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1. From LLM to NMT: Advancing Low-Resource Machine Translation with Claude

Author

Enis, Maxim and Hopkins, Mark

Subjects
Computer Science - Computation and Language, Computer Science - Artificial Intelligence
Abstract

We show that Claude 3 Opus, a large language model (LLM) released by Anthropic in March 2024, exhibits stronger machine translation competence than other LLMs. Though we find evidence of data contamination with Claude on FLORES-200, we curate new benchmarks that corroborate the effectiveness of Claude for low-resource machine translation into English. We find that Claude has remarkable \textit{resource efficiency} -- the degree to which the quality of the translation model depends on a language pair's resource level. Finally, we show that advancements in LLM translation can be compressed into traditional neural machine translation (NMT) models. Using Claude to generate synthetic data, we demonstrate that knowledge distillation advances the state-of-the-art in Yoruba-English translation, meeting or surpassing strong baselines like NLLB-54B and Google Translate., Comment: 17 pages, 15 figures

Published
2024

3. Normal Forms for Elements of ${}^*$-Continuous Kleene Algebras Representing the Context-Free Languages

Author

Hopkins, Mark and Leiß, Hans

Subjects
Computer Science - Formal Languages and Automata Theory, F.4.3
Abstract

Within the tensor product $K \mathop{\otimes_{\cal R}} C_2'$ of any ${}^*$-continuous Kleene algebra $K$ with the polycyclic ${}^*$-continuous Kleene algebra $C_2'$ over two bracket pairs there is a copy of the fixed-point closure of $K$: the centralizer of $C_2'$ in $K \mathop{\otimes_{\cal R}} C_2'$. Using an automata-theoretic representation of elements of $K\mathop{\otimes_{\cal R}} C_2'$ \`a la Kleene, with the aid of normal form theorems that restrict the occurrences of brackets on paths through the automata, we develop a foundation for a calculus of context-free expressions without variable binders. We also give some results on the bra-ket ${}^*$-continuous Kleene algebra $C_2$, motivate the ``completeness equation'' that distinguishes $C_2$ from $C_2'$, and show that $C_2'$ already validates a relativized form of this equation., Comment: Revised version. 43 pages, 4 figures

Published
2023

7. Normal Forms for Elements of the

Author

Hopkins, Mark, Leiß, Hans, Goos, Gerhard, Founding Editor, Hartmanis, Juris, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Glück, Roland, editor, Santocanale, Luigi, editor, and Winter, Michael, editor

Published
2023
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8. Reed at SemEval-2020 Task 9: Fine-Tuning and Bag-of-Words Approaches to Code-Mixed Sentiment Analysis

Author

Gopalan, Vinay and Hopkins, Mark

Subjects
Computer Science - Computation and Language
Abstract

We explore the task of sentiment analysis on Hinglish (code-mixed Hindi-English) tweets as participants of Task 9 of the SemEval-2020 competition, known as the SentiMix task. We had two main approaches: 1) applying transfer learning by fine-tuning pre-trained BERT models and 2) training feedforward neural networks on bag-of-words representations. During the evaluation phase of the competition, we obtained an F-score of 71.3% with our best model, which placed $4^{th}$ out of 62 entries in the official system rankings.

Published
2020

12. Clinical features and management of individuals admitted to hospital with monkeypox and associated complications across the UK: a retrospective cohort study

Author

Dunning, Jake, Fink, Douglas L, Milligan, Iain D, Luintel, Akish, Rodger, Alison J, Bhagani, Sanjay R, Lamb, Lucy E, Moores, Rachel C, Lee, Simon F K, Brown, Colin S, Hopkins, Susan, Mepham, Stephen, Warren, Simon, Molloy, Aoife, Cropley, Ian, Kew, Alex, Karunaharan, Natasha, Scobie, Antonia, Hart, Jennifer, Irish, Dianne, Haque, Tanzina, Jalal, Hamid, Smith, Robin, Mack, Damien, Barber, Tristan, Burns, Fiona, Miller, Robert, Hamlyn, Eleanor, Simoes, Pedro, Athan, Breda, Abrahamsen, Jennifer, Joyce, Jessica, Taylor, Caroline, Reddecliffe, Sally, Miller, Chloe, Reeve, Brooke, Kingston, Hugh, Crocker-Buque, Tim, Massie, Nicolas, Dhariwal, Ankush, Jayakumar, Angelina, Hammond, Robert, Bramley, Alexandra, Kanitkar, Tanmay, Maynard-Smith, Laura, Gil, Eliza, O'Connor, Cavan, Cocker, Derek, Spicer, Wendy, Lanzman, Marisa, Thacker, Meera, Anorson, Zoe O, Patel, Dharmesh, Williams, Alan, Houlihan, Catherine F, Wakerley, Dominic, Gordon, Claire N, Callaby, Helen, Bailey, Daniel J, Furneaux, Jenna, Bown, Abbie M, Truelove, Elizabeth J, Killip, Marian J, Jackson, David, Beetar-King, Tracy L B, Arnold, Ulrike M V, Strachan, Rhea M, Matthew, Jones, Matthew, Hannah J, Osborne, Jane C, Rampling, Tommy, Vipond, Richard, Gibney, Barry, Owen, Jodie, Bond, Helena, Beynon, Will, Hunter, Michael, McCorry, Louise, Emerson, Carol, Quah, Say, Todd, Suzanne, McCarty, Emma, Walker, Eoin, Feeney, Susan, Curran, Tanya, Li, Kathy, Mullan, JD, Jackson, Kate, Nelson, Peter, Lewis, Kevin, McNicol, Mark, Pratt, Marcus, Smith, Anna, Vos, Erin, Alsalemee, Fahad, O Leary, Daniel, Canny, John, McGinnity, Katherine, Culbert, Carly, McDowell, Conor, McQuillan, Cathy, Jeong, Eunjin, Glass, Lynsey, Dyche, Jessica, McClean, Paula, Stewart, Rebecca, Ursolino, Harold, Perry, Melissa, McCormick, Hannah, Lim, Eleanor Y, Gkrania-Klotsas, Effrossyni, Bracchi, Margherita, Heskin, Joseph, Brown, Nicklas, Juniper, Thomas, Mora-Peris, Borja, Dalla-Pria, Alessia, Mackie, Nicola, Garvey, Lucy, Winston, Alan, Cooke, Graham, Nelson, Mark, Kilbride, Emer, Elbishi, Ala, Kerrigan, William, Silva, Joshua, Gohil, Jesal, Payagala, Sasha, Walters, Yasmin, Smith, Joanna, Goodfellow, Jonathan, Lyons, Kitty, Tung, Hsiu, Patel, Kinjal, Henderson, Merle, Butler, Michael, Peres, Edu, Silva Carvalho, Taiana, Joly, Antoine, Dickinson, Molly, Moore, Luke S P, Mughal, Nabeela, Hughes, Stephen, Chitlangia, Shrada, Viramgana, Priyanka, Byrne, Ruth, Randell, Paul, Strangis, Luigi, Poveda, Nicola, Bovey, Deborah, Richardson, Poppy, Heaslip, Vivian, Higgs, Christopher, Boffito, Marta, Girometti, Nicolo, Whitlock, Gary, Tittle, Victoria, Jones, Rachel, Rayment, Michael, Scott, Christopher, Asboe, David, Pond, Marcus, Muir, David, Rathish, Balram, O'Hara, Geraldine, Abeywickrema, Movin, Bailey, Sarah-Lou, Boyd, Sara E, Da Silva Fontoura, Dayana, Daunt, Anna, Mason, Claire Y, Murphy, Jamie, Naidu, Vasanth V, Patel, Aatish, Pley, Caitlin, Redmore, Ethan, Sharrocks, Katherine, Snell, Luke B, Sundramoorthi, Rohan, Tam, Jerry C H, Brown, Aisling, Douthwaite, Sam, Goodman, Anna, Nebbia, Gaia, Newsholme, William, Price, Nicholas, Shaw, Emily, Salam, Alex, van Nispen tot Pannerden, Claire, Winslow, Helen, Bilinska, Julia, Keegan, Sarah, Coleman, Harry, Doctor, Jessica, Moini, Nasreen, Chilton, Daniella, Haidari, Golaleh, Simons, Rebecca, Kulasegaram, Rajababu, Larbalestier, Nick, Nori, Achyuta, Potter, Jack R, Tuudah, Cecilia, Wade, Paul, Travers, Alexandra, Dunford, Sarah, Greenwood, Joshua, Oledimmah, Georgina, Gyampo, Lesley, SA Pinto, Pedro, Muse, AbdulKadir, Parker, Zoe, Alexander, Charlotte, Khan, Alexander, Ajayi, Medinat, Baltazar, Abigail, Sharella, Davis, Hersi, Nasra, Nguyen, Thuy, Timbo, Rugiatu, Jalloh, Ismail, Bryan, Susan, Clarke, Patricia, Kerr, Marcia, Amedu, Fidelis, BohoBonaba, Maria, Haque, Sarah, Howson, Michelle, Tambilawan, Norbai, Yupanqui Estay, Soledad, Bangura, Hawanatu, Gideon, Tseday, Jerome-oboh, Damilola, Tetteh, Linda, Nwagu, Chioma, Agbaglah, Viwoalo, Narag, Nona, Zaveri, Mahima, Ni Luanaigh, Maedhbh, Keane, Peggy, Peters, Joanna R, Rimmer, Stephanie, Abbara, Aula, Dosekun, Olamide, Bolland, Mhairi, Stafford, Adam, Saleh, Dina, Sheridan, Rhianna, Davies, Ella, Sun, Kristi, Gilchrist, Mark, Kukadia, Priti, Embrahimsa, Muhammed, Chiu, Christopher, Taylor, Lauren, Short, Charlotte, Alagratnam, Jasmini, Jayaweera, Iresh, Gundugola, Kavitha, Payne, Lara V S, Mody, Nisha, Quinn, Killian, Nic Fhogartaigh, Caoimhe, Kaur, Nivenjit, Bholah, Salmaan, Kantha, Kajann, Youngs, Jonathan, Lampejo, Temi, Pitto, Nicholas, Lawrence, David S, Middleditch, Holly, Dominguez-Dominguez, Lourdes, Ratnappuli, Ayoma, Al-Hashimi, Sara, Oliveira, Amelia, Ottaway, Zoe, Mulka, Larissa, Hodgson, Bethany, Lewthwaite, Penny, Neary, Anne M, Downey, Michael R, Lucy, Danielle C, McCallum, Craig I, Beadsworth, Michael, Ratcliffe, Libuse, Fletcher, Tom E, Davies, Gerry, Wong, Nicholas, Aston, Stephen, Wingfield, Thomas E, Blanchard, Thomas, Hine, Paul, Lester, Rebecca, Woolley, Stephen D, Gould, Susie, Smith, Christopher, Abouyannis, Michael, Atomode, Abolaji, Cruise, James, Samual, Merna, Scott, Nicola, Srirathan, Vino, Lewis, Joseph, Richards, Lauren, Cummings, Mary-Ann, Gillan, Emily, Peers, Rebecca, Tickle, Amy, Keating, Grace, Chinyanda, Tendi, Sanchez, Mav, Harrison, Daniel, Hoyle, Metcalfe, Ben, Taylor, Jennifer, Johnson, Nicky, Kelle, Neil, McDowell, Kirsty, Richardson, Ian, Saguidan, Monette, Farmer, Nicky, Gillespie, Angella, Willoughby, Shay, Parker, Samantha, Avulan, Shamseena, Arif, Shazia, Marshall, Suzanne, Carlisle, David, Rezaei, Mohsen, Booth, Angela, Watts, Joanne, Tremarco, Lauren, Jeyanayagam, Priyanga, Ubochi, Odinaka, Vagianos, Daniel, Richardson, Mark, Jarvis, Anthony, Gow, Kyra, Walmsley, Jade, O'keefe, Adam, Smielewska, Anna, Hopkins, Mark, Balane, Fatima, Bradley, Sarah, Corrah, Tumena, Daquiz, Venus, Dugan, Christopher, Elliot, Joshua, Foley, Fiona, Friday, Dawn, Gamit, May, Garner, David, Gokani, Karishma, John, Laurence, Joseph, Deepa, Khan, Nuzhath, Mamuyac, Cherifer, McGregor, Alastair, McSorley, John, Parris, Victoria, Rubinstein, Luciana, Rycroft, Julian, Salinas, Kelcy, Salinas, Jason, Sebatian, Jency, Smith, Melanie, Tejero Garcia, Marina, Ume, Uchenna, Vicentine, Margarete, Wallis, Gabriel, Sturdy, Ann, Whittington, Ashley, Jacobs, Nathan, Johnson, Leann, Bonington, Alec, Uriel, Alison, Ustianowski, Andrew, Dancso, Balazs, Hogan, Celia, van Halsema, Clare, Vilar, F Javier, Devine, Karen, Ajdukiewicz, Katherine, Rajendran, Rajesh, Ghosh, Samit, Riste, Michael, Machin, Nicholas, Babu, Chitra, Ahmad, Shazaad, Obeng, Dorcas, Dave, Farnaz, Conolley, Gavin, Thompson, Joseph, Tickell-Painter, Maya, Chakravorty, Prasun, Pringle, Rachel, Zafar, Mohammad R, Lawrence, Sarah, Sanchez-Gonzalez, Amada, Fernandez, Cristina, Goodwin, Lynsey, Carey, David, Howarth-Maddison, Molly, Moody, Samuel, Upton, Rebecca, Apthorp, Christina, Murray, Charlotte, Salthouse, Kirstie, Nadeem, Sabah, Ridley, Grant, White, Francesca, Brown, Andrew, Lawless, Michael, Mohamed, Mohamed, Mulligan, Robert, Belfield, Amy, Brolly, Jacob, Calderon, Maria, Cheveau, James, Cullinan, Milo, Garrad, Sophie, Griffiths, Will, Ireland, Aidan, Ireland, Peter, Milne, Charlotte, Nwajiugo, Paul, Quartey, John, Ghavami-Kia, Bijan, Duncan, Chris, Evans, Adam, Hunter, Ewan, Price, Ashley, Schmid, Matthias, Schwab, Uli, Taha, Yusri, Payne, Brendan, Elliott, Ivo A M, Crowe, Stewart, Woodrow, Charles J, Karageorgopoulos, Drosos E, Davis, Peter J, Lord, Emily, Bannister, Oliver J, Dagens, Andrew B, Harrison, Thomas, Cole, Joby, Tunbridge, Anne, Choudry, Saher, Telfer, Adam, Jhibril, Ihsan, Atta, Syed N, Stone, Ben, Evans, Cariad, Ankcorn, Mike, Akili, Suha, Yavuz, Mehmet, Goodall, Vicky, Farrow, Sam, Mountford, Georgina, Cusack, Tomas-Paul, Beard, Kate, Sutton, Julian, Clark, Tristan, Mason, Annette, Vickers, Mike, Macallan, Derek, Bicanic, Tihana, Houston, Angela, Pope, Cassie, Tan, NgeeKeong, Ward, Christopher, Jones, Imogen, Banerjee, Rishi, Cohen, Jonathan, Emonts-le Clercq, Marieke, Porter, David, Riordan, Andrew, Sinha, Ruchi, Whittaker, Elizabeth, Beynon, William, Heskin, Jospeh, Milligan, Iain, Payne, Lara, AI Payne, Brendan, Elliott, Ivo AM, and Beard, Katie

Published
2023
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14. HTLV seroprevalence in people using HIV pre-exposure prophylaxis in England

Author

Bradshaw, Daniel, Khawar, Arham, Patel, Poorvi, Tosswill, Jennifer, Brown, Colin, Ogaz, Dana, Mason, Emily, Osman, Roeann, Mitchell, Holly, Dosekun, Olamide, Peris, Borja Mora, Pickard, Graham, Rayment, Michael, Jones, Rachael, Hopkins, Mark, Williams, Andy, Kingston, Margaret, Machin, Nicholas, Taha, Yusri, Duncan, Sarah, Turner, Neil, Gill, Noel, Andrews, Nick, Raza, Mohammad, Tazzyman, Simon, Nori, Achyuta, Cunningham, Emma, and Taylor, Graham P

Published
2023
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16. Demanding Epistemic Democracy and Indirect Civics Pedagogy: The Performance-Oriented Music Ensemble

Author

Pyrcz, Greg, MacLean, Tessa, and Hopkins, Mark

Abstract

The participation of young adults in performance-oriented music ensembles can be seen to enhance democratic capacities and virtues. Much, however, turns on the particular conception of democracy at work. Although contemporary currents in music education tend towards models of liberal and participatory democracy to govern music ensembles, this essay contends that demanding epistemic democracy allows performance-oriented music ensembles the achievement of democratic virtues without sacrificing excellence as a central regulatory ideal. The inclusion of both men and women is shown to be particularly significant in this light. Central to its democratic epistemic ambition, the role of the conductor is considered in the last section of this article.

Published
2017

17. The Effect of Greater Area Deprivation and Medicaid Insurance Status on Timing of Care and Rate of Reinjury After Anterior Cruciate Ligament Reconstruction

Author

Cherelstein, Rachel E., primary, Natal-Albelo, Eduardo J., additional, Kuenze, Christopher M., additional, Curley, Andrew J., additional, Bodendorfer, Blake M., additional, Hopkins, Mark, additional, Conroy, Christine M., additional, Fryar, Caroline M., additional, Wang, David X., additional, and Chang, Edward S., additional

Published
2024
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18. IMPROVE 2022 International Meeting on Pathway‐Related Obesity: Vision of Excellence

Author

Kühnen, Peter, primary, Argente, Jesús, additional, Clément, Karine, additional, Dollfus, Hélène, additional, Dubern, Béatrice, additional, Farooqi, Sadaf, additional, de Groot, Corjan, additional, Grüters, Annette, additional, Holm, Jens‐Christian, additional, Hopkins, Mark, additional, Kleinendorst, Lotte, additional, Körner, Antje, additional, Meeker, David, additional, Rydén, Mikael, additional, von Schnurbein, Julia, additional, Tschöp, Matthias, additional, Yeo, Giles S. H., additional, Zorn, Stefanie, additional, and Wabitsch, Martin, additional

Published
2024
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19. Short, frequent, light‐intensity walking activity improves postprandial vascular‐inflammatory biomarkers in people with type 1 diabetes: The SIT‐LESS randomized controlled trial

Author

Safdar, Nawaz Z., primary, Alobaid, Anwar M., additional, Hopkins, Mark, additional, Dempsey, Paddy C., additional, Pearson, Sam M., additional, Kietsiriroje, Noppadol, additional, Churm, Rachel, additional, Ajjan, Ramzi A., additional, and Campbell, Matthew D., additional

Published
2024
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20. Extending a Parser to Distant Domains Using a Few Dozen Partially Annotated Examples

Author

Joshi, Vidur, Peters, Matthew, and Hopkins, Mark

Subjects
Computer Science - Computation and Language
Abstract

We revisit domain adaptation for parsers in the neural era. First we show that recent advances in word representations greatly diminish the need for domain adaptation when the target domain is syntactically similar to the source domain. As evidence, we train a parser on the Wall Street Jour- nal alone that achieves over 90% F1 on the Brown corpus. For more syntactically dis- tant domains, we provide a simple way to adapt a parser using only dozens of partial annotations. For instance, we increase the percentage of error-free geometry-domain parses in a held-out set from 45% to 73% using approximately five dozen training examples. In the process, we demon- strate a new state-of-the-art single model result on the Wall Street Journal test set of 94.3%. This is an absolute increase of 1.7% over the previous state-of-the-art of 92.6%., Comment: ACL 2018

Published
2018

21. Applying distributed embedded electronic instrumentation to the measurement and analysis of multiple acoustic and ultrasonic signals

Author

Hopkins, Mark B., Lee, Peter, and Waller, Winston

Subjects
620.2
Abstract

In many industrial applications there is a requirement to monitor acoustic and ultrasonic signals at selected locations across large structures - and leak detection in power station boilers would be a good example of such an application. Conventional topologies dictate that the analogue output signals from the acoustic and ultrasonic sensors are routed individually back to a central computer in the control room, where they are digitised and then analysed for the purposes demanded. Such topologies require long (and expensive) individual runs of specialist cables (sometimes lengths in the order of 500 meters), over which the sensor signals suffer significant degradation and exposure to interference. The central computer also requires high levels of processing bandwidth, if the sensors signals are to be processed concurrently. This thesis describes an alternative and novel approach, with the design and development of distributed electronic instrumentation (containing embedded microcontrollers), utilised to locally measure and analyse acoustic and ultrasonic signals. These instruments are mounted on the structure adjacent to each sensor location (thereby maintaining very short transducer cable lengths). They also incorporate a digital interface to the central computer via an Ethernet IP network, or a 'multidrop' Profibus system, greatly simplifying the cabling requirements. The local signal processing largely obviates the need for real time high speed communications over this interface. A dedicated serial interface is also provided to stream live audio data back to the control room, where it may be monitored by the plant operators. This analysis of the sensor signals locally greatly improves digitised signal fidelity, markedly reduces noise, and provides a powerful dedicated processing resource for every sensor. The local digital signal analysis includes various techniques working in both the time and frequency domains - such as amplitude trends, bandpass filtering, autocorrelations and Fast Fourier Transforms. High speed synchronised collection of sensor data may implemented, for subsequent 'off line' processing (for applications such as acoustic signal source location, and Acoustic Emission analysis). This work also includes the development of a very low noise charge preamplifier for piezo electric transducers, much improving the sensitivity of measurements with these sensors.

Published
2018
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25. Increasing Educational Opportunity: How Iowa's Private Four-Year Colleges and Public Universities Responded to the State's New Public Two-Year Colleges, 1965-1975

Author

Hopkins, Mark Loren

Abstract

Using archival records preserved by Iowa's community colleges, private four-year colleges, and public universities, this dissertation examines how Iowa's established higher education institutions responded to and adjusted to the "presence" of new two-year colleges from 1965 to 1975. This decade was a critical period of development for Iowa two-year colleges as they were most vulnerable to and influenced by other education institutions during an economic downturn. This study also explores how the curricular tension between vocational education and liberal arts education shaped early relationships between Iowa's new two-year colleges and other higher education institutions. Specifically, this dissertation examines six two-year colleges, seventeen private four-year colleges, and three public universities to understand how the curricular purpose, mission and identity, position in the higher education hierarchy, and reputation of each type of institution played a role in early relationship-building. Ultimately, this study sought to answer the question whether the state's new two-year colleges developed relationships with other higher education institutions that increased educational opportunities for Iowa students. Chapter 2 explains how officials from Merged Area I and Western Iowa Tech, two of Iowa's two-year colleges founded as vocational-only institutions, persisted in their efforts to offer liberal arts education. Officials from neighboring private colleges resisted their efforts because they believed two-year colleges that offered liberal arts education posed a competitive threat. Chapter 3 explores how Iowa's two-year colleges posed a financial threat, as well as a curricular threat. Part I highlights how Iowa private college officials confronted the financial threat by collaborating with the Iowa Association of Private Colleges and Universities to advocate for the Iowa Tuition Grant. Part II shows how eight private colleges responded to the curricular threat in three distinct ways: strengthening their role as a liberal arts college, making significant institutional changes for long-term survival, and changing or creating new curricular programs. This dissertation also considers the contributions of Iowa's three public universities, Northern Iowa, Iowa State University, and the University of Iowa. Chapter 4 explains how each university responded in a distinct way to the presence of two-year colleges. This dissertation concludes by explaining how this study contributes to the debate between scholars about whether two-year colleges were egalitarian institutions or diversion institutions, specifically, whether two-year colleges and their relationships with other higher education institutions provided Iowa students with more educational opportunities and the path to a baccalaureate degree. I concluded that the presence of Iowa's two-year colleges pressured private college officials to respond in ways that increased educational opportunity, and officials from Iowa's three public universities to respond in ways that helped two-year colleges secure a stronger position in the higher education system hierarchy, which strengthened the ability of two-year colleges to provide a path to a baccalaureate degree. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]

Published
2019

26. Orthoses

Author

Hopkins, Mark S., primary and González-Fernández, Marlís, additional

Published
2021
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28. An exploratory investigation of the impact of 'fast' and 'feed' days during intermittent energy restriction on free-living energy balance behaviours and subjective states in women with overweight/obesity

Author

Beaulieu, Kristine, Casanova, Nuno, Oustric, Pauline, Hopkins, Mark, Varady, Krista, Finlayson, Graham, and Gibbons, Catherine

Subjects
Women -- Physiological aspects, Obesity -- Health aspects -- Demographic aspects, Fasting -- Methods -- Evaluation, Weight loss -- Methods, Food/cooking/nutrition, Health
Abstract

Background/objectives This controlled-feeding randomised controlled trial examined free-living appetite and physical activity (PA) on 'fast' and 'feed' days during intermittent energy restriction (IER), compared to continuous energy restriction (CER). Subjects/methods Forty-six women with overweight/obesity (age = 35 [plus or minus] 10 years, BMI = 29.1 [plus or minus] 2.3 kg/m.sup.2) were randomised to IER (n = 24; alternate fast days at 25% energy requirements and ad libitum feed days) or CER (n = 22; 75% energy requirements daily) to [greater than or equal to]5% weight loss (WL) or up to 12 weeks. Self-reported energy intake (EI; online food record), objectively measured PA (SenseWear Armband) and retrospective daily hunger and food cravings were measured over 7 days at baseline, week 2 and final week. Intent-to-treat analyses were performed using linear mixed models. Results Final WL (M.sub.[DELTA] = 4.7 [95% confidence interval 4.2, 5.2] kg, 5.9%) did not differ between IER and CER (interaction P = 0.307). During IER, feed-day EI did not differ from baseline and was lower in the final week compared to week 2 (M.sub.[DELTA] = 295 [81, 509] kcal, P = 0.004). Daily hunger was greater on fast compared to feed days (M.sub.[DELTA] = 15 [10, 21] mm, P < 0.001), but food cravings did not differ. Light PA was lower on fast relative to feed days (M.sub.[DELTA] = 18 [2, 34] min/day, P = 0.024), with no other differences in PA. Compared to CER, IER increased hunger and led to smaller improvements in craving control (both interactions P [less than or equal to] 0.034). Conclusions IER fast days were associated with increased free-living hunger and lower light PA compared to feed days, but had no impact on food cravings or self-reported ad libitum daily EI. IER may be less favourable than CER for the free-living day-to-day control of hunger and food cravings., Author(s): Kristine Beaulieu [sup.1] , Nuno Casanova [sup.2] , Pauline Oustric [sup.1] , Mark Hopkins [sup.2] , Krista Varady [sup.3] , Graham Finlayson [sup.1] , Catherine Gibbons [sup.1] Author Affiliations: [...]

Published
2021
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32. Structure–Activity Relationship of 18F‑Labeled Phosphoramidate Peptidomimetic Prostate-Specific Membrane Antigen (PSMA)-Targeted Inhibitor Analogues for PET Imaging of Prostate Cancer

Author

Dannoon, Shorouk, Ganguly, Tanushree, Cahaya, Hendry, Geruntho, Jonathan J, Galliher, Matthew S, Beyer, Sophia K, Choy, Cindy J, Hopkins, Mark R, Regan, Melanie, Blecha, Joseph E, Skultetyova, Lubica, Drake, Christopher R, Jivan, Salma, Barinka, Cyril, Jones, Ella F, Berkman, Clifford E, and VanBrocklin, Henry F

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Biomedical Imaging, Prostate Cancer, Urologic Diseases, Aging, Cancer, Amides, Animals, Antigens, Surface, Dose-Response Relationship, Drug, Fluorine Radioisotopes, Glutamate Carboxypeptidase II, Humans, Male, Mice, Mice, Nude, Models, Molecular, Molecular Structure, Neoplasms, Experimental, Peptidomimetics, Phosphoric Acids, Positron-Emission Tomography, Prostatic Neoplasms, Structure-Activity Relationship, Tumor Cells, Cultured, Medicinal and Biomolecular Chemistry, Organic Chemistry, Pharmacology and Pharmaceutical Sciences, Medicinal & Biomolecular Chemistry, Pharmacology and pharmaceutical sciences, Medicinal and biomolecular chemistry, Organic chemistry
Abstract

A series of phosphoramidate-based prostate specific membrane antigen (PSMA) inhibitors of increasing lipophilicity were synthesized (4, 5, and 6), and their fluorine-18 analogs were evaluated for use as positron emission tomography (PET) imaging agents for prostate cancer. To gain insight into their modes of binding, they were also cocrystallized with the extracellular domain of PSMA. All analogs exhibited irreversible binding to PSMA with IC50 values ranging from 0.4 to 1.3 nM. In vitro assays showed binding and rapid internalization (80-95%, 2 h) of the radiolabeled ligands in PSMA(+) cells. In vivo distribution demonstrated significant uptake in CWR22Rv1 (PSMA(+)) tumor, with tumor to blood ratios of 25.6:1, 63.6:1, and 69.6:1 for [(18)F]4, [(18)F]5, and [(18)F]6, respectively, at 2 h postinjection. Installation of aminohexanoic acid (AH) linkers in the phosphoramidate scaffold improved their PSMA binding and inhibition and was critical for achieving suitable in vivo imaging properties, positioning [(18)F]5 and [(18)F]6 as favorable candidates for future prostate cancer imaging clinical trials.

Published
2016

34. A high-affinity [18 F]-labeled phosphoramidate peptidomimetic PSMA-targeted inhibitor for PET imaging of prostate cancer

Author

Ganguly, Tanushree, Dannoon, Shorouk, Hopkins, Mark R, Murphy, Stephanie, Cahaya, Hendry, Blecha, Joseph E, Jivan, Salma, Drake, Christopher R, Barinka, Cyril, Jones, Ella F, VanBrocklin, Henry F, and Berkman, Clifford E

Subjects
Biomedical Imaging, Cancer, Aging, Urologic Diseases, Prostate Cancer, Amides, Animals, Antigens, Surface, Biological Transport, Cell Line, Tumor, Drug Stability, Fluorine Radioisotopes, Glutamate Carboxypeptidase II, Humans, Inhibitory Concentration 50, Isotope Labeling, Male, Mice, Models, Molecular, Peptidomimetics, Phosphoric Acids, Positron-Emission Tomography, Prostatic Neoplasms, Protease Inhibitors, Protein Conformation, Tissue Distribution, Flourine-18, PET, PSMA, Phosphoramidate, Clinical Sciences, Nuclear Medicine & Medical Imaging
Abstract

IntroductionIn this study, a structurally modified phosphoramidate scaffold, with improved prostate-specific membrane antigen (PSMA) avidity, stability and in vivo characteristics, as a PET imaging agent for prostate cancer (PCa), was prepared and evaluated.Methodsp-Fluorobenzoyl-aminohexanoate and 2-(3-hydroxypropyl)glycine were introduced into the PSMA-targeting scaffold yielding phosphoramidate 5. X-ray crystallography was performed on the PSMA/5 complex. [(18)F]5 was synthesized, and cell uptake and internalization studies were conducted in PSMA(+) LNCaP and CWR22Rv1 cells and PSMA(-) PC-3 cells. In vivo PET imaging and biodistribution studies were performed at 1 and 4 h post injection in mice bearing CWR22Rv1 tumor, with or without blocking agent.ResultsThe crystallographic data showed interaction of the p-fluorobenzoyl group with an arene-binding cleft on the PSMA surface. In vitro studies revealed elevated uptake of [(18)F]5 in PSMA(+) cells (2.2% in CWR22Rv1 and 12.1% in LNCaP) compared to PSMA(-) cells (0.08%) at 4 h. In vivo tumor uptake of 2.33% ID/g and tumor-to-blood ratio of 265:1 was observed at 4 h.ConclusionsWe have successfully synthesized, radiolabeled and evaluated a new PSMA-targeted PET agent. The crystal structure of the PSMA/5 complex highlighted the interactions within the arene-binding cleft contributing to the overall complex stability. The high target uptake and rapid non-target clearance exhibited by [(18)F]5 in PSMA(+) xenografts substantiates its potential use for PET imaging of PCa.Advances in knowledgeThe only FDA-approved imaging agent for PCa, Prostascint®, targets PSMA but suffers from inherent shortcomings. The data acquired in this manuscript confirmed that our new generation of [(18)F]-labeled PSMA inhibitor exhibited promising in vivo performance as a PET imaging agent for PCa and is well-positioned for subsequent clinical trials. Implications for Patient Care Our preliminary data demonstrate that this tracer possesses the required imaging characteristics to be sensitive and specific for PCa imaging in patients at all stages of the disease.

Published
2015

38. C-Dioids and -Continuous Chomsky-Algebras

Author

Leiß, Hans, Hopkins, Mark, Hutchison, David, Series Editor, Kanade, Takeo, Series Editor, Kittler, Josef, Series Editor, Kleinberg, Jon M., Series Editor, Mattern, Friedemann, Series Editor, Mitchell, John C., Series Editor, Naor, Moni, Series Editor, Pandu Rangan, C., Series Editor, Steffen, Bernhard, Series Editor, Terzopoulos, Demetri, Series Editor, Tygar, Doug, Series Editor, Weikum, Gerhard, Series Editor, Desharnais, Jules, editor, Guttmann, Walter, editor, and Joosten, Stef, editor

Published
2018
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39. Coequalizers and Tensor Products for Continuous Idempotent Semirings

Author

Hopkins, Mark, Leiß, Hans, Hutchison, David, Series Editor, Kanade, Takeo, Series Editor, Kittler, Josef, Series Editor, Kleinberg, Jon M., Series Editor, Mattern, Friedemann, Series Editor, Mitchell, John C., Series Editor, Naor, Moni, Series Editor, Pandu Rangan, C., Series Editor, Steffen, Bernhard, Series Editor, Terzopoulos, Demetri, Series Editor, Tygar, Doug, Series Editor, Weikum, Gerhard, Series Editor, Desharnais, Jules, editor, Guttmann, Walter, editor, and Joosten, Stef, editor

Published
2018
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40. LAYERWIDTH: Analysis of a New Metric for Directed Acyclic Graphs

Author

Hopkins, Mark

Subjects
Computer Science - Data Structures and Algorithms, Computer Science - Artificial Intelligence, Computer Science - Discrete Mathematics
Abstract

We analyze a new property of directed acyclic graphs (DAGs), called layerwidth, arising from a class of DAGs proposed by Eiter and Lukasiewicz. This class of DAGs permits certain problems of structural model-based causality and explanation to be tractably solved. In this paper, we first address an open question raised by Eiter and Lukasiewicz - the computational complexity of deciding whether a given graph has a bounded layerwidth. After proving that this problem is NP-complete, we proceed by proving numerous important properties of layerwidth that are helpful in efficiently computing the optimal layerwidth. Finally, we compare this new DAG property to two other important DAG properties: treewidth and bandwidth., Comment: Appears in Proceedings of the Nineteenth Conference on Uncertainty in Artificial Intelligence (UAI2003)

Published
2012

43. A study of pod constriction in a peanut population with mixed wild and cultivated genetics.

Author

Ballén‐Taborda, Carolina, Maharjan, Namrata, Hopkins, Mark, Guimarães, Larissa Arrais, Lindsey, Duncan, Bertioli, David J., and Leal‐Bertioli, Soraya C. M.

Subjects
PEANUTS, LOCUS (Genetics), PEANUT breeding, GENETICS, ALLELES in plants, SEED pods, GENETIC markers
Abstract

Wild relatives comprise a diverse genetic source from which to introduce beneficial alleles for peanut breeding. However, when using wild species for breeding, unadapted agronomic characteristics are often co‐inherited along with favorable traits. Previously, an advanced backcross population was developed from a cross between Arachis hypogaea and the wild‐derived induced allotetraploid (Arachis batizocoi × Arachis stenosperma)4x to incorporate nematode resistance genes into elite peanut. We observed additional wild alleles unintentionally inherited throughout the genome, possibly causing variation in several pod and seed characteristics. To identify the wild introgressions controlling the variation in pod constriction (PC), a critical trait for peanut's acceptability and marketability, we performed an association analysis using 419 SNPs and phenotypic data of 72 BC3F2/3 families. An introgression on the top of chromosome B08 (pod constriction‐quantitative trait locus [PC‐QTL], 3.7 Mbp) derived from A. batizocoi was found to be controlling 47.3% of the PC variation. To confirm the PC‐QTL, six BC3F4 families harboring the wild loci in a homozygous or heterozygous state were selected and used for segregation analysis. All progenies from the backcross families carrying the homozygous allele had severely constricted pods, whereas progenies from families with the heterozygous allele were segregated for PC. Finally, analyses using end‐point genotyping with four linked SNP assays confirmed the association of the PC‐QTL with PC. The present work studied PC and developed DNA markers to assist the selection against constricted pods while retaining the new and beneficial wild‐derived genes. Core Ideas: In peanut, pod and seed traits are important for yield and quality.When incorporating beneficial traits from wild germplasm, unadapted wild pod and seed traits are also inherited.A major pod constriction quantitative trait locus was discovered in a backcross population harboring wild‐derived segments.Molecular markers developed and validated can be used for selection against wild‐type deep pod constriction. [ABSTRACT FROM AUTHOR]

Published
2024
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46. Interrupting prolonged sitting with frequent short bouts of light‐intensity activity in people with type 1 diabetes improves glycaemic control without increasing hypoglycaemia: The SIT‐LESS randomised controlled trial

Author

Campbell, Matthew D., primary, Alobaid, Anwar M., additional, Hopkins, Mark, additional, Dempsey, Paddy C., additional, Pearson, Sam M., additional, Kietsiriroje, Noppadol, additional, Churm, Rachel, additional, and Ajjan, Ramzi A., additional

Published
2023
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49. Low frequency of genotypic resistance in HIV-1-infected patients failing an atazanavir-containing regimen: a clinical cohort study

Author

Dolling, David I, Dunn, David T, Sutherland, Katherine A, Pillay, Deenan, Mbisa, Jean L, Parry, Chris M, Post, Frank A, Sabin, Caroline A, Cane, Patricia A, Aitken, Celia, Asboe, David, Webster, Daniel, Cane, Patricia, Castro, Hannah, Dunn, David, Dolling, David, Chadwick, David, Churchill, Duncan, Clark, Duncan, Collins, Simon, Delpech, Valerie, Geretti, Anna Maria, Goldberg, David, Hale, Antony, Hué, Stéphane, Kaye, Steve, Kellam, Paul, Lazarus, Linda, Leigh-Brown, Andrew, Mackie, Nicola, Orkin, Chloe, Rice, Philip, Phillips, Andrew, Sabin, Caroline, Smit, Erasmus, Templeton, Kate, Tilston, Peter, Tong, William, Williams, Ian, Zhang, Hongyi, Zuckerman, Mark, Greatorex, Jane, Wildfire, Adrian, O'Shea, Siobhan, Mullen, Jane, Mbisa, Tamyo, Cox, Alison, Tandy, Richard, Hale, Tony, Fawcett, Tracy, Hopkins, Mark, Ashton, Lynn, Booth, Claire, Garcia-Diaz, Ana, Shepherd, Jill, Schmid, Matthias L, Payne, Brendan, Hay, Phillip, Rice, Phillip, Paynter, Mary, Bibby, David, Kirk, Stuart, MacLean, Alasdair, Gunson, Rory, Coughlin, Kate, Fearnhill, Esther, Fradette, Lorraine, Porter, Kholoud, Ainsworth, Jonathan, Anderson, Jane, Babiker, Abdel, Fisher, Martin, Gazzard, Brian, Gilson, Richard, Gompels, Mark, Hill, Teresa, Johnson, Margaret, Kegg, Stephen, Leen, Clifford, Nelson, Mark, Palfreeman, Adrian, Post, Frank, Sachikonye, Memory, Schwenk, Achim, Walsh, John, Huntington, Susie, Jose, Sophie, Thornton, Alicia, Glabay, Adam, Orkin, C, Garrett, N, Lynch, J, Hand, J, de Souza, C, Fisher, M, Perry, N, Tilbury, S, Gazzard, B, and Nelson, M

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Clinical Sciences, Clinical Trials and Supportive Activities, Infectious Diseases, Antimicrobial Resistance, Clinical Research, Infection, Adult, Anti-HIV Agents, Atazanavir Sulfate, Cohort Studies, Drug Resistance, Viral, Female, HIV Infections, HIV Protease, HIV-1, Humans, Male, Medication Adherence, Middle Aged, Mutation Rate, Mutation, Missense, Oligopeptides, Pyridines, Treatment Failure, United States, UK HIV Drug Resistance Database, UK Collaborative HIV Cohort Study, HIV, drug resistance mutations, naive patients, protease inhibitors, virological failure, Microbiology, Pharmacology and Pharmaceutical Sciences, Clinical sciences, Pharmacology and pharmaceutical sciences
Abstract

ObjectivesTo determine protease mutations that develop at viral failure for protease inhibitor (PI)-naive patients on a regimen containing the PI atazanavir.MethodsResistance tests on patients failing atazanavir, conducted as part of routine clinical care in a multicentre observational study, were randomly matched by subtype to resistance tests from PI-naive controls to account for natural polymorphisms. Mutations from the consensus B sequence across the protease region were analysed for association and defined using the IAS-USA 2011 classification list.ResultsFour hundred and five of 2528 (16%) patients failed therapy containing atazanavir as a first PI over a median (IQR) follow-up of 1.76 (0.84-3.15) years and 322 resistance tests were available for analysis. Recognized major atazanavir mutations were found in six atazanavir-experienced patients (P < 0.001), including I50L and N88S. The minor mutations most strongly associated with atazanavir experience were M36I, M46I, F53L, A71V, V82T and I85V (P < 0.05). Multiple novel mutations, I15S, L19T, K43T, L63P/V, K70Q, V77I and L89I/T/V, were also associated with atazanavir experience.ConclusionsViral failure on atazanavir-containing regimens was not common and major resistance mutations were rare, suggesting that adherence may be a major contributor to viral failure. Novel mutations were described that have not been previously documented.

Published
2013

50. Influence of body composition, metabolism and physical activity on mechanisms controlling energy intake

Author

Hopkins, Mark

Subjects
613.2
Abstract

Background: Current models of appetite control embody the view that tonic and episodic inhibitory signals modulate a constant and recurring drive to eat, but the source of this excitatory drive has been poorly defined. A motivational drive arising from energy needs would appear logical, but the influence of energy expenditure on energy intake remains unclear. Furthermore, while changes in eating behaviour and body composition following acute and chronic exercise are highly variable, a greater understanding of the compensatory mechanisms that mediate this heterogeneity is needed. Methods: A multi-level experimental platform was used in which body composition, metabolism and eating behaviour were measured concurrently in overweight and obese individuals in response to either an acute bout of aerobic exercise, or 12 weeks of supervised aerobic exercise training. This approach allowed for the disclosure of any interdependent relationships between physiological and behavioural components of energy balance. Results: The key findings of this thesis are novel and demonstrated that: • Fat-free mass is a physiological source of hunger that drives day-to-day food intake at a level proportional to basal energy requirements. This homeostatic signal of energy demand was apparent under sedentary conditions, and during exercise-induced weight loss. In contrast, fat mass did not appear to exert a major influence on hunger or food intake under sedentary conditions. • Following 12 weeks of aerobic exercise, marked individual variability existed in exercise-induced weight loss. • While there was no mean change in food intake following 12 weeks of aerobic exercise, fasting hunger increased significantly following the exercise intervention. However, this increase in orexigenic drive was off-set by a parallel increase in meal-related satiety. • Some individuals experienced a greater than expected decline in resting metabolic rate following the 12 week exercise intervention (that could not be explained by changes in body composition). Importantly, these individuals also demonstrated a concomitant increase in food intake following the intervention. • Leptin was found to play a key role in co-ordinating the physiological and behavioural responses to exercise-induced weight loss, with a decline in fasting leptin (independent of fat mass) associated with a greater than expected decline in resting metabolic rate, a smaller increase in resting fat oxidation, an increase in daily hunger, and an increased liking for high fat foods following the 12 week exercise intervention. Conclusions: An important role for fat-free mass in the control of appetite was identified. Furthermore, the impact of exercise on appetite control and body weight regulation was found to be mediated through a cluster of inter-related physiological and behavioural pathways, with leptin potentially acting to co-ordinate these adaptive responses.

Published
2013

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