduces engraftment of IL-12 conditioned (Tc1) CD8+ T cells in lymphodepleted mice. Figure S2. Blockade of cytokine signaling does not reduce the functionality of donor CD8+ T cells. Figure S3. Activated CD8+ T cells do not require TCR engagement for engraftment in an irradiated host. Figure S4. IL-7 mediated proliferation of Tc1 is STAT5 and PI3K dependent. Figure S5. Tc1 cells generated from IL-7Ralpha+/- and wildtype mice exhibit a similar profile except for IL-7Ralpha expression. Figure S6. The level of TCR stimulation, costimulation, and IL-12 drive IL-7Ralpha expression after CD8+ T cell activation.

Published
2023
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33. Data from Effector CD8+ T-cell Engraftment and Antitumor Immunity in Lymphodepleted Hosts Is IL7Rα Dependent

Author

Mark P. Rubinstein, David J. Cole, Shikhar Mehrotra, Elizabeth Garrett-Mayer, Kevin F. Staveley-O'Carroll, Guangfu Li, Stuart C. Gilreath, Bennett R. May, Brian P. Riesenberg, and C. Bryce Johnson

Abstract

Adoptive cellular therapy, in which activated tumor-reactive T cells are transferred into lymphodepleted recipients, is a promising cancer treatment option. Activation of T cells decreases IL7 responsiveness; therefore, IL15 is generally considered the main driver of effector T-cell responses in this setting. However, we found in lymphodepleted mice that CD8+ T cells activated with IL12 showed enhanced engraftment that was initially dependent on host IL7, but not IL15. Mechanistically, enhanced IL7 responsiveness was conferred by elevated IL7Rα expression, which was critical for antitumor immunity. Elevated IL7Rα expression was achievable without IL12, as polyclonal CD8+ T cells activated with high T-cell receptor (TCR) stimulation depended on T-cell IL7Rα expression and host IL7 for maximal engraftment. Finally, IL12 conditioning during the activation of human CD8+ T cells, including TCR-modified T cells generated using a clinically relevant protocol, led to enhanced IL7Rα expression. Our results demonstrate the importance of the donor IL7Rα/host IL7 axis for effector CD8+ T-cell engraftment and suggest novel strategies to improve adoptive cellular therapy as a cancer treatment. Cancer Immunol Res; 3(12); 1364–74. ©2015 AACR.

Published
2023
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35. 3D modelling of tibial plateau fractures: Variability in fracture location and characteristics across Schatzker fracture types

Author

François Fraysse, Stuart C. Millar, Lucian B. Solomon, Dominic Thewlis, John B. Arnold, Millar, Stuart C, Fraysse, Francois, Arnold, John B, Thewlis, Dominic, and Solomon, Lucian B

Subjects
Male, CT reconstruction, 3d model, Imaging data, Condyle, Fracture Fixation, Internal, 03 medical and health sciences, 0302 clinical medicine, Tibial plateau fracture, Humans, Medicine, Fracture type, Retrospective Studies, General Environmental Science, Orthodontics, 030222 orthopedics, geography, Plateau, geography.geographical_feature_category, Tibia, business.industry, 030208 emergency & critical care medicine, Articular surface, medicine.disease, 3D modelling, Tibial Fractures, classification, Fracture (geology), General Earth and Planetary Sciences, Female, Joints, tibial plateau fracture, Tomography, X-Ray Computed, business
Abstract

Introduction: Numerous classifications have been developed to assess tibial plateau fractures (TPF). Of these, the Schatzker system is the most widely reported in the literature yet this system is limited in its characterisation of morphological fracture features underlying the fracture location. The purpose of this study was to compare 3D morphological features of TPFs across different Schatzker types. Methods: This study retrospectively analysed preoperative TPF imaging data to reconstruct 3D models of the fractures. Ninety-one fractures (29 female, 62 male) were analysed and classified using Schatzker. Fracture location across Schatzker types was compared based on division of the articular surface into six ‘zones’. Additionally, morphological characteristics of the fractures were compared based on fracture type, including; the number, volume and shape of the fragments. Results: Schatzker II, IV and VI fractures were most common, making up 41%, 16% and 20%, respectively. Type II fractures commonly involved both the lateral and central aspect of the tibial plateau, similarly, type IV fractures incorporated the lateral condyle in most cases. Considering the morphological metrics, statistically significant differences were observed between Schatzker types for the number of; total, articular, cortical and volumetrically significant (all P < 0.001) fragments along with the volume of both primary (P < 0.001) and secondary (P = 0.02) fragments. Discussion: Assessment of underlying fracture characteristics in addition to fracture location can serve to provide greater detail relating to fracture morphology, which has the potential to assist with both surgical decision making and assessment of postoperative outcomes. Incorporating this information as part of a hierarchical or multifactorial framework for classifying fractures may help distinguish subtle differences between fracture types that are classifiable using the most current systems. Refereed/Peer-reviewed

Published
2021
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36. Biologic characterization of ABCA3 variants in lung tissue from infants and children with ABCA3 deficiency

Author

Kathryn K. Xu, Daniel J. Wegner, Lucille C. Geurts, Hillary B. Heins, Ping Yang, Aaron Hamvas, Pirooz Eghtesady, Stuart C. Sweet, F. Sessions Cole, and Jennifer A. Wambach

Subjects
Pulmonary and Respiratory Medicine, Respiratory Distress Syndrome, Newborn, DNA, Complementary, Nucleotides, Infant, Newborn, DNA, Article, Epigenesis, Genetic, Mutation, Pediatrics, Perinatology and Child Health, Humans, RNA, ATP-Binding Cassette Transporters, Child, Lung
Abstract

ABCA3 is a phospholipid transporter protein required for surfactant assembly in lamellar bodies of alveolar type II cells. Biallelic pathogenic ABCA3 variants cause severe neonatal respiratory distress syndrome or childhood interstitial lung disease. However, ABCA3 genotype alone does not explain the diversity in disease presentation, severity, and progression. Additionally, monoallelic ABCA3 variants have been reported in infants and children with ABCA3-deficient phenotypes. The effects of most ABCA3 variants identified in patients have not been characterized at the RNA level. ABCA3 allele-specific expression occurs in some cell types due to epigenetic regulation. We obtained lung tissue at transplant or autopsy from 16 infants and children with ABCA3 deficiency due to compound heterozygous ABCA3 variants for biologic characterization of the predicted effects of ABCA3 variants at the RNA level and determination of ABCA3 allele expression. We extracted DNA and RNA from frozen lung tissue and reverse-transcribed cDNA from mRNA. We performed Sanger sequencing to assess allele-specific expression by comparing the heights of variant nucleotide peaks in amplicons from genomic DNA and cDNA. We found similar genomic and cDNA variant nucleotide peak heights and no evidence of allele-specific expression among explant or autopsy samples with biallelic missense ABCA3 variants (n = 6). We observed allele-specific expression of missense alleles in trans with frameshift (n = 4) or nonsense (n = 1) variants, attributable to nonsense-mediated decay. The missense variant c.53 A > G;p.Gln18Arg, located near an exon-intron junction, encoded abnormal splicing with skipping of exon 4. Biologic characterization of ABCA3 variants can inform discovery of variant-specific disease mechanisms.

Published
2022
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37. A numerically stable T-matrix method for acoustic scattering by nonspherical particles with large aspect ratios and size parameters

Author

M. Ganesh and Stuart C. Hawkins

Subjects
Acoustics and Ultrasonics, Arts and Humanities (miscellaneous)
Abstract

We consider a two-part method for computing the acoustic scattering T-matrix of a three dimensional particle. The first part involves accurately computing the far fields by solving a number of particular scattering problems. The second part calculates the T-matrix from these far fields using the Fourier transform over the sphere. The two-part method was first introduced in Ganesh and Hawkins [J. Comput. Appl. Math. 234, 1702–1709]. The focus of this work is to demonstrate the numerical stability and physical correctness of the two-part method for scattering by nonspherical particles with large aspect ratios and size parameters that are at the upper limit of numerical stability for the current state-of-the-art algorithm. The numerical stability of the method is attributed to elimination of the Hankel functions by working with the far field. The numerical experiments use our recently developed open-source software package (TMATROM3) that implements the two-part method.

Published
2022
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38. Risk of hepatocellular carcinoma in treatment‐naïve chronic hepatitis B patients receiving tenofovir disoproxil fumarate versus entecavir in the United States

Author

W. Ray Kim, Laura E. Telep, Belinda Jump, Mei Lu, Heribert Ramroth, John Flaherty, Anuj Gaggar, Anand P. Chokkalingam, and Stuart C. Gordon

Subjects
Adult, Male, Hepatitis B virus, Carcinoma, Hepatocellular, Guanine, Hepatology, Liver Neoplasms, Gastroenterology, Antiviral Agents, United States, Hepatitis B, Chronic, Treatment Outcome, Humans, Female, Pharmacology (medical), Tenofovir, Retrospective Studies
Abstract

Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are the first-line treatment agents for chronic hepatitis B virus (HBV). Recently, whether the degree to which the risk of hepatocellular carcinoma (HCC) may be reduced by ETV vs TDF has been debated. We compared the incidence of HCC among treatment-naïve patients receiving TDF vs ETV in the United States.From a large administrative medical claims database of commercially insured patients, we identified 166,933 adults with a diagnosis of chronic hepatitis B and a minimum of 12 months of prior enrolment, of whom 3934 and 6127 initiated ETV and TDF respectively. Fine-Gray hazard regression models incorporating treatment propensity scores (PS) were used to estimate the risk of HCC incidence associated with TDF vs ETV; variables considered for adjustment included demographic characteristics, concomitant medication use and baseline comorbidities, as well as competing events including liver transplantation and medication changes.After PS weighting, the TDF and ETV groups were well-matched. During the follow-up, 90 patients developed HCC, including 50 receiving ETV and 40 receiving TDF, giving rise to crude incidence rates of 0.62 per 100 person-years (PY) and 0.30 per 100 PY respectively. In PS-weighted, multivariable analysis, TDF was associated with a subdistribution hazard ratio for HCC of 0.58 (95% confidence interval [CI]: 0.38-0.89) compared to ETV. Results were similar when patients ≥40 years and men and women were analysed separately.Among commercially insured, treatment-naïve patients with chronic hepatitis B in the United States, treatment with TDF was associated with significantly lower risk of HCC than ETV.

Published
2022
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39. Shoulder Pain, Function, and Ultrasound-Determined Structure in Elite Wheelchair-Using Para Athletes: An Observational Study

Author

Cheri A, Blauwet, Julian, Chakraverty, Wayne, Derman, Guzel, Idrisova, Paul, Martin, Stuart C, Miller, Dylan, Morrissey, and Nick, Webborn

Subjects
Shoulder, Wheelchairs, Athletes, Para-Athletes, Shoulder Pain, Humans, Physical Therapy, Sports Therapy and Rehabilitation, Orthopedics and Sports Medicine
Abstract

This study aimed to determine the relationship between shoulder pain, physical examination, and tissue pathology in manual wheelchair users competing in elite sport.Eighty elite para athletes who used a manual wheelchair for daily mobility were recruited from international track (n = 40), field (n = 19), and powerlifting (n = 21) competitions. Athletes were surveyed regarding shoulder pain history and symptoms (Wheelchair User's Shoulder Pain Index (WUSPI)), whereas independent blind observers measured signs (Physical Examination of the Shoulder Scale (PESS)) and tissue pathology (Ultrasound Shoulder Pathology Rating Scale (USPRS)). Relationships between measures for the total cohort and for subgroups defined by sporting discipline were calculated.A large proportion of athletes reported a history of upper limb pain (39% dominant and 35% nondominant). For the total cohort, WUSPI score was 22.3 ± 26.9, PESS score was 7.4 ± 6.7, and USPRS score was 5.2 ± 4.0. There were no USPRS score differences between athlete subgroups; however, track athletes had lower WUSPI and PESS scores, especially compared with field athletes. The first principal component explained most of the variance in the WUSPI and PESS, which were strongly correlated (r = 0.71), and the second orthogonal component explained the USPRS, which did not correlate with either the PESS (r = 0.21) or WUSPI (r = 0.20). Subgroup analysis showed that track athletes had lower symptom scores for a given physical examination score.Elite para athletes who use manual wheelchairs for daily mobility have a high prevalence of shoulder symptoms, positive signs on physical examination, and ultrasound-determined tissue pathology. Ultrasound-determined tissue pathology does not correlate with symptoms or signs. This information can help to guide clinicians in managing shoulder problems in this athlete population at high risk of injury.

Published
2022
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40. Incidence of Malignancies Among Patients With Chronic Hepatitis B in US Health Care Organizations, 2006–2018

Author

Philip R Spradling, Jian Xing, Yuna Zhong, Loralee B Rupp, Anne C Moorman, Mei Lu, Eyasu H Teshale, Mark A Schmidt, Yihe G Daida, Joseph A Boscarino, and Stuart C Gordon

Subjects
Hepatitis B virus, Carcinoma, Hepatocellular, Hepatitis B, Chronic, Infectious Diseases, Incidence, Liver Neoplasms, Humans, Immunology and Allergy, Hepatitis B, Delivery of Health Care, digestive system diseases
Abstract

Hepatitis B virus (HBV) infection causes hepatocellular carcinoma but its association with other cancers is not well established. We compared age-adjusted incidence of primary cancers among 5773 HBV-infected persons with US cancer registries during 2006–2018. Compared with the US population, substantially higher incidence among HBV-infected persons was observed for hepatocellular carcinoma (standardized rate ratio [SRR], 30.79), gastric (SRR, 7.95), neuroendocrine (SRR, 5.88), cholangiocarcinoma (SRR, 4.62), and ovarian (SRR, 3.72) cancers, and non-Hodgkin lymphoma (SRR, 2.52). Clinicians should be aware of a heightened potential for certain nonhepatic malignancies among hepatitis B patients, as earlier diagnosis favors improved survival.

Published
2022
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41. CTOTC-08: A multicenter randomized controlled trial of rituximab induction to reduce antibody development and improve outcomes in pediatric lung transplant recipients

Author

Jonah Odim, Thalachallour Mohanakumar, Carol Conrad, Lara Danziger-Isakov, Brian Armstrong, Hyunsook Chin, Marc G. Schecter, Samuel Goldfarb, Don Hayes, N. Williams, Joshua Blatter, Peter S. Heeger, Stuart C. Sweet, Ranjithkumar Ravichandran, Gary A. Visner, Gregory A. Storch, Victoria Lyou, and E. Melicoff-Portillo

Subjects
Transplantation, medicine.medical_specialty, Lung, business.industry, Bronchiolitis obliterans, Placebo, medicine.disease, law.invention, Clinical trial, medicine.anatomical_structure, Randomized controlled trial, law, Bronchiolitis, Internal medicine, Immunology and Allergy, Medicine, Pharmacology (medical), Rituximab, business, Adverse effect, medicine.drug
Abstract

We conducted a randomized, placebo-controlled, double-blind study of pediatric lung transplant recipients, hypothesizing that rituximab plus rabbit anti-thymocyte globulin induction would reduce de novo donor-specific human leukocyte antigen antibodies (DSA) development and improve outcomes. We serially obtained clinical data, blood, and respiratory samples for at least one year posttransplant. We analyzed peripheral blood lymphocytes by flow cytometry, serum for antibody development, and respiratory samples for viral infections using multiplex PCR. Of 45 subjects enrolled, 34 were transplanted and 27 randomized to rituximab (n = 15) or placebo (n = 12). No rituximab-treated subjects versus five placebo-treated subjects developed de novo DSA with mean fluorescence intensity >2000. There was no difference between treatment groups in time to the primary composite outcome endpoint (death, bronchiolitis obliterans syndrome [BOS] grade 0-p, obliterative bronchiolitis or listing for retransplant). A post-hoc analysis substituting more stringent chronic lung allograft dysfunction criteria for BOS 0-p showed no difference in outcome (p = .118). The incidence of adverse events including infection and rejection episodes was no different between treatment groups. Although the study was underpowered, we conclude that rituximab induction may have prevented early DSA development in pediatric lung transplant recipients without adverse effects and may improve outcomes (Clinical Trials: NCT02266888).

Published
2022
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43. Figure S1 from The MEK5–ERK5 Kinase Axis Controls Lipid Metabolism in Small-Cell Lung Cancer

Author

Julien Sage, Kévin Contrepois, Michael P. Snyder, Lauren Averett Byers, Laurent Le Cam, Andrew He, Alexandros P. Drainas, Jun W. Kim, Stuart C. Williamson, Triparna Sen, Siqi Cao, Julia Arand, Maya Gershkovitz, Daniel Hornburg, Garry L. Coles, and Sandra Cristea

Abstract

Related to Figure 1: MEK5 and ERK5 mRNA and protein knock-down inhibits the expansion of SCLC cells in culture

Published
2023
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44. Supplementary Figure 1, Table 1 from Natural product derivative Bis(4-fluorobenzyl)trisulfide inhibits tumor growth by modification of β-tubulin at Cys 12 and suppression of microtubule dynamics

Author

Xiao Xu, Xiaobo Wang, Meihua Sui, Weimin Fan, Huifang Yan, Baoqin Geng, Michelle Gaylord, Stuart C. Feinstein, Yama Abassi, Jenny Zhu, Haoyun An, Jieying Wu, Biao Xi, and Wanhong Xu

Abstract

Supplementary Figure 1, Table 1 from Natural product derivative Bis(4-fluorobenzyl)trisulfide inhibits tumor growth by modification of β-tubulin at Cys 12 and suppression of microtubule dynamics

Published
2023
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45. Figure S7 from The MEK5–ERK5 Kinase Axis Controls Lipid Metabolism in Small-Cell Lung Cancer

Author

Julien Sage, Kévin Contrepois, Michael P. Snyder, Lauren Averett Byers, Laurent Le Cam, Andrew He, Alexandros P. Drainas, Jun W. Kim, Stuart C. Williamson, Triparna Sen, Siqi Cao, Julia Arand, Maya Gershkovitz, Daniel Hornburg, Garry L. Coles, and Sandra Cristea

Abstract

Related to Figure 5: Human SCLC cells are sensitive to inhibition of the mevalonate pathway

Published
2023
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46. Data from The MEK5–ERK5 Kinase Axis Controls Lipid Metabolism in Small-Cell Lung Cancer

Author

Julien Sage, Kévin Contrepois, Michael P. Snyder, Lauren Averett Byers, Laurent Le Cam, Andrew He, Alexandros P. Drainas, Jun W. Kim, Stuart C. Williamson, Triparna Sen, Siqi Cao, Julia Arand, Maya Gershkovitz, Daniel Hornburg, Garry L. Coles, and Sandra Cristea

Abstract

Small-cell lung cancer (SCLC) is an aggressive form of lung cancer with dismal survival rates. While kinases often play key roles driving tumorigenesis, there are strikingly few kinases known to promote the development of SCLC. Here, we investigated the contribution of the MAPK module MEK5–ERK5 to SCLC growth. MEK5 and ERK5 were required for optimal survival and expansion of SCLC cell lines in vitro and in vivo. Transcriptomics analyses identified a role for the MEK5–ERK5 axis in the metabolism of SCLC cells, including lipid metabolism. In-depth lipidomics analyses showed that loss of MEK5/ERK5 perturbs several lipid metabolism pathways, including the mevalonate pathway that controls cholesterol synthesis. Notably, depletion of MEK5/ERK5 sensitized SCLC cells to pharmacologic inhibition of the mevalonate pathway by statins. These data identify a new MEK5–ERK5–lipid metabolism axis that promotes the growth of SCLC.Significance:This study is the first to investigate MEK5 and ERK5 in SCLC, linking the activity of these two kinases to the control of cell survival and lipid metabolism.

Published
2023
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47. Supplementary File from Peripheral Neuropathy Induced by Microtubule-Targeted Chemotherapies: Insights into Acute Injury and Long-term Recovery

Author

Barbara S. Slusher, Michael Polydefkis, Guido Cavaletti, Stuart C. Feinstein, Mary A. Jordan, Leslie Wilson, Christopher DesJardins, Sean Eckley, Krista Condon, Kenichi Nomoto, Bruce A. Littlefield, Brett M. Cook, Sara Semperboni, Eleonora Pozzi, Paola Alberti, Elisa Ballarini, Virginia Rodriguez-Menendez, Valentina A. Carozzi, Ying Liu, Ying Wu, James J. Vornov, and Krystyna M. Wozniak

Abstract

File contains description of supplementary methods used for sciatic nerve immunofluorescence data generation and quantification with Supplementary Fig 1 showing how raw fluorescence intensity values were normalized in order to compare levels of acetylated alpha tubulin from samples across treatment groups. Supplementary Figs 2 thru 4 show DRG and sciatic nerve morphology/morphometrics for chemotherapies other than PACLI. Supplementary Table 1 adds perspective to how MTD used to compare the chemotherapies in this study relates to their pharmacokinetic and IC50 properties.

Published
2023
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48. Supplementary Data from The MEK5–ERK5 Kinase Axis Controls Lipid Metabolism in Small-Cell Lung Cancer

Author

Julien Sage, Kévin Contrepois, Michael P. Snyder, Lauren Averett Byers, Laurent Le Cam, Andrew He, Alexandros P. Drainas, Jun W. Kim, Stuart C. Williamson, Triparna Sen, Siqi Cao, Julia Arand, Maya Gershkovitz, Daniel Hornburg, Garry L. Coles, and Sandra Cristea

Abstract

The 16 Supplementary Tables in the document provide information (including raw data) related to data throughout the manuscript

Published
2023
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49. Data from Natural product derivative Bis(4-fluorobenzyl)trisulfide inhibits tumor growth by modification of β-tubulin at Cys 12 and suppression of microtubule dynamics

Author

Xiao Xu, Xiaobo Wang, Meihua Sui, Weimin Fan, Huifang Yan, Baoqin Geng, Michelle Gaylord, Stuart C. Feinstein, Yama Abassi, Jenny Zhu, Haoyun An, Jieying Wu, Biao Xi, and Wanhong Xu

Abstract

Bis(4-fluorobenzyl)trisulfide (BFBTS) is a synthetic molecule derived from a bioactive natural product, dibenzyltrisulfide, found in a subtropical shrub, Petiveria allieacea. BFBTS has potent anticancer activities to a broad spectrum of tumor cell lines with IC50 values from high nanomolar to low micromolar and showed equal anticancer potency between tumor cell lines overexpressing multidrug-resistant gene, MDR1 (MCF7/adr line and KBv200 line), and their parental MCF7 line and KB lines. BFBTS inhibited microtubule polymerization dynamics in MCF7 cells, at a low nanomolar concentration of 54 nmol/L, while disrupting microtubule filaments in cells at low micromolar concentration of 1 μmol/L. Tumor cells treated with BFBTS were arrested at G2-M phase, conceivably resulting from BFBTS-mediated antimicrotubule activities. Mass spectrometry studies revealed that BFBTS bound and modified β-tubulin at residue Cys12, forming β-tubulin-SS-fluorobenzyl. The binding site differs from known antimicrotubule agents, suggesting that BFBTS functions as a novel antimicrotubule agent. BFBTS at a dose of 25 mg/kg inhibited tumor growth with relative tumor growth rates of 19.91%, 18.5%, and 23.42% in A549 lung cancer, Bcap-37 breast cancer, and SKOV3 ovarian cancer xenografts, respectively. Notably, BFBTS was more potent against MDR1-overexpressing MCF7/adr breast cancer xenografts with a relative tumor growth rate of 12.3% than paclitaxel with a rate of 43.0%. BFBTS displays a novel antimicrotubule agent with potentials for cancer therapeutics. [Mol Cancer Ther 2009;8(12):3318–30]

Published
2023
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