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1. MLPerf Power: Benchmarking the Energy Efficiency of Machine Learning Systems from Microwatts to Megawatts for Sustainable AI

Author

Tschand, Arya, Rajan, Arun Tejusve Raghunath, Idgunji, Sachin, Ghosh, Anirban, Holleman, Jeremy, Kiraly, Csaba, Ambalkar, Pawan, Borkar, Ritika, Chukka, Ramesh, Cockrell, Trevor, Curtis, Oliver, Fursin, Grigori, Hodak, Miro, Kassa, Hiwot, Lokhmotov, Anton, Miskovic, Dejan, Pan, Yuechao, Manmathan, Manu Prasad, Raymond, Liz, John, Tom St., Suresh, Arjun, Taubitz, Rowan, Zhan, Sean, Wasson, Scott, Kanter, David, and Reddi, Vijay Janapa

Subjects
Computer Science - Hardware Architecture, Computer Science - Distributed, Parallel, and Cluster Computing, Computer Science - Machine Learning
Abstract

Rapid adoption of machine learning (ML) technologies has led to a surge in power consumption across diverse systems, from tiny IoT devices to massive datacenter clusters. Benchmarking the energy efficiency of these systems is crucial for optimization, but presents novel challenges due to the variety of hardware platforms, workload characteristics, and system-level interactions. This paper introduces MLPerf Power, a comprehensive benchmarking methodology with capabilities to evaluate the energy efficiency of ML systems at power levels ranging from microwatts to megawatts. Developed by a consortium of industry professionals from more than 20 organizations, MLPerf Power establishes rules and best practices to ensure comparability across diverse architectures. We use representative workloads from the MLPerf benchmark suite to collect 1,841 reproducible measurements from 60 systems across the entire range of ML deployment scales. Our analysis reveals trade-offs between performance, complexity, and energy efficiency across this wide range of systems, providing actionable insights for designing optimized ML solutions from the smallest edge devices to the largest cloud infrastructures. This work emphasizes the importance of energy efficiency as a key metric in the evaluation and comparison of the ML system, laying the foundation for future research in this critical area. We discuss the implications for developing sustainable AI solutions and standardizing energy efficiency benchmarking for ML systems., Comment: 16 pages, 11 figures, 1 table

Published
2024

2. Experience of the first adult-focussed undiagnosed disease program in Australia (AHA-UDP): solving rare and puzzling genetic disorders is ageless

Author

Wallis, Mathew, Bodek, Simon D., Munro, Jacob, Rafehi, Haloom, Bennett, Mark F., Ye, Zimeng, Schneider, Amy, Gardiner, Fiona, Valente, Giulia, Murdoch, Emma, Uebergang, Eloise, Hunter, Jacquie, Stutterd, Chloe, Huq, Aamira, Salmon, Lucinda, Scheffer, Ingrid, Eratne, Dhamidhu, Meyn, Stephen, Fong, Chun Y., John, Tom, Mullen, Saul, White, Susan M., Brown, Natasha J., McGillivray, George, Chen, Jesse, Richmond, Chris, Hughes, Andrew, Krzesinski, Emma, Fennell, Andrew, Chambers, Brian, Santoreneos, Renee, Le Fevre, Anna, Hildebrand, Michael S., Bahlo, Melanie, Christodoulou, John, Delatycki, Martin, and Berkovic, Samuel F.

Published
2024
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3. MLPerf HPC: A Holistic Benchmark Suite for Scientific Machine Learning on HPC Systems

Author

Farrell, Steven, Emani, Murali, Balma, Jacob, Drescher, Lukas, Drozd, Aleksandr, Fink, Andreas, Fox, Geoffrey, Kanter, David, Kurth, Thorsten, Mattson, Peter, Mu, Dawei, Ruhela, Amit, Sato, Kento, Shirahata, Koichi, Tabaru, Tsuguchika, Tsaris, Aristeidis, Balewski, Jan, Cumming, Ben, Danjo, Takumi, Domke, Jens, Fukai, Takaaki, Fukumoto, Naoto, Fukushi, Tatsuya, Gerofi, Balazs, Honda, Takumi, Imamura, Toshiyuki, Kasagi, Akihiko, Kawakami, Kentaro, Kudo, Shuhei, Kuroda, Akiyoshi, Martinasso, Maxime, Matsuoka, Satoshi, Mendonça, Henrique, Minami, Kazuki, Ram, Prabhat, Sawada, Takashi, Shankar, Mallikarjun, John, Tom St., Tabuchi, Akihiro, Vishwanath, Venkatram, Wahib, Mohamed, Yamazaki, Masafumi, and Yin, Junqi

Subjects
Computer Science - Machine Learning, Computer Science - Distributed, Parallel, and Cluster Computing
Abstract

Scientific communities are increasingly adopting machine learning and deep learning models in their applications to accelerate scientific insights. High performance computing systems are pushing the frontiers of performance with a rich diversity of hardware resources and massive scale-out capabilities. There is a critical need to understand fair and effective benchmarking of machine learning applications that are representative of real-world scientific use cases. MLPerf is a community-driven standard to benchmark machine learning workloads, focusing on end-to-end performance metrics. In this paper, we introduce MLPerf HPC, a benchmark suite of large-scale scientific machine learning training applications driven by the MLCommons Association. We present the results from the first submission round, including a diverse set of some of the world's largest HPC systems. We develop a systematic framework for their joint analysis and compare them in terms of data staging, algorithmic convergence, and compute performance. As a result, we gain a quantitative understanding of optimizations on different subsystems such as staging and on-node loading of data, compute-unit utilization, and communication scheduling, enabling overall $>10 \times$ (end-to-end) performance improvements through system scaling. Notably, our analysis shows a scale-dependent interplay between the dataset size, a system's memory hierarchy, and training convergence that underlines the importance of near-compute storage. To overcome the data-parallel scalability challenge at large batch sizes, we discuss specific learning techniques and hybrid data-and-model parallelism that are effective on large systems. We conclude by characterizing each benchmark with respect to low-level memory, I/O, and network behavior to parameterize extended roofline performance models in future rounds.

Published
2021

4. MLPerf Mobile Inference Benchmark

Author

Reddi, Vijay Janapa, Kanter, David, Mattson, Peter, Duke, Jared, Nguyen, Thai, Chukka, Ramesh, Shiring, Ken, Tan, Koan-Sin, Charlebois, Mark, Chou, William, El-Khamy, Mostafa, Hong, Jungwook, John, Tom St., Trinh, Cindy, Buch, Michael, Mazumder, Mark, Markovic, Relia, Atta, Thomas, Cakir, Fatih, Charkhabi, Masoud, Chen, Xiaodong, Chiang, Cheng-Ming, Dexter, Dave, Heo, Terry, Schmuelling, Gunther, Shabani, Maryam, and Zika, Dylan

Subjects
Computer Science - Machine Learning, Computer Science - Distributed, Parallel, and Cluster Computing
Abstract

This paper presents the first industry-standard open-source machine learning (ML) benchmark to allow perfor mance and accuracy evaluation of mobile devices with different AI chips and software stacks. The benchmark draws from the expertise of leading mobile-SoC vendors, ML-framework providers, and model producers. It comprises a suite of models that operate with standard data sets, quality metrics and run rules. We describe the design and implementation of this domain-specific ML benchmark. The current benchmark version comes as a mobile app for different computer vision and natural language processing tasks. The benchmark also supports non-smartphone devices, such as laptops and mobile PCs. Benchmark results from the first two rounds reveal the overwhelming complexity of the underlying mobile ML system stack, emphasizing the need for transparency in mobile ML performance analysis. The results also show that the strides being made all through the ML stack improve performance. Within six months, offline throughput improved by 3x, while latency reduced by as much as 12x. ML is an evolving field with changing use cases, models, data sets and quality targets. MLPerf Mobile will evolve and serve as an open-source community framework to guide research and innovation for mobile AI.

Published
2020

5. Transcriptional perturbation of protein arginine methyltransferase-5 exhibits MTAP-selective oncosuppression.

Author

Busacca, Sara, Zhang, Qi, Sharkey, Annabel, Dawson, Alan G, Moore, David A, Waller, David A, Nakas, Apostolos, Jones, Carolyn, Cain, Kelvin, Luo, Jin-Li, Salcedo, Adriana, Salaroglio, Iris Chiara, Riganti, Chiara, Le Quesne, John, John, Tom, Boutros, Paul C, Zhang, Shu-Dong, and Fennell, Dean A

Subjects
Genetics, Lung, 5.1 Pharmaceuticals, 2.1 Biological and endogenous factors
Abstract

We hypothesized that small molecule transcriptional perturbation could be harnessed to target a cellular dependency involving protein arginine methyltransferase 5 (PRMT5) in the context of methylthioadenosine phosphorylase (MTAP) deletion, seen frequently in malignant pleural mesothelioma (MPM). Here we show, that MTAP deletion is negatively prognostic in MPM. In vitro, the off-patent antibiotic Quinacrine efficiently suppressed PRMT5 transcription, causing chromatin remodelling with reduced global histone H4 symmetrical demethylation. Quinacrine phenocopied PRMT5 RNA interference and small molecule PRMT5 inhibition, reducing clonogenicity in an MTAP-dependent manner. This activity required a functional PRMT5 methyltransferase as MTAP negative cells were rescued by exogenous wild type PRMT5, but not a PRMT5E444Q methyltransferase-dead mutant. We identified c-jun as an essential PRMT5 transcription factor and a probable target for Quinacrine. Our results therefore suggest that small molecule-based transcriptional perturbation of PRMT5 can leverage a mutation-selective vulnerability, that is therapeutically tractable, and has relevance to 9p21 deleted cancers including MPM.

Published
2021

7. MLPerf Inference Benchmark

Author

Reddi, Vijay Janapa, Cheng, Christine, Kanter, David, Mattson, Peter, Schmuelling, Guenther, Wu, Carole-Jean, Anderson, Brian, Breughe, Maximilien, Charlebois, Mark, Chou, William, Chukka, Ramesh, Coleman, Cody, Davis, Sam, Deng, Pan, Diamos, Greg, Duke, Jared, Fick, Dave, Gardner, J. Scott, Hubara, Itay, Idgunji, Sachin, Jablin, Thomas B., Jiao, Jeff, John, Tom St., Kanwar, Pankaj, Lee, David, Liao, Jeffery, Lokhmotov, Anton, Massa, Francisco, Meng, Peng, Micikevicius, Paulius, Osborne, Colin, Pekhimenko, Gennady, Rajan, Arun Tejusve Raghunath, Sequeira, Dilip, Sirasao, Ashish, Sun, Fei, Tang, Hanlin, Thomson, Michael, Wei, Frank, Wu, Ephrem, Xu, Lingjie, Yamada, Koichi, Yu, Bing, Yuan, George, Zhong, Aaron, Zhang, Peizhao, and Zhou, Yuchen

Subjects
Computer Science - Machine Learning, Computer Science - Performance, Statistics - Machine Learning
Abstract

Machine-learning (ML) hardware and software system demand is burgeoning. Driven by ML applications, the number of different ML inference systems has exploded. Over 100 organizations are building ML inference chips, and the systems that incorporate existing models span at least three orders of magnitude in power consumption and five orders of magnitude in performance; they range from embedded devices to data-center solutions. Fueling the hardware are a dozen or more software frameworks and libraries. The myriad combinations of ML hardware and ML software make assessing ML-system performance in an architecture-neutral, representative, and reproducible manner challenging. There is a clear need for industry-wide standard ML benchmarking and evaluation criteria. MLPerf Inference answers that call. In this paper, we present our benchmarking method for evaluating ML inference systems. Driven by more than 30 organizations as well as more than 200 ML engineers and practitioners, MLPerf prescribes a set of rules and best practices to ensure comparability across systems with wildly differing architectures. The first call for submissions garnered more than 600 reproducible inference-performance measurements from 14 organizations, representing over 30 systems that showcase a wide range of capabilities. The submissions attest to the benchmark's flexibility and adaptability., Comment: ISCA 2020

Published
2019

8. MLPerf Training Benchmark

Author

Mattson, Peter, Cheng, Christine, Coleman, Cody, Diamos, Greg, Micikevicius, Paulius, Patterson, David, Tang, Hanlin, Wei, Gu-Yeon, Bailis, Peter, Bittorf, Victor, Brooks, David, Chen, Dehao, Dutta, Debojyoti, Gupta, Udit, Hazelwood, Kim, Hock, Andrew, Huang, Xinyuan, Ike, Atsushi, Jia, Bill, Kang, Daniel, Kanter, David, Kumar, Naveen, Liao, Jeffery, Ma, Guokai, Narayanan, Deepak, Oguntebi, Tayo, Pekhimenko, Gennady, Pentecost, Lillian, Reddi, Vijay Janapa, Robie, Taylor, John, Tom St., Tabaru, Tsuguchika, Wu, Carole-Jean, Xu, Lingjie, Yamazaki, Masafumi, Young, Cliff, and Zaharia, Matei

Subjects
Computer Science - Machine Learning, Computer Science - Performance, Statistics - Machine Learning
Abstract

Machine learning (ML) needs industry-standard performance benchmarks to support design and competitive evaluation of the many emerging software and hardware solutions for ML. But ML training presents three unique benchmarking challenges absent from other domains: optimizations that improve training throughput can increase the time to solution, training is stochastic and time to solution exhibits high variance, and software and hardware systems are so diverse that fair benchmarking with the same binary, code, and even hyperparameters is difficult. We therefore present MLPerf, an ML benchmark that overcomes these challenges. Our analysis quantitatively evaluates MLPerf's efficacy at driving performance and scalability improvements across two rounds of results from multiple vendors., Comment: MLSys 2020

Published
2019

9. Biomarkers for immunotherapy resistance in non-small cell lung cancer.

Author

Rother, Catriona, John, Tom, and Wong, Annie

Subjects
PROGRAMMED death-ligand 1, IMMUNE checkpoint inhibitors, NON-small-cell lung carcinoma, TUMOR markers, PATIENT experience
Abstract

Immunotherapy has revolutionised the treatment landscape of non-small cell lung cancer (NSCLC), significantly improving survival outcomes and offering renewed hope to patients with advanced disease. However, the majority of patients experience limited long-term benefits from immune checkpoint inhibition (ICI) due to the development of primary or acquired immunotherapy resistance. Accurate predictive biomarkers for immunotherapy resistance are essential for individualising treatment strategies, improving survival outcomes, and minimising potential treatment-related harm. This review discusses the mechanisms underlying resistance to immunotherapy, addressing both cancer cell-intrinsic and cancer cell-extrinsic resistance processes. We summarise the current utility and limitations of two clinically established biomarkers: programmed death ligand 1 (PD-L1) expression and tumour mutational burden (TMB). Following this, we present a comprehensive review of emerging immunotherapy biomarkers in NSCLC, including tumour neoantigens, epigenetic signatures, markers of the tumour microenvironment (TME), genomic alterations, host–microbiome composition, and circulating biomarkers. The potential clinical applications of these biomarkers, along with novel approaches to their biomarker identification and targeting, are discussed. Additionally, we explore current strategies to overcome immunotherapy resistance and propose incorporating predictive biomarkers into an adaptive clinical trial design, where specific immune signatures guide subsequent treatment selection. [ABSTRACT FROM AUTHOR]

Published
2025
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12. Rehabilitation outcomes for people with lung cancer (UNITE): protocol for the development of a core outcome set

Author

Edbrooke, Lara, Granger, Catherine L, Francis, Jill J, John, Tom, Kaadan, Nasreen, Halloran, Emma, Connolly, Bronwen, and Denehy, Linda

Subjects
Lung Neoplasms, Treatment Outcome, Delphi Technique, SDG 3 - Good Health and Well-being, Research Design, Lung Cancer, Quality of Life, Humans, Pulmonary Rehabilitation, Exercise, Systematic Reviews as Topic
Abstract

Introduction: With treatment-related improvements in survival, rehabilitation is essential to improve function and health-related quality of life and manage the high symptom burden associated with lung cancer. Despite this, significant heterogeneity exists in the outcomes and instruments used to evaluate lung cancer rehabilitation programme impact. This study aims to develop a core set of clinically relevant lung cancer rehabilitation outcomes for use in clinical practice.Methods and analysis: An international Delphi consensus study involving consumer, healthcare professional and researcher stakeholders to determine which outcomes to include and how to measure these. Stage 1 (preliminary): mixed methods to develop the potential list of outcomes (1) overview of systematic reviews of lung cancer exercise interventions and (2) focus groups and individual interviews with people with lung cancer. Stage 2: outcomes were grouped according to the International Classification of Functioning, Disability and Health domains. Stage 3: to determine priority outcomes for core outcome set (COS) inclusion participants will rate each outcome’s importance (one-nine-point Likert scale) over two-three survey rounds. Stage 4: following review by the steering committee, a consensus meeting will be held if agreement on the COS has not been reached.Stage 5: recommendations will be made regarding a single instrument for measuring each COS outcome by reviewing existing resources where consensus has already been reached. Where resources do not exist the quality and feasibility of potential measurement instruments will be appraised, and the Delphi consensus survey and meeting process outlined in stages 3–4 will be repeated.

Published
2023
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14. Therapeutic misunderstandings in modern research.

Author

Heynemann, Sarah, Lipworth, Wendy, McLachlan, Sue‐Anne, Philip, Jennifer, John, Tom, and Kerridge, Ian

Subjects
OCCUPATIONAL roles, HUMAN research subjects, CLINICAL trials, PATIENT selection, RESEARCH methodology, RESEARCH ethics, INFORMED consent (Medical law), COMMUNICATION, TUMORS, BIOETHICS
Abstract

Clinical trials play a crucial role in generating evidence about healthcare interventions and improving outcomes for current and future patients. For individual trial participants, however, there are inevitably trade‐offs involved in clinical trial participation, given that trials have traditionally been designed to benefit future patient populations rather than to offer personalised care. Failure to understand the distinction between research and clinical care and the likelihood of benefit from participation in clinical trials has been termed the 'therapeutic misconception'. The evolution of the clinical trials landscape, including greater integration of clinical trials into healthcare and development of novel trial methodologies, may reinforce the significance of the therapeutic misconception and other forms of misunderstanding while at the same time (paradoxically) challenging its salience. Using cancer clinical trials as an exemplar, we describe how methodological changes in early‐ and late‐phase clinical trial designs, as well as changes in the design and delivery of healthcare, impact upon the therapeutic misconception. We suggest that this provides an impetus to re‐examine the ethics of clinical research, particularly in relation to trial access, participant selection, communication and consent, and role delineation. [ABSTRACT FROM AUTHOR]

Published
2024
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18. Egg-Derived Anti-SARS-CoV-2 Immunoglobulin Y (IgY) With Broad Variant Activity as Intranasal Prophylaxis Against COVID-19

Author

Frumkin, Lyn R., primary, Lucas, Michaela, additional, Scribner, Curtis L., additional, Ortega-Heinly, Nastassja, additional, Rogers, Jayden, additional, Yin, Gang, additional, Hallam, Trevor J., additional, Yam, Alice, additional, Bedard, Kristin, additional, Begley, Rebecca, additional, Cohen, Courtney A., additional, Badger, Catherine V., additional, Abbasi, Shawn A., additional, Dye, John M., additional, McMillan, Brian, additional, Wallach, Michael, additional, Bricker, Traci L., additional, Joshi, Astha, additional, Boon, Adrianus C. M., additional, Pokhrel, Suman, additional, Kraemer, Benjamin R., additional, Lee, Lucia, additional, Kargotich, Stephen, additional, Agochiya, Mahima, additional, John, Tom St., additional, and Mochly-Rosen, Daria, additional

Published
2022
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26. Thermal ablation in non-small cell lung cancer: a review of treatment modalities and the evidence for combination with immune checkpoint inhibitors

Author

Rangamuwa, Kanishka, primary, Leong, Tracy, additional, Weeden, Clare, additional, Asselin-Labat, Marie-Liesse, additional, Bozinovski, Steven, additional, Christie, Michael, additional, John, Tom, additional, Antippa, Phillip, additional, Irving, Louis, additional, and Steinfort, Daniel, additional

Published
2021
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27. Plasma pre-treatment T790M relative allelic frequency in patients with advanced EGFR-mutated non-small cell lung cancer predicts treatment response to subsequent-line osimertinib

Author

Ding, Pei N., primary, Roberts, Tara L., additional, Chua, Wei, additional, Becker, Therese M., additional, Caixeiro, Nicole, additional, de Souza, Paul, additional, Gao, Bo, additional, Lee, Chee K., additional, Itchins, Malinda, additional, Westman, Helen, additional, Clarke, Stephen, additional, Blinman, Prunella, additional, Kao, Steven, additional, John, Tom, additional, Leal, Jose L., additional, and Bray, Victoria J., additional

Published
2021
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28. Cloning and characterization of a new intercellular adhesion molecule ICAM-R

Author

Vazeux, Rosemay, Hoffman, Patricia A., Tomita, Judy K., Dickinson, Edna S., Jasman, Richard L., St. John, Tom, and Gallatin, W. Michael

Subjects
Cell adhesion molecules -- Physiological aspects, Leukocytes -- Physiological aspects, Immune response -- Molecular aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The molecular clone of a newly identified human intercellular adhesion molecule (ICAM), designated ICAM-R, has been obtained. ICAM-R is expressed by a complementary DNA molecule whose 1,781 base pairs generate a protein with five extracellular immunoglobulin-related type domains. Like the previously identified ICAMs, ICAM-R participates in regulating the immune response by influencing the leukocyte function-associated antigen.

Published
1992

29. Abstract CT192: Entrectinib in locally advanced or metastatic ROS1 fusion-positive non-small cell lung cancer (NSCLC): Integrated analysis of ALKA-372-001, STARTRK-1 and STARTRK-2

Author

Drilon, Alexander, primary, Barlesi, Fabrice, additional, Braud, Filippo De, additional, Cho, Byoung Chul, additional, Ahn, Myung-Ju, additional, Siena, Salvatore, additional, Krebs, Matthew G., additional, Lin, Chia-Chi, additional, John, Tom, additional, Tan, Daniel SW, additional, Seto, Takashi, additional, Dziadziuszko, Rafal, additional, Arkenau, Hendrick-Tobias, additional, Rolfo, Christian, additional, Wolf, Jürgen, additional, Ye, Chenglin, additional, Riehl, Todd, additional, Eng, Susan, additional, and Doebele, Robert C., additional

Published
2019
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30. Abstract CT131: Entrectinib in NTRK-fusion positive (NTRK-FP) non-small cell lung cancer (NSCLC): Integrated analysis of patients enrolled in three trials (STARTRK-2, STARTRK-1 and ALKA-372-001)

Author

Doebele, Robert, primary, Paz-Ares, Luis, additional, Farago, Anna F., additional, Liu, Stephen V., additional, Chawla, Sant P., additional, Tosi, Diego, additional, Blakely, Collin M., additional, Krauss, John C., additional, Sigal, Darren, additional, Bazhenova, Lyudmila, additional, John, Tom, additional, Besse, Benjamin, additional, Wolf, Jürgen, additional, Seto, Takashi, additional, Chow-Maneval, Edna, additional, Ye, Chenglin, additional, Simmons, Brian, additional, and Demetri, George D., additional

Published
2019
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31. DREAM: A phase II study of durvalumab with first line chemotherapy in mesothelioma-First results

Author

Nowak, Anna K., Lesterhuis, Willem Joost, Hughes, Brett Gordon Maxwell, Brown, Chris, Kok, Peey Sei, O'Byrne, Kenneth John, John, Tom, Pavlakis, Nick, Kao, Steven Chuan-hao, Yip, Sonia, Karikios, Deme John, Lam, Wei-sen, Langford, Ailsa, Stockler, Martin R., Nowak, Anna K., Lesterhuis, Willem Joost, Hughes, Brett Gordon Maxwell, Brown, Chris, Kok, Peey Sei, O'Byrne, Kenneth John, John, Tom, Pavlakis, Nick, Kao, Steven Chuan-hao, Yip, Sonia, Karikios, Deme John, Lam, Wei-sen, Langford, Ailsa, and Stockler, Martin R.

Abstract

Background: DREAM is an open-label, single arm, multi-centre, phase II trial with a safety run in designed to determine the activity, safety and tolerability of durvalumab combined with cisplatin and pemetrexed as first line therapy in malignant pleural mesothelioma (MPM). ANZ Clinical trial registry number: ACTRN12616001170415. Methods: Chemotherapy-naïve patients with MPM of all histological subtypes, planned for first-line cisplatin and pemetrexed who had not received prior radiotherapy and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 were eligible. Patients received durvalumab (1125mg), cisplatin (75mg/m2) and pemetrexed (500mg/m2) 3-weekly for a maximum of 6 cycles, followed by durvalumab alone (1125 mg 3-weekly) until progression or to 12 months total therapy. Primary endpoint was progression-free survival at 6 months (PFS6). The design provides >90% power if the true PFS6 rate is 65%, with 5% type I error using an expected PFS6 from standard treatment of 45%. Matching tissue and bloods were collected for translational research. Results: Between Dec 2016 to Sep 2017 54 participants were recruited. The median age was 68 (42-82) with 82% male and 60% ECOG 0. They received a median of 6 cycles of chemotherapy (range 1-6) and 7 of durvalumab (given with and without chemotherapy) (range 1-18). The 6-patient safety run in confirmed the tolerability of chemoimmunotherapy. In the first 31 evaluable patients (pre-specified primary interim analysis), PFS6 based on modified RECIST (mRECIST) for MPM was 71%. The objective response rate (ORR) was 61% using mRECIST and 53% using iRECIST. Thirty-one patients (57%) experienced adverse events (AEs) that were grade ≥3. Nineteen patients (35%) had immune-related (ir) AEs including 2 grade 3 irAEs. Conclusions: In MPM, adding durvalumab to first line treatment with cisplatin and pemetrexed had higher rates of PFS6 and ORR than expected for chemotherapy alone, with acceptable tolerability. The final r

Published
2018

33. Familiarity and the perception of dissonance in musical intervals and chords

Author

Marco, David John-Tom and Marco, David John-Tom

Abstract

Complex relationships exist between the physical world and the perceptual world. In the auditory domain, the impact of stimulus characteristics on the perception of sound has received a wealth of attention in the literature over the last 60 years. This thesis examined differences in stimulus familiarity, the discrimination of concurrent pitch information and the experience of sensory dissonance. There is still no consensus among researchers regarding the mechanisms responsible for accurate pitch perception. The principle aim of this thesis was to explore the role of training in pitch processing for a range of musical sounds varying in familiarity, as outlined in a new model of sound perception (McLachlan & Wilson, 2010). An additional aim of this thesis was to investigate the perception of dissonance in musicians with varying types of musical training and pitch identification ability. This thesis was divided into two main parts as a means of exploring these aims. Four general hypotheses and nine specific hypotheses were postulated in Part I. The first general hypothesis predicted that pitch matching performance would be better for musicians trained on inharmonic Gamelan instruments compared to musicians with similar levels of training who have not been exposed to these instrumental timbres. It was predicted that Gamelan musicians would rate Gamelan instruments as more familiar than Western musicians in the absence of musical context, and that Gamelan musicians would be better at matching the pitch of inharmonic Gamelan instruments than musicians with similar levels of musical training on Western instruments. The second general hypothesis proposed that trained musicians would exhibit higher levels of pitch matching accuracy for intervals and chords that are more familiar. It was specifically hypothesised that highly trained musicians would rate intervals and chords as higher in familiarity than musicians with less training. It was also predicted that pitch matching p

Published
2014

39. Protocadherin Pcdh2 shows properties similar to, but distinct from, those of classical cadherins

Author

Obata, Shuichi, Sago, Haruhiko, Mori, Nozomu, Rochelle, Julie M., Seldin, Michael F., Davidson, Mari, John, Tom St, Taketani, Shigeru, and Suzuki, Shintaro T.

Abstract

Cell adhesion and several other properties of a recently identified cadherin-related protein, protocadherin Pcdh2, were characterized. A chimeric Pcdh2 in which the original cytoplasmic domain was replaced with the cytoplasmic domain of E-cadherin was expressed in mouse L cells. The expressed protein had a molecular mass of about 150 kDa and was localized predominantly at the cell periphery, as was the wild-type Pcdh2. In a conventional cell aggregation assay, the transfectants showed cell aggregation activity comparable to that of classical cadherins. This activity was Ca2+-dependent and was inhibited by the addition of anti-Pcdh2 antibody, indicating that the chimeric Pcdh2, and probably the wild-type Pcdh2, has Ca2+-dependent cell aggregation activity. Mixed cell aggregation assay using L cells and different types of transfectants showed that the activity of Pcdh2 was homophilic and molecular type specific and that Pcdh2 transfectants did not aggregate with other types of transfectants or with L cells. In immunoprecipitation, the chimeric Pcdh2 co-precipitated with a 105 kDa and a 95 kDa protein, whereas wild-type Pcdh2 co-precipitated with no major protein. Pcdh2 was easily solubilized with non-ionic detergent, in contrast to the case of classical cadherins. On immunofluorescence microscopy, the somas of Purkinje cells were diffusely stained with anti-human Pcdh2 antibody. Mouse Pcdh1 and Pcdh2 were mapped to a small segment of chromosome 18, suggesting that various protocadherins form a gene cluster at this region. The present results suggest that Pcdh2, and possibly other protocadherins as well as proto-cadherin-related proteins such as Drosophila fat, mediate Ca2+-dependent and specific homophilic cell-cell interaction in vivo and play an important role in cell adhesion, cell recognition, and/or some other basic cell processes.

Published
1995
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40. Characterization of cadherin-4 and cadherin-5 reveals new aspects of cadherins

Author

Tanihara, Hidenobu, Kido, Mitsuru, Obata, Shuichi, Heimark, Ronald L., Davidson, Mari, John, Tom St, and Suzuki, Shintaro

Abstract

Several properties of cadherin-4 and cadherin-5 were char- acterized by using the cDNA transfection approach. The proteins of both cadherins had a relative molecular mass of about 130 kDa and were present at the cell periphery, especially at cell-cell contact sites. These cadherins were easily digested with trypsin, and Ca2+ protected cadherin- 4, but not cadherin-5, from the digestion. In immunopre- cipitation, cadherin-4 co-precipitated with two major proteins of 105 kDa and 95 kDa, respectively. The 105 kDa and the 95 kDa proteins are likely to correspond to α- and β-catenins. Cadherin-5 co-precipitated with only one major protein of 95 kDa, but seems to associate with the 105 kDa protein. On the other hand, plakoglobin or γ-catenin did not co-precipitate well with either cadherin-4 or cadherin- 5 in immunoprecipitation, but plakoglobin also appears to associate weakly with these cadherins. Cadherin-4 trans- fectants aggregated within 30 minutes in a cell aggregation assay, but cadherin-5 transfectants did not aggregate under the same conditions. Furthermore, the transfectants of chimeric cadherin-4 with cadherin-5 cytoplasmic domain showed cell aggregation activity comparable to that of wild- type cadherin-4 transfectants, whereas the transfectants of chimeric cadherin-5 with cadherin-4 cytoplasmic domain did not show appreciable cell aggregation, suggesting that the extracellular domains of cadherins, in conjunction with their cytoplasmic domains, play an important role in cell aggregation activity. These results show that cadherin-4 is very similar to the classical cadherins, whereas cadherin-5 is functionally as well as structurally distinct from classical cadherins.

Published
1994
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41. SYNTHESIS AND BIOLOGICAL ACTIVITY OF ENKEPHALIN ANALOGS

Author

PELTON, JOHN TOM and PELTON, JOHN TOM

Abstract

The synthesis and biological activity of two types of enkephalin analogs are reported: those in which the C-terminal carboxylic acid group was replaced by a chloromethyl ketone, and those in which the C-terminus was replaced by lysine, or a derivative of lysine. The substitution of the terminal carboxyl group of leucine enkephalin and D-Ala('2)-leucine enkephalin with a chloromethyl ketone uniformly increased the potency in the guinea pig ileum assay by a factor of six. The chloromethyl ketones were also more potent in inhibiting the stereospecific binding of {('3)H}-naloxone to opiate receptors in the rat brain. While the chloromethyl ketone analogs had the potential to act as irreversible agonists it was not clear from the present studies that such binding did indeed occur. The increased activity of these derivatives was related to the increased lipophilic character of the peptide C-terminus. Since decreasing the hydrophilic character of C-6, -7 and -8 of the C-ring of morphine leads to increased analgesic activity, the increased activity of the more hydrophobic chloromethyl ketones supports the suggestion that the Leu('5) carboxyl group of enkephalins overlaps the 6-hydroxyl group of morphine in the region of the C-ring. The biological activity of analogs substituted at the C-terminus with lysine, or a derivative of lysine containing either a formyl-, acetyl-, octanoyl-, or carbobenzyoxy-group attached to the (epsilon)-amino function, confirmed the importance of a hydrophobic group at that position. The most potent analog, D-Ala('2), N-(epsilon)-carbobenzyoxy-Lys('5)-enkephalin, was found to be almost three times more potent than the corresponding leucine enkephalin compound in the guinea pig ileum assay. These studies show that relatively large groups can be accommodated at the terminal position, without loss of activity. The synthesis of an LHRH precursor, in which the amino acid side chain functional groups are blocked by protecting groups, is also reported. S

Published
1982

42. Killashee, Longphort

Author

Killashee, Longphort, Muireadhaigh, Seán Ó, Casey, Maggie Rose, Edgeworth, John Tom, Gilleran, Mary, Lee, Madeline Frances, Casey, Edward James, Casey, John, Casey, Elizabeth, Lee, Madeline, Toher, Michael, Furey, Rose-Lena, Rollins, Eva, Edgeworth, T., Lee, Rose, Greally, Michael, Smith, Mary, Tyrrell, Agnes, Greally, Danny, Gilleran, Mollie, Edgeworth, John Thomas, Casey, Tess, Casey, Patrick J., Casey, Mary Tess, Casey, Edward J., Gilleran, Rose, Dowd, Mary, Edgeworth, John T., Mahon, Larry, Casey, Edward, and Gilleran, Maggie

Subjects
Folklore
Abstract

A collection of folklore and local history stories from Killashee, Longphort (school) (Killashee and Aghakeeran, Co. Longford), collected as part of the Schools' Folklore Scheme, 1937-1938 under the supervision of teacher Seán Ó Muireadhaigh., Story - The Haunted House / Casey, Maggie Rose -- Story about Ballynakill Racecourse / Edgeworth, John Tom -- Story - The Bell of Ballinakill / Gilleran, Mary -- Story - Protestant Landlord and Jockey / Gilleran, Mary -- Story - Toorla Goorla / Lee, Madeline Frances -- Story - The Cats / Lee, Madeline Frances -- Story - The Three Lamps / Lee, Madeline Frances -- Story - The Mare / Casey, Edward James -- Story - The Stolen Child / Casey, John -- Story - The Black Men / Casey, John -- Story - The Stone Boat / Casey, Edward James -- Story - The Magic Stick / Casey, Elizabeth -- Story - The Boy that was Haunted / Casey, Maggie Rose -- Story - The Banshee / Casey, Maggie Rose -- Story - The Furloo River / Gilleran, Mary -- Story - The Witch of Carraig / Lee, Madeline -- Selection of Fairy Tales - Taken by the Fairies / Toher, Michael -- Selection of Fairy Tales - The Fairy King's Birthday / Casey, Edward James -- Selection of Fairy Tales - The Stolen Child / Casey, John -- Selection of Fairy Tales - The Dancer / Furey, Rose-Lena -- Selection of Fairy Tales - The Fairy Man / Rollins, Eva -- Selection of Fairy Tales - The Lost Wand / Rollins, Eva -- Selection of Fairy Tales - The Whitethorn Bush / Edgeworth, T. -- Selection of Fairy Tales - The Pot of Gold / Lee, Rose -- Selection of Fairy Tales - The Good People / Furey, Rose Lena -- Selection of Fairy Tales - The Eel / Casey, John -- Fairy Forts - An Old Liseen / Casey, John -- Fairy Forts - The Fort in Knappogue / Greally, Michael -- Fairy Forts - Fort in Brianstown / Smith, Mary -- Fairy Forts - Fort in Clonmore / Casey, Edward James -- Fairy Forts - The Whirl-Blast / Rollins, Eva -- Fairy Forts - A Fort in Lyneen / Tyrrell, Agnes -- Fairy Forts - The Fort in Aughakeeran / Edgeworth, John Tom -- Fairy Forts - Killeeny Fort / Casey, Elizabeth -- Fairy Forts - The Fort in Cloontirm / Greally, Danny -- Hidden Treasure - The Poor Scholar / Furey, Rose Lena -- Hidden Treasure - Treasure in Cloonkeel / Gilleran, Mollie -- Hidden Treasure - Treasure in Rapparee Hill / Casey, Elizabeth -- Hidden Treasure - Treasure in Skeagh / Edgeworth, John Thomas -- Houses of Long Ago / Casey, Tess -- Houses of Long Ago / Casey, Maggie Rose -- Houses of Long Ago / Lee, Madeline Frances -- Houses of Long Ago / Toher, Michael -- Houses of Long Ago / Gilleran, Mary -- Baking / Casey, Maggie Rose -- Baking / Gilleran, Mollie -- Baking / Lee, Rose -- Baking / Casey, Patrick J. -- Festival Customs / Furey, Rose-Lena -- Festival Customs / Casey, John -- Festival Customs / Casey, Elizabeth -- Festival Customs / Casey, Mary Tess -- Festival Customs / Rollins, Eva -- Old Crafts / Gilleran, Mary -- Old Crafts / Edgeworth, John Tom -- Old Crafts / Lee, Madeline Frances -- Games - Potato-Throwing and Cock-Fighting / Lee, Madeline Frances -- Games - Football Competitions / Gilleran, Mary -- Games - Ball-Alleys / Gilleran, Mary -- Games / Casey, Edward J. -- Fowl / Edgeworth, John Thomas -- Fowl / Lee, Rose -- Fowl / Rollins, Eva -- Fowl / Casey, Elizabeth -- Fowl / Casey, Mary Tess -- Fowl / Gilleran, Mollie -- Fowl - The Hens Going to Denmark / Casey, John -- Churning / Lee, Madeline Frances -- Churning / Casey, Elizabeth -- Churning / Casey, Mary Tess -- Lore of Certain Days / Casey, Mary Tess -- Lore of Certain Days / Lee, Madeline Frances -- Lore of Certain Days / Gilleran, Rose -- Lore of Certain Days / Dowd, Mary -- Lore of Certain Days / Casey, Patrick J. -- Old Roads / Edgeworth, John T. -- Old Roads / Casey, John -- Old Roads / Lee, Madeline Frances -- Old Roads / Casey, Elizabeth -- Selection of Stories - The Fairy Horses / Edgeworth, John Thomas -- Selection of Stories - The Murdered Child / Casey, Mary Tess -- Selection of Stories - The Woman and the Fairies / Casey, John -- Selection of Stories - A Tragic Pool / Edgeworth, John Tom -- Selection of Stories - Park na Crois / Edgeworth, John T. -- Selection of Stories - A Visit from the Fairies / Mahon, Larry -- Selection of Stories - The Moving Well / Casey, Maggie Rose -- Selection of Stories - The Two Dogs / Casey, Maggie Rose -- Selection of Stories - The Quern Stone / Edgeworth, John Tom -- Selection of Stories - Paddy the Piper / Toher, Michael -- Selection of Stories - A Strong Man / Toher, Michael -- Selection of Stories - The Gray Horse / Casey, Edward -- Selection of Stories - The Landlord of Middleton / Casey, Maggie Rose -- Cry of the Bean Sí / Gilleran, Rose -- Selection of Stories - The Sheep / Lee, Rose -- Miscellaneous - Local Fairs / Casey, John -- Miscellaneous - Herbs / Lee, Rose -- Miscellaneous - Luke's Bush / Casey, Elizabeth -- Miscellaneous - Stories of Clough / Rollins, Eva -- Miscellaneous - Leipreachan / Rollins, Eva -- Miscellaneous - From Flax to Linen / Gilleran, Maggie -- Miscellaneous - Rats / Gilleran, Mollie -- Miscellaneous - The Bishop's Grave / Toher, Michael -- Miscellaneous - The Year of the Hounds / Toher, Michael, Supported by funding from the Department of Arts, Heritage and the Gaeltacht (Ireland), University College Dublin, and the National Folklore Foundation (Fondúireacht Bhéaloideas Éireann), 2014-2016.

Published
1937
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45. Letters.

Author

ST. JOHN, TOM, TAYLOR, JON, ROLLINS, DENNIS, FUSILIER, PHIL, POTTS, NIGEL J., GROSZKRUGER, FRITZ, MIYATAKE, KURT, WRIGHT, TERRY, SLAVIN, ED, MEHL, JOSH, ENGLISH, JOHN, PETERSON, GREGG, CAGE, PETE, and CANTAMESSA, PETER

Subjects
*AUDI automobiles, *CRASH testing of automobiles
Abstract

Several letters to the editor are presented in response to articles in previous issue including a report by Zach Bowman on Audi S3 car, guest column by Peter Egan and the article "Crash-Test Human" by John Krewson.

Published
2015

48. The Grizzly Bears of Yellowstone (Book).

Author

John, Tom, Craighead, John J., Sumner, Jay S., and Mitchell, John A.

Subjects
GRIZZLY Bears of Yellowstone, The (Book), CRAIGHEAD, John J., 1916-2016, SUMMER, Jay, MITCHELL, John A.
Abstract

Reviews the book 'The Grizzly Bears of Yellowstone: Their Ecology in the Yellowstone Ecosystem,' by John J. Craighead, Jay S. Summer and John A. Mitchell.

Published
1997

49. Biomarkers for immunotherapy resistance in non-small cell lung cancer.

Author

Rother C, John T, and Wong A

Abstract

Immunotherapy has revolutionised the treatment landscape of non-small cell lung cancer (NSCLC), significantly improving survival outcomes and offering renewed hope to patients with advanced disease. However, the majority of patients experience limited long-term benefits from immune checkpoint inhibition (ICI) due to the development of primary or acquired immunotherapy resistance. Accurate predictive biomarkers for immunotherapy resistance are essential for individualising treatment strategies, improving survival outcomes, and minimising potential treatment-related harm. This review discusses the mechanisms underlying resistance to immunotherapy, addressing both cancer cell-intrinsic and cancer cell-extrinsic resistance processes. We summarise the current utility and limitations of two clinically established biomarkers: programmed death ligand 1 (PD-L1) expression and tumour mutational burden (TMB). Following this, we present a comprehensive review of emerging immunotherapy biomarkers in NSCLC, including tumour neoantigens, epigenetic signatures, markers of the tumour microenvironment (TME), genomic alterations, host-microbiome composition, and circulating biomarkers. The potential clinical applications of these biomarkers, along with novel approaches to their biomarker identification and targeting, are discussed. Additionally, we explore current strategies to overcome immunotherapy resistance and propose incorporating predictive biomarkers into an adaptive clinical trial design, where specific immune signatures guide subsequent treatment selection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Rother, John and Wong.)

Published
2024
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