PNNL-13501 - Pacific Northwest National Laboratory

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To illustrate the potential impact of detailed, threedimensional tumor response modeling, we used our modeling tools to examine ways that the temporal and spatial delivery of radiation to a tumor can be modulated to improve treatment outcome (Stewart and Traub in press). Figure 1 shows an illustration of a idealized cylindrical tumor that has been subdivided into 3,133 rectangular tissue regions. Figure 2 shows the results of two simulated radiation treatments. The first treatment design (Figure 2, left panel) shows tumor-cell survival after a conventional radiation treatment that delivers a uniform dose of radiation to all parts of the tumor. The right panel in Figure 2 shows the expected outcome of a radiation treatment that has been optimized to preferentially kill the radioresistant tumor cells located in region 4 (refer to Figure 1). Calculations (Stewart and Traub in press) suggest that biologically motivated treatment optimization could potentially improve some treatment designs by factors on the order of 5 to 20% (isoeffect dose). 1 4 3 2 Figure 1. Cylindrical tumor model with heterogeneous biophysical properties (Stewart and Traub in press). The properties of the tumor cells in the four tumor regions give the same apparent “intrinsic radiosensitivity,” as determined by a single acute dose of radiation. However, the cell density and damage repair characteristics used in the model are slightly different. For visualization purposes, the tumor is shown with a section cutout. Tissue region 4 is a particularly radioresistant portion of the tumor. Summary and Conclusions We have successfully demonstrated that detailed molecular and cellular dose-response models can be integrated into three-dimensional tissue simulations. Although calculations to date have focused on high-dose exposure conditions such as those found in radiation therapy, the basic framework of our model is equally applicable to low-dose exposure conditions. In fiscal year 2000, we plan to conduct several experiments to collect the data needed to further refine and test the damage repair model so that it is more useful for low-dose exposure studies and also for combined exposure to radiation and benzene, an organic solvent commonly found at many DOE sites. References Deschavanne PJ, B Fertil, N Chavaudra, and EP Malaise. 1990. The relationship between radiosensitivity and repair of potentially lethal damage in human tumor cell lines with implications for radioresponsiveness.” Radiat. Res. 122(1): 29-37. Stewart RD, and RJ Traub. “Radiobiological Modeling in Voxel Constructs.” In Proceedings of the MC2000. An International Conference on Advanced Monte Carlo for Radiation Physics, Particle Transport Simulation and Applications. October 23-26, 2000 Lisbon, Portugal (in press). Publications and Presentations Marler RT and RD Stewart. “A Quasi-Newton code package to find the minimum value of a function.” software package completed and benchmarked. User manual in progress. Marler RT and RD Stewart. “GACM: A genetic algorithm code model to locate the global minimum of a multidimensional function.” Initial version of software completed. Code testing and user manual in progress. Stewart RD. 1999. “On the complexity of the DNA damages created by endogenous processes.” Radiat. Res. 152(1), 101-105. Stewart RD, JK Shultis, and BA Montelone. 2000. A kinetic biological effects model for quiescent cells. PNNL-13258, Pacific Northwest National Laboratory, Richland, Washington. Stewart RD and RJ Traub R.J. “Temporal optimization of radiotherapy treatment fractions.” In Proceedings of the ANS (RPS 2000). Radiation Protection for our National Priorities, Medicine, the Environment, and the Legacy, Spokane, Washington, September 17-21, 2000 (in press). Human Health and Safety 295
Figure 2. KBEM simulation of a 55 Gy radiation treatment delivered in 30 daily dose fractions (Stewart and Traub in press). Eight collimator beam configurations are used to deliver the dose fractions. Darker shades indicate regions where one or more tumor cells are likely to survive the treatment and lighter shades indicate tumor regions where no tumor cells are likely to survive. The cylindrical tumor, composed of about 10 11 tumor cells, is subdivided into 3,133 voxels. Survival calculations are based on in vitro intrinsic radiosensitivity data for colon adenocarcinoma cells (Deschavanne et al. 1990). Left panel: uniform dose delivered to entire tumor. Right panel: the intensity and timing of the collimator beams have been optimized to preferentially eradicate the radioresistant tumor cells located in tissue region 4 (refer to Figure 1). Stewart RD and RJ Traub. “Radiobiological modeling in voxel constructs.” In Proceedings of the MC2000. An International Conference on Advanced Monte Carlo for Radiation Physics, Particle Transport Simulation and Applications. October 23-26, 2000 Lisbon, Portugal (in press). Stewart RD. “Testing the LPL model.” Radiat. Res. (submitted). Stewart RD. November 2000. “Radiobiological modeling in voxel constructs.” Abstract accepted for presentation. International Workshop on Monte Carlo Treatment Planning, Stanford, California. Stewart RD and RJ Traub. October 2000. “Radiobiological modeling in voxel constructs.” Abstract accepted for presentation at MC2000. An International Conference on Advanced Monte Carlo for Radiation Physics, Particle Transport Simulation and Applications. Lisbon, Portugal. 296 FY 2000 Laboratory Directed Research and Development Annual Report Stewart RD and RJ Traub. September 2000. “Temporal optimization of radiotherapy treatment fractions.” Abstract accepted for presentation. ANS Topical RPS 2000. Radiation Protection for our National Priorities, Medicine, the Environment, and the Legacy, Spokane, Washington. Stewart RD. May 2000. “Temporal optimization of radiotherapy treatment fractions.” Invited talk. Lovelace Respiratory Research Institute, Albuquerque, NM. Stewart RD. August 1999. “From dosimetry to biological effect—Implications for radiation therapy.” Third International Workshop on Electron and Photon Transport Theory Applied to Radiation Dose Calculation, Indianapolis, Indiana.
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Laboratory Directed Research and De
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Laboratory Directed Research and De
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Computational Science and Engineeri
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Policy and Management Sciences Asse
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Introduction Department of Energy O
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5. After reviews by the Technical a
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• The Technical Council peer revi
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methods applicable to combustion, s
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Summary Each national laboratory mu
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Study Control Number: PN0004/1411 A
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Table 1. Positive and negative ions
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m/z Arbitrary Units Figure 1. Mass
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introduce low-volatility compounds
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arrangement, but the charge is reta
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two liquid chromatographic gradient
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Integrated Microfabricated Devices
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Matrix Assisted Laser Desorption/Io
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Molecular Beam Synthesis and Charac
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temperature distribution of the des
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expected to result in significant a
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Study Control Number: PN99069/1397
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Seuss DT and KA Prather. 1999. “M
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Analysis of Receptor-Modulated Ion
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laboratory (Lu and Xie 1997; Lu et
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Automated DNA Fingerprinting Microa
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Comparison of 4 Xanthomonas Isolate
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Approach Hematopoietic (bone marrow
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Anti-Human lgG Human lgG Protein G
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Characterization of Global Gene Reg
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PCR products for immobilization on
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identify novel proteins of importan
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Immunoprecipitaton of tyrosinephosp
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Coupled NMR and Confocal Microscopy
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In the optical microscopy image, th
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Development and Applications of a M
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Figure 3. Hepa-1 cells undergoing a
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cellular processing (such as post-t
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8. Initial demonstration of an off-
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expression systems for several year
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accumulation of protein products, i
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Fungal Conversion of Agricultural W
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Fungal Conversion of Waste Glucose/
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Summary and Conclusions We demonstr
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are shown in Figure 1(a) and 1(b),
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Anchorage-Independent Growth (% con
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selection of seedlings demonstratin
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NMR-Based Structural Genomics Micha
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Solution-State Structure and Fold-C
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Plant Root Exudates and Microbial G
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Summary and Conclusions • The gre
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Jones-Oliveira JB, JS Oliveira, HE
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• securely moves files to a targe
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Plenary invited lecture, “The Ele
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Figure 1. X3DGEN tetrahedral mesh o
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Figure 5a. OSO volume rendering of
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Development of Models of Cell-Signa
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SOS p 23 EGFR Professor Rodland at
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Oliveira JS, JB Jones-Oliveira, and
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Figure 2. Associating a dataset mar
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to 1) incorporate three-dimensional
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shown in Figure 1. Simulated result
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HostBuilder: A Tool for the Combina
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Invariant Discretization Methods fo
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Graphics, Inc., workstation. The co
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Mixed Hamiltonian Methods for Geoch
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guyanaite, and grimaldiite (see Fig
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in the Environmental Molecular Scie
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Simulation and Modeling of Electroc
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Summary and Conclusions We implemen
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Since the implementation of the gen
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asis of previous performance, perce
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Bioinformatics for High-Throughput
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Summary and Conclusions In previous
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User Cat - Supervisor (client) Anal
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The second goal was to research way
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Figure 1. A visualization technique
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and interactions. The flexibility o
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Figure 4. A filtered version of Fig
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Development of Modeling Tools for J
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Figure 2. Schematic of experimental
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Integrated Modeling and Simulation
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(a) (b) (c) (d) Figure 1. Results o
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Thurman DA. August 2000. Collaborat
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MARC Input initial m esh and result
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(Johnson 1999; Colligan 1999; Gould
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Modeling of High-Velocity Forming f
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Global divergence error 1 10 -14 0
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that users were unlikely to appreci
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Earth System Science
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the lateral extent of the plume so
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Biogeochemical Processes and Microb
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Analyses of populations of viable a
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The first task was to establish fiv
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purged for 2 minutes. The gas sampl
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developing code architecture to min
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Berkowitz, CM. June 2000. “Atmosp
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environmental monitoring, 2) portab
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corresponded to a current density o
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Enhancing Emissions Pre-Processing
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Environmental Fate and Effects of D
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nitrogen and unpredictable eutrophi
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Figure 1. Ordinary kriging of 2 m d
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precipitation of calcite occurred i
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Interrelationships Between Processe
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phenanthrene resistant fraction con
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injection of an immiscible gas phas
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still some key kinetic issues that
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Application of a Crop Model The res
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Page 260 and 261: allowable parameters using thermody
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Intensity (a.u.) 0 100 200 300 400
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integrated voltage (V) 0.10 0.08 0.
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The first step was to implement thi
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Spontaneous Formation of Cu2O Nano-
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Actinide Chemistry at the Aqueous-M
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Figure 5. Close-up atomic force mic
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to 300°C and 400°C. Unfortunately
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Summary and Conclusions Transmutati
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Advanced Calibration/Registration T
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Figure 1a. Violet filter Figure 1b.
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Autonomous Ultrasonic Probe for Pro
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containing nitrous oxide, an optica
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Chemical Detection Using Cavity Enh
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Figure 3 is a color rendered simula
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appropriate study has been performe
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Exploitation of Conventional Chemic
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Figures 3 and 4 illustrate the impa
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enefits of using a modified spread-
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Single Channel Signal 0.0025 0.0020
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Therefore, in order to extract the
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A next-generation technology is nee
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Wind Dir. Figure 2. Negative ion co
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Volumetric Imaging of Materials by
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amplitude and peak frequency change
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Figure 3. 13 C NMR spectrum of corn
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Approach Two flow loops, one that o
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Modification of Ion Exchange Resins
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Permanganate Treatment for the Deco
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minimized by medium exchange. After
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Figure 1. Thermogravimetric analysi
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Validation and Scale-Up of Monosacc
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Concentration (g/100g solution) Con
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Analysis of High-Volume, Hyper-Dime
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ecent figure of merit values. Shoul
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Probabilistic Methods Development f
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a) Traditional PCA-based process co
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Acronyms and Abbreviations 2-D two-
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