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3. Sectoral portfolio optimization by judicious selection of financial ratios via PCA

Author

Dhingra, Vrinda, Sharma, Amita, and Gupta, Shiv K.

Subjects
Quantitative Finance - Portfolio Management
Abstract

Embedding value investment in portfolio optimization models has always been a challenge. In this paper, we attempt to incorporate it by employing principal component analysis to filter out dominant financial ratios from each sector and thereafter, use the portfolio optimization model incorporating second-order stochastic dominance criteria to derive an optimal investment. We consider a total of $11$ financial ratios corresponding to each sector representing four categories of ratios, namely liquidity, solvency, profitability, and valuation. PCA is then applied over a period of 10 years to extract dominant ratios from each sector in two ways, one from the component solution and the other from each category on the basis of their communalities. The two-step Sectoral Portfolio Optimization (SPO) model is then utilized to build an optimal portfolio. The strategy formed using the formerly extracted ratios is termed PCA-SPO(A) and the latter PCA-SPO(B). The results obtained from the proposed strategies are compared with those from mean-variance, minimum variance, SPO, and nominal SSD models, with and without financial ratios. The empirical performance of proposed strategies is analyzed in two ways, viz., using a rolling window scheme and using market trend scenarios for S\&P BSE 500 (India) and S\&P 500 (U.S.) markets. We observe that the proposed strategy PCA-SPO(B) outperforms all other models in terms of downside deviation, CVaR, VaR, Sortino, Rachev, and STARR ratios over almost all out-of-sample periods. This highlights the importance of value investment where ratios are carefully selected and embedded quantitatively in portfolio selection process., Comment: 30 pages, 13 tables, 6 figures

Published
2021

4. Pre-clinical modeling of navtemadlin pharmacokinetics (PK), pharmacodynamics (PD), and efficacy in glioblastoma, IDH-wildtype.

Author

Vaubel, Rachael A., primary, Zhang, Wenjuan, additional, Mladek, Ann C, additional, Pasa, Tugce I, additional, Waller, Katie L, additional, Stopka, Sylwia A, additional, Regan, Michael S, additional, Decker, Paul A, additional, Gupta, Shiv K, additional, Jain, Sonia, additional, Hu, Zeng, additional, Carlson, Brett L, additional, Bakken, Katrina K, additional, Talele, Surabhi, additional, Oh, Ju-Hee, additional, Eckel-Passow, Jeanette, additional, Burgenske, Danielle M, additional, Agar, Nathalie, additional, Elmquist, William F, additional, and Sarkaria, Jann Nagina, additional

Published
2024
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5. PK-PD-efficacy modeling of brigimadlin in MDM2-amplified glioblastoma.

Author

Vaubel, Rachael A., primary, Zhang, Wenjuan, additional, Burgenske, Danielle M, additional, Waller, Katie L, additional, Decker, Paul A, additional, Kosel, Matt L, additional, Gupta, Shiv K, additional, Hu, Zeng, additional, Ott, Lauren L, additional, Carlson, Brett L, additional, Bakken, Katrina K, additional, Talele, Surabhi, additional, Oh, Ju-Hee, additional, Eckel-Passow, Jeanette, additional, Sini, Patrizia, additional, Galanis, Evanthia, additional, Elmquist, William F, additional, and Sarkaria, Jann Nagina, additional

Published
2024
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6. Bystander effects, pharmacokinetics, and linker-payload stability of EGFR-targeting antibody-drug conjugates Losatuxizumab vedotin and Depatux-M in glioblastoma models

Author

Jain, Sonia, primary, Griffith, Jessica I., additional, Porath, Kendra A., additional, Rathi, Sneha, additional, Le, Jiayan, additional, Pasa, Tugce I., additional, Decker, Paul A., additional, Gupta, Shiv K., additional, Hu, Zeng, additional, Carlson, Brett L., additional, Bakken, Katrina, additional, Burgenske, Danielle M., additional, Feldsien, Thomas M., additional, Lefebvre, Didier R., additional, Vaubel, Rachael A., additional, Eckel-Passow, Jeanette E., additional, Reilly, Edward B., additional, Elmquist, William F., additional, and Sarkaria, Jann N., additional

Published
2024
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7. Differential Distribution of the DNA-PKcs Inhibitor Peposertib Selectively Radiosensitizes Patient-derived Melanoma Brain Metastasis Xenografts

Author

Ji, Jianxiang, primary, Dragojevic, Sonja, additional, Callaghan, Cameron M., additional, Smith, Emily J., additional, Talele, Surabhi, additional, Zhang, Wenjuan, additional, Connors, Margaret A., additional, Mladek, Ann C., additional, Hu, Zeng, additional, Bakken, Katrina K., additional, Sarkaria, Paige P., additional, Carlson, Brett L., additional, Burgenske, Danielle M., additional, Decker, Paul A., additional, Rashid, Mohammad Abdur, additional, Jang, Mi-hyeon, additional, Gupta, Shiv K., additional, Eckel-Passow, Jeanette E., additional, Elmquist, William F., additional, and Sarkaria, Jann N., additional

Published
2024
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10. Aberrant ATM signaling and homology-directed DNA repair as a vulnerability of p53-mutant GBM to AZD1390-mediated radiosensitization.

Author

Chen, Jiajia, Laverty, Daniel J., Talele, Surabhi, Bale, Ashwin, Carlson, Brett L., Porath, Kendra A., Bakken, Katrina K., Burgenske, Danielle M., Decker, Paul A., Vaubel, Rachael A., Eckel-Passow, Jeanette E., Bhargava, Rohit, Lou, Zhenkun, Hamerlik, Petra, Harley, Brendan, Elmquist, William F., Nagel, Zachary D., Gupta, Shiv K., and Sarkaria, Jann N.

Subjects
DNA repair, GLIOBLASTOMA multiforme, HOMOLOGOUS recombination, AUTOMATED teller machines, RADIATION-sensitizing agents, GENE targeting, TUMOR suppressor proteins
Abstract

ATM is a key mediator of radiation response, and pharmacological inhibition of ATM is a rational strategy to radiosensitize tumors. AZD1390 is a brain-penetrant ATM inhibitor and a potent radiosensitizer. This study evaluated the spectrum of radiosensitizing effects and the impact of TP53 mutation status in a panel of IDH1 wild-type (WT) glioblastoma (GBM) patient-derived xenografts (PDXs). AZD1390 suppressed radiation-induced ATM signaling, abrogated G0-G1 arrest, and promoted a proapoptotic response specifically in p53-mutant GBM in vitro. In a preclinical trial using 10 orthotopic GBM models, AZD1390/RT afforded benefit in a cohort of TP53-mutant tumors but not in TP53-WT PDXs. In mechanistic studies, increased endogenous DNA damage and constitutive ATM signaling were observed in TP53-mutant, but not in TP53-WT, PDXs. In plasmid-based reporter assays, GBM43 (TP53-mutant) showed elevated DNA repair capacity compared with that in GBM14 (p53-WT), whereas treatment with AZD1390 specifically suppressed homologous recombination (HR) efficiency, in part, by stalling RAD51 unloading. Furthermore, overexpression of a dominant-negative TP53 (p53DD) construct resulted in enhanced basal ATM signaling, HR activity, and AZD1390-mediated radiosensitization in GBM14. Analyzing RNA-seq data from TCGA showed up-regulation of HR pathway genes in TP53-mutant human GBM. Together, our results imply that increased basal ATM signaling and enhanced dependence on HR represent a unique susceptibility of TP53-mutant cells to ATM inhibitor–mediated radiosensitization. Editor's summary: Standard of care for glioblastoma (GBM) includes treatment with radiation therapy (RT) and temozolomide; however, long-term survival remains rare. To improve RT, Chen et al. investigated the use of AZD1390, a brain-penetrant ATM inhibitor and radiosensitizer in combination with RT in mouse models. They saw that this combination was beneficial for a cohort of patient-derived xenografts that were TP53-mutant, suppressing homologous recombination efficiency and extending survival. This represents a potential therapy that could benefit patients with TP53-mutant GBM and warrants further study. —Dorothy Hallberg [ABSTRACT FROM AUTHOR]

Published
2024
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11. Figure S1 from Restricted Delivery of Talazoparib Across the Blood–Brain Barrier Limits the Sensitizing Effects of PARP Inhibition on Temozolomide Therapy in Glioblastoma

Author

Kizilbash, Sani H., primary, Gupta, Shiv K., primary, Chang, Kenneth, primary, Kawashima, Ryo, primary, Parrish, Karen E., primary, Carlson, Brett L., primary, Bakken, Katrina K., primary, Mladek, Ann C., primary, Schroeder, Mark A., primary, Decker, Paul A., primary, Kitange, Gaspar J., primary, Shen, Yuqiao, primary, Feng, Ying, primary, Protter, Andrew A., primary, Elmquist, William F., primary, and Sarkaria, Jann N., primary

Published
2023
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12. Data from Restricted Delivery of Talazoparib Across the Blood–Brain Barrier Limits the Sensitizing Effects of PARP Inhibition on Temozolomide Therapy in Glioblastoma

Author

Kizilbash, Sani H., primary, Gupta, Shiv K., primary, Chang, Kenneth, primary, Kawashima, Ryo, primary, Parrish, Karen E., primary, Carlson, Brett L., primary, Bakken, Katrina K., primary, Mladek, Ann C., primary, Schroeder, Mark A., primary, Decker, Paul A., primary, Kitange, Gaspar J., primary, Shen, Yuqiao, primary, Feng, Ying, primary, Protter, Andrew A., primary, Elmquist, William F., primary, and Sarkaria, Jann N., primary

Published
2023
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13. Supplementary Information from Restricted Delivery of Talazoparib Across the Blood–Brain Barrier Limits the Sensitizing Effects of PARP Inhibition on Temozolomide Therapy in Glioblastoma

Author

Kizilbash, Sani H., primary, Gupta, Shiv K., primary, Chang, Kenneth, primary, Kawashima, Ryo, primary, Parrish, Karen E., primary, Carlson, Brett L., primary, Bakken, Katrina K., primary, Mladek, Ann C., primary, Schroeder, Mark A., primary, Decker, Paul A., primary, Kitange, Gaspar J., primary, Shen, Yuqiao, primary, Feng, Ying, primary, Protter, Andrew A., primary, Elmquist, William F., primary, and Sarkaria, Jann N., primary

Published
2023
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14. Figure S1 from In Vivo Efficacy of Tesevatinib in EGFR-Amplified Patient-Derived Xenograft Glioblastoma Models May Be Limited by Tissue Binding and Compensatory Signaling

Author

Kizilbash, Sani H., primary, Gupta, Shiv K., primary, Parrish, Karen E., primary, Laramy, Janice K., primary, Kim, Minjee, primary, Gampa, Gautham, primary, Carlson, Brett L., primary, Bakken, Katrina K., primary, Mladek, Ann C., primary, Schroeder, Mark A., primary, Decker, Paul A., primary, Elmquist, William F., primary, and Sarkaria, Jann N., primary

Published
2023
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17. Supplementary Methods and Legend from The Efficacy of the Wee1 Inhibitor MK-1775 Combined with Temozolomide Is Limited by Heterogeneous Distribution across the Blood–Brain Barrier in Glioblastoma

Author

Pokorny, Jenny L., primary, Calligaris, David, primary, Gupta, Shiv K., primary, Iyekegbe, Dennis O., primary, Mueller, Dustin, primary, Bakken, Katrina K., primary, Carlson, Brett L., primary, Schroeder, Mark A., primary, Evans, Debra L., primary, Lou, Zhenkun, primary, Decker, Paul A., primary, Eckel-Passow, Jeanette E., primary, Pucci, Vincenzo, primary, Ma, Bennett, primary, Shumway, Stuart D., primary, Elmquist, William F., primary, Agar, Nathalie Y.R., primary, and Sarkaria, Jann N., primary

Published
2023
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18. Supplementary Figure S1 from The Efficacy of the Wee1 Inhibitor MK-1775 Combined with Temozolomide Is Limited by Heterogeneous Distribution across the Blood–Brain Barrier in Glioblastoma

Author

Pokorny, Jenny L., primary, Calligaris, David, primary, Gupta, Shiv K., primary, Iyekegbe, Dennis O., primary, Mueller, Dustin, primary, Bakken, Katrina K., primary, Carlson, Brett L., primary, Schroeder, Mark A., primary, Evans, Debra L., primary, Lou, Zhenkun, primary, Decker, Paul A., primary, Eckel-Passow, Jeanette E., primary, Pucci, Vincenzo, primary, Ma, Bennett, primary, Shumway, Stuart D., primary, Elmquist, William F., primary, Agar, Nathalie Y.R., primary, and Sarkaria, Jann N., primary

Published
2023
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19. Supplementary Figure 3 from Inhibition of Histone Deacetylation Potentiates the Evolution of Acquired Temozolomide Resistance Linked to MGMT Upregulation in Glioblastoma Xenografts

Author

Kitange, Gaspar J., primary, Mladek, Ann C., primary, Carlson, Brett L., primary, Schroeder, Mark A., primary, Pokorny, Jenny L., primary, Cen, Ling, primary, Decker, Paul A., primary, Wu, Wenting, primary, Lomberk, Gwen A., primary, Gupta, Shiv K., primary, Urrutia, Raul A., primary, and Sarkaria, Jann N., primary

Published
2023
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21. Supplementary Table 1 from Inhibition of Histone Deacetylation Potentiates the Evolution of Acquired Temozolomide Resistance Linked to MGMT Upregulation in Glioblastoma Xenografts

Author

Kitange, Gaspar J., primary, Mladek, Ann C., primary, Carlson, Brett L., primary, Schroeder, Mark A., primary, Pokorny, Jenny L., primary, Cen, Ling, primary, Decker, Paul A., primary, Wu, Wenting, primary, Lomberk, Gwen A., primary, Gupta, Shiv K., primary, Urrutia, Raul A., primary, and Sarkaria, Jann N., primary

Published
2023
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22. Supplementary Table 2 from Inhibition of Histone Deacetylation Potentiates the Evolution of Acquired Temozolomide Resistance Linked to MGMT Upregulation in Glioblastoma Xenografts

Author

Kitange, Gaspar J., primary, Mladek, Ann C., primary, Carlson, Brett L., primary, Schroeder, Mark A., primary, Pokorny, Jenny L., primary, Cen, Ling, primary, Decker, Paul A., primary, Wu, Wenting, primary, Lomberk, Gwen A., primary, Gupta, Shiv K., primary, Urrutia, Raul A., primary, and Sarkaria, Jann N., primary

Published
2023
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23. Supplementary Figure 2 from Inhibition of Histone Deacetylation Potentiates the Evolution of Acquired Temozolomide Resistance Linked to MGMT Upregulation in Glioblastoma Xenografts

Author

Kitange, Gaspar J., primary, Mladek, Ann C., primary, Carlson, Brett L., primary, Schroeder, Mark A., primary, Pokorny, Jenny L., primary, Cen, Ling, primary, Decker, Paul A., primary, Wu, Wenting, primary, Lomberk, Gwen A., primary, Gupta, Shiv K., primary, Urrutia, Raul A., primary, and Sarkaria, Jann N., primary

Published
2023
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24. Supplementary Figure 1 from Inhibition of Histone Deacetylation Potentiates the Evolution of Acquired Temozolomide Resistance Linked to MGMT Upregulation in Glioblastoma Xenografts

Author

Kitange, Gaspar J., primary, Mladek, Ann C., primary, Carlson, Brett L., primary, Schroeder, Mark A., primary, Pokorny, Jenny L., primary, Cen, Ling, primary, Decker, Paul A., primary, Wu, Wenting, primary, Lomberk, Gwen A., primary, Gupta, Shiv K., primary, Urrutia, Raul A., primary, and Sarkaria, Jann N., primary

Published
2023
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28. Integrated mapping of pharmacokinetics and pharmacodynamics in a patient-derived xenograft model of glioblastoma

Author

Randall, Elizabeth C., Emdal, Kristina B., Laramy, Janice K., Kim, Minjee, Roos, Alison, Calligaris, David, Regan, Michael S., Gupta, Shiv K., Mladek, Ann C., Carlson, Brett L., Johnson, Aaron J., Lu, Fa-Ke, Xie, X. Sunney, Joughin, Brian A., Reddy, Raven J., Peng, Sen, Abdelmoula, Walid M., Jackson, Pamela R., Kolluri, Aarti, Kellersberger, Katherine A., Agar, Jeffrey N., Lauffenburger, Douglas A., Swanson, Kristin R., Tran, Nhan L., Elmquist, William F., White, Forest M., Sarkaria, Jann N., and Agar, Nathalie Y. R.

Published
2018
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32. Abstract 2598: AZD1390 radio-sensitizes p53-mutant GBM via disrupting homology directed DNA repair

Author

Gupta, Shiv K., primary, Chen, Jiajia, additional, Laverty, Daniel J., additional, Talele, Surabhi, additional, Carlson, Brett L., additional, Tuma, Ann C. Mladek, additional, Burgenske, Danielle, additional, Kitange, Gaspar J., additional, Hamerlik, Petra, additional, Nagel, Zachary D., additional, Durant, Stephen T., additional, Elmquist, William F., additional, and Sarkaria, Jann N., additional

Published
2022
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33. Cubic Polynomials with Rational Roots and Critical Points

Author

Gupta, Shiv K. and Szymanski, Waclaw

Abstract

If you want your students to graph a cubic polynomial, it is best to give them one with rational roots and critical points. In this paper, we describe completely all such cubics and explain how to generate them.

Published
2010
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36. Delineation of MGMT Hypermethylation as a Biomarker for Veliparib-Mediated Temozolomide-Sensitizing Therapy of Glioblastoma

Author

Gupta, Shiv K., Kizilbash, Sani H., Carlson, Brett L., Mladek, Ann C., Boakye-Agyeman, Felix, Bakken, Katrina K., Pokorny, Jenny L., Schroeder, Mark A., Decker, Paul A., Cen, Ling, Eckel-Passow, Jeanette E., Sarkar, Gobinda, Ballman, Karla V., Reid, Joel M., Jenkins, Robert B., Verhaak, Roeland G., Sulman, Erik P., Kitange, Gaspar J., and Sarkaria, Jann N.

Published
2016
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37. Convection enhanced delivery of EGFR targeting antibody-drug conjugates Serclutamab talirine and Depatux-M in glioblastoma patient-derived xenografts

Author

Porath, Kendra A, primary, Regan, Michael S, additional, Griffith, Jessica I, additional, Jain, Sonia, additional, Stopka, Sylwia A, additional, Burgenske, Danielle M, additional, Bakken, Katrina K, additional, Carlson, Brett L, additional, Decker, Paul A, additional, Vaubel, Rachael A, additional, Dragojevic, Sonja, additional, Mladek, Ann C, additional, Connors, Margaret A, additional, Hu, Zeng, additional, He, Lihong, additional, Kitange, Gaspar J, additional, Gupta, Shiv K, additional, Feldsien, Thomas M, additional, Lefebvre, Didier R, additional, Agar, Nathalie Y R, additional, Eckel-Passow, Jeanette E, additional, Reilly, Edward B, additional, Elmquist, William F, additional, and Sarkaria, Jann N, additional

Published
2022
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