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Atsuto Inoue - One of the best experts on this subject based on the ideXlab platform.
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Etelcalcetide decreases the PTH–calcium setpoint without changing maximum and minimum PTH secretion in mice with primary hyperparathyroidism
Journal of Bone and Mineral Metabolism, 2020Co-Authors: Noriyuki Hayashi, Yasuo Imanishi, Tomoe Hirakawa, Ikue Kobayashi, Tomomi Tateishi, Daichi Miyaoka, Yuki Nagata, Katsuhito Mori, Tomoaki Morioka, Atsuto InoueAbstract:Introduction Etelcalcetide binds to the extracellular domain of the calcium-sensing receptor (CaSR), while cinacalcet binds to the 7-transmembrane domain of the CaSR; however, it is unknown, whether etelcalcetide has similar effects to cinacalcet on parathyroid hormone (PTH) secretion. Materials and methods The PTH–calcium setpoint and maximum and minimum PTH secretion were determined using an ‘in vivo setpoint analyses.’ The PTH–calcium setpoint was obtained in a mouse model of primary hyperparathyroidism (PC) and wild-type (WT) mice, with PC mice divided into two groups. The setpoint was obtained after 7 days of etelcalcetide (3.0 mg/kg BW/day) or vehicle administration via anosmotic pump. After 7 days of crossover administration, the setpoint was obtained again. Parathyroid glands were obtained after crossover administration, and CaSR expression was analyzed by immunohistochemistry. Results Etelcalcetide administration significantly decreased the setpoint from 9.03 ± 0.56 mg/dL to 6.80 ± 0.28 mg/dL, which was restored to 8.81 ± 0.38 mg/dL after vehicle administration. In the second group of mice, vehicle administration did not alter the setpoint (8.84 ± 0.69 mg/dL to 8.98 ± 0.63 mg/dL), but subsequent etelcalcetide administration significantly decreased it to 7.10 ± 0.72 mg/dL. There was no significant change in maximum and minimum PTH secretion. Expression levels of parathyroid CaSR were lower in PC mice than in WT mice; however, no significant differences were observed between the two mouse groups. Conclusion Etelcalcetide decreased the PTH–calcium setpoint without changing maximum and minimum PTH secretion in PC mice, suggesting that like cinacalcet, etelcalcetide has calcimimetic potency.
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Etelcalcetide decreases the PTH-calcium setpoint without changing maximum and minimum PTH secretion in mice with primary hyperparathyroidism.
Journal of bone and mineral metabolism, 2020Co-Authors: Noriyuki Hayashi, Yasuo Imanishi, Tomoe Hirakawa, Ikue Kobayashi, Tomomi Tateishi, Daichi Miyaoka, Yuki Nagata, Katsuhito Mori, Tomoaki Morioka, Atsuto InoueAbstract:Introduction Etelcalcetide binds to the extracellular domain of the calcium-sensing receptor (CaSR), while cinacalcet binds to the 7-transmembrane domain of the CaSR; however, it is unknown, whether etelcalcetide has similar effects to cinacalcet on parathyroid hormone (PTH) secretion. Materials and methods The PTH-calcium setpoint and maximum and minimum PTH secretion were determined using an 'in vivo setpoint analyses.' The PTH-calcium setpoint was obtained in a mouse model of primary hyperparathyroidism (PC) and wild-type (WT) mice, with PC mice divided into two groups. The setpoint was obtained after 7 days of etelcalcetide (3.0 mg/kg BW/day) or vehicle administration via anosmotic pump. After 7 days of crossover administration, the setpoint was obtained again. Parathyroid glands were obtained after crossover administration, and CaSR expression was analyzed by immunohistochemistry. Results Etelcalcetide administration significantly decreased the setpoint from 9.03 ± 0.56 mg/dL to 6.80 ± 0.28 mg/dL, which was restored to 8.81 ± 0.38 mg/dL after vehicle administration. In the second group of mice, vehicle administration did not alter the setpoint (8.84 ± 0.69 mg/dL to 8.98 ± 0.63 mg/dL), but subsequent etelcalcetide administration significantly decreased it to 7.10 ± 0.72 mg/dL. There was no significant change in maximum and minimum PTH secretion. Expression levels of parathyroid CaSR were lower in PC mice than in WT mice; however, no significant differences were observed between the two mouse groups. Conclusion Etelcalcetide decreased the PTH-calcium setpoint without changing maximum and minimum PTH secretion in PC mice, suggesting that like cinacalcet, etelcalcetide has calcimimetic potency.
Duk Joo Yoon - One of the best experts on this subject based on the ideXlab platform.
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Optimization for Setpoints of steam generator water level control systems in power-uprated YGN 1 & 2 and kori 3 & 4
Journal of Nuclear Science and Technology, 2005Co-Authors: Duk Joo YoonAbstract:Korean nuclear industry has performed power uprating project for YGN 1&2 and Kori 3&4 to increase the plant licensed power by 4.5%. The power uprating of 4.5% changes the plant operating conditions. Particularly, it reduces the capacity of steam dump valves from 70 to 59.1% of turbine steam flow at the full power. Thus, we evaluated the bounding transient of 95% load rejection as a function of a proportional band (PB) of SDCS whether the steam dump capacity was sufficient to accommodate the increased thermal load without the modification of component. Also, we performed the sensitivity studies for a PB of SDCS and a KPFM of FWCS to determine the optimized Setpoints of FWCS and SDCS which minimized the fluctuation of steam generator (SG) water level due to swelling and shrinking. From these analyses results, we determined the optimized Setpoints of FWCS and SDCS in power uprated YGN 1&2 and Kori 3&4. After then, we verified the appropriateness of these Setpoints through analyzing SG level setpoint step cha...
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optimization for Setpoints of steam generator water level control systems in power uprated ygn 1 2 and kori 3 4
Journal of Nuclear Science and Technology, 2005Co-Authors: Duk Joo Yoon, Yong Soo Kim, Jae Yong Lee, Hwang Yong Jun, Joo Sung KimAbstract:Korean nuclear industry has performed power uprating project for YGN 1&2 and Kori 3&4 to increase the plant licensed power by 4.5%. The power uprating of 4.5% changes the plant operating conditions. Particularly, it reduces the capacity of steam dump valves from 70 to 59.1% of turbine steam flow at the full power. Thus, we evaluated the bounding transient of 95% load rejection as a function of a proportional band (PB) of SDCS whether the steam dump capacity was sufficient to accommodate the increased thermal load without the modification of component. Also, we performed the sensitivity studies for a PB of SDCS and a KPFM of FWCS to determine the optimized Setpoints of FWCS and SDCS which minimized the fluctuation of steam generator (SG) water level due to swelling and shrinking. From these analyses results, we determined the optimized Setpoints of FWCS and SDCS in power uprated YGN 1&2 and Kori 3&4. After then, we verified the appropriateness of these Setpoints through analyzing SG level setpoint step cha...
Sigurd Skogestad - One of the best experts on this subject based on the ideXlab platform.
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Multiple-Input Single-Output Control for Extending the Steady-State Operating Range—Use of Controllers with Different Setpoints
Processes, 2019Co-Authors: Adriana Reyes-lúa, Sigurd SkogestadAbstract:This paper deals with a case when multiple inputs are needed to cover the steady-state operating range. The most common implementation is to use split range control with a single controller. However, this approach has some limitations. In this paper, we use multiple controllers with different Setpoints and demonstrate that this structure can be optimal in some cases when the cost of the input can be traded off against the penalty of deviating from the desired setpoint. We describe a procedure to find the optimal setpoint deviations. We illustrate our procedure in a case in which three inputs (cooling and two sources of heating) are used to control the temperature of a room with a PID-based control structure and without the need of online optimization.
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multiple input single output control for extending the steady state operating range use of controllers with different Setpoints
Processes, 2019Co-Authors: Adriana Reyeslua, Sigurd SkogestadAbstract:This paper deals with a case when multiple inputs are needed to cover the steady-state operating range. The most common implementation is to use split range control with a single controller. However, this approach has some limitations. In this paper, we use multiple controllers with different Setpoints and demonstrate that this structure can be optimal in some cases when the cost of the input can be traded off against the penalty of deviating from the desired setpoint. We describe a procedure to find the optimal setpoint deviations. We illustrate our procedure in a case in which three inputs (cooling and two sources of heating) are used to control the temperature of a room with a PID-based control structure and without the need of online optimization.
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selection of controlled variables and robust Setpoints
Industrial & Engineering Chemistry Research, 2005Co-Authors: Marius S Govatsmark, Sigurd SkogestadAbstract:Optimal operation of chemical plants is usually accomplished by first finding the optimal steady state using the present (nominal) set of disturbances. This is usually implemented by sending constant Setpoints for selected variables to the control system. The Setpoints are then the nominally optimal values. However, because of disturbances this may result in feasibility problems, which we here try to avoid by adjusting the Setpoints (backoff). First, we need to avoid infeasibility in the active constraints (constraint backoff). Second, we need to adjust the Setpoints of the unconstrained controlled variables. This may be done by offline computation of robust Setpoints (optimal backoff) or by online feasibility correction (flexible backoff). As a case study, we consider a reactor-separator-recycle process. For this process, the control structures based on Luyben's rule (fix a flow in every recycle loop) are infeasible if we use the nominal Setpoints but are feasible with reasonable loss if we use robust Setpoints.
Noriyuki Hayashi - One of the best experts on this subject based on the ideXlab platform.
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Etelcalcetide decreases the PTH–calcium setpoint without changing maximum and minimum PTH secretion in mice with primary hyperparathyroidism
Journal of Bone and Mineral Metabolism, 2020Co-Authors: Noriyuki Hayashi, Yasuo Imanishi, Tomoe Hirakawa, Ikue Kobayashi, Tomomi Tateishi, Daichi Miyaoka, Yuki Nagata, Katsuhito Mori, Tomoaki Morioka, Atsuto InoueAbstract:Introduction Etelcalcetide binds to the extracellular domain of the calcium-sensing receptor (CaSR), while cinacalcet binds to the 7-transmembrane domain of the CaSR; however, it is unknown, whether etelcalcetide has similar effects to cinacalcet on parathyroid hormone (PTH) secretion. Materials and methods The PTH–calcium setpoint and maximum and minimum PTH secretion were determined using an ‘in vivo setpoint analyses.’ The PTH–calcium setpoint was obtained in a mouse model of primary hyperparathyroidism (PC) and wild-type (WT) mice, with PC mice divided into two groups. The setpoint was obtained after 7 days of etelcalcetide (3.0 mg/kg BW/day) or vehicle administration via anosmotic pump. After 7 days of crossover administration, the setpoint was obtained again. Parathyroid glands were obtained after crossover administration, and CaSR expression was analyzed by immunohistochemistry. Results Etelcalcetide administration significantly decreased the setpoint from 9.03 ± 0.56 mg/dL to 6.80 ± 0.28 mg/dL, which was restored to 8.81 ± 0.38 mg/dL after vehicle administration. In the second group of mice, vehicle administration did not alter the setpoint (8.84 ± 0.69 mg/dL to 8.98 ± 0.63 mg/dL), but subsequent etelcalcetide administration significantly decreased it to 7.10 ± 0.72 mg/dL. There was no significant change in maximum and minimum PTH secretion. Expression levels of parathyroid CaSR were lower in PC mice than in WT mice; however, no significant differences were observed between the two mouse groups. Conclusion Etelcalcetide decreased the PTH–calcium setpoint without changing maximum and minimum PTH secretion in PC mice, suggesting that like cinacalcet, etelcalcetide has calcimimetic potency.
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Etelcalcetide decreases the PTH-calcium setpoint without changing maximum and minimum PTH secretion in mice with primary hyperparathyroidism.
Journal of bone and mineral metabolism, 2020Co-Authors: Noriyuki Hayashi, Yasuo Imanishi, Tomoe Hirakawa, Ikue Kobayashi, Tomomi Tateishi, Daichi Miyaoka, Yuki Nagata, Katsuhito Mori, Tomoaki Morioka, Atsuto InoueAbstract:Introduction Etelcalcetide binds to the extracellular domain of the calcium-sensing receptor (CaSR), while cinacalcet binds to the 7-transmembrane domain of the CaSR; however, it is unknown, whether etelcalcetide has similar effects to cinacalcet on parathyroid hormone (PTH) secretion. Materials and methods The PTH-calcium setpoint and maximum and minimum PTH secretion were determined using an 'in vivo setpoint analyses.' The PTH-calcium setpoint was obtained in a mouse model of primary hyperparathyroidism (PC) and wild-type (WT) mice, with PC mice divided into two groups. The setpoint was obtained after 7 days of etelcalcetide (3.0 mg/kg BW/day) or vehicle administration via anosmotic pump. After 7 days of crossover administration, the setpoint was obtained again. Parathyroid glands were obtained after crossover administration, and CaSR expression was analyzed by immunohistochemistry. Results Etelcalcetide administration significantly decreased the setpoint from 9.03 ± 0.56 mg/dL to 6.80 ± 0.28 mg/dL, which was restored to 8.81 ± 0.38 mg/dL after vehicle administration. In the second group of mice, vehicle administration did not alter the setpoint (8.84 ± 0.69 mg/dL to 8.98 ± 0.63 mg/dL), but subsequent etelcalcetide administration significantly decreased it to 7.10 ± 0.72 mg/dL. There was no significant change in maximum and minimum PTH secretion. Expression levels of parathyroid CaSR were lower in PC mice than in WT mice; however, no significant differences were observed between the two mouse groups. Conclusion Etelcalcetide decreased the PTH-calcium setpoint without changing maximum and minimum PTH secretion in PC mice, suggesting that like cinacalcet, etelcalcetide has calcimimetic potency.
Thomas De Beer - One of the best experts on this subject based on the ideXlab platform.
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liquid to solid ratio control as an advanced process control solution for continuous twin screw wet granulation
Aiche Journal, 2018Co-Authors: Niels Nicolai, Fien De Leersnyder, Dana Copot, Michiel Stock, Claramihaela Ionescu, Krist V. Gernaey, Ingmar Nopens, Thomas De BeerAbstract:Assuring compliance of intermediate and final quality attributes in a continuous pharmaceutical manufacturing campaign is of utmost importance. Application of corrective actions might be required in real-time. This work exemplifies the steps needed to identify a linear pulse transfer function for the dynamic behavior of the granule liquid-to-solid ratio (%w/w) at the end of the granulation unit of a commercial ConsiGma(TM)-25 production line. Near-infrared spectroscopy was used to monitor the granule composition in-line. The outcome for both the tracking and regulator problem using either conventional or model predictive control was implemented and evaluated. Dynamic Setpoints were correctly followed and an RMSE of 0.25%w/w with respect to the setpoint was obtained when inducing artificial disturbances. Important practical challenges were also tackled. Examples are fouling, computational limitations, and the limited flexibility of the automation software. Applying the proposed advanced process control solution offers an answer to upstream material flow rate deviations. (c) 2018 American Institute of Chemical Engineers AIChE J, 64: 2500-2514, 2018
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Liquid‐to‐solid ratio control as an advanced process control solution for continuous twin‐screw wet granulation
Aiche Journal, 2018Co-Authors: Niels Nicolai, Fien De Leersnyder, Dana Copot, Michiel Stock, Claramihaela Ionescu, Krist V. Gernaey, Ingmar Nopens, Thomas De BeerAbstract:Assuring compliance of intermediate and final quality attributes in a continuous pharmaceutical manufacturing campaign is of utmost importance. Application of corrective actions might be required in real-time. This work exemplifies the steps needed to identify a linear pulse transfer function for the dynamic behavior of the granule liquid-to-solid ratio (%w/w) at the end of the granulation unit of a commercial ConsiGma(TM)-25 production line. Near-infrared spectroscopy was used to monitor the granule composition in-line. The outcome for both the tracking and regulator problem using either conventional or model predictive control was implemented and evaluated. Dynamic Setpoints were correctly followed and an RMSE of 0.25%w/w with respect to the setpoint was obtained when inducing artificial disturbances. Important practical challenges were also tackled. Examples are fouling, computational limitations, and the limited flexibility of the automation software. Applying the proposed advanced process control solution offers an answer to upstream material flow rate deviations. (c) 2018 American Institute of Chemical Engineers AIChE J, 64: 2500-2514, 2018
