The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Rainer Fischer - One of the best experts on this subject based on the ideXlab platform.
-
predictive models for transient protein expression in tobacco nicotiana tabacum l can optimize Process Time yield and downstream costs
Biotechnology and Bioengineering, 2012Co-Authors: J F Buyel, Rainer FischerAbstract:The transient expression of recombinant biopharmaceutical proteins in plants can suffer inter-batch variation, which is considered a major drawback under the strict regulatory demands imposed by current good manufacturing practice (cGMP). However, we have achieved transient expression of the monoclonal antibody 2G12 and the fluorescent marker protein DsRed in tobacco leaves with ∼15% intra-batch coefficients of variation, which is within the range reported for transgenic plants. We developed models for the transient expression of both proteins that predicted quantitative expression levels based on five parameters: The OD600nm of Agrobacterium tumefaciens (from 0.13 to 2.00), post-inoculation incubation temperature (15–30°C), plant age (harvest at 40 or 47 days after seeding), leaf age, and position within the leaf. The expression models were combined with a model of plant biomass distribution and extraction, generating a yield model for each target protein that could predict the amount of protein in specific leaf parts, individual leaves, groups of leaves, and whole plants. When the yield model was combined with a cost function for the production Process, we were able to perform calculations to optimize Process Time, yield, or downstream costs. We illustrate this procedure by transferring the cost function from a production Process using transgenic plants to a hypothetical Process for the transient expression of 2G12. Our models allow the economic evaluation of new plant-based production Processes and provide greater insight into the parameters that affect transient protein expression in plants. Biotechnol. Bioeng. 2012; 109: 2575–2588. © 2012 Wiley Periodicals, Inc.
Michael Gillin - One of the best experts on this subject based on the ideXlab platform.
-
quantitative analysis of treatment Process Time and throughput capacity for spot scanning proton therapy
Medical Physics, 2016Co-Authors: Kazumichi Suzuki, Matthew B. Palmer, Narayan Sahoo, Xiaodong Zhang, Falk Poenisch, Dennis Mackin, Steven J. Frank, Amy Y Liu, Ronald X Zhu, Michael GillinAbstract:Purpose: To determine the patient throughput and the overall efficiency of the spot scanning system by analyzing treatment Time, equipment availability, and maximum daily capacity for the current spot scanning port at Proton Therapy Center Houston and to assess the daily throughput capacity for a hypothetical spot scanning proton therapy center. Methods: At their proton therapy center, the authors have been recording in an electronic medical record system all treatment data, including disease site, number of fields, number of fractions, delivered dose, energy, range, number of spots, and number of layers for every treatment field. The authors analyzed delivery system downTimes that had been recorded for every equipment failure and associated incidents. These data were used to evaluate the patient census, patient distribution as a function of the number of fields and total target volume, and equipment clinical availability. The duration of each treatment session from patient walk-in to patient walk-out of the spot scanning treatment room was measured for 64 patients with head and neck, central nervous system, thoracic, and genitourinary cancers. The authors retrieved data for total target volume and the numbers of layers and spots for all fields from treatment plans for a total of 271 patients (including the above 64 patients). A sensitivity analysis of daily throughput capacity was performed by varying seven parameters in a throughput capacity model. Results: The mean monthly equipment clinical availability for the spot scanning port in April 2012–March 2015 was 98.5%. Approximately 1500 patients had received spot scanning proton therapy as of March 2015. The major disease sites treated in September 2012–August 2014 were the genitourinary system (34%), head and neck (30%), central nervous system (21%), and thorax (14%), with other sites accounting for the remaining 1%. Spot scanning beam delivery Time increased with total target volume and accounted for approximately 30%–40% of total treatment Time for the total target volumes exceeding 200 cm3, which was the case for more than 80% of the patients in this study. When total treatment Time was modeled as a function of the number of fields and total target volume, the model overestimated total treatment Time by 12% on average, with a standard deviation of 32%. A sensitivity analysis of throughput capacity for a hypothetical four-room spot scanning proton therapy center identified several priority items for improvements in throughput capacity, including operation Time, beam delivery Time, and patient immobilization and setup Time. Conclusions: The spot scanning port at our proton therapy center has operated at a high performance level and has been used to treat a large number of complex cases. Further improvements in efficiency may be feasible in the areas of facility operation, beam delivery, patient immobilization and setup, and optimization of treatment scheduling.
J.e. Rooda - One of the best experts on this subject based on the ideXlab platform.
-
generating cycle Time throughput curves using effective Process Time based aggregate modeling
IEEE Transactions on Semiconductor Manufacturing, 2010Co-Authors: C P L Veeger, L. F.pascal Etman, J Van Herk, J.e. RoodaAbstract:In semiconductor manufacturing, cycle Time-throughput (CT-TH) curves are often used for planning purposes. To generate CT-TH curves, detailed simulation models or analytical queueing approximations may be used. Detailed models require much development Time and computational effort. On the contrary, analytical models, such as the popular closed-form queueing expression, may not be sufficiently accurate, in particular, for integrated Processing equipment that have wafers of more than one lot in Process. Recently, an aggregate simulation model representation of workstations with integrated Processing equipment has been proposed. This aggregate model is a type of system with a workload-dependent Process Time distribution, which is obtained from lot arrival and departure events. This paper presents a first proof of concept of the method in semiconductor practice. We develop the required extensions to generate CT-TH curves for workstations in a semiconductor manufacturing environment where usually only a limited amount of arrival and departure data is available. We present a simulation and an industry case to illustrate the proposed method.
-
generating cycle Time throughput curves using effective Process Time based aggregate modeling
Advanced Semiconductor Manufacturing Conference, 2008Co-Authors: C P L Veeger, L. F.pascal Etman, J Van Herk, J.e. RoodaAbstract:In semiconductor manufacturing, cycle Time-throughput (CT-TH) curves are often used to make a trade-off between throughput and mean cycle Time of bottleneck workstations. To generate CT-TH curves, detailed simulation models, and analytical queueing approximations are typically used. However, detailed models require much development Time and are computationally expensive. Analytical models based on for instance a closed-form G/G/m queueing expression may not generate accurate curves for semiconductor equipment, in particular for equipment that have wafers of multiple lots in Process at the same Time. In this paper we show that a recently developed aggregate modeling approach based on the effective Process Time is able to generate more accurate CT-TH curves for equipment with multiple Process steps.
-
performance measurement and lumped parameter modelling of single server flowlines subject to blocking an effective Process Time approach
SE report, 2006Co-Authors: A A A Kock, L. F.pascal Etman, F J J Wullems, F Nijsse, I J B F Adan, J.e. RoodaAbstract:The present paper extends the so-called Effective Process Time (EPT) approach to single server flowlines with finite buffers and blocking. The power of the EPT approach is that it quantifies variability in workstation Process Times without the need to identify each of the contributing disturbances, and that it directly provides an algorithm for the actual computation of EPTs. It is shown that EPT realizations can be simply obtained from arrival and departure Times of lots, by using sample path equations. The measured EPTs can be used for bottleneck analysis and for lumped parameter modeling. Simulation experiments show that for lumped parameter modeling of flowlines with finite buffers, in addition to the mean and variance, offset is also a relevant parameter of the Process Time distribution. A case from the automotive industry illustrates the approach.
-
effective Process Times for multi server flowlines with finite buffers
SE report, 2006Co-Authors: A A A Kock, L. F.pascal Etman, J.e. RoodaAbstract:An effective Process Time (EPT) approach is proposed for aggregate model building of multi-server tandem queues with finite buffers. Effective Process Time distributions of the workstations in the flow line are measured without identifying the contributing factors. A sample path equation is used to compute the EPT realizations from arrival and departure events of lots at the respective workstations. If the amount of blocking in the line is high, the goodness of the EPT distribution fits determines the accuracy of the EPT-based aggregate model. Otherwise, an aggregate model based on just the first two moments of the EPT distributions is sufficient to obtain accurate predictions. The approach is illustrated in an industrial case study using both simulation and analytical queueing approximations as aggregate models.
-
Quantifying operational Time variability: the missing parameter for cycle Time reduction
Advanced Semiconductor Manufacturing Conference 2001 IEEE SEMI, 2001Co-Authors: J. H. Jacobs, J.e. Rooda, L. F.pascal Etman, E. J.j. Van CampenAbstract:Operational Time variability is one of the key parameters determining the average cycle Time of lots. Many different sources of variability can be identified such as equipment breakdowns, set-up, and operator availability. However, an appropriate measure to quantify variability is missing. Measures such as the overall equipment efficiency (OEE) in the semiconductor industry are entirely based on mean value analysis and do not include variances. The main contribution of this paper is the development of a new algorithm that enables estimation of the mean effective Process Time te and the coefficient of variation ce2 of a multiple machine equipment family from real fab data. The algorithm formalizes the effective Process Time definitions as given by Hopp and Spearman (2000), and Sattler (1996). The algorithm quantifies the claims of machine capacity by lots, which includes Time losses due to down Time, set-up Time, or other irregularities. The estimated te and ce 2 values can be interpreted in accordance with the well-known G/G/m queueing relations. A test example as well as an elaborate case from the semiconductor industry show the potential of the new effective Process Time (EPT) algorithm for cycle Time reduction programs
Peter Czermak - One of the best experts on this subject based on the ideXlab platform.
-
minimizing the Process Time for ultrafiltration diafiltration under gel polarization conditions
Journal of Membrane Science, 2011Co-Authors: Radoslav Paulen, Miroslav Fikar, Greg Foley, Peter Czermak, Zoltan KovacsAbstract:Abstract This study examines a generalized ultrafiltration/diafiltration Process that is designed to reduce the initial volume of a given Process liqueur and to eliminate impurities from the product solution. This theoretical investigation focuses on applications where the permeate flux is given by the gel polarization model. The goal of this paper is to use optimal control theory to determine optimal Time-varying diluant addition that minimizes treatment Time. We propose a diafiltration model in a dimensionless form with normalized model equations in order to determine general features of optimal diluant utilization strategy. Based on the model, we formulate the optimal control problem and apply the theory of optimal control exploiting the Pontryagin’s minimum principle. We confirm the analytical results by numerical computations using numerical methods of dynamic optimization. We prove that optimal control strategy is to perform a constant-volume diafiltration step at optimal macro-solute concentration that guarantees maximal removal of micro-solute at any Time instant. This constant-volume diafiltration step is preceded and followed by optional ultrafiltration or pure dilution steps that force the concentrations at first to arrive to the optimal macro-solute concentration and at last to arrive to the desired final concentrations. Finally, we provide practical optimization diagrams that allow decision makers to determine the optimal diluant control of a given separation task.
-
Process optimization of diafiltration with Time dependent water adding for albumin production
Chemical Engineering and Processing, 2011Co-Authors: Radoslav Paulen, Miroslav Fikar, Peter Czermak, Zoltan KovacsAbstract:Abstract In this paper we investigate optimal Time-dependent diluant adding in a diafiltration Process that is designed to purify and to concentrate human albumin. Previous attempts considered arbitrarily constructed schemes, which may be, but need not to be, optimal. Employing methods of dynamic optimization we address two problems of optimal Process operation: (1) the minimization of Process Time, and (2) the minimization of applied diluant volume. Control vector parameterization approach is applied considering different parameterized forms of the control function such as constant, linear, and N × piece-wise constant schemes. We found that traditionally used Process operation, involving a pre-concentration and a constant-volume dilution mode step, is optimal in case of minimization of overall diluant consumption. Optimal control differs from the traditionally used operation types in case of Process Time minimization but the overall improvement is rather small for this specific application.
Hiroyuki Kokawa - One of the best experts on this subject based on the ideXlab platform.
-
effects of Process Time and thread on tensile shear strength of al alloy lap joint produced by friction stir spot welding
Welding International, 2010Co-Authors: Mitsuo Fujimoto, Daisuke Watanabe, Natsumi Abe, Sato S Yutaka, Hiroyuki KokawaAbstract:In automotive applications, friction stir spot welding (FSSW) has been practically used in the construction of aluminium car bodies. In this study, the weld strength and factors governing the weld strength in the friction stir spot welded aluminium alloy 6061-T6 were examined. The weld strength increased with the Process Time during FSSW up to 3 s, beyond which it decreased. The fracture path changed from the lapped interface into the shoulder edge as the Process Time increased, and the maximum strength was obtained at the Process Time when the transition of the fracture path occurred. The cross-sectional microstructure depended on the threads on the probe surface, i.e. the elliptical zone was formed in the stir zone by the threads, but an effect of the thread on the weld strength was hardly found. The present study suggests that the weld strength was strongly related to the size of the well-consolidated region, which was larger than the elliptical zone observed in the vicinity of the exit hole.
-
effects of Process Time and thread on tensile shear strength of al alloy lap joint produced by friction stir spot welding
Quarterly Journal of The Japan Welding Society, 2008Co-Authors: Mitsuo Fujimoto, Daisuke Watanabe, Natsumi Abe, Yutaka S Sato, Hiroyuki KokawaAbstract:Friction Stir Spot Welding (FSSW) has been practically used to the construction of aluminum car-body in the automotive application. In this study, the weld strength and factors governing the weld strength in friction stir spot welded aluminum alloy 6061-T6 was examined. The weld strength increased with the Process Time during FSSW up to 3 s, beyond which it decreased. The fracture path changed from the lapped interface into the shoulder edge as the Process Time increased, and the maximum strength was obtained at the Process Time when the transition of the fracture path occurred. The cross-sectional microstructure depended on the threads on the probe surface, i.e. the elliptical zone was formed in the stir zone by the threads, but effect of the thread on the weld strength was hardly found. The present study suggests that the weld strength was strongly related with size of the well-consolidated region which was larger than the elliptical zone observed in the vicinity of the exit hole.
