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2. The instabilities of large learning rate training: a loss landscape view

Author

Wang, Lawrence and Roberts, Stephen

Subjects
Computer Science - Machine Learning
Abstract

Modern neural networks are undeniably successful. Numerous works study how the curvature of loss landscapes can affect the quality of solutions. In this work we study the loss landscape by considering the Hessian matrix during network training with large learning rates - an attractive regime that is (in)famously unstable. We characterise the instabilities of gradient descent, and we observe the striking phenomena of \textit{landscape flattening} and \textit{landscape shift}, both of which are intimately connected to the instabilities of training., Comment: arXiv admin note: text overlap with arXiv:2305.18490

Published
2023

5. Treatment of Palm Oil Mill Effluent

Author

Sabiani, Nor Habsah Md, Alkarimiah, Rosnani, Ayub, Khairul Rahmah, Makhtar, Muaz Mohd Zaini, Aziz, Hamidi Abdul, Hung, Yung-Tse, Wang, Lawrence K., Wang, Mu-Hao Sung, Wang, Lawrence K., Series Editor, Wang, Mu-Hao Sung, Series Editor, Sung Wang, Mu-Hao, editor, and Hung, Yung-Tse, editor

Published
2024
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9. SANE: The phases of gradient descent through Sharpness Adjusted Number of Effective parameters

Author

Wang, Lawrence and Roberts, Stephen J.

Subjects
Computer Science - Machine Learning
Abstract

Modern neural networks are undeniably successful. Numerous studies have investigated how the curvature of loss landscapes can affect the quality of solutions. In this work we consider the Hessian matrix during network training. We reiterate the connection between the number of "well-determined" or "effective" parameters and the generalisation performance of neural nets, and we demonstrate its use as a tool for model comparison. By considering the local curvature, we propose Sharpness Adjusted Number of Effective parameters (SANE), a measure of effective dimensionality for the quality of solutions. We show that SANE is robust to large learning rates, which represent learning regimes that are attractive but (in)famously unstable. We provide evidence and characterise the Hessian shifts across "loss basins" at large learning rates. Finally, extending our analysis to deeper neural networks, we provide an approximation to the full-network Hessian, exploiting the natural ordering of neural weights, and use this approximation to provide extensive empirical evidence for our claims.

Published
2023

10. Fast Weakness Identification for Adaptive Feedback

Author

Morland, Raymond, Wang, Lawrence, Lin, Fuhua, 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, Sifaleras, Angelo, editor, and Lin, Fuhua, editor

Published
2024
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12. Natural malaria infection elicits rare but potent neutralizing antibodies to the blood-stage antigen RH5

Author

Wang, Lawrence T., Cooper, Andrew J.R., Farrell, Brendan, Miura, Kazutoyo, Diouf, Ababacar, Müller-Sienerth, Nicole, Crosnier, Cécile, Purser, Lauren, Kirtley, Payton J., Maciuszek, Maciej, Barrett, Jordan R., McHugh, Kirsty, Ogwang, Rodney, Tucker, Courtney, Li, Shanping, Doumbo, Safiatou, Doumtabe, Didier, Pyo, Chul-Woo, Skinner, Jeff, Nielsen, Carolyn M., Silk, Sarah E., Kayentao, Kassoum, Ongoiba, Aissata, Zhao, Ming, Nguyen, Doan C., Lee, F. Eun-Hyung, Minassian, Angela M., Geraghty, Daniel E., Traore, Boubacar, Seder, Robert A., Wilder, Brandon K., Crompton, Peter D., Wright, Gavin J., Long, Carole A., Draper, Simon J., Higgins, Matthew K., and Tan, Joshua

Published
2024
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13. Analysis of the diverse antigenic landscape of the malaria protein RH5 identifies a potent vaccine-induced human public antibody clonotype

Author

Barrett, Jordan R., Pipini, Dimitra, Wright, Nathan D., Cooper, Andrew J.R., Gorini, Giacomo, Quinkert, Doris, Lias, Amelia M., Davies, Hannah, Rigby, Cassandra A., Aleshnick, Maya, Williams, Barnabas G., Bradshaw, William J., Paterson, Neil G., Martinson, Thomas, Kirtley, Payton, Picard, Luc, Wiggins, Christine D., Donnellan, Francesca R., King, Lloyd D.W., Wang, Lawrence T., Popplewell, Jonathan F., Silk, Sarah E., de Ruiter Swain, Jed, Skinner, Katherine, Kotraiah, Vinayaka, Noe, Amy R., MacGill, Randall S., King, C. Richter, Birkett, Ashley J., Soisson, Lorraine A., Minassian, Angela M., Lauffenburger, Douglas A., Miura, Kazutoyo, Long, Carole A., Wilder, Brandon K., Koekemoer, Lizbé, Tan, Joshua, Nielsen, Carolyn M., McHugh, Kirsty, and Draper, Simon J.

Published
2024
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14. Laboratory Waste Management and Treatment

Author

Zahari, M. Shahrir M., Jaafar, Izan, Ismail, Shahrul, Harun, Mohammad Hakim Che, Hashim, Nor Haslina, Wang, Mu-Hao Sung, Wang, Lawrence K., Wang, Lawrence K., Series Editor, Wang, Mu-Hao Sung, Series Editor, and Hung, Yung-Tse, editor

Published
2023
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18. Removal of Fe and Mn from Groundwater

Author

Lee, Wen Si, Aziz, Hamidi Abdul, Akbar, Nor Azliza, Wang, Mu-Hao Sung, Wang, Lawrence K., Wang, Lawrence K., Series Editor, Wang, Mu-Hao Sung, Series Editor, and Hung, Yung-Tse, editor

Published
2023
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20. HumBugDB: A Large-scale Acoustic Mosquito Dataset

Author

Kiskin, Ivan, Sinka, Marianne, Cobb, Adam D., Rafique, Waqas, Wang, Lawrence, Zilli, Davide, Gutteridge, Benjamin, Dam, Rinita, Marinos, Theodoros, Li, Yunpeng, Msaky, Dickson, Kaindoa, Emmanuel, Killeen, Gerard, Herreros-Moya, Eva, Willis, Kathy J., and Roberts, Stephen J.

Subjects
Computer Science - Sound, Computer Science - Computer Vision and Pattern Recognition, Electrical Engineering and Systems Science - Audio and Speech Processing, E.0, I.2.1, J.3
Abstract

This paper presents the first large-scale multi-species dataset of acoustic recordings of mosquitoes tracked continuously in free flight. We present 20 hours of audio recordings that we have expertly labelled and tagged precisely in time. Significantly, 18 hours of recordings contain annotations from 36 different species. Mosquitoes are well-known carriers of diseases such as malaria, dengue and yellow fever. Collecting this dataset is motivated by the need to assist applications which utilise mosquito acoustics to conduct surveys to help predict outbreaks and inform intervention policy. The task of detecting mosquitoes from the sound of their wingbeats is challenging due to the difficulty in collecting recordings from realistic scenarios. To address this, as part of the HumBug project, we conducted global experiments to record mosquitoes ranging from those bred in culture cages to mosquitoes captured in the wild. Consequently, the audio recordings vary in signal-to-noise ratio and contain a broad range of indoor and outdoor background environments from Tanzania, Thailand, Kenya, the USA and the UK. In this paper we describe in detail how we collected, labelled and curated the data. The data is provided from a PostgreSQL database, which contains important metadata such as the capture method, age, feeding status and gender of the mosquitoes. Additionally, we provide code to extract features and train Bayesian convolutional neural networks for two key tasks: the identification of mosquitoes from their corresponding background environments, and the classification of detected mosquitoes into species. Our extensive dataset is both challenging to machine learning researchers focusing on acoustic identification, and critical to entomologists, geo-spatial modellers and other domain experts to understand mosquito behaviour, model their distribution, and manage the threat they pose to humans., Comment: Accepted at the 35th Conference on Neural Information Processing Systems (NeurIPS 2021) Track on Datasets and Benchmarks. 10 pages main, 39 pages including appendix. This paper accompanies the dataset found at https://zenodo.org/record/4904800 with corresponding code at https://github.com/HumBug-Mosquito/HumBugDB

Published
2021

21. Development of antimalarial human monoclonal antibodies against Plasmodium falciparum

Author

Wang, Lawrence T., Draper, Simon, and Seder, Robert

Subjects
Immunology, infectious diseases, vaccinology
Abstract

Advances in high-throughput isolation of neutralizing human monoclonal antibodies (mAbs) have enabled development of mAb-based therapeutics for many viruses (e.g., HIV-1, Ebola, SARS-CoV-2). This approach has recently been applied to isolate antimalarial human mAbs against the Plasmodium falciparum circumsporozoite protein (CSP) on sporozoites (SPZ) and reticulocyte-binding protein homolog 5 (RH5) on merozoites (MZ). CSP and RH5 are leading malaria vaccine targets because they are respectively required for the SPZ and MZ stages of malaria parasites to invade host hepatocytes and erythrocytes. CSP has three domains: an N-terminus, a central region composed of repeating NPDP/NVDP/NANP tetrapeptides, and a C-terminus. A truncated form of CSP containing 19 NANP repeats and the C-terminus is the antigenic target of the world's only approved malaria vaccine (RTS,S). RTS,S formulated with the adjuvant AS01 elicited protective CSP antibodies but was only 30-50% effective at preventing malaria in a phase III trial. The focus of this Thesis is the isolation of potent human mAbs that bind new sites of vulnerability on CSP (and RH5) in order to facilitate clinical development of promising antimalarial mAbs and improve designs of vaccines targeting these antigens. Here, and in a Report featured on the cover of Immunity, I describe the first human NVDP-specific CSP mAb (L9) that preferentially binds two adjacent NVDP repeats while cross-reacting with NANP repeats. L9 was more potently protective against SPZ challenge in mice than seven published neutralizing human NPDP- and NANP-specific CSP mAbs. Isothermal titration calorimetry and multiphoton microscopy showed that L9 and the other most protective mAbs bound CSP with a unique "two-step" binding phenotype and mediated protection by killing SPZ in the liver and preventing their egress from sinusoids to invade hepatocytes. This study defined the subdominant NVDP repeats as protective CSP epitopes not included in RTS,S, identified an in vitro correlate of mAb-mediated SPZ neutralization, and showed that the liver is an important site for CSP-specific antibodies to prevent malaria. Based on its high potency, a half-life extended version of L9 (L9LS) was clinically developed and completed Phase I testing at the NIH in December 2021 (NCT05019729). Here, and in a Report published in Cell Reports, I show that L9 lineage B cells have baseline NVDP affinity and evolve to acquire NANP reactivity. Pairing the L9 light chain with clonally-related heavy chains resulted in chimeric mAbs that preferentially bound two adjacent NVDP with high affinity, cross-reacted with NANP, and more potently neutralized SPZ compared to their original light chain. X-ray crystal structures of these chimeric mAbs revealed that they bound NANP and NVDP in a similar type-1 β-turn. These data provide insight into the ontogeny and binding mechanisms of the potent NVDP-specific mAb L9 and suggest that RTS,S might be improved by presenting ≥2 adjacent NVDP minor repeats. Here, and in a Research Article published in PLOS Pathogens, I demonstrate that combining two neutralizing "repeat" mAbs against the NPDP/NVDP/NANP tetrapeptides in the central repeat region of CSP, or combining a repeat mAb with mAbs against the C-terminus of CSP, did not provide improved protection against SPZ challenge in mice compared to a single repeat mAb. However, passive transfer of a repeat mAb (e.g., L9) into mice immunized with a RTS,S-like vaccine (which induces polyclonal antibodies against the repeat region and C-terminus of CSP) provided superior protection compared to the mAb or vaccine alone. These data show that, while combining two mAbs against the repeat region and C-terminus of CSP was ineffective at enhancing SPZ neutralization in vivo, protection was enhanced when a mAb was combined with vaccine-induced polyclonal antibodies. Given that RTS,S was recently recommended for widespread usage by the World Health Organization and CSP mAbs like L9 are scheduled to begin Phase II testing in Africa in 2022, these data suggest that combining RTS,S vaccination with passive transfer of potent CSP mAbs should provide even greater protection against malaria. Additionally, I isolated a panel of >200 human mAbs against RH5 (and its two accessory proteins, CyRPA and Ripr) from naturally infected subjects living in a malaria endemic region of Mali and from naïve subjects in the UK immunized with a RH5 vaccine. Only one study has reported the isolation of 17 RH5 human mAbs, while no CyRPA and Ripr human mAbs have been isolated to date. Determination of the epitopes bound by these mAbs, as well as their potency, is ongoing. If a potent RH5-CyRPA-Ripr-specific mAb is identified, it can potentially be combined with L9 in a multi-stage antimalarial mAb cocktail against both SPZ and MZ.

Published
2022

22. HumBug Zooniverse: a crowd-sourced acoustic mosquito dataset

Author

Kiskin, Ivan, Cobb, Adam D., Wang, Lawrence, and Roberts, Stephen

Subjects
Computer Science - Machine Learning, Computer Science - Sound, Electrical Engineering and Systems Science - Audio and Speech Processing, Statistics - Machine Learning
Abstract

Mosquitoes are the only known vector of malaria, which leads to hundreds of thousands of deaths each year. Understanding the number and location of potential mosquito vectors is of paramount importance to aid the reduction of malaria transmission cases. In recent years, deep learning has become widely used for bioacoustic classification tasks. In order to enable further research applications in this field, we release a new dataset of mosquito audio recordings. With over a thousand contributors, we obtained 195,434 labels of two second duration, of which approximately 10 percent signify mosquito events. We present an example use of the dataset, in which we train a convolutional neural network on log-Mel features, showcasing the information content of the labels. We hope this will become a vital resource for those researching all aspects of malaria, and add to the existing audio datasets for bioacoustic detection and signal processing., Comment: Awarded Best Paper at the 2019 NeurIPS ML4D workshop. Accepted at ICASSP 2020

Published
2020

25. Management and Treatment of Livestock Wastes

Author

Vanderholm, Dale H., Day, Donald L., Muehling, Arthur J., Wang, Lawrence K., Hung, Yung-Tse, Butler, Erick, Wang, Mu-Hao Sung, Yehya, Haneen, Wang, Lawrence K., Series Editor, Wang, Mu-Hao Sung, Series Editor, and Hung, Yung-Tse, editor

Published
2022
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30. Composting by Black Soldier Fly

Author

Aziz, Hamidi Abdul, Lee, Wen Si, Hasan, Hadura Abu, Hassan, Hasnuri Mat, Wang, Lawrence K., Wang, Mu-Hao Sung, Hung, Yung-Tse, Wang, Lawrence K., Series Editor, Wang, Mu-Hao Sung, Series Editor, and Hung, Yung-Tse, editor

Published
2022
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31. Landfill Leachate Treatment

Author

Aziz, Hamidi Abdul, Zahari, Mohamed Shahrir Mohamed, Ahmed, Zaber, Ismail, Shahrul, Jaafar, Izan, Yusoff, Mohd Suffian, Wang, Lawrence K., Wang, Mu-Hao Sung, Wang, Lawrence K., Series Editor, Wang, Mu-Hao Sung, Series Editor, and Hung, Yung-Tse, editor

Published
2022
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32. Solid Waste Management in the Tourism Industry

Author

Yusoff, Mohd Suffian, Kamaruddin, Mohamad Anuar, Hanif, Mohamad Haziq Mohd, Norashiddin, Faris Aiman, Shadi, Abdubaki Mohamed Hussen, Wang, Lawrence K., Wang, Mu-Hao Sung, Wang, Lawrence K., Series Editor, Wang, Mu-Hao Sung, Series Editor, and Hung, Yung-Tse, editor

Published
2022
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33. Energy Recovery from Solid Waste

Author

Alkarimiah, Rosnani, Makhtar, Muaz Mohd Zaini, Aziz, Hamidi Abdul, Vesilind, P. Aarne, Wang, Lawrence K., Hung, Yung-Tse, Wang, Lawrence K., Series Editor, Wang, Mu-Hao Sung, Series Editor, and Hung, Yung-Tse, editor

Published
2022
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36. Solid Waste and Marine Litter Management

Author

Murshed, Mohamad Fared, Kamal, Nurul Hana Mokhtar, Fagbenro, Oluwakemi Kehinde, Wang, Lawrence K., Wang, Mu-Hao Sung, Wang, Lawrence K., Series Editor, Wang, Mu-Hao Sung, Series Editor, and Hung, Yung-Tse, editor

Published
2022
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37. Sanitary Landfill Types and Design

Author

Palaniandy, Puganeshwary, Aziz, Hamidi Abdul, Wang, Lawrence K., Michael Terlecky, P., Jr, Hung, Yung-Tse, Wang, Lawrence K., Series Editor, Wang, Mu-Hao Sung, Series Editor, and Hung, Yung-Tse, editor

Published
2022
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38. Restaurant Waste Recycle and Disposal

Author

Dahlan, Irvan, Yusoff, Mohd Suffian, Akinbile, Christopher Oluwakunmi, Wang, Lawrence K., Wang, Mu-Hao Sung, Wang, Lawrence K., Series Editor, Wang, Mu-Hao Sung, Series Editor, and Hung, Yung-Tse, editor

Published
2022
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39. Sustainable Solid Waste Management

Author

George, Fadugba O., Yusoff, Mohd Suffian, Arogundade, Suhaib, Adam, Nor Hana, Wang, Lawrence K., Wang, Mu-Hao Sung, Wang, Lawrence K., Series Editor, Wang, Mu-Hao Sung, Series Editor, and Hung, Yung-Tse, editor

Published
2022
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40. Superior antibody immunogenicity of a viral-vectored RH5 blood-stage malaria vaccine in Tanzanian infants as compared to adults

Author

Silk, Sarah E., Kalinga, Wilmina F., Mtaka, Ivanny M., Lilolime, Nasoro S., Mpina, Maximillian, Milando, Florence, Ahmed, Saumu, Diouf, Ababacar, Mkwepu, Fatuma, Simon, Beatus, Athumani, Thabit, Rashid, Mohammed, Mohammed, Latipha, Lweno, Omary, Ali, Ali M., Nyaulingo, Gloria, Mwalimu, Bakari, Mswata, Sarah, Mwamlima, Tunu G., Barrett, Jordan R., Wang, Lawrence T., Themistocleous, Yrene, King, Lloyd D.W., Hodgson, Susanne H., Payne, Ruth O., Nielsen, Carolyn M., Lawrie, Alison M., Nugent, Fay L., Cho, Jee-Sun, Long, Carole A., Miura, Kazutoyo, Draper, Simon J., Minassian, Angela M., and Olotu, Ally I.

Published
2023
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41. Cytotoxicity of human antibodies targeting the circumsporozoite protein is amplified by 3D substrate and correlates with protection

Author

Aguirre-Botero, Manuela C., Wang, Lawrence T., Formaglio, Pauline, Aliprandini, Eduardo, Thiberge, Jean-Michel, Schön, Arne, Flores-Garcia, Yevel, Mathis-Torres, Shamika, Flynn, Barbara J., da Silva Pereira, Lais, Le Duff, Yann, Hurley, Mathew, Nacer, Adéla, Bowyer, Paul W., Zavala, Fidel, Idris, Azza H., Francica, Joseph R., Seder, Robert A., and Amino, Rogerio

Published
2023
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42. Optimizing Screening for HIV.

Author

Chaillon, Antoine, Hoenigl, Martin, Freitas, Lorri, Feldman, Haruna, Tilghman, Winston, Wang, Lawrence, Smith, Davey, Little, Susan, and Mehta, Sanjay R

Subjects
HIV, prevalence, screening, sexually transmitted infections, Prevention, Health Services, HIV/AIDS, Clinical Research, Sexually Transmitted Infections, Infectious Diseases, Infection
Abstract

BackgroundThe HIV epidemic is unevenly distributed throughout the United States, even within neighborhoods. This study evaluated how effectively current testing approaches reached persons at risk for HIV infection across San Diego (SD) County, California.MethodsHIV case and testing data, sexually transmitted infection (STI) data, and sociodemographic data for SD County were collected from the SD Health and Human Services Agency and the "Early Test" community-based HIV screening program between 1998 and 2016. Relationships between HIV diagnoses, HIV prevalence, and STI diagnoses with screening at the ZIP code level were evaluated.ResultsOverall, 379 074 HIV tests were performed. The numbers of HIV tests performed on persons residing in a ZIP code or region overall strongly correlated with prevalent HIV cases (R 2 = .714), new HIV diagnoses (R 2 = .798), and STI diagnoses (R 2 = .768 [chlamydia], .836 [gonorrhea], .655 [syphilis]) in those regions. ZIP codes with the highest HIV prevalence had the highest number of tests per resident and fewest number of tests per diagnosis. Even though most screening tests occurred at fixed venues located in high-prevalence areas, screening of residents from lower-prevalence areas was mostly proportional to the prevalence of HIV and rates of new HIV and STI diagnoses in those locales.ConclusionsThis study supported the ability of a small number of standalone testing centers to reach at-risk populations dispersed across SD County. These methods can also be used to highlight geographic areas or demographic segments that may benefit from more intensive screening.

Published
2020

44. Sanitary Landfill Operation and Management

Author

Kamaruddin, Mohamad Anuar, Norashiddin, Faris Aiman, Yusoff, Mohd Suffian, Hanif, Mohamad Haziq Mohd, Wang, Lawrence K., Wang, Mu-Hao Sung, Wang, Lawrence K., Series Editor, Wang, Mu-Hao Sung, Series Editor, and Hung, Yung-Tse, editor

Published
2021
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45. Introduction to Solid Waste Management

Author

Aziz, Hamidi Abdul, Abu Amr, Salem S., Vesilind, P. Aarne, Wang, Lawrence K., Hung, Yung-Tse, Wang, Lawrence K., Series Editor, Wang, Mu-Hao Sung, Series Editor, and Hung, Yung-Tse, editor

Published
2021
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46. Combustion and Incineration

Author

Zakaria, Ridzuan, Aziz, Hamidi Abdul, Wang, Lawrence K., Hung, Yung-Tse, Wang, Lawrence K., Series Editor, Wang, Mu-Hao Sung, Series Editor, and Hung, Yung-Tse, editor

Published
2021
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47. Characterization and Measurement of Solid Waste

Author

Kamaruddin, Mohamad Anuar, Norashiddin, Faris Aiman, Hanif, Mohamad Haziq Mohd, Shadi, Abdubaki Mohamed Hussen, Yusoff, Mohd Suffian, Wang, Lawrence K., Wang, Mu-Hao Sung, Wang, Lawrence K., Series Editor, Wang, Mu-Hao Sung, Series Editor, and Hung, Yung-Tse, editor

Published
2021
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48. Legislation for Solid Waste Management

Author

Hassan, Siti Hafizan, Halim, Azhar Abdul, Yusoff, Mohd Suffian, Wang, Lawrence K., Wang, Mu-Hao Sung, Wang, Lawrence K., Series Editor, Wang, Mu-Hao Sung, Series Editor, and Hung, Yung-Tse, editor

Published
2021
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