| 1. |
- Friberg, Lena E., et al.
(författare)
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Model of Chemotherapy-Induced Myelosuppression With Parameter Consistency Across Drugs
- 2002
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 20:24, s. 4713-4721
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To develop a semimechanistic pharmacokinetic-pharmacodynamic model describing chemotherapy-induced myelosuppression through drug-specific parameters and system-related parameters, which are common to all drugs. PATIENTS AND METHODS: Patient leukocyte and neutrophil data after administration of docetaxel, paclitaxel, and etoposide were used to develop the model, which was also applied to myelosuppression data from 2'-deoxy-2'-methylidenecytidine (DMDC), irinotecan (CPT-11), and vinflunine administrations. The model consisted of a proliferating compartment that was sensitive to drugs, three transit compartments that represented maturation, and a compartment of circulating blood cells. Three system-related parameters were estimated: baseline, mean transit time, and a feedback parameter. Drug concentration-time profiles affected the proliferation of sensitive cells by either an inhibitory linear model or an inhibitory E(max) model. To evaluate the model, system-related parameters were fixed to the same values for all drugs, which were based on the results from the estimations, and only drug-specific parameters were estimated. All modeling was performed using NONMEM software. RESULTS: For all investigated drugs, the model successfully described myelosuppression. Consecutive courses and different schedules of administration were also well characterized. Similar system-related parameter estimates were obtained for the different drugs and also for leukocytes compared with neutrophils. In addition, when system-related parameters were fixed, the model well characterized chemotherapy-induced myelosuppression for the different drugs. CONCLUSION: This model predicted myelosuppression after administration of one of several different chemotherapeutic drugs. In addition, with fixed system-related parameters to proposed values, and only drug-related parameters estimated, myelosuppression can be predicted. We propose that this model can be a useful tool in the development of anticancer drugs and therapies.
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| 3. |
- Nguyen, Hugo, et al.
(författare)
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Micropropulsion systems research and manufacture in Sweden
- 2003
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Ingår i: Proceedings of the 4th Round Table on Micro/Nano Technology for Space, ESTEC, Noordwijk, The Netherlands. - : ESTEC/ESA. ; , s. 476-485
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Konferensbidrag (refereegranskat)abstract
- Micropropulsion for spacecraft is an enabling technology for many future missions, and may increase the performance and drastically reduce the mass required for advanced propulsion systems. The Swedish activities in micropropulsion at The Angstrom Space Technology Centre (ASTC) are outlined. The research targets two major issues: the development of system parts, and the research into integration techniques and strategies. This paper collects a multitude of devices relevant to the micropropulsion system design, together with representative functional demonstrations. The items are mainly intended for chemical micropropulsion systems or fuel-feed systems for electric propulsion. In particular, gas handling devices, sensors, and actuators are presented. These include silicon nozzles, thin film heaters, suspended microcoil heaters, proportional piezoelectric valves, proportional and isolation valves using phase-change material, thermal throttle flow-regulators, high-pressure regulators, 3D-particle filters, and sensors for strain, pressure, flow, and thrust. Moreover, integration techniques and interface structures are presented, for example low-temperature plasma-assisted silicon wafer bonding, multiwafer bonding, thin film soldering, hermetic electric through-wafer via connections, and multiconnector through-wafer vias. Emphasis is on how these items are designed to allow for system integration in a multiwafer silicon stack, comprising a complete micropropulsion system. In this manner, all items form a parts collection available to the system design. This strategy is exemplified by three micropropulsion systems researched at the ASTC. First, the cold/hot gas micropropulsion system is suitable for small spacecraft or when the demands on stability and pointing precision are extreme. The system performance depends strongly on the use of gas flow control. The complete gas handling system of four independent thrusters is integrated in the assembly of four structured silicon wafers. Each independent thruster contains a proportional valve, sensors for pressure, temperature, and thrust feedback, a converging-diverging micronozzle, and a suspended microcoil heater. The mass of the system is below 60 g. In total, this will provide the spacecraft with a safe, clean, low-powered, redundant, and flexible system for three-axis stabilization and attitude control. Second, a Xenon feed system for ion propulsion is heavily miniaturized using microsystems technology. Basically, a micromachined high-pressure regulator receives the gas from the storage, and the flow is further modulated by a thermally controlled flow restrictor. The flow restrictor microsystem comprises narrow ducts, thin film heaters, suspended parts for heat management, and flow sensors. Hereby, the amount of xenon required by the electric propulsion systems can be promptly delivered. The complete system mass is estimated to 150g. Third, within the EU IST program, the ASTC participates in the development of a micro-pyrotechnic actuator system (Micropyros), suitable for short-duration space propulsion. The Micropyros integrate a full matrix of minute solid combustion rocket engines into panels situated on the spacecraft hull. The thrusters can be individually ignited, and each deliver thrust in the millinewton range. The ASTC focuses on the integration of the propulsion part by low-temperature bonding, and the characterization of the complete system.
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| 4. |
- Nguyen, Hugo, et al.
(författare)
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The merits of cold gas micropropulsion in state-of-the-art space missions
- 2002
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Konferensbidrag (refereegranskat)abstract
- Cold gas micropropulsion is a sound choice for space missions that require extreme stabilisation, pointing precision or contamination-free operation. The use of forces in the micronewton range for spacecraft operations has been identified as a mission-critical item in several demanding space systems currently under development. Cold gas micropropulsion systems share merits with traditional cold gas systems in being simple in design, clean, safe, and robust. They do not generate net charge to the spacecraft, and typically operate on low-power. The minute size is suitable not only for inclusion on high-performance nanosatellites but also for high-demanding future space missions of larger sizes. By using differently sized nozzles in parallel systems the dynamic range of a cold gas micropropulsion system can be quite wide (e.g. 0 – 10 mN), while the smallest nozzle pair can deliver thrust of zero to 0.5 or 1 mN using continuously proportional gas flow control systems. The leakage is turned into an advantage enabling the system for continuous drag compensation. In this manner, the propellant mass efficiency can be many times as higher than that in a conventional cold gas propulsion system using ON-OFF-control. The analysis in this work shows that cold gas micropropulsion has emerged as a high-performance propulsion principle for future state-of-the-art space missions. These systems enable spacecraft with extreme demands on stability, cleanliness and precision, without compromising the performance or scientific return of the mission.
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