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425 results on '"Kagan, Leonid"'

1. On disintegration of lean hydrogen flames in narrow gaps

Author

Yanez, Jorge, Kagan, Leonid, Kuznetsov, Mike, and Sivashinsky, Gregory

Subjects
Physics - Fluid Dynamics
Abstract

The disintegration of near limit flames propagating through the gap of Hele-Shaw cells has recently become a subject of active research. In this paper, the flamelets resulting from the disintegration of the continuous front are interpreted in terms of the Zeldovich flame-balls stabilized by volumetric heat losses. A complicated free-boundary problem for 2D self-drifting near circular flamelets is reduced to a 1D model. The 1D formulation is then utilized to obtain the locus of the flamelet velocity, size, heat losses and Lewis numbers at which the self-drifting flamelets may exist., Comment: 10 pages, 12 figures. arXiv admin note: text overlap with arXiv:2308.08537

Published
2024

2. On dynamics of gasless combustion in slowly varying periodic media: periodic fronts, their stability and propagation-extinction-diffusion-reignition pattern

Author

Matson, Amanda, Kagan, Leonid, Brauner, Claude-Michel, Sivashinsky, Gregory, and Gordon, Peter V.

Subjects
Nonlinear Sciences - Pattern Formation and Solitons, Mathematics - Analysis of PDEs
Abstract

In this paper we consider a classical model of gasless combustion in a one dimensional formulation under the assumption of ignition temperature kinetics. We study the propagation of flame fronts in this model when the initial distribution of the solid fuel is a spatially periodic function that varies on a large scale. It is shown that in certain parametric regimes the model supports periodic traveling fronts. An accurate asymptotic formula for the velocity of the flame front is derived and studied. The stability of periodic fronts is also explored, and a critical condition in terms of parameters of the problem is derived. It is also shown that the instability of periodic fronts, in a certain parametric regimes, results in a propagation-extinction-diffusion-reignition pattern which is studied numerically., Comment: 14 pages, 13 figures

Published
2024

5. Modeling of 2D self-drifting flame-balls in Hele-Shaw cells

Author

Yanez, Jorge, Kagan, Leonid, Sivashinsky, Gregory, and Kuznetsov, Mike

Subjects
Physics - Fluid Dynamics, Physics - Chemical Physics, 7610, 76V05
Abstract

The disintegration of near limit flames propagating through the gap of Hele-Shaw cells has recently become a subject of active research. In this paper, the flamelets resulting from the disintegration of the continuous front a reinterpreted in terms of the Zeldovich flame-balls stabilized by volumetric heat losses. A complicated free-boundary problem for 2D self-drifting near circular flamelets is reduced to a 1D model. The 1D formulation is then utilized to obtain the locus of the flamelet velocity, radius, heat losses and Lewis numbers at which the self-drifting flamelet exists., Comment: 19 pages, 22 figures

Published
2023

8. Modeling of thermonuclear fusion flames : transition to detonation

Author

Gordon, Peter V., Kagan, Leonid, and Sivashinsky, Gregory

Subjects
Physics - Fluid Dynamics, Astrophysics - High Energy Astrophysical Phenomena
Abstract

The paper is concerned with identification of the key mechanisms controlling deflagration-to-detonation transition in stellar medium. The issue of thermal runaway triggered by positive feedback between the advancing flame and the flame-driven precompression is discussed in the framework of a one-dimensional flame-folding model. The paper is an extension of the authors' previous study dealing with the non-stoichiometric fusion, $fuel \to products$, kinetics (Phys.Rev.E, 103(2021)) over physically more relevant, $fuel+fuel \to products$, kinetics. Despite this change the runaway effect endures. The transition occurs prior to merging of the flame with the flame-supported precursor shock, i.e. the pretransition flame does not reach the threshold of Chapman-Jouguet deflagration., Comment: 10 pages, 8 figures, 1 table

Published
2021

15. Deflagration-to-detonation transition in an unconfined space: II. Expanding hydrogen-oxygen flames

Author

Koksharov, Andrey, Kagan, Leonid, and Sivashinsky, Gregory

Subjects
Physics - Fluid Dynamics
Abstract

The problem of deflagration-to-detonation transition in an unconfined environment is revisited. With a freely expanding self-accelerating hydrogen-oxygen flame as an example, it is shown that deflagration-to-detonation transition is indeed possible provided the flame is large enough. The transition occurs prior to merging of the flame with the flame-supported precursor shock. The pre-transition flame does not reach the threshold of CJ-deflagration. Numerical simulations employed are based on the recently developed pseudo-spectral method with time and space adaptation.

Published
2019

19. Epidural methadone and morphine pharmacokinetics and clinical effects in healthy volunteers: A randomized, crossover‐design trial.

Author

Hincker, Alexander, Reschke, Matthew, Ginosar, Yehuda, Kagan, Leonid, Kharasch, Evan D., Siemiątkowska, Anna, Park, Celine, Bakos, Kristopher, Ben‐Abdallah, Arbi, and Haroutounian, Simon

Subjects
PAIN threshold, LUMBAR pain, POSTOPERATIVE pain, METHADONE hydrochloride, MORPHINE
Abstract

Aims: Epidural opioids can provide effective analgesia for acute postoperative pain. Due to its unique physicochemical properties and long systemic elimination half‐life, epidural methadone may provide lasting analgesia with minimal adverse effects; however, human studies are lacking. The aim of the study was to test the hypothesis that epidural methadone would exhibit greater segmental analgesia (analgesia at the dermatome of injection vs. distant dermatomes) than epidural morphine. Methods: In a prospective, randomized, double‐blinded, crossover study, thirteen healthy volunteers received a 4‐mg epidural bolus of methadone or morphine at L3–L4 and underwent repeated assessment of dermatomal heat pain tolerance and pressure pain threshold at lumbar (L3) and trigeminal (V2) dermatomes, pupil diameter, respiratory parameters and venous opioid concentration for 24 h. The primary outcome was selective (lumbar vs. trigeminal) segmental analgesia for heat pain, as a marker of a spinal analgesic mechanism. Results: The degree of segmental analgesia to heat pain tolerance was not different between morphine and methadone (P =.09), although morphine (P =.0009) but not methadone (P =.81) produced significant analgesia to heat pain at the lumbar vs. trigeminal dermatome over 0–12 h. Morphine overall provided longer lasting analgesia to heat pain vs. methadone (24 vs. 2 h, respectively). Morphine elicited greater systemic effects, including miosis (P =.009) and opioid‐related adverse effects (P =.002). Conclusions: These results suggest that, with equal epidural doses, both methadone and morphine produced analgesia and methadone did not produce greater segmental effects than morphine. Epidural methadone provided a more favourable adverse effect profile. [ABSTRACT FROM AUTHOR]

Published
2024
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20. Strongly nonlinear asymptotic model of cellular instabilities in premixed flames with stepwise ignition temperature kinetics

Author

Kilker, Nathan, Golovaty, Dmitry, Gordon, Peter V., Kagan, Leonid, and Sivashinsky, Gregory I.

Subjects
Nonlinear Sciences - Chaotic Dynamics
Abstract

In this paper we consider ignition-temperature, first-order reaction model of thermo-diffusive combustion that describes dynamics of thick flames arising in a theory of combustion of hydrogen-oxygen and ethylene-oxygen mixtures. These flames often assume the shape of propagating curved interfaces that correspond to level sets of constant temperature. We derive a fully nonlinear equation that governs dynamics of these level sets under a single assumption of small curvature. We study this equation for various asymptotic parameter regimes and discuss the ranges of validity of the corresponding simplified models. Our theoretical findings are supported by numerical simulations.

Published
2016

21. Effects of intestine-specific deletion of FGF15 on the development of fatty liver disease with vertical sleeve gastrectomy

Author

Chow, Monica D., primary, Otersen, Katherine, additional, Wassef, Andrew, additional, Kong, Bo, additional, Yamarthy, Sowmya, additional, Rizzolo, Daniel, additional, Yang, Ill, additional, Buckley, Brian, additional, Lu, Alexander, additional, Crook, Naomi, additional, Lee, Matthew, additional, Gao, Judy, additional, Naganand, Sareena, additional, Stofan, Mary F., additional, Armstrong, Laura, additional, Schumacher, Justin, additional, Taylor, Rulaiha, additional, Henry, Zakiyah, additional, Basaly, Veronia, additional, Yang, Zhenning, additional, Zhang, Min, additional, Huang, Mingxing, additional, Kagan, Leonid, additional, Brunetti, Luigi, additional, Sadek, Ragui, additional, Lee, Yi-Horng, additional, and Guo, Grace L., additional

Published
2024
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27. Challenging the Norm: A Multidisciplinary Perspective on Intravenous to Subcutaneous Bridging Strategies for Biologics

Author

Ait‐Oudhia, Sihem, primary, Wang, Yow‐Ming, additional, Dosne, Anne‐Gaelle, additional, Roy, Amit, additional, Jin, Jin Y., additional, Shen, Jun, additional, Kagan, Leonid, additional, Musuamba, Flora T., additional, Zhang, Lucia, additional, Kijima, Shinichi, additional, Gastonguay, Marc R, additional, and Ouellet, Daniele, additional

Published
2023
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33. Challenging the Norm: A Multidisciplinary Perspective on Intravenous to Subcutaneous Bridging Strategies for Biologics.

Author

Ait‐Oudhia, Sihem, Wang, Yow‐Ming, Dosne, Anne‐Gaelle, Roy, Amit, Jin, Jin Y., Shen, Jun, Kagan, Leonid, Musuamba, Flora T., Zhang, Lucia, Kijima, Shinichi, Gastonguay, Marc R., and Ouellet, Daniele

Subjects
PATIENT experience, BIOLOGICALS, PATIENTS' attitudes, CLINICAL pharmacology, DRUG development
Abstract

The transition from intravenous (i.v.) to subcutaneous (s.c.) administration of biologics is a critical strategy in drug development aimed at improving patient convenience, compliance, and therapeutic outcomes. Focusing on the increasing role of model‐informed drug development (MIDD) in the acceleration of this transition, an in‐depth overview of the essential clinical pharmacology, and regulatory considerations for successful i.v. to s.c. bridging for biologics after the i.v. formulation has been approved are presented. Considerations encompass multiple aspects beginning with adequate pharmacokinetic (PK) and pharmacodynamic (i.e., exposure‐response) evaluations which play a vital role in establishing comparability between the i.v. and s.c. routes of administrations. Selected key recommendations and points to consider include: (i) PK characterization of the s.c. formulation, supported by the increasing preclinical understanding of the s.c. absorption, and robust PK study design and analyses in humans; (ii) a thorough characterization of the exposure‐response profiles including important metrics of exposure for both efficacy and safety; (iii) comparability studies designed to meet regulatory considerations and support approval of the s.c. formulation, including noninferiority studies with PK and/or efficacy and safety as primary end points; and (iv) comprehensive safety package addressing assessments of immunogenicity and patients' safety profile with the new route of administration. Recommendations for successful bridging strategies are evolving and MIDD approaches have been used successfully to accelerate the transition to s.c. dosing, ultimately leading to improved patient experiences, adherence, and clinical outcomes. [ABSTRACT FROM AUTHOR]

Published
2024
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34. Simplified urine-based method to detect rifampin underexposure in adults with tuberculosis: a prospective diagnostic accuracy study

Author

Xie, Yingda L., primary, Modi, Nisha, additional, Handler, Deborah, additional, Yu, Sijia, additional, Rao, Prakruti, additional, Kagan, Leonid, additional, Petros de Guex, Kristen, additional, Reiss, Robert, additional, Siemiątkowska, Anna, additional, Narang, Anshika, additional, Narayanan, Navaneeth, additional, Hearn, Jasie, additional, Khalil, Amanda, additional, Woods, Patricia, additional, Young, Laura, additional, Lardizabal, Alfred, additional, Subbian, Selvakumar, additional, Peloquin, Charles A., additional, Vinnard, Christopher, additional, Thomas, Tania A., additional, and Heysell, Scott K., additional

Published
2023
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36. Lipophilic activated ester prodrug approach for drug delivery to the intestinal lymphatic system

Author

Lee, Jong Bong, Zgair, Atheer, Malec, Jed, Kim, Tae Hwan, Kim, Min Gi, Ali, Joseph, Qin, Chaolong, Feng, Wanshan, Chiang, Manting, Gao, Xizhe, Voronin, Gregory, Garces, Aimie E., Lau, Chun Long, Chan, Ting-Hoi, Hume, Amy, McIntosh, Tecashanell M., Soukarieh, Fadi, Al-Hayali, Mohammed, Cipolla, Elena, Collins, Hilary M., Heery, David M., Shin, Beom Soo, Yoo, Sun Dong, Kagan, Leonid, Stocks, Michael J., Bradshaw, Tracey D., Fischer, Peter M., and Gershkovich, Pavel

Published
2018
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44. The Sequence of the Human Genome

Author

Venter, J. Craig, Adams, Mark D., Myers, Eugene W., Li, Peter W., Mural, Richard J., Sutton, Granger G., Smith, Hamilton O., Yandell, Mark, Evans, Cheryl A., Holt, Robert A., Gocayne, Jeannine D., Amanatides, Peter, Ballew, Richard M., Huson, Daniel H., Wortman, Jennifer Russo, Zhang, Qing, Kodira, Chinnappa D., Zheng, Xiangqun H., Chen, Lin, Skupski, Marian, Subramanian, Gangadharan, Thomas, Paul D., Zhang, Jinghui, Nelson, Catherine, Broder, Samuel, Clark, Andrew G., Nadeau, Joe, McKusick, Victor A., Zinder, Norton, Levine, Arnold J., Roberts, Richard J., Simon, Mel, Slayman, Carolyn, Hunkapiller, Michael, Bolanos, Randall, Delcher, Arthur, Dew, Ian, Fasulo, Daniel, Flanigan, Michael, Florea, Liliana, Halpern, Aaron, Hannenhalli, Sridhar, Kravitz, Saul, Levy, Samuel, Mobarry, Clark, Reinert, Knut, Remington, Karin, Abu-Threideh, Jane, Beasley, Ellen, Biddick, Kendra, Bonazzi, Vivien, Brandon, Rhonda, Cargill, Michele, Chandramouliswaran, Ishwar, Charlab, Rosane, Chaturvedi, Kabir, Deng, Zuoming, Di Francesco, Valentina, Dunn, Patrick, Eilbeck, Karen, Evangelista, Carlos, Gabrielian, Andrei E., Gan, Weiniu, Ge, Wangmao, Gong, Fangcheng, Gu, Zhiping, Guan, Ping, Heiman, Thomas J., Higgins, Maureen E., Ji, Rui-Ru, Ke, Zhaoxi, Ketchum, Karen A., Lai, Zhongwu, Lei, Yiding, Li, Zhenya, Li, Jiayin, Liang, Yong, Lin, Xiaoying, Lu, Fu, Merkulov, Gennady V., Milshina, Natalia, Moore, Helen M., Naik, Ashwinikumar K, Narayan, Vaibhav A., Neelam, Beena, Nusskern, Deborah, Rusch, Douglas B., Salzberg, Steven, Shao, Wei, Shue, Bixiong, Sun, Jingtao, Wang, Zhen Yuan, Wang, Aihui, Wang, Xin, Wang, Jian, Wei, Ming-Hui, Wides, Ron, Xiao, Chunlin, Yan, Chunhua, Yao, Alison, Ye, Jane, Zhan, Ming, Zhang, Weiqing, Zhang, Hongyu, Zhao, Qi, Zheng, Liansheng, Zhong, Fei, Zhong, Wenyan, Zhu, Shiaoping C., Zhao, Shaying, Gilbert, Dennis, Baumhueter, Suzanna, Spier, Gene, Carter, Christine, Cravchik, Anibal, Woodage, Trevor, Ali, Feroze, An, Huijin, Awe, Aderonke, Baldwin, Danita, Baden, Holly, Barnstead, Mary, Barrow, Ian, Beeson, Karen, Busam, Dana, Carver, Amy, Cheng, Ming Lai, Curry, Liz, Danaher, Steve, Davenport, Lionel, Desilets, Raymond, Dietz, Susanne, Dodson, Kristina, Doup, Lisa, Ferriera, Steven, Garg, Neha, Gluecksmann, Andres, Hart, Brit, Haynes, Jason, Haynes, Charles, Heiner, Cheryl, Hladun, Suzanne, Hostin, Damon, Houck, Jarrett, Howland, Timothy, Ibegwam, Chinyere, Johnson, Jeffery, Kalush, Francis, Kline, Lesley, Koduru, Shashi, Love, Amy, Mann, Felecia, May, David, McCawley, Steven, Mclntosh, Tina, McMullen, Ivy, Moy, Mee, Moy, Linda, Murphy, Brian, Nelson, Keith, Pfannkoch, Cynthia, Pratts, Eric, Puri, Vinita, Qureshi, Hina, Reardon, Matthew, Rodriguez, Robert, Rogers, Yu-Hui, Romblad, Deanna, Ruhfel, Bob, Scott, Richard, Sitter, Cynthia, Smallwood, Michelle, Stewart, Erin, Strong, Renee, Suh, Ellen, Thomas, Reginald, Tint, Tse, Sukyee, Vech, Claire, Wang, Gary, Wetter, Jeremy, Williams, Sherita, Williams, Monica, Windsor, Sandra, Winn-Deen, Emily, Wolfe, Keriellen, Zaveri, Jayshree, Zaveri, Karena, Abril, Josep F., Guigó, Roderic, Campbell, Michael J., Sjolander, Kimmen V., Karlak, Brian, Kejariwal, Anish, Mi, Huaiyu, Lazareva, Betty, Hatton, Thomas, Narechania, Apurva, Diemer, Karen, Muruganujan, Anushya, Guo, Nan, Sato, Shinji, Bafna, Vineet, Istrail, Sorin, Lippert, Ross, Schwartz, Russell, Walenz, Brian, Yooseph, Shibu, Allen, David, Basu, Anand, Baxendale, James, Blick, Louis, Caminha, Marcelo, Carnes-Stine, John, Caulk, Parris, Chiang, Yen-Hui, Coyne, My, Dahlke, Carl, Mays, Anne Deslattes, Dombroski, Maria, Donnelly, Michael, Ely, Dale, Esparham, Shiva, Fosler, Carl, Gire, Harold, Glanowski, Stephen, Glasser, Kenneth, Glodek, Anna, Gorokhov, Mark, Graham, Ken, Gropman, Barry, Harris, Michael, Heil, Jeremy, Henderson, Scott, Hoover, Jeffrey, Jennings, Donald, Jordan, Catherine, Jordan, James, Kasha, John, Kagan, Leonid, Kraft, Cheryl, Levitsky, Alexander, Lewis, Mark, Liu, Xiangjun, Lopez, John, Ma, Daniel, Majoros, William, McDaniel, Joe, Murphy, Sean, Newman, Matthew, Nguyen, Trung, Nguyen, Ngoc, Nodell, Marc, Pan, Sue, Peck, Jim, Peterson, Marshall, Rowe, William, Sanders, Robert, Scott, John, Simpson, Michael, Smith, Thomas, Sprague, Arlan, Stockwell, Timothy, Turner, Russell, Venter, Eli, Wang, Mei, Wen, Meiyuan, Wu, David, Wu, Mitchell, Xia, Ashley, Zandieh, Ali, and Zhu, Xiaohong

Published
2001

45. Pharmacology Research & Perspectives

Author

Deshpande, Kiran, Lange, Keith R., Stone, William B., Yohn, Christine, Schlesinger, Naomi, Kagan, Leonid, Auguste, Albert J., Firestein, Bonnie L., and Brunetti, Luigi

Subjects
drug-metabolizing enzymes, SARS-CoV-2, COVID-19, hACE2, drug transporters
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting Coronavirus disease 2019 emerged in late 2019 and is responsible for significant morbidity and mortality worldwide. A hallmark of severe COVID-19 is exaggerated systemic inflammation, regarded as a "cytokine storm," which contributes to the damage of various organs, primarily the lungs. The inflammation associated with some viral illnesses is known to alter the expression of drug-metabolizing enzymes and transporters. These alterations can lead to modifications in drug exposure and the processing of various endogenous compounds. Here, we provide evidence to support changes in the mitochondrial ribonucleic acid expression of a subset of drug transporters (84 transporters) in the liver, kidneys, and lungs and metabolizing enzymes (84 enzymes) in the liver in a humanized angiotensin-converting enzyme 2 receptor mouse model. Specifically, three drug transporters (Abca3, Slc7a8, Tap1) and the pro-inflammatory cytokine IL-6 were upregulated in the lungs of SARS-CoV-2 infected mice. We also found significant downregulation of drug transporters responsible for the movement of xenobiotics in the liver and kidney. Additionally, expression of cytochrome P-450 2f2 which is known to metabolize some pulmonary toxicants, was significantly decreased in the liver of infected mice. The significance of these findings requires further exploration. Our results suggest that further research should emphasize altered drug disposition when investigating therapeutic compounds, whether re-purposed or new chemical entities, in other animal models and ultimately in individuals infected with SARS-CoV-2. Moreover, the influence and impact of these changes on the processing of endogenous compounds also require further investigation. IDCare Published version IDCare

Published
2023

48. Rifampin urinary excretion to predict serum targets in children with tuberculosis: a prospective diagnostic accuracy study

Author

Thomas, Tania, primary, Lukumay, Saning'o, additional, Yu, Sijia, additional, Rao, Prakruti, additional, Siemiątkowska, Anna, additional, Kagan, Leonid, additional, Augustino, Domitila, additional, Mejan, Paulo, additional, Mosha, Restituta, additional, Handler, Deborah, additional, Petros de Guex, Kristen, additional, Mmbaga, Blandina, additional, Pfaeffle, Herman, additional, Reiss, Robert, additional, Peloquin, Charles A, additional, Vinnard, Christopher, additional, Mduma, Estomih, additional, Xie, Yinda, additional, and Heysell, Scott, additional

Published
2023
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49. The influence of SARS-CoV-2 infection on expression of drug-metabolizing enzymes and transporters in a hACE2 murine model

Author

Deshpande, Kiran, Lange, Keith R., Stone, William B., Yohn, Christine, Schlesinger, Naomi, Kagan, Leonid, Auguste, Albert J., Firestein, Bonnie L., Brunetti, Luigi, Deshpande, Kiran, Lange, Keith R., Stone, William B., Yohn, Christine, Schlesinger, Naomi, Kagan, Leonid, Auguste, Albert J., Firestein, Bonnie L., and Brunetti, Luigi

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting Coronavirus disease 2019 emerged in late 2019 and is responsible for significant morbidity and mortality worldwide. A hallmark of severe COVID-19 is exaggerated systemic inflammation, regarded as a "cytokine storm," which contributes to the damage of various organs, primarily the lungs. The inflammation associated with some viral illnesses is known to alter the expression of drug-metabolizing enzymes and transporters. These alterations can lead to modifications in drug exposure and the processing of various endogenous compounds. Here, we provide evidence to support changes in the mitochondrial ribonucleic acid expression of a subset of drug transporters (84 transporters) in the liver, kidneys, and lungs and metabolizing enzymes (84 enzymes) in the liver in a humanized angiotensin-converting enzyme 2 receptor mouse model. Specifically, three drug transporters (Abca3, Slc7a8, Tap1) and the pro-inflammatory cytokine IL-6 were upregulated in the lungs of SARS-CoV-2 infected mice. We also found significant downregulation of drug transporters responsible for the movement of xenobiotics in the liver and kidney. Additionally, expression of cytochrome P-450 2f2 which is known to metabolize some pulmonary toxicants, was significantly decreased in the liver of infected mice. The significance of these findings requires further exploration. Our results suggest that further research should emphasize altered drug disposition when investigating therapeutic compounds, whether re-purposed or new chemical entities, in other animal models and ultimately in individuals infected with SARS-CoV-2. Moreover, the influence and impact of these changes on the processing of endogenous compounds also require further investigation.

Published
2023

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