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2. A practical guide to multi-objective reinforcement learning and planning

Author

Hayes, CF, Rădulescu, R, Bargiacchi, E, Källström, J, Macfarlane, M, Reymond, M, Verstraeten, T, Zintgraf, LM, Dazeley, Richard, Heintz, F, Howley, E, Irissappane, AA, Mannion, P, Nowé, A, Ramos, G, Restelli, M, Vamplew, P, Roijers, DM, Hayes, CF, Rădulescu, R, Bargiacchi, E, Källström, J, Macfarlane, M, Reymond, M, Verstraeten, T, Zintgraf, LM, Dazeley, Richard, Heintz, F, Howley, E, Irissappane, AA, Mannion, P, Nowé, A, Ramos, G, Restelli, M, Vamplew, P, and Roijers, DM

Abstract

Real-world sequential decision-making tasks are generally complex, requiring trade-offs between multiple, often conflicting, objectives. Despite this, the majority of research in reinforcement learning and decision-theoretic planning either assumes only a single objective, or that multiple objectives can be adequately handled via a simple linear combination. Such approaches may oversimplify the underlying problem and hence produce suboptimal results. This paper serves as a guide to the application of multi-objective methods to difficult problems, and is aimed at researchers who are already familiar with single-objective reinforcement learning and planning methods who wish to adopt a multi-objective perspective on their research, as well as practitioners who encounter multi-objective decision problems in practice. It identifies the factors that may influence the nature of the desired solution, and illustrates by example how these influence the design of multi-objective decision-making systems for complex problems.

Published
2022

8. Gene Expression Profiling of B Cell Lymphoma in Dogs Reveals Dichotomous Metabolic Signatures Distinguished by Oxidative Phosphorylation

Author

Wu, Y, Chang, Y M, Polton, G, Stell, A J, Szladovits, B, Macfarlane, M, Peters, L M, Priestnall, S L, Bacon, N J, Kow, K, Stewart, S, Sharma, E, Goulart, Mi R, Gribben, J, Xia, D, and Garden, O A

Subjects
immune system diseases, hemic and lymphatic diseases
Abstract

Gene expression profiling has revealed molecular heterogeneity of diffuse large B cell lymphoma (DLBCL) in both humans and dogs. Two DLBCL subtypes based on cell of origin are generally recognized, germinal center B (GCB)-like and activated B cell (ABC)-like. A pilot study to characterize the transcriptomic phenotype of 11 dogs with multicentric BCL yielded two molecular subtypes distinguished on the basis of genes important in oxidative phosphorylation. We propose a metabolic classification of canine BCL that transcends cell of origin and shows parallels to a similar molecular phenotype in human DLBCL. We thus confirm the validity of this classification scheme across widely divergent mammalian taxa and add to the growing body of literature suggesting cellular and molecular similarities between human and canine non-Hodgkin lymphoma. Our data support a One Health approach to the study of DLBCL, including the advancement of novel therapies of relevance to both canine and human health.

Published
2020

29. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018

Author

Galluzzi, L, Vitale, I, Aaronson, SA, Abrams, JM, Adam, D, Agostinis, P, Alnemri, ES, Altucci, L, Amelio, I, Andrews, DW, Annicchiarico-Petruzzelli, M, Antonov, AV, Arama, E, Baehrecke, EH, Barlev, NA, Bazan, NG, Bernassola, F, Bertrand, MJM, Bianchi, K, Blagosklonny, MV, Blomgren, K, Borner, C, Boya, P, Brenner, C, Campanella, M, Candi, E, Carmona-Gutierrez, D, Cecconi, F, Chan, FK-M, Chandel, NS, Cheng, EH, Chipuk, JE, Cidlowski, JA, Ciechanover, A, Cohen, GM, Conrad, M, Cubillos-Ruiz, JR, Czabotar, PE, D'Angiolella, V, Dawson, TM, Dawson, VL, De laurenzi, V, De Maria, R, Debatin, K-M, DeBerardinis, RJ, Deshmukh, M, Di Daniele, N, Di Virgilio, F, Dixit, VM, Dixon, SJ, Duckett, CS, Dynlacht, BD, El-Deiry, WS, Elrod, JW, Fimia, GM, Fulda, S, Garcia-Saez, AJ, Garg, AD, Garrido, C, Gavathiotis, E, Golstein, P, Gottlieb, E, Green, DR, Greene, LA, Gronemeyer, H, Gross, A, Hajnoczky, G, Hardwick, JM, Harris, IS, Hengartner, MO, Hetz, C, Ichijo, H, Jaattela, M, Joseph, B, Jost, PJ, Juin, PP, Kaiser, WJ, Karin, M, Kaufmann, T, Kepp, O, Kimchi, A, Kitsis, RN, Klionsky, DJ, Knight, RA, Kumar, S, Lee, SW, Lemasters, JJ, Levine, B, Linkermann, A, Lipton, SA, Lockshin, RA, Lopez-Otin, C, Lowe, SW, Luedde, T, Lugli, E, MacFarlane, M, Madeo, F, Malewicz, M, Malorni, W, Manic, G, Marine, J-C, Martin, SJ, Martinou, J-C, Medema, JP, Mehlen, P, Meier, P, Melino, S, Miao, EA, Molkentin, JD, Moll, UM, Munoz-Pinedo, C, Nagata, S, Nunez, G, Oberst, A, Oren, M, Overholtzer, M, Pagano, M, Panaretakis, T, Pasparakis, M, Penninger, JM, Pereira, DM, Pervaiz, S, Peter, ME, Piacentini, M, Pinton, P, Prehn, JHM, Puthalakath, H, Rabinovich, GA, Rehm, M, Rizzuto, R, Rodrigues, CMP, Rubinsztein, DC, Rudel, T, Ryan, KM, Sayan, E, Scorrano, L, Shao, F, Shi, Y, Silke, J, Simon, H-U, Sistigu, A, Stockwell, BR, Strasser, A, Szabadkai, G, Tait, SWG, Tang, D, Tavernarakis, N, Thorburn, A, Tsujimoto, Y, Turk, B, Vanden Berghe, T, Vandenabeele, P, Heiden, MGV, Villunger, A, Virgin, HW, Vousden, KH, Vucic, D, Wagner, EF, Walczak, H, Wallach, D, Wang, Y, Wells, JA, Wood, W, Yuan, J, Zakeri, Z, Zhivotovsky, B, Zitvogel, L, Melino, G, Kroemer, G, Galluzzi, L, Vitale, I, Aaronson, SA, Abrams, JM, Adam, D, Agostinis, P, Alnemri, ES, Altucci, L, Amelio, I, Andrews, DW, Annicchiarico-Petruzzelli, M, Antonov, AV, Arama, E, Baehrecke, EH, Barlev, NA, Bazan, NG, Bernassola, F, Bertrand, MJM, Bianchi, K, Blagosklonny, MV, Blomgren, K, Borner, C, Boya, P, Brenner, C, Campanella, M, Candi, E, Carmona-Gutierrez, D, Cecconi, F, Chan, FK-M, Chandel, NS, Cheng, EH, Chipuk, JE, Cidlowski, JA, Ciechanover, A, Cohen, GM, Conrad, M, Cubillos-Ruiz, JR, Czabotar, PE, D'Angiolella, V, Dawson, TM, Dawson, VL, De laurenzi, V, De Maria, R, Debatin, K-M, DeBerardinis, RJ, Deshmukh, M, Di Daniele, N, Di Virgilio, F, Dixit, VM, Dixon, SJ, Duckett, CS, Dynlacht, BD, El-Deiry, WS, Elrod, JW, Fimia, GM, Fulda, S, Garcia-Saez, AJ, Garg, AD, Garrido, C, Gavathiotis, E, Golstein, P, Gottlieb, E, Green, DR, Greene, LA, Gronemeyer, H, Gross, A, Hajnoczky, G, Hardwick, JM, Harris, IS, Hengartner, MO, Hetz, C, Ichijo, H, Jaattela, M, Joseph, B, Jost, PJ, Juin, PP, Kaiser, WJ, Karin, M, Kaufmann, T, Kepp, O, Kimchi, A, Kitsis, RN, Klionsky, DJ, Knight, RA, Kumar, S, Lee, SW, Lemasters, JJ, Levine, B, Linkermann, A, Lipton, SA, Lockshin, RA, Lopez-Otin, C, Lowe, SW, Luedde, T, Lugli, E, MacFarlane, M, Madeo, F, Malewicz, M, Malorni, W, Manic, G, Marine, J-C, Martin, SJ, Martinou, J-C, Medema, JP, Mehlen, P, Meier, P, Melino, S, Miao, EA, Molkentin, JD, Moll, UM, Munoz-Pinedo, C, Nagata, S, Nunez, G, Oberst, A, Oren, M, Overholtzer, M, Pagano, M, Panaretakis, T, Pasparakis, M, Penninger, JM, Pereira, DM, Pervaiz, S, Peter, ME, Piacentini, M, Pinton, P, Prehn, JHM, Puthalakath, H, Rabinovich, GA, Rehm, M, Rizzuto, R, Rodrigues, CMP, Rubinsztein, DC, Rudel, T, Ryan, KM, Sayan, E, Scorrano, L, Shao, F, Shi, Y, Silke, J, Simon, H-U, Sistigu, A, Stockwell, BR, Strasser, A, Szabadkai, G, Tait, SWG, Tang, D, Tavernarakis, N, Thorburn, A, Tsujimoto, Y, Turk, B, Vanden Berghe, T, Vandenabeele, P, Heiden, MGV, Villunger, A, Virgin, HW, Vousden, KH, Vucic, D, Wagner, EF, Walczak, H, Wallach, D, Wang, Y, Wells, JA, Wood, W, Yuan, J, Zakeri, Z, Zhivotovsky, B, Zitvogel, L, Melino, G, and Kroemer, G

Abstract

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.

Published
2018

30. Smoking in pregnancy is a key factor for sudden infant death among Māori

Author

MacFarlane, M, primary, Thompson, J M D, additional, Zuccollo, J, additional, McDonald, G, additional, Elder, D, additional, Stewart, A W, additional, Lawton, B, additional, Percival, T, additional, Baker, N, additional, Schlaud, M, additional, Fleming, P, additional, Taylor, B, additional, and Mitchell, E A, additional

Published
2018
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32. Efficacy and Long-Term Outcomes of Palivizumab Prophylaxis to Prevent Respiratory Syncytial Virus Infection in Infants with Cystic Fibrosis in Northern Ireland

Author

Groves, H E, Jenkins, L, Macfarlane, M, Reid, A, Lynn, F, and Shields, M D

Abstract

BACKGROUND: RSV causes considerable morbidity and mortality in children. In cystic fibrosis (CF) viral infections are associated with worsening respiratory symptoms and bacterial colonization. Palivizumab is effective in reducing RSV hospitalization in high risk patient groups. Evidence regarding its effectiveness and safety in CF is inconclusive. CF screening in N. Ireland enabled timely palivizumab prophylaxis, becoming routine in 2002.OBJECTIVES: To determine the effect of palivizumab on RSV-related hospitalization and compare lung function and bacterial colonization at age 6 years for those born pre- and post-introduction of palivizumab prophylaxis.METHODS: A retrospective audit was conducted for all patients diagnosed with CF during the period from 1997 to 2007 inclusive. RSV-related hospitalization, time to Pseudomonas aeruginosa (PA) 1st isolate, lung function and growth parameters were recorded. Comparisons were made for outcomes pre- and post-introduction of routine palivizumab administration in 2002. A cost evaluation was also performed.RESULTS: Ninety-two children were included; 47 pre- and 45 post-palivizumab introduction. The overall RSV-positive hospitalization rate was 13%. The relative risk of RSV infection in palivizumab non-recipients versus recipients was 4.78 (95%CI: 1.1-20.7), P = 0.027. Notably, PA 1st isolate was significantly earlier in the palivizumab recipient cohort versus non-recipient cohort (median 57 vs. 96 months, P CONCLUSION: Palivizumab was effective in reducing RSV-related hospitalization infection in CF patients. Surprisingly, we found a significantly earlier time to 1st isolate of PA in palivizumab recipients which we could not explain by altered or improved diagnostic tests.

Published
2016

33. Feasibility study of inversely-optimized Intensity Modulated Grid-therapy for bulky lung tumors

Author

MacFarlane, M, Lam, J, Dar, R, Yu, E, Jordan, K, and Chen, JZ

Subjects
Lung Neoplasms, Biophysics
Abstract

Purpose/Objective(s): Grid therapy with megavoltage photon beams has been clinically shown to improve local control of bulky tumors. The purpose of this study is to develop intensity modulated grid therapy (IMGT) with multiple beams. We hypothesize that when compared to conventional single-field grid therapy, IMGT will provide lower spatially fractionated doses to the surrounding organs at risk (OAR) while increasing the minimum dose to the whole tumor volume and thus improve tumor control probability as supported by conventionalradiobiology. Materials/Methods: IMGT was developed with multiple photon beams using dynamic MLC segments and orthogonal blocks. Spatially fractionated fluence patterns for all beams were first optimized by inverse planning. The optimized intensity modulated grid patterns were then segmented by an in-house sliding window technique for radiation dose delivery. To evaluate IMGT, a retrospective planning study was performed on 10 lung patients with bulky tumors (volume _ 500 cc and maximum diameters _ 10 cm). IMGT plans were compared with conventional singlefield grid therapy plans with the prescription dose normalized to a maximum dose of 15 Gy to the planning target volume (PTV) in one fraction. A paired two-tailed t-test was performed on dose volume parameters to identify differences in target volume coverage and OAR sparing. Results: The results of our analysis is summarized in Table 1, where the V7.2Gy and V16.9Gy metrics represent biological equivalent doses (fractions Z 30, a/b Z 3) of V20Gy for lung and V65Gy for skin respectively. Compared to conventional single-field grid therapy plans, IMGT plans improve dose coverage to the target volume significantly. With the exception of the mean dose to the lung, IMGT either maintained or reduced doses to the OARs. Conclusion: Intensity modulated grid therapy improves target volume dose coverage while reducing or maintaining the spatially fractionated dose distributions to most of the surrounding organs at risk.

Published
2015

38. Molecular profiling reveals primary mesothelioma cell lines recapitulate human disease

Author

Chernova, T, primary, Sun, X M, additional, Powley, I R, additional, Galavotti, S, additional, Grosso, S, additional, Murphy, F A, additional, Miles, G J, additional, Cresswell, L, additional, Antonov, A V, additional, Bennett, J, additional, Nakas, A, additional, Dinsdale, D, additional, Cain, K, additional, Bushell, M, additional, Willis, A E, additional, and MacFarlane, M, additional

Published
2016
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42. Coronary-artery bypass surgery in patients with left ventricular dysfunction

Author

Velazquez, E, Lee, K, Deja, Ma:, J, A, Sopko, G, Marchenko, A, Ali, I, Pohost, G, Gradinac, S, Abraham, W, Yii, M, Prabhakaran, D, Szwed, H, Ferrazzi, P, Petrie, M, O'Connor, C, Panchavinnin, P, She, L, Bonow, R, Rankin, G, Jones, R, Rouleau, J, Cherniavsky, A, Romanov, A, Wos, S, Deja, M, Golba, K, Malinowski, M, Kosevic, D, Vukovic, M, Djokovic, L, Krzeminska Pakula, M, Jaszewski, R, Drozdz, J, Chrzanowski, L, Rajda, M, Howlett, J, Macfarlane, M, Jain, A, Shah, H, Rakshak, D, Saxena, A, Zembala, M, Przybylski, R, Kukulski, T, Wasilewski, J, Wiechowski, S, Brykczynski, M, Kurowski, M, Mokrzycki, K, Sadowski, J, Kapelak, B, Sobczyk, D, Plicner, D, Wrobel, K, Piegas, L, Paulista, P, Farsky, P, Veiga Kantorowitz, C, Sadowski, Z, Juraszynski, Z, Dabrowski, R, Rogowski, J, Pawlaczyk, R, Rynkiewicz, A, Betlejewski, P, Siepe, M, Geibel Zehender, A, Cuerten, C, Higgins, R, Crestanello, J, Binkley, P, Jones, D, Sun, B, Smith, P, Milano, C, Adams, P, Hill, J, Beaver, T, Leach, D, Airan, B, Das, S, Prior, D, Mack, J, Rao, V, Iwanochko, R, Renton, J, Phuangkaew, N, Bochenek, A, Krejca, M, Trusz Gluza, M, Wita, K, Gavazzi, A, Senni, M, Natarajan, S, Padmanabhan, C, Racine, N, Bouchard, D, Ducharme, A, Brown, H, Alotti, N, Lupkovics, G, Kumar, S, Agarwal, S, Sinha, N, Rai, H, Andersson, B, Janssen, A, Lamy, A, Demers, C, Rizzo, T, Doenst, T, Garbade, J, Thiele, H, Richter, M, Murday, A, Shaw, M, Raju, K, Mannam, G, Reddy, G, Rao, K, Nicolau, J, Stolf, N, Vieira, A, Chua, Y, Lim, C, Kwok, B, Gan, Y, Cleland, J, Cale, A, Thackray, S, Lammiman, M, Michler, R, Swayze, R, Maurer, G, Grimm, M, Lang, I, Adlbrecht, C, Daly, R, Rodeheffer, R, Nelson, S, Larbalestier, R, Wang, X, Haddad, H, Hendry, P, Donaldson, J, Menicanti, L, Di Donato, M, Castelvecchio, S, Sirvydis, V, Voluckiene, E, Di Benedetto, G, Attisano, T, Favaloro, R, Favaloro, L, Diez, M, Riccitelli, M, Picone, V, Koslowski, P, Gaito, M, Al mohammad, A, Braidley, P, Steele, H, Nawarawong, W, Woragidpoonpol, S, Kuanprasert, S, Mekara, W, Kon, N, Hammon, J, Wells, G, Tilley, W, Drazner, M, Di Maio, M, Peschka, S, Pasquale, D, Knight, C, J, Aylward, P, Thomas, C, Gullestad, L, Sorensen, G, Kaul, U, Gupta, R, Schmedtje, Jj, Arnold, S, Wilson, V, Grayburn, P, Hamman, B, Hebeler, R, Aston, S, Birjiniuk, V, Harrington, M, Dupree, C, Sheridan, B, Schuler, C, Helou, J, Denis, I, Bigalli, D, Gutierrez, F, Russo, N, Batlle, C, White, H, Alison, P, Stewart, R, Borthwick, L, Philippides, G, Shemin, R, Fitzgerald, C, Dagenais, F, Dussault, G, Kamath, P, Busmann, C, Ferrari, G, Botto, M, Horkay, F, Hartyanszky, I, Bartha, E, Simor, T, Papp, L, Toth, L, Varga Szemes, A, Szekely, L, Keltai, M, Edes, I, Szathmarine, V, Yakub, M, Sarip, S, Maitland, A, Isaac, D, Holland, M, Bogats, G, Csepregi, L, Maia, L, Soares, M, Mouco, O, Souza, A, da Rocha, A, Brito, J, Pitella, F, Camara, A, Horowitz, J, Knight, J, Rose, J, Mcrae, Rj, Geiss, D, Clemson, B, Pierson, M, Kron, I, Kern, J, Bergin, J, Phillips, J, Rich, J, Herre, J, Pine, L, Chin, D, Spyt, T, Logtens, E, Amuchastegui, L, Bracco, D, Ruengsakulrach, P, Pitiguagool, V, Sukhum, P, Srinualta, D, Hayward, C, Herrera, C, Zimmermann, R, Patterson, G, Stephens, W, Dignan, R, French, J, Sequalino, N, Vaishnav, S, Panda, R, Chavan, A, Benetis, R, Jankauskiene, L, Kalil, R, Nesralla, I, Santos, M, de Moraes, M, Friedrich, I, Buerke, M, Paraforos, A, Konda, S, Leone, C, Murphy, E, Ravichandran, P, Avalos, K, Hetzer, R, Knosalla, C, Hoffmann, K, Landolfo, K, Landolfo, C, Park, M, Chiariello, L, Nardi, P, Stapleton, D, Hoey, K, Hasaniya, N, Wang, N, Bijou, R, Naka, Y, Ascheim, D, Mikati, I, Arnold, M, Mckenzie, N, Smith, J, Gheorghiade, M, Fullerton, D, Roberts, L, Carson, P, Miller, A, Pina, I, Selzman, C, Wertheimer, J, Goldstein, S, Cohn, F, Hlatky, M, Kennedy, K, Rankin, S, Robbins, R, Zaret, B, Barfield, T, Desvigne Nickens, P, Oh, J, Panza, J, Apte, P, Doyle, M, Forder, J, Ocon, M, Pai, R, Reddy, V, Santos, N, Tripathi, R, Varadarajan, P, Pellikka, P, Miller, Fj, Lin, G, Borgeson, D, Ommen, S, Casaclang Verzosa, G, Miller, D, Springer, R, Blahnik, F, Manahan, B, Welper, J, Wiste, H, Mark, D, Anstrom, K, Baloch, K, Burnette, A, Cowper, P, Davidson Ray, N, Drew, L, Harding, T, Hunt, V, Knight, D, Patterson, A, Redick, T, Sanderford, B, Feldman, A, Bristow, M, Chan, T, Maisel, A, Mann, D, Mcnamara, D, Holly, T, Berman, D, Leonard, S, Helmer, D, Woods, M, Mcnulty, M, Asch, F, Rumsey, M, Bieganski, S, Roberts, B, Handschumacher, M, Mccormick, A, Albright, J, Dandridge, R, Rittenhouse, L, Wagstaff, D, Williams, M, Bailey, D, Glover, D, Parrish, L, Wakeley, N, Jackson, V, Nicholson, B, Mcdaniel, A, Al Khalidi, H, Greene, D, and Moore, V

Subjects
Male, medicine.medical_specialty, Coronary Artery Disease, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, law.invention, Coronary artery disease, 03 medical and health sciences, Coronary artery bypass surgery, Ventricular Dysfunction, Left, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, Clinical endpoint, Humans, 03.02. Klinikai orvostan, cardiovascular diseases, 030212 general & internal medicine, Coronary Artery Bypass, Aged, Proportional Hazards Models, Heart Failure, Intention-to-treat analysis, Proportional hazards model, business.industry, Hazard ratio, Settore MED/23 - Chirurgia Cardiaca, General Medicine, Middle Aged, medicine.disease, Combined Modality Therapy, 3. Good health, Surgery, Intention to Treat Analysis, Hospitalization, surgical procedures, operative, Cardiovascular Diseases, Heart failure, Cardiology, Female, business
Abstract

The role of coronary-artery bypass grafting (CABG) in the treatment of patients with coronary artery disease and heart failure has not been clearly established.Between July 2002 and May 2007, a total of 1212 patients with an ejection fraction of 35% or less and coronary artery disease amenable to CABG were randomly assigned to medical therapy alone (602 patients) or medical therapy plus CABG (610 patients). The primary outcome was the rate of death from any cause. Major secondary outcomes included the rates of death from cardiovascular causes and of death from any cause or hospitalization for cardiovascular causes.The primary outcome occurred in 244 patients (41%) in the medical-therapy group and 218 (36%) in the CABG group (hazard ratio with CABG, 0.86; 95% confidence interval [CI], 0.72 to 1.04; P=0.12). A total of 201 patients (33%) in the medical-therapy group and 168 (28%) in the CABG group died from an adjudicated cardiovascular cause (hazard ratio with CABG, 0.81; 95% CI, 0.66 to 1.00; P=0.05). Death from any cause or hospitalization for cardiovascular causes occurred in 411 patients (68%) in the medical-therapy group and 351 (58%) in the CABG group (hazard ratio with CABG, 0.74; 95% CI, 0.64 to 0.85; P

Published
2011

43. Myocardial viability and survival in ischemic left ventricular dysfunction

Author

Bonow, R, Maurer, G, Lee, K, Holly, T, Binkley, P, Desvigne Nickens, P, Drozdz, J, Farsky, P, Feldman, A, Doenst, T, Michler, R, Berman, D, Nicolau, J, Pellikka, P, Wrobel, K, Alotti, N, Asch, F, Favaloro, L, She, L, Velazquez, E, Jones, R, Panza, J, Cherniavsky, A, Marchenko, A, Romanov, A, Wos, S, Deja, M, Golba, K, Malinowski, M, Gradinac, S, Kosevic, D, Vukovic, M, Djokovic, L, Krzeminska Pakula, M, Jaszewski, R, Chrzanowski, L, Rajda, M, Ali, I, Howlett, J, Macfarlane, M, Jain, A, Shah, H, Rakshak, D, Saxena, A, Zembala, M, Przybylski, R, Kukulski, T, Wasilewski, J, Wiechowski, S, Brykczynski, M, Kurowski, M, Mokrzycki, K, Sadowski, J, Kapelak, B, Sobczyk, D, Plicner, C, Piegas, L, Paulista, P, Veiga Kantorowitz, C, Sadowski, Z, Juraszynski, Z, Szwed, H, Dabrowski, R, Rogowski, J, Pawlaczyk, R, Rynkiewicz, A, Betlejewski, P, Siepe, M, Geibel Zehender, A, Cuerten, C, Higgins, R, Crestanello, J, Jones, D, Sun, B, Smith, P, Milano, C, Adams, P, Hill, J, Beaver, T, Leach, D, Airan, B, Das, S, Yii, M, Prior, D, Mack, J, Rao, V, Iwanochko, R, Renton, J, Panchavinnin, P, Phuangkaew, N, Bochenek, A, Krejca, M, Trusz Gluza, M, Wita, K, Ferrazzi, P, Gavazzi, A, Senni, M, Natarajan, S, Padmanabhan, C, Racine, N, Bouchard, D, Ducharme, A, Brown, H, Lupkovics, G, Kumar, S, Agarwal, S, Sinha, N, Rai, H, Andersson, B, Janssen, A, Lamy, A, Demers, C, Rizzo, T, Garbade, J, Thiele, H, Richter, M, Petrie, M, Murday, A, Shaw, M, Raju, K, Mannam, G, Reddy, G, Rao, K, Stolf, N, Vieira, A, Chua, Y, Lim, C, Kwok, B, Gan, Y, Cleland, J, Cale, A, Thackray, S, Lammiman, M, Swayze, R, Grimm, M, Lang, I, Adlbrecht, C, Daly, R, Rodeheffer, R, Nelson, S, Larbalestier, R, Wang, X, Haddad, H, Hendry, P, Donaldson, J, Menicanti, L, Di Donato, M, Castelvecchio, S, Sirvydis, V, Voluckiene, E, Di Benedetto, G, Attisano, T, Favaloro, R, Diez, M, Riccitelli, M, Picone, V, Koslowski, P, Gaito, M, Al mohammad, A, Braidley, P, Steele, H, Nawarawong, W, Woragidpoonpol, S, Kuanprasert, S, Mekara, W, Kon, N, Hammon, J, Wells, G, Tilley, W, Drazner, M, Dimaio, M, Peschka, S, De Pasquale, C, Knight, J, Aylward, P, Thomas, C, Gullestad, L, Sorensen, G, Kaul, U, Gupta, R, Schmedtje, Jr, J, Arnold, S, Wilson, V, Grayburn, P, Hamman, B, Hebeler, R, Aston, S, Birjiniuk, V, Harrington, M, Dupree, C, Sheridan, B, Schuler, C, Helou, J, Denis, I, Bigalli, D, Gutierrez, F, Russo, N, Batlle, C, White, H, Alison, P, Stewart, R, Borthwick, L, Philippides, G, Shemin, R, Fitzgerald, C, Dagenais, F, Dussault, G, Kamath, P, Busmann, C, Ferrari, G, Botto, M, Horkay, F, Hartyanszky, I, Bartha, E, Simor, T, Papp, L, Toth, L, Varga Szemes, A, Szekely, L, Keltai, M, Edes, I, Szathmarine, V, Yakub, M, Sarip, S, Maitland, A, Isaac, D, Holland, M, Bogats, G, Csepregi, L, Maia, L, Soares, M, Mouco, O, Souza, A, da Rocha, A, Brito, J, Pitella, F, Camara, A, Horowitz, J, Rose, J, Mcrae, Rj, Geiss, D, Clemson, B, Pierson, M, Kron, I, Kern, J, Bergin, J, Phillips, J, Rich, J, Herre, J, Pine, L, Chin, D, Spyt, T, Logtens, E, Amuchastegui, L, Bracco, D, Ruengsakulrach, P, Pitiguagool, V, Sukhum, P, Srinualta, D, Hayward, C, Herrera, C, Zimmermann, R, Patterson, G, Stephens, W, Dignan, R, French, J, Sequalino, N, Vaishnav, S, Panda, R, Chavan, A, Benetis, R, Jankauskiene, L, Kalil, R, Nesralla, I, Santos, M, Moraes, D, M, Friedrich, I, Buerke, M, Paraforos, A, Konda, S, Leone, C, Murphy, E, Ravichandran, P, Avalos, K, Hetzer, R, Knosalla, C, Hoffmann, K, Landolfo, K, Landolfo, C, Park, M, Chiariello, L, Nardi, P, Stapleton, D, Hoey, K, Hasaniya, N, Wang, N, Bijou, R, Naka, Y, Ascheim, D, Mikati, I, Arnold, M, Mckenzie, N, Smith, J, Gheorghiade, M, Fullerton, D, Roberts, L, Carson, P, Miller, A, Pina, I, Selzman, C, Wertheimer, J, Goldstein, S, Cohn, F, Hlatky, M, Kennedy, K, Rankin, S, Robbins, R, Zaret, B, Rouleau, J, Barfield, T, O'Connor, C, Oh, J, Rankin, G, Sopko, G, Pohost, G, Apte, P, Doyle, M, Forder, J, Ocon, M, Pai, R, Reddy, V, Santos, N, Tripathi, R, Varadarajan, P, Miller, Fj, Lin, G, Borgeson, D, Ommen, S, Casaclang Verzosa, G, Miller, D, Springer, R, Blahnik, F, Manahan, B, Welper, J, Wiste, H, Mark, D, Anstrom, K, Baloch, K, Burnette, A, Cowper, P, Davidson Ray, N, Drew, L, Harding, T, Hunt, V, Knight, D, Patterson, A, Redick, T, Sanderford, B, Bristow, M, Chan, T, Maisel, A, Mann, D, Mcnamara, D, Leonard, S, Helmer, D, Woods, M, Mcnulty, M, Rumsey, M, Bieganski, S, Roberts, B, Handschumacher, M, Mccormick, A, Albright, J, Dandridge, R, Rittenhouse, L, Wagstaff, D, Williams, M, Bailey, D, Glover, D, Parrish, L, Wakeley, N, Jackson, V, Nicholson, B, Mcdaniel, A, Al Khalidi, H, Greene, D, and Moore, V

Subjects
Settore MED/23 - Chirurgia Cardiaca
Published
2011

44. Autophagy limits proliferation and glycolytic metabolism in acute myeloid leukemia

Author

Watson, AS, primary, Riffelmacher, T, additional, Stranks, A, additional, Williams, O, additional, De Boer, J, additional, Cain, K, additional, MacFarlane, M, additional, McGouran, J, additional, Kessler, B, additional, Khandwala, S, additional, Chowdhury, O, additional, Puleston, D, additional, Phadwal, K, additional, Mortensen, M, additional, Ferguson, D, additional, Soilleux, E, additional, Woll, P, additional, Jacobsen, SEW, additional, and Simon, AK, additional

Published
2015
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45. Resistance to HSP90 inhibition involving loss of MCL1 addiction

Author

Busacca, S, primary, Law, E W P, additional, Powley, I R, additional, Proia, D A, additional, Sequeira, M, additional, Le Quesne, J, additional, Klabatsa, A, additional, Edwards, J M, additional, Matchett, K B, additional, Luo, J L, additional, Pringle, J H, additional, El-Tanani, M, additional, MacFarlane, M, additional, and Fennell, D A, additional

Published
2015
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49. Caspase-independent cell death induced by anti-CD2 or staurosporine in activated human peripheral T lymphocytes

Author

Deas, O., Dumont, C., Macfarlane, M., Matthieu Rouleau, Hebib, C., Harper, F., Hirsch, F., Charpentier, B., Cohen, G. M., and Senik, A.

Subjects
Immunology, CD2 Antigens, Apoptosis, Cysteine Proteinase Inhibitors, Poly(ADP-ribose) Polymerase Inhibitors, Lymphocyte Activation, Amino Acid Chloromethyl Ketones, T-Lymphocyte Subsets, Immunology and Allergy, Humans, fas Receptor, Caspase 7, Cell Death, Caspase 3, Hydrolysis, Caspase 2, Antibodies, Monoclonal, Nuclear Proteins, Proteins, Staurosporine, Diploidy, Lamins, Enzyme Activation, Cysteine Endopeptidases, Caspases, Poly(ADP-ribose) Polymerases
Abstract

We examined the effects of the cell-permeable, broad spectrum peptide caspase inhibitors, benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethyl ketone (Z-VAD.fmk), and BOC-Asp(OMe)-fluoromethyl ketone (BOC-D.fmk), on apoptosis induced by anti-CD2, anti-Fas, and the protein kinase inhibitor staurosporine in activated human peripheral T lymphocytes. We monitored ultrastructural, flow cytometric, and biochemical apoptotic changes, including externalization of phosphatidylserine, cleavage of poly(ADP-ribose) polymerase (PARP) and lamins, activation of caspase-3 and caspase-7, decrease in mitochondrial membrane potential, and DNA fragmentation. Z-VAD.fmk and BOC-D.fmk completely inhibited all the biochemical and ultrastructural changes of apoptosis in anti-Fas-treated cells. In marked contrast, neither Z-VAD.fmk nor BOC-D.fmk inhibited CD2- or staurosporine-mediated cell shrinkage, dilatation of the endoplasmic reticulum (seen in anti-CD2-treated cells), externalization of phosphatidylserine, and loss of mitochondrial membrane potential that accompanied cell death. However, these inhibitors did inhibit the cleavage of PARP and lamins and the formation of hypodiploid cells, and partially inhibited chromatin condensation. These results demonstrate that in activated T cells, anti-CD2 and staurosporine induce a caspase-independent cell death pathway that exhibits prominent cytoplasmic features of apoptosis. However, caspase activation is required for the proteolytic degradation of nuclear substrates such as PARP and lamins together with the DNA fragmentation and extreme chromatin condensation that occur in apoptotic cells.

Published
1998

50. A role for eukaryotic initiation factor 4B overexpression in the pathogenesis of diffuse large B-cell lymphoma

Author

Horvilleur, E, primary, Sbarrato, T, additional, Hill, K, additional, Spriggs, R V, additional, Screen, M, additional, Goodrem, P J, additional, Sawicka, K, additional, Chaplin, L C, additional, Touriol, C, additional, Packham, G, additional, Potter, K N, additional, Dirnhofer, S, additional, Tzankov, A, additional, Dyer, M J S, additional, Bushell, M, additional, MacFarlane, M, additional, and Willis, A E, additional

Published
2013
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