The Experts below are selected from a list of 306 Experts worldwide ranked by ideXlab platform
Geoffrey I. Shapiro - One of the best experts on this subject based on the ideXlab platform.
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microrna mediated suppression of the tgf β pathway confers transmissible and reversible cdk4 6 inhibitor resistance
Cell Reports, 2019Co-Authors: Liam Cornell, Seth A. Wander, Tanvi Visal, Nikhil Wagle, Geoffrey I. ShapiroAbstract:Summary CDK4/6 inhibition is now part of the standard armamentarium for patients with estrogen receptor-positive (ER+) breast cancer, so that defining mechanisms of resistance is a pressing issue. Here, we identify increased CDK6 expression as a key determinant of acquired resistance after palbociclib treatment in ER+ breast cancer Cells. CDK6 expression is critical for Cellular survival during palbociclib exposure. The increased CDK6 expression observed in resistant Cells is dependent on TGF-β pathway suppression via miR-432-5p expression. Exosomal miR-432-5p expression mediates the transfer of the resistance phenotype between Neighboring Cell populations. Levels of miR-432-5p are higher in primary breast cancers demonstrating CDK4/6 resistance compared to those that are sensitive. These data are further confirmed in pre-treatment and post-progression biopsies from a parotid cancer patient who had responded to ribociclib, demonstrating the clinical relevance of this mechanism. Finally, the CDK4/6 inhibitor resistance phenotype is reversible in vitro and in vivo by a prolonged drug holiday.
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MicroRNA-Mediated Suppression of the TGF-β Pathway Confers Transmissible and Reversible CDK4/6 Inhibitor Resistance
Elsevier, 2019Co-Authors: Liam Cornell, Seth A. Wander, Tanvi Visal, Nikhil Wagle, Geoffrey I. ShapiroAbstract:Summary: CDK4/6 inhibition is now part of the standard armamentarium for patients with estrogen receptor-positive (ER+) breast cancer, so that defining mechanisms of resistance is a pressing issue. Here, we identify increased CDK6 expression as a key determinant of acquired resistance after palbociclib treatment in ER+ breast cancer Cells. CDK6 expression is critical for Cellular survival during palbociclib exposure. The increased CDK6 expression observed in resistant Cells is dependent on TGF-β pathway suppression via miR-432-5p expression. Exosomal miR-432-5p expression mediates the transfer of the resistance phenotype between Neighboring Cell populations. Levels of miR-432-5p are higher in primary breast cancers demonstrating CDK4/6 resistance compared to those that are sensitive. These data are further confirmed in pre-treatment and post-progression biopsies from a parotid cancer patient who had responded to ribociclib, demonstrating the clinical relevance of this mechanism. Finally, the CDK4/6 inhibitor resistance phenotype is reversible in vitro and in vivo by a prolonged drug holiday. : Cornell et al. demonstrate a mechanism of acquired CDK4/6 inhibitor resistance that is independent of inherent genetic mutations, is conferred through extraCellular signaling, and is reversible in vitro and in vivo. Resistance was mediated by exosomal miRNA, causing increased expression of CDK6 to overcome G1 arrest and promote Cell survival. Keywords: breast cancer, drug resistance, targeted therapy, exosomes, CDK6, microRNA, TGF-β, SMAD4, palbociclib, ribocicli
Olivier Trescases - One of the best experts on this subject based on the ideXlab platform.
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a Cell level differential power processing ic for concentrating pv systems with bidirectional hysteretic current mode control and closed loop frequency regulation
IEEE Transactions on Power Electronics, 2015Co-Authors: Mohammad Shawkat Zaman, Ryan Fernandes, Berry Buter, T S Doorn, Marcel Dijkstra, Henk Jan Bergveld, Olivier TrescasesAbstract:This paper describes an integrated power management IC with bidirectional current capability, aimed at compensating differences in output current between series-connected Cells in concentrating photovoltaic (CPV) systems. The integrated 3.6-MHz power stage allows building a small-form-factor converter per Cell. A hysteretic current-mode controller regulates the bidirectional converter's current to equalize Neighboring Cell voltages. A phase-locked loop controls the inductor current ripple around the average value to stabilize the switching frequency. The use of hysteretic current-mode control with a novel bidirectional senseFET scheme provides inherent current protection and high reliability. The converter can operate from an input voltage as low as 1.8 V and with an inductor current up to $\pm$ 1.5 A, while achieving a system efficiency above 90% for current mismatches between Cells up to 60%. Measurement results show that the converter maximizes the output power of series-connected CPV Cells with mismatched output currents.
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a Cell level differential power processing ic for concentrating pv systems with bidirectional hysteretic current mode control and closed loop frequency regulation
IEEE Transactions on Power Electronics, 2015Co-Authors: Mohammad Shawkat Zaman, Ryan Fernandes, Berry Buter, T S Doorn, Marcel Dijkstra, Henk Jan Bergveld, Yue Wen, Olivier TrescasesAbstract:This paper describes an integrated power management IC with bidirectional current capability, aimed at compensating differences in output current between series-connected Cells in concentrating photovoltaic (CPV) systems. The integrated 3.6-MHz power stage allows building a small-form-factor converter per Cell. A hysteretic current-mode controller regulates the bidirectional converter's current to equalize Neighboring Cell voltages. A phase-locked loop controls the inductor current ripple around the average value to stabilize the switching frequency. The use of hysteretic current-mode control with a novel bidirectional senseFET scheme provides inherent current protection and high reliability. The converter can operate from an input voltage as low as 1.8 V and with an inductor current up to $\pm$ 1.5 A, while achieving a system efficiency above 90% for current mismatches between Cells up to 60%. Measurement results show that the converter maximizes the output power of series-connected CPV Cells with mismatched output currents.
Mohammad Shawkat Zaman - One of the best experts on this subject based on the ideXlab platform.
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a Cell level differential power processing ic for concentrating pv systems with bidirectional hysteretic current mode control and closed loop frequency regulation
IEEE Transactions on Power Electronics, 2015Co-Authors: Mohammad Shawkat Zaman, Ryan Fernandes, Berry Buter, T S Doorn, Marcel Dijkstra, Henk Jan Bergveld, Olivier TrescasesAbstract:This paper describes an integrated power management IC with bidirectional current capability, aimed at compensating differences in output current between series-connected Cells in concentrating photovoltaic (CPV) systems. The integrated 3.6-MHz power stage allows building a small-form-factor converter per Cell. A hysteretic current-mode controller regulates the bidirectional converter's current to equalize Neighboring Cell voltages. A phase-locked loop controls the inductor current ripple around the average value to stabilize the switching frequency. The use of hysteretic current-mode control with a novel bidirectional senseFET scheme provides inherent current protection and high reliability. The converter can operate from an input voltage as low as 1.8 V and with an inductor current up to $\pm$ 1.5 A, while achieving a system efficiency above 90% for current mismatches between Cells up to 60%. Measurement results show that the converter maximizes the output power of series-connected CPV Cells with mismatched output currents.
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a Cell level differential power processing ic for concentrating pv systems with bidirectional hysteretic current mode control and closed loop frequency regulation
IEEE Transactions on Power Electronics, 2015Co-Authors: Mohammad Shawkat Zaman, Ryan Fernandes, Berry Buter, T S Doorn, Marcel Dijkstra, Henk Jan Bergveld, Yue Wen, Olivier TrescasesAbstract:This paper describes an integrated power management IC with bidirectional current capability, aimed at compensating differences in output current between series-connected Cells in concentrating photovoltaic (CPV) systems. The integrated 3.6-MHz power stage allows building a small-form-factor converter per Cell. A hysteretic current-mode controller regulates the bidirectional converter's current to equalize Neighboring Cell voltages. A phase-locked loop controls the inductor current ripple around the average value to stabilize the switching frequency. The use of hysteretic current-mode control with a novel bidirectional senseFET scheme provides inherent current protection and high reliability. The converter can operate from an input voltage as low as 1.8 V and with an inductor current up to $\pm$ 1.5 A, while achieving a system efficiency above 90% for current mismatches between Cells up to 60%. Measurement results show that the converter maximizes the output power of series-connected CPV Cells with mismatched output currents.
Liam Cornell - One of the best experts on this subject based on the ideXlab platform.
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microrna mediated suppression of the tgf β pathway confers transmissible and reversible cdk4 6 inhibitor resistance
Cell Reports, 2019Co-Authors: Liam Cornell, Seth A. Wander, Tanvi Visal, Nikhil Wagle, Geoffrey I. ShapiroAbstract:Summary CDK4/6 inhibition is now part of the standard armamentarium for patients with estrogen receptor-positive (ER+) breast cancer, so that defining mechanisms of resistance is a pressing issue. Here, we identify increased CDK6 expression as a key determinant of acquired resistance after palbociclib treatment in ER+ breast cancer Cells. CDK6 expression is critical for Cellular survival during palbociclib exposure. The increased CDK6 expression observed in resistant Cells is dependent on TGF-β pathway suppression via miR-432-5p expression. Exosomal miR-432-5p expression mediates the transfer of the resistance phenotype between Neighboring Cell populations. Levels of miR-432-5p are higher in primary breast cancers demonstrating CDK4/6 resistance compared to those that are sensitive. These data are further confirmed in pre-treatment and post-progression biopsies from a parotid cancer patient who had responded to ribociclib, demonstrating the clinical relevance of this mechanism. Finally, the CDK4/6 inhibitor resistance phenotype is reversible in vitro and in vivo by a prolonged drug holiday.
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MicroRNA-Mediated Suppression of the TGF-β Pathway Confers Transmissible and Reversible CDK4/6 Inhibitor Resistance
Elsevier, 2019Co-Authors: Liam Cornell, Seth A. Wander, Tanvi Visal, Nikhil Wagle, Geoffrey I. ShapiroAbstract:Summary: CDK4/6 inhibition is now part of the standard armamentarium for patients with estrogen receptor-positive (ER+) breast cancer, so that defining mechanisms of resistance is a pressing issue. Here, we identify increased CDK6 expression as a key determinant of acquired resistance after palbociclib treatment in ER+ breast cancer Cells. CDK6 expression is critical for Cellular survival during palbociclib exposure. The increased CDK6 expression observed in resistant Cells is dependent on TGF-β pathway suppression via miR-432-5p expression. Exosomal miR-432-5p expression mediates the transfer of the resistance phenotype between Neighboring Cell populations. Levels of miR-432-5p are higher in primary breast cancers demonstrating CDK4/6 resistance compared to those that are sensitive. These data are further confirmed in pre-treatment and post-progression biopsies from a parotid cancer patient who had responded to ribociclib, demonstrating the clinical relevance of this mechanism. Finally, the CDK4/6 inhibitor resistance phenotype is reversible in vitro and in vivo by a prolonged drug holiday. : Cornell et al. demonstrate a mechanism of acquired CDK4/6 inhibitor resistance that is independent of inherent genetic mutations, is conferred through extraCellular signaling, and is reversible in vitro and in vivo. Resistance was mediated by exosomal miRNA, causing increased expression of CDK6 to overcome G1 arrest and promote Cell survival. Keywords: breast cancer, drug resistance, targeted therapy, exosomes, CDK6, microRNA, TGF-β, SMAD4, palbociclib, ribocicli
Ryan Fernandes - One of the best experts on this subject based on the ideXlab platform.
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a Cell level differential power processing ic for concentrating pv systems with bidirectional hysteretic current mode control and closed loop frequency regulation
IEEE Transactions on Power Electronics, 2015Co-Authors: Mohammad Shawkat Zaman, Ryan Fernandes, Berry Buter, T S Doorn, Marcel Dijkstra, Henk Jan Bergveld, Olivier TrescasesAbstract:This paper describes an integrated power management IC with bidirectional current capability, aimed at compensating differences in output current between series-connected Cells in concentrating photovoltaic (CPV) systems. The integrated 3.6-MHz power stage allows building a small-form-factor converter per Cell. A hysteretic current-mode controller regulates the bidirectional converter's current to equalize Neighboring Cell voltages. A phase-locked loop controls the inductor current ripple around the average value to stabilize the switching frequency. The use of hysteretic current-mode control with a novel bidirectional senseFET scheme provides inherent current protection and high reliability. The converter can operate from an input voltage as low as 1.8 V and with an inductor current up to $\pm$ 1.5 A, while achieving a system efficiency above 90% for current mismatches between Cells up to 60%. Measurement results show that the converter maximizes the output power of series-connected CPV Cells with mismatched output currents.
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a Cell level differential power processing ic for concentrating pv systems with bidirectional hysteretic current mode control and closed loop frequency regulation
IEEE Transactions on Power Electronics, 2015Co-Authors: Mohammad Shawkat Zaman, Ryan Fernandes, Berry Buter, T S Doorn, Marcel Dijkstra, Henk Jan Bergveld, Yue Wen, Olivier TrescasesAbstract:This paper describes an integrated power management IC with bidirectional current capability, aimed at compensating differences in output current between series-connected Cells in concentrating photovoltaic (CPV) systems. The integrated 3.6-MHz power stage allows building a small-form-factor converter per Cell. A hysteretic current-mode controller regulates the bidirectional converter's current to equalize Neighboring Cell voltages. A phase-locked loop controls the inductor current ripple around the average value to stabilize the switching frequency. The use of hysteretic current-mode control with a novel bidirectional senseFET scheme provides inherent current protection and high reliability. The converter can operate from an input voltage as low as 1.8 V and with an inductor current up to $\pm$ 1.5 A, while achieving a system efficiency above 90% for current mismatches between Cells up to 60%. Measurement results show that the converter maximizes the output power of series-connected CPV Cells with mismatched output currents.
