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3. Reuse-Aware Cache Partitioning Framework for Data-Sharing Multicore Systems

Author

Ghosh, Soma N., Sahula, Vineet, and Bhargava, Lava

Subjects
Computer Science - Hardware Architecture, Computer Science - Distributed, Parallel, and Cluster Computing, C.1.4, D.4.2
Abstract

Multi-core processors improve performance, but they can create unpredictability owing to shared resources such as caches interfering. Cache partitioning is used to alleviate the Worst-Case Execution Time (WCET) estimation by isolating the shared cache across each thread to reduce interference. It does, however, prohibit data from being transferred between parallel threads running on different cores. In this paper we present (SRCP) a cache replacement mechanism for partitioned caches that is aware of data being shared across threads, prevents shared data from being replicated across partitions and frequently used data from being evicted from caches. Our technique outperforms TA-DRRIP and EHC, which are existing state-of-the-art cache replacement algorithms, by 13.34% in cache hit-rate and 10.4% in performance over LRU (least recently used) cache replacement policy., Comment: 2 pages. 7th IEEE International Symposium on Smart Electronic Systems (iSES) 2021

Published
2022
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4. AXL and error-prone DNA replication confer drug resistance and offer strategies to treat EGFR-mutant lung cancer.

Author

Noronha, Ashish, Belugali Nataraj, Nishanth, Sang Lee, Joo, Zhitomirsky, Benny, Oren, Yaara, Oster, Sara, Lindzen, Moshit, Mukherjee, Saptaparna, Will, Rainer, Ghosh, Soma, Simoni-Nieves, Arturo, Verma, Aakanksha, Chatterjee, Rishita, Borgoni, Simone, Robinson, Welles, Sinha, Sanju, Brandis, Alexander, Kerr, D Lucas, Wu, Wei, Sekar, Arunachalam, Giri, Suvendu, Chung, Youngmin, Drago-Garcia, Diana, Danysh, Brian P, Lauriola, Mattia, Fiorentino, Michelangelo, Ardizzoni, Andrea, Oren, Moshe, Blakely, Collin M, Ezike, Jideofor, Wiemann, Stefan, Parida, Laxmi, Bivona, Trever G, Aqeilan, Rami I, Brugge, Joan S, Regev, Aviv, Getz, Gad, Ruppin, Eytan, and Yarden, Yosef

Abstract

Anti-cancer therapies have been limited by emergence of mutations and other adaptations. In bacteria, antibiotics activate the SOS response, which mobilizes error-prone factors that allow for continuous replication at the cost of mutagenesis. We investigated whether treatment of lung cancer with EGFR inhibitors (EGFRi) similarly engages hypermutators. In cycling drug-tolerant persister (DTP) cells and in EGFRi-treated patients presenting residual disease we observed upregulation of GAS6, while ablation of GAS6's receptor, AXL, eradicated resistance. Reciprocally, AXL overexpression enhanced DTP survival and accelerated the emergence of T790M, an EGFR mutation typical to resistant cells. Mechanistically, AXL induces low-fidelity DNA polymerases and activates their organizer, RAD18, by promoting neddylation. Metabolomics uncovered another hypermutator, AXL-driven activation of MYC and increased purine synthesis that is unbalanced by pyrimidines. Aligning anti-AXL combination treatments with the transition from DTPs to resistant cells cured patient-derived xenografts. Hence, similar to bacteria, tumors tolerate therapy by engaging pharmacologically targetable endogenous mutators.

Published
2022

13. An analysis and evaluation of the WeFold collaborative for protein structure prediction and its pipelines in CASP11 and CASP12.

Author

Keasar, Chen, McGuffin, Liam J, Wallner, Björn, Chopra, Gaurav, Adhikari, Badri, Bhattacharya, Debswapna, Blake, Lauren, Bortot, Leandro Oliveira, Cao, Renzhi, Dhanasekaran, BK, Dimas, Itzhel, Faccioli, Rodrigo Antonio, Faraggi, Eshel, Ganzynkowicz, Robert, Ghosh, Sambit, Ghosh, Soma, Giełdoń, Artur, Golon, Lukasz, He, Yi, Heo, Lim, Hou, Jie, Khan, Main, Khatib, Firas, Khoury, George A, Kieslich, Chris, Kim, David E, Krupa, Pawel, Lee, Gyu Rie, Li, Hongbo, Li, Jilong, Lipska, Agnieszka, Liwo, Adam, Maghrabi, Ali Hassan A, Mirdita, Milot, Mirzaei, Shokoufeh, Mozolewska, Magdalena A, Onel, Melis, Ovchinnikov, Sergey, Shah, Anand, Shah, Utkarsh, Sidi, Tomer, Sieradzan, Adam K, Ślusarz, Magdalena, Ślusarz, Rafal, Smadbeck, James, Tamamis, Phanourios, Trieber, Nicholas, Wirecki, Tomasz, Yin, Yanping, Zhang, Yang, Bacardit, Jaume, Baranowski, Maciej, Chapman, Nicholas, Cooper, Seth, Defelicibus, Alexandre, Flatten, Jeff, Koepnick, Brian, Popović, Zoran, Zaborowski, Bartlomiej, Baker, David, Cheng, Jianlin, Czaplewski, Cezary, Delbem, Alexandre Cláudio Botazzo, Floudas, Christodoulos, Kloczkowski, Andrzej, Ołdziej, Stanislaw, Levitt, Michael, Scheraga, Harold, Seok, Chaok, Söding, Johannes, Vishveshwara, Saraswathi, Xu, Dong, Foldit Players consortium, and Crivelli, Silvia N

Subjects
Foldit Players consortium, Humans, Caspases, Computational Biology, Protein Conformation, Models, Molecular, Software, Caspase 12, Models, Molecular, Biochemistry and Cell Biology, Other Physical Sciences
Abstract

Every two years groups worldwide participate in the Critical Assessment of Protein Structure Prediction (CASP) experiment to blindly test the strengths and weaknesses of their computational methods. CASP has significantly advanced the field but many hurdles still remain, which may require new ideas and collaborations. In 2012 a web-based effort called WeFold, was initiated to promote collaboration within the CASP community and attract researchers from other fields to contribute new ideas to CASP. Members of the WeFold coopetition (cooperation and competition) participated in CASP as individual teams, but also shared components of their methods to create hybrid pipelines and actively contributed to this effort. We assert that the scale and diversity of integrative prediction pipelines could not have been achieved by any individual lab or even by any collaboration among a few partners. The models contributed by the participating groups and generated by the pipelines are publicly available at the WeFold website providing a wealth of data that remains to be tapped. Here, we analyze the results of the 2014 and 2016 pipelines showing improvements according to the CASP assessment as well as areas that require further adjustments and research.

Published
2018

23. US Food and Drug Administration Approval Summary: Elacestrant for Estrogen Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative, ESR1 -Mutated Advanced or Metastatic Breast Cancer.

Author

Shah, Mirat, Lingam, Hima, Gao, Xin, Gittleman, Haley, Fiero, Mallorie H., Krol, Danielle, Biel, Nikolett, Ricks, Tiffany K., Fu, Wentao, Hamed, Salaheldin, Li, Fang, Sun, Jillian, Fan, Jianghong, Schuck, Robert, Grimstein, Manuela, Tang, Liuya, Kalavar, Shyam, Abukhdeir, Abdelrahmman, Pathak, Anand, and Ghosh, Soma

Published
2024
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29. Legionella pneumophila usurps host cell lipids for vacuole expansion and bacterial growth.

Author

Ghosh, Soma, Bandyopadhyay, Saumya, Smith, Danielle M., Adak, Sangeeta, Semenkovich, Clay F., Nagy, Laszlo, Wolfgang, Michael J., and O'Connor, Tamara J.

Subjects
*LEGIONELLA pneumophila, *BACTERIAL growth, *FATTY acids, *LEGIONELLA, *LIPIDS, *IMMUNE system, *CELL compartmentation
Abstract

Vacuolar pathogens reside in membrane-bound compartments within host cells. Maintaining the integrity of this compartment is paramount to bacterial survival and replication as it protects against certain host surveillance mechanisms that function to eradicate invading pathogens. Preserving this compartment during bacterial replication requires expansion of the vacuole membrane to accommodate the increasing number of bacteria, and yet, how this is accomplished remains largely unknown. Here, we show that the vacuolar pathogen Legionella pneumophila exploits multiple sources of host cell fatty acids, including inducing host cell fatty acid scavenging pathways, in order to promote expansion of the replication vacuole and bacteria growth. Conversely, when exogenous lipids are limited, the decrease in host lipid availability restricts expansion of the replication vacuole membrane, resulting in a higher density of bacteria within the vacuole. Modifying the architecture of the vacuole prioritizes bacterial growth by allowing the greatest number of bacteria to remain protected by the vacuole membrane despite limited resources for its expansion. However, this trade-off is not without risk, as it can lead to vacuole destabilization, which is detrimental to the pathogen. However, when host lipid resources become extremely scarce, for example by inhibiting host lipid scavenging, de novo biosynthetic pathways, and/or diverting host fatty acids to storage compartments, bacterial replication becomes severely impaired, indicating that host cell fatty acid availability also directly regulates L. pneumophila growth. Collectively, these data demonstrate dual roles for host cell fatty acids in replication vacuole expansion and bacterial proliferation, revealing the central functions for these molecules and their metabolic pathways in L. pneumophila pathogenesis. Author summary: The pathogenesis of bacteria depends on their ability to avoid detection and killing by the host immune system while simultaneously competing with the host for nutrients. Here, we demonstrate that host cell fatty acids are paramount to the intracellular survival and replication of the bacterial pathogen Legionella. Legionella infection induces host cell fatty acid scavenging allowing for critical expansion of its replication vacuole, which protects against recognition by host surveillance pathways, and mediates robust bacterial proliferation. However, if host cell fatty acid availability becomes limited, vacuole membrane expansion is constrained, often leading to vacuole destabilization, and bacterial growth is restricted. Our findings reveal a central role for host cell fatty acids and their metabolic pathways in bacterial pathogenesis, whereby both the host and the pathogen define a gradient of available host fatty acids that can be manipulated by either organism to their benefit. [ABSTRACT FROM AUTHOR]

Published
2024
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35. FDA Approval Summary: Mirvetuximab soravtansine-gynx for FRα-positive, Platinum-Resistant Ovarian Cancer

Author

Dilawari, Asma, primary, Shah, Mirat, additional, Ison, Gwynn, additional, Gittleman, Haley, additional, Fiero, Mallorie H., additional, Shah, Ankit, additional, Hamed, Salaheldin S., additional, Qiu, Junshan, additional, Yu, Jingyu, additional, Manheng, Wimolnut, additional, Ricks, Tiffany K., additional, Pragani, Rajan, additional, Arudchandran, Arulvathani, additional, Patel, Paresma, additional, Zaman, Shadia, additional, Roy, Arpita, additional, Kalavar, Shyam, additional, Ghosh, Soma, additional, Pierce, William F., additional, Rahman, Nam Atiqur., additional, Tang, Shenghui, additional, Mixter, Bronwyn D., additional, Kluetz, Paul G., additional, Pazdur, Richard, additional, and Amiri-Kordestani, Laleh, additional

Published
2023
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36. FDA Approval Summary: Amivantamab for the Treatment of Patients with Non–Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations

Author

Chon, Katie, primary, Larkins, Erin, additional, Chatterjee, Somak, additional, Mishra-Kalyani, Pallavi S., additional, Aungst, Stephanie, additional, Wearne, Emily, additional, Subramaniam, Sriram, additional, Li, Yangbing, additional, Liu, Jiang, additional, Sun, Jielin, additional, Charlab, Rosane, additional, Zhao, Hong, additional, Saritas-Yildirim, Banu, additional, Bikkavilli, Rama Kamesh, additional, Ghosh, Soma, additional, Philip, Reena, additional, Beaver, Julia A., additional, and Singh, Harpreet, additional

Published
2023
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37. Supplementary Figure from AXL and Error-Prone DNA Replication Confer Drug Resistance and Offer Strategies to Treat EGFR-Mutant Lung Cancer

Author

Noronha, Ashish, primary, Belugali Nataraj, Nishanth, primary, Lee, Joo Sang, primary, Zhitomirsky, Benny, primary, Oren, Yaara, primary, Oster, Sara, primary, Lindzen, Moshit, primary, Mukherjee, Saptaparna, primary, Will, Rainer, primary, Ghosh, Soma, primary, Simoni-Nieves, Arturo, primary, Verma, Aakanksha, primary, Chatterjee, Rishita, primary, Borgoni, Simone, primary, Robinson, Welles, primary, Sinha, Sanju, primary, Brandis, Alexander, primary, Kerr, D. Lucas, primary, Wu, Wei, primary, Sekar, Arunachalam, primary, Giri, Suvendu, primary, Chung, Youngmin, primary, Drago-Garcia, Diana, primary, Danysh, Brian P., primary, Lauriola, Mattia, primary, Fiorentino, Michelangelo, primary, Ardizzoni, Andrea, primary, Oren, Moshe, primary, Blakely, Collin M., primary, Ezike, Jideofor, primary, Wiemann, Stefan, primary, Parida, Laxmi, primary, Bivona, Trever G., primary, Aqeilan, Rami I., primary, Brugge, Joan S., primary, Regev, Aviv, primary, Getz, Gad, primary, Ruppin, Eytan, primary, and Yarden, Yosef, primary

Published
2023
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38. Data from AXL and Error-Prone DNA Replication Confer Drug Resistance and Offer Strategies to Treat EGFR-Mutant Lung Cancer

Author

Noronha, Ashish, primary, Belugali Nataraj, Nishanth, primary, Lee, Joo Sang, primary, Zhitomirsky, Benny, primary, Oren, Yaara, primary, Oster, Sara, primary, Lindzen, Moshit, primary, Mukherjee, Saptaparna, primary, Will, Rainer, primary, Ghosh, Soma, primary, Simoni-Nieves, Arturo, primary, Verma, Aakanksha, primary, Chatterjee, Rishita, primary, Borgoni, Simone, primary, Robinson, Welles, primary, Sinha, Sanju, primary, Brandis, Alexander, primary, Kerr, D. Lucas, primary, Wu, Wei, primary, Sekar, Arunachalam, primary, Giri, Suvendu, primary, Chung, Youngmin, primary, Drago-Garcia, Diana, primary, Danysh, Brian P., primary, Lauriola, Mattia, primary, Fiorentino, Michelangelo, primary, Ardizzoni, Andrea, primary, Oren, Moshe, primary, Blakely, Collin M., primary, Ezike, Jideofor, primary, Wiemann, Stefan, primary, Parida, Laxmi, primary, Bivona, Trever G., primary, Aqeilan, Rami I., primary, Brugge, Joan S., primary, Regev, Aviv, primary, Getz, Gad, primary, Ruppin, Eytan, primary, and Yarden, Yosef, primary

Published
2023
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40. Supplementary Data from AXL and Error-Prone DNA Replication Confer Drug Resistance and Offer Strategies to Treat EGFR-Mutant Lung Cancer

Author

Noronha, Ashish, primary, Belugali Nataraj, Nishanth, primary, Lee, Joo Sang, primary, Zhitomirsky, Benny, primary, Oren, Yaara, primary, Oster, Sara, primary, Lindzen, Moshit, primary, Mukherjee, Saptaparna, primary, Will, Rainer, primary, Ghosh, Soma, primary, Simoni-Nieves, Arturo, primary, Verma, Aakanksha, primary, Chatterjee, Rishita, primary, Borgoni, Simone, primary, Robinson, Welles, primary, Sinha, Sanju, primary, Brandis, Alexander, primary, Kerr, D. Lucas, primary, Wu, Wei, primary, Sekar, Arunachalam, primary, Giri, Suvendu, primary, Chung, Youngmin, primary, Drago-Garcia, Diana, primary, Danysh, Brian P., primary, Lauriola, Mattia, primary, Fiorentino, Michelangelo, primary, Ardizzoni, Andrea, primary, Oren, Moshe, primary, Blakely, Collin M., primary, Ezike, Jideofor, primary, Wiemann, Stefan, primary, Parida, Laxmi, primary, Bivona, Trever G., primary, Aqeilan, Rami I., primary, Brugge, Joan S., primary, Regev, Aviv, primary, Getz, Gad, primary, Ruppin, Eytan, primary, and Yarden, Yosef, primary

Published
2023
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47. Supplementary Figure S1, S2 and S3 from A Combination of Approved Antibodies Overcomes Resistance of Lung Cancer to Osimertinib by Blocking Bypass Pathways

Author

Romaniello, Donatella, primary, Mazzeo, Luigi, primary, Mancini, Maicol, primary, Marrocco, Ilaria, primary, Noronha, Ashish, primary, Kreitman, Matthew, primary, Srivastava, Swati, primary, Ghosh, Soma, primary, Lindzen, Moshit, primary, Salame, Tomer Meir, primary, Onn, Amir, primary, Bar, Jair, primary, and Yarden, Yosef, primary

Published
2023
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48. Supplementary Tables S1-S3 from FDA Approval Summary: Pralsetinib for the Treatment of Lung and Thyroid Cancers With RET Gene Mutations or Fusions

Author

Kim, Janice, primary, Bradford, Diana, primary, Larkins, Erin, primary, Pai-Scherf, Lee H., primary, Chatterjee, Somak, primary, Mishra-Kalyani, Pallavi S., primary, Wearne, Emily, primary, Helms, Whitney S., primary, Ayyoub, Amal, primary, Bi, Youwei, primary, Sun, Jielin, primary, Charlab, Rosane, primary, Liu, Jiang, primary, Zhao, Hong, primary, Liang, Dun, primary, Ghosh, Soma, primary, Philip, Reena, primary, Pazdur, Richard, primary, Theoret, Marc R., primary, Beaver, Julia A., primary, and Singh, Harpreet, primary

Published
2023
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49. Supplementary tables from Sustained Aurora Kinase B Expression Confers Resistance to PI3K Inhibition in Head and Neck Squamous Cell Carcinoma

Author

Shah, Pooja A., primary, Sambandam, Vaishnavi, primary, Fernandez, Anne M., primary, Zhao, Hongyun, primary, Mazumdar, Tuhina, primary, Shen, Li, primary, Wang, Qi, primary, Ahmed, Kazi M., primary, Ghosh, Soma, primary, Frederick, Mitchell J., primary, Wang, Jing, primary, and Johnson, Faye M., primary

Published
2023
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50. Supplementary Figures from Sustained Aurora Kinase B Expression Confers Resistance to PI3K Inhibition in Head and Neck Squamous Cell Carcinoma

Author

Shah, Pooja A., primary, Sambandam, Vaishnavi, primary, Fernandez, Anne M., primary, Zhao, Hongyun, primary, Mazumdar, Tuhina, primary, Shen, Li, primary, Wang, Qi, primary, Ahmed, Kazi M., primary, Ghosh, Soma, primary, Frederick, Mitchell J., primary, Wang, Jing, primary, and Johnson, Faye M., primary

Published
2023
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