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2. Role of signal degradation in directional chemosensing

Author

LeFebre, Ryan, Landsittel, Joseph A., Stone, David E., and Mugler, Andrew

Subjects
Physics - Biological Physics
Abstract

Directional chemosensing is ubiquitous in cell biology, but some cells such as mating yeast paradoxically degrade the signal they aim to detect. While the data processing inequality suggests that such signal modification cannot increase the sensory information, we show using a reaction-diffusion model and an exactly solvable discrete-state reduction that it can. We identify a non-Markovian step in the information chain allowing the system to evade the data processing inequality, reflecting the nonlocal nature of diffusion. Our results apply to any sensory system in which degradation couples to diffusion. Experimental data suggest that mating yeast operate in the beneficial regime where degradation improves sensing., Comment: 13 pages, 3 figures

Published
2023

5. Application Experiences on a GPU-Accelerated Arm-based HPC Testbed

Author

Elwasif, Wael, Godoy, William, Hagerty, Nick, Harris, J. Austin, Hernandez, Oscar, Joo, Balint, Kent, Paul, Lebrun-Grandie, Damien, Maccarthy, Elijah, Vergara, Veronica G. Melesse, Messer, Bronson, Miller, Ross, Opal, Sarp, Bastrakov, Sergei, Bussmann, Michael, Debus, Alexander, Steinger, Klaus, Stephan, Jan, Widera, Rene, Bryngelson, Spencer H., Berre, Henry Le, Radhakrishnan, Anand, Young, Jefferey, Chandrasekaran, Sunita, Ciorba, Florina, Simsek, Osman, Spiga, Kate Clark Filippo, Hammond, Jeff, Hardy, John E. Stone. David, Keller, Sebastian, and Trott, Jean-Guillaume Piccinali. Christian

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

This paper assesses and reports the experience of ten teams working to port,validate, and benchmark several High Performance Computing applications on a novel GPU-accelerated Arm testbed system. The testbed consists of eight NVIDIA Arm HPC Developer Kit systems built by GIGABYTE, each one equipped with a server-class Arm CPU from Ampere Computing and A100 data center GPU from NVIDIA Corp. The systems are connected together using Infiniband high-bandwidth low-latency interconnect. The selected applications and mini-apps are written using several programming languages and use multiple accelerator-based programming models for GPUs such as CUDA, OpenACC, and OpenMP offloading. Working on application porting requires a robust and easy-to-access programming environment, including a variety of compilers and optimized scientific libraries. The goal of this work is to evaluate platform readiness and assess the effort required from developers to deploy well-established scientific workloads on current and future generation Arm-based GPU-accelerated HPC systems. The reported case studies demonstrate that the current level of maturity and diversity of software and tools is already adequate for large-scale production deployments.

Published
2022

7. A proteogenomic view of Parkinson’s disease causality and heterogeneity

Author

Kaiser, Sergio, Zhang, Luqing, Mollenhauer, Brit, Jacob, Jaison, Longerich, Simonne, Del-Aguila, Jorge, Marcus, Jacob, Raghavan, Neha, Stone, David, Fagboyegun, Olumide, Galasko, Douglas, Dakna, Mohammed, Bilican, Bilada, Dovlatyan, Mary, Kostikova, Anna, Li, Jingyao, Peterson, Brant, Rotte, Michael, Sanz, Vinicius, Foroud, Tatiana, Hutten, Samantha J., Frasier, Mark, Iwaki, Hirotaka, Singleton, Andrew, Marek, Ken, Crawford, Karen, Elwood, Fiona, Messa, Mirko, and Serrano-Fernandez, Pablo

Published
2023
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13. Prediction of Blood Lactate Values in Critically Ill Patients: A Retrospective Multi-center Cohort Study

Author

Mamandipoor, Behrooz, Yeung, Wesley, Agha-Mir-Salim, Louis, Stone, David J., Osmani, Venet, and Celi, Leo Anthony

Subjects
Quantitative Biology - Quantitative Methods, Computer Science - Computers and Society, Computer Science - Machine Learning, Statistics - Applications
Abstract

Purpose. Elevations in initially obtained serum lactate levels are strong predictors of mortality in critically ill patients. Identifying patients whose serum lactate levels are more likely to increase can alert physicians to intensify care and guide them in the frequency of tending the blood test. We investigate whether machine learning models can predict subsequent serum lactate changes. Methods. We investigated serum lactate change prediction using the MIMIC-III and eICU-CRD datasets in internal as well as external validation of the eICU cohort on the MIMIC-III cohort. Three subgroups were defined based on the initial lactate levels: i) normal group (<2 mmol/L), ii) mild group (2-4 mmol/L), and iii) severe group (>4 mmol/L). Outcomes were defined based on increase or decrease of serum lactate levels between the groups. We also performed sensitivity analysis by defining the outcome as lactate change of >10% and furthermore investigated the influence of the time interval between subsequent lactate measurements on predictive performance. Results. The LSTM models were able to predict deterioration of serum lactate values of MIMIC-III patients with an AUC of 0.77 (95% CI 0.762-0.771) for the normal group, 0.77 (95% CI 0.768-0.772) for the mild group, and 0.85 (95% CI 0.840-0.851) for the severe group, with a slightly lower performance in the external validation. Conclusion. The LSTM demonstrated good discrimination of patients who had deterioration in serum lactate levels. Clinical studies are needed to evaluate whether utilization of a clinical decision support tool based on these results could positively impact decision-making and patient outcomes., Comment: 15 pages, 6 Appendices

Published
2021
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25. Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture

Author

Chia, Ruth, Sabir, Marya S, Bandres-Ciga, Sara, Saez-Atienzar, Sara, Reynolds, Regina H, Gustavsson, Emil, Walton, Ronald L, Ahmed, Sarah, Viollet, Coralie, Ding, Jinhui, Makarious, Mary B, Diez-Fairen, Monica, Portley, Makayla K, Shah, Zalak, Abramzon, Yevgeniya, Hernandez, Dena G, Blauwendraat, Cornelis, Stone, David J, Eicher, John, Parkkinen, Laura, Ansorge, Olaf, Clark, Lorraine, Honig, Lawrence S, Marder, Karen, Lemstra, Afina, St George-Hyslop, Peter, Londos, Elisabet, Morgan, Kevin, Lashley, Tammaryn, Warner, Thomas T, Jaunmuktane, Zane, Galasko, Douglas, Santana, Isabel, Tienari, Pentti J, Myllykangas, Liisa, Oinas, Minna, Cairns, Nigel J, Morris, John C, Halliday, Glenda M, Van Deerlin, Vivianna M, Trojanowski, John Q, Grassano, Maurizio, Calvo, Andrea, Mora, Gabriele, Canosa, Antonio, Floris, Gianluca, Bohannan, Ryan C, Brett, Francesca, Gan-Or, Ziv, Geiger, Joshua T, Moore, Anni, May, Patrick, Krüger, Rejko, Goldstein, David S, Lopez, Grisel, Tayebi, Nahid, Sidransky, Ellen, Norcliffe-Kaufmann, Lucy, Palma, Jose-Alberto, Kaufmann, Horacio, Shakkottai, Vikram G, Perkins, Matthew, Newell, Kathy L, Gasser, Thomas, Schulte, Claudia, Landi, Francesco, Salvi, Erika, Cusi, Daniele, Masliah, Eliezer, Kim, Ronald C, Caraway, Chad A, Monuki, Edwin S, Brunetti, Maura, Dawson, Ted M, Rosenthal, Liana S, Albert, Marilyn S, Pletnikova, Olga, Troncoso, Juan C, Flanagan, Margaret E, Mao, Qinwen, Bigio, Eileen H, Rodríguez-Rodríguez, Eloy, Infante, Jon, Lage, Carmen, González-Aramburu, Isabel, Sanchez-Juan, Pascual, Ghetti, Bernardino, Keith, Julia, Black, Sandra E, Masellis, Mario, Rogaeva, Ekaterina, Duyckaerts, Charles, Brice, Alexis, Lesage, Suzanne, Xiromerisiou, Georgia, Barrett, Matthew J, Tilley, Bension S, Gentleman, Steve, Logroscino, Giancarlo, and Serrano, Geidy E

Subjects
Biological Sciences, Genetics, Human Genome, Alzheimer's Disease Related Dementias (ADRD), Prevention, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer's Disease, Aging, Dementia, Brain Disorders, Acquired Cognitive Impairment, Lewy Body Dementia, Biotechnology, Parkinson's Disease, Neurosciences, Neurodegenerative, 2.1 Biological and endogenous factors, Aetiology, Neurological, Adaptor Proteins, Signal Transducing, Alzheimer Disease, Case-Control Studies, Gene Expression Profiling, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Glucosylceramidase, Humans, Lewy Body Disease, Nuclear Proteins, Parkinson Disease, Polymorphism, Single Nucleotide, Tumor Suppressor Proteins, alpha-Synuclein, American Genome Center, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic architecture of this understudied form of dementia, and to generate a resource for the scientific community. Genome-wide association analysis identified five independent risk loci, whereas genome-wide gene-aggregation tests implicated mutations in the gene GBA. Genetic risk scores demonstrate that LBD shares risk profiles and pathways with Alzheimer's disease and Parkinson's disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition.

Published
2021

30. Reply

Author

Columbo, Jesse A., primary, Scali, Salvatore T., additional, and Stone, David H., additional

Published
2024
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36. Genome-wide structural variant analysis identifies risk loci for non-Alzheimer’s dementias

Author

Soltis, Anthony R., Viollet, Coralie, Sukumar, Gauthaman, Alba, Camille, Lott, Nathaniel, McGrath Martinez, Elisa, Tuck, Meila, Singh, Jatinder, Bacikova, Dagmar, Zhang, Xijun, Hupalo, Daniel N., Adeleye, Adelani, Wilkerson, Matthew D., Pollard, Harvey B., Dalgard, Clifton L., Black, Sandra E., Gan-Or, Ziv, Keith, Julia, Masellis, Mario, Rogaeva, Ekaterina, Brice, Alexis, Lesage, Suzanne, Xiromerisiou, Georgia, Calvo, Andrea, Canosa, Antonio, Chio, Adriano, Logroscino, Giancarlo, Mora, Gabriele, Krüger, Reijko, May, Patrick, Alcolea, Daniel, Clarimon, Jordi, Fortea, Juan, Gonzalez-Aramburu, Isabel, Infante, Jon, Lage, Carmen, Lleó, Alberto, Pastor, Pau, Sanchez-Juan, Pascual, Brett, Francesca, Aarsland, Dag, Al-Sarraj, Safa, Attems, Johannes, Gentleman, Steve, Hardy, John A., Hodges, Angela K., Love, Seth, McKeith, Ian G., Morris, Christopher M., Morris, Huw R., Palmer, Laura, Pickering-Brown, Stuart, Ryten, Mina, Thomas, Alan J., Troakes, Claire, Albert, Marilyn S., Barrett, Matthew J., Beach, Thomas G., Bekris, Lynn M., Bennett, David A., Boeve, Bradley F., Dawson, Ted M., Dickson, Dennis W., Faber, Kelley, Ferman, Tanis, Ferrucci, Luigi, Flanagan, Margaret E., Foroud, Tatiana M., Ghetti, Bernardino, Gibbs, J. Raphael, Goate, Alison, Goldstein, David S., Graff-Radford, Neill R., Kaufmann, Horacio, Kukull, Walter A., Leverenz, James B., Lopez, Grisel, Mao, Qinwen, Masliah, Eliezer, Monuki, Edwin, Newell, Kathy L., Palma, Jose-Alberto, Perkins, Matthew, Pletnikova, Olga, Renton, Alan E., Resnick, Susan M., Rosenthal, Liana S., Ross, Owen A., Scherzer, Clemens R., Serrano, Geidy E., Shakkottai, Vikram G., Sidransky, Ellen, Tanaka, Toshiko, Tayebi, Nahid, Topol, Eric, Torkamani, Ali, Troncoso, Juan C., Woltjer, Randy, Wszolek, Zbigniew K., Scholz, Sonja W., Baloh, Robert H., Bowser, Robert, Broach, James, Camu, William, Chiò, Adriano, Cooper-Knock, John, Drepper, Carsten, Drory, Vivian E., Dunckley, Travis L., Feldman, Eva, Fratta, Pietro, Gerhard, Glenn, Gibson, Summer B., Glass, Jonathan D., Harms, Matthew B., Heiman-Patterson, Terry D., Jansson, Lilja, Kirby, Janine, Kwan, Justin, Laaksovirta, Hannu, Landers, John E., Landi, Francesco, Le Ber, Isabelle, Lumbroso, Serge, MacGowan, Daniel J.L., Maragakis, Nicholas J., Mouzat, Kevin, Myllykangas, Liisa, Orrell, Richard W., Ostrow, Lyle W., Pamphlett, Roger, Pioro, Erik, Pulst, Stefan M., Ravits, John M., Robberecht, Wim, Rothstein, Jeffrey D., Sendtner, Michael, Shaw, Pamela J., Sidle, Katie C., Simmons, Zachary, Stein, Thor, Stone, David J., Tienari, Pentti J., Traynor, Bryan J., Valori, Miko, Van Damme, Philip, Van Deerlin, Vivianna M., Van Den Bosch, Ludo, Zinman, Lorne, Kaivola, Karri, Chia, Ruth, Ding, Jinhui, Rasheed, Memoona, Fujita, Masashi, Menon, Vilas, Walton, Ronald L., Collins, Ryan L., Billingsley, Kimberley, Brand, Harrison, Talkowski, Michael, Zhao, Xuefang, Dewan, Ramita, Stark, Ali, Ray, Anindita, Solaiman, Sultana, Alvarez Jerez, Pilar, Malik, Laksh, Tienari, Pentti, Mazzini, Letizia, D'Alfonso, Sandra, Moglia, Cristina, and De Jager, Philip L.

Published
2023
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38. Student Success and the High School-University Transition: 100 Years of Chemistry Education Research

Author

Stone, David C.

Abstract

The 100th anniversary of the first article (published in 1921) examining student success and the high school to university transition in chemistry provides an excellent opportunity to consider what has -- and has not -- changed in chemistry education. This review details the development and findings of chemistry education research specifically as it relates to student learning and success over this extended time period. After considering the changing educational context and definition of success, this research will be described under three main themes: different ways of knowing (learning objectives and outcomes), thinking (scientific reasoning and problem solving), and learning (preferences and approaches to studying). A key finding is that while our understanding of effective teaching and learning has advanced significantly since the early 1900s, so too have the curriculum expectations and cognitive demands placed upon students increased significantly. Thus despite the many advances and innovations in chemistry education, an achievement gap persists between high school and post-secondary education for many students to this day. A comprehensive picture of the factors influencing student success developed from the research literature not only helps understand this disconnect; it also provides an opportunity to reflect on lessons learned for teaching, learning, and directions for future research.

Published
2021
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41. Developing an Enterprise Control Management Program: One Bank's Journey to Operational Excellence

Author

Stone, David

Subjects
Banks (Finance), Customer service, Support services, Company business management, Customer service, Banking, finance and accounting industries, Business
Abstract

Zions Bancorporation has been working to align IT, Sarbanes Oxley (SOX), and operational controls into a single program for managing controls across the enterprise and control management lifecycle. Doing so [...]

Published
2023

43. Decision aids for patients with carotid stenosis

Author

Krafcik, Brianna M., primary, Jarmel, Isabel A., additional, Beach, Jocelyn M., additional, Suckow, Bjoern D., additional, Stableford, Jennifer A., additional, Stone, David H., additional, Goodney, Philip P., additional, and Columbo, Jesse A., additional

Published
2024
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46. Withholding or withdrawing invasive interventions may not accelerate time to death among dying ICU patients

Author

Ramazzotti, Daniele, Clardy, Peter, Celi, Leo Anthony, Stone, David J., and Rudin, Robert S.

Subjects
Computer Science - Computers and Society, Computer Science - Machine Learning, Statistics - Machine Learning
Abstract

We considered observational data available from the MIMIC-III open-access ICU database and collected within a study period between year 2002 up to 2011. If a patient had multiple admissions to the ICU during the 30 days before death, only the first stay was analyzed, leading to a final set of 6,436 unique ICU admissions during the study period. We tested two hypotheses: (i) administration of invasive intervention during the ICU stay immediately preceding end-of-life would decrease over the study time period and (ii) time-to-death from ICU admission would also decrease, due to the decrease in invasive intervention administration. To investigate the latter hypothesis, we performed a subgroups analysis by considering patients with lowest and highest severity. To do so, we stratified the patients based on their SAPS I scores, and we considered patients within the first and the third tertiles of the score. We then assessed differences in trends within these groups between years 2002-05 vs. 2008-11. Comparing the period 2002-2005 vs. 2008-2011, we found a reduction in endotracheal ventilation among patients who died within 30 days of ICU admission (120.8 vs. 68.5 hours for the lowest severity patients, p<0.001; 47.7 vs. 46.0 hours for the highest severity patients, p=0.004). This is explained in part by an increase in the use of non-invasive ventilation. Comparing the period 2002-2005 vs. 2008-2011, we found a reduction in the use of vasopressors and inotropes among patients with the lowest severity who died within 30 days of ICU admission (41.8 vs. 36.2 hours, p<0.001) but not among those with the highest severity. Despite a reduction in the use of invasive interventions, we did not find a reduction in the time to death between 2002-2005 vs. 2008-2011 (7.8 days vs. 8.2 days for the lowest severity patients, p=0.32; 2.1 days vs. 2.0 days for the highest severity patients, p=0.74).

Published
2018
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48. Comparative transcriptomics of choroid plexus in Alzheimer’s disease, frontotemporal dementia and Huntington’s disease: implications for CSF homeostasis

Author

Stopa, Edward G, Tanis, Keith Q, Miller, Miles C, Nikonova, Elena V, Podtelezhnikov, Alexei A, Finney, Eva M, Stone, David J, Camargo, Luiz M, Parker, Lisan, Verma, Ajay, Baird, Andrew, Donahue, John E, Torabi, Tara, Eliceiri, Brian P, Silverberg, Gerald D, and Johanson, Conrad E

Subjects
Acquired Cognitive Impairment, Rare Diseases, Aging, Brain Disorders, Dementia, Neurosciences, Alzheimer's Disease, Genetics, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurodegenerative, Neurological, Adult, Aged, Aged, 80 and over, Alzheimer Disease, Choroid Plexus, Female, Frontotemporal Dementia, Gene Expression, Homeostasis, Humans, Huntington Disease, Male, Microarray Analysis, Middle Aged, Transcriptome, Choroid plexus transcriptome, Neuroimmune CSF regulation, Blood-CSF barrier inflammatome, Janus kinase/signal transducers and activators of transcription, Peroxisome-proliferator-activated receptor, Cadherin-mediated adhesion, Vascular endothelial growth factor, LRP-1, Choroid plexus methionine, CSF homocysteine, Mechanistic target of rapamycin, Blood–CSF barrier inflammatome, Biological Sciences, Medical and Health Sciences
Abstract

BackgroundIn Alzheimer's disease, there are striking changes in CSF composition that relate to altered choroid plexus (CP) function. Studying CP tissue gene expression at the blood-cerebrospinal fluid barrier could provide further insight into the epithelial and stromal responses to neurodegenerative disease states.MethodsTranscriptome-wide Affymetrix microarrays were used to determine disease-related changes in gene expression in human CP. RNA from post-mortem samples of the entire lateral ventricular choroid plexus was extracted from 6 healthy controls (Ctrl), 7 patients with advanced (Braak and Braak stage III-VI) Alzheimer's disease (AD), 4 with frontotemporal dementia (FTD) and 3 with Huntington's disease (HuD). Statistics and agglomerative clustering were accomplished with MathWorks, MatLab; and gene set annotations by comparing input sets to GeneGo ( http://www.genego.com ) and Ingenuity ( http://www.ingenuity.com ) pathway sets. Bonferroni-corrected hypergeometric p-values of

Published
2018

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