Imperial College London

ProfessorStratosPistikopoulos

Faculty of EngineeringDepartment of Chemical Engineering

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 7594 6620e.pistikopoulos

 
 
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Location

 

C508Roderic Hill BuildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

461 results found

Fuentes Gari M, Misener R, Pefani E, Garcia Munzer D, Kostoglou M, Georgiadis MC, Panoskaltsis N, Pistikopoulos EN, Mantalaris Aet al., 2015, Cell cycle model selection for leukemia and its impact in chemotherapy outcomes, Computer Aided Chemical Engineering, Vol: 37, Pages: 2159-2164, ISSN: 1570-7946

The cell cycle is the biological process used by cells to replicate their genetic material and give birth to new cells that are in turn eligible to proliferate. It is highly regulated by the timed expression of proteins which trigger cell cycle events such as the start of DNA replication or the commencement of mitosis (when the cell physically divides into two daughter cells). Mathematical models of the cell cycle have been widely developed both at the intracellular (protein kinetics) and macroscopic (cell duplication) levels. Due to the cell cycle specificity of most chemotherapeutic drugs, these models are increasingly being used for the study and simulation of cellular kinetics in the area of cancer treatment.In this work, we present a population balance model (PBM) of the cell cycle in leukemia that uses intracellular protein expression as state variable to represent phase progress. Global sensitivity analysis highlighted cell cycle phase durations as the most significant parameters; experiments were performed to extract them and the model was validated. Our model was then tested against other differential cell cycle models (ODEs, delay differential equations (DDEs)) in their ability to fit experimental data and oscillatory behavior. We subsequently coupled each of them with a pharmacokinetic / pharmacodynamic model of chemotherapy delivery that was previously developed by our group. Our results suggest that the particular cell cycle model chosen highly affects the outcome of the simulated treatment, given the same steady-state kinetic parameters and drug dosage/scheduling, with our PBM appearing to be the most sensitive under the same dose.

Journal article

Savvopoulos SV, Misener R, Panoskaltsis N, Pistikopoulos EN, Mantalaris Aet al., 2015, Global Sensitivity Analysis for a Dynamic Model of Chronic Lymphocytic Leukemia Disease Trajectories, Computer Aided Chemical Engineering, ISSN: 1570-7946

This paper implements global sensitivity analysis in the Savvopoulos et al. (2014) mathematical model of B cell chronic lymphocytic leukaemia (B-CLL); this dynamic model represents a frame- work for modelling dynamic B-CLL trajectories. B-CLL is a heterogeneous, slowly-progressing disease where a type of white blood cell, B lymphocytes, accumulates in bone marrow, peripheral blood, lymph nodes and spleen. The Savvopoulos et al. (2014) modelling framework integrates both temporal and spatial disease aspects; delay differential equations capture latency in the cell proliferation cycle and population balance equations between disease centres represent inter-tissue B-CLL migration. This manuscript conducts global sensitivity analysis using the random sampling - high dimensional mathematical representation (RS-HDMR) method to: (1) uncover which are the most critical model parameters; (2) analyse the system of model equations; (3) provide clinically-relevant patient testing recommendations leading to effective model parametrisations.

Journal article

Kiparissides A, Pistikopoulos EN, Mantalaris A, 2015, On the Model-Based Optimization of Secreting Mammalian Cell (GS-NS0) Cultures, BIOTECHNOLOGY AND BIOENGINEERING, Vol: 112, Pages: 536-548, ISSN: 0006-3592

Journal article

Nascu I, Krieger A, Ionescu CM, Pistikopoulos ENet al., 2015, Advanced Model-Based Control Studies for the Induction and Maintenance of Intravenous Anaesthesia, IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, Vol: 62, Pages: 832-841, ISSN: 0018-9294

Journal article

García Münzer DG, Ivarsson M, Usaku C, Habicher T, Soos M, Morbidelli M, Pistikopoulos EN, Mantalaris Aet al., 2015, An unstructured model of metabolic and temperature dependent cell cycle arrest in hybridoma batch and fed-batch cultures, Biochemical Engineering Journal, Vol: 93, Pages: 260-273, ISSN: 1369-703X

Abstract Cell productivity in fed-batch processes can be increased by cell cycle arrest through mild hypothermia. However, hypothermia can simultaneously reduce cell growth, which is regulated by the cell cycle. Consequently, the time point for the temperature shift is important and requires optimization while considering the cell cycle. An unstructured cell cycle model which includes the distribution of proliferating (G1, S, G2/M) and arrested cells (G0) has been proposed in order to predict the time point of temperature shift in fed-batch cultures. A model development and analysis framework that enables the evaluation of the required model parameters is described. The parameters are estimated from (fed)-batch cultivations, carried out at 37 °C and at 33 °C in order to characterize temperature dependency. The batch cultures are also used to evaluate substrate depletion and fed-batch cultures are used to study the impact of metabolite accumulation on the cell cycle. The reliability of the proposed framework for parameter estimation is validated using a mAb-producing hybridoma cell culture and the model predicts hypothermic transitions within the cell population at different shift time points. In conclusion, this framework can be used to optimize the time point of the temperature shift, which is commonly adjusted in industrial fed-batch processes in order to obtain a good balance between temperature induced growth limitation and cell cycle specific enhanced productivity.

Journal article

Rivotti P, Pistikopoulos EN, 2015, A dynamic programming based approach for explicit model predictive control of hybrid systems, COMPUTERS & CHEMICAL ENGINEERING, Vol: 72, Pages: 126-144, ISSN: 0098-1354

Journal article

Floudas CA, Pistikopoulos EN, 2015, Professor Ignacio E. Grossmann-Tribute, COMPUTERS & CHEMICAL ENGINEERING, Vol: 72, Pages: 1-2, ISSN: 0098-1354

Journal article

Krieger A, Pistikopoulos EN, 2014, Model predictive control of anesthesia under uncertainty, COMPUTERS & CHEMICAL ENGINEERING, Vol: 71, Pages: 699-707, ISSN: 0098-1354

Journal article

Rivotti P, Pistikopoulos EN, 2014, Constrained dynamic programming of mixed-integer linear problems by multi-parametric programming, COMPUTERS & CHEMICAL ENGINEERING, Vol: 70, Pages: 172-179, ISSN: 0098-1354

Journal article

Misener R, Fuentes Gari M, Rende M, Velliou E, Panoskaltsis N, Pistikopoulos EN, Mantalaris Aet al., 2014, Global Superstructure Optimisation of Red Blood Cell Production in a Parallelised Hollow Fibre Bioreactor, Computers & Chemical Engineering, ISSN: 0098-1354

Recent work developed a novel, biomimetic, cost-effective three-dimensional hollow fibre bioreactor for growing healthy red blood cells ex vivo (Panoskaltsis et al., 2012). This bioreactor recapitulates architectural and functional properties of erythrocyte formation and thereby reduces the need for expensive growth factors by more than an order of magnitude. Individual experiments to empirically improve the bioreactor are intensive, so we propose global superstructure optimisation for bioreactor design. Our approach integrates topological design choices with operating conditions. Design choices include: number of parallelised bioreactors; number and type of hollow fibres; size and aspect ratio. Operating conditions are: feed concentrations; flowrate through the reactor. This manuscript quantitatively demonstrates, for the first time, the potential for ex vivo red blood cell production to compete openly against the transfusion market for rare blood. We discuss the potential of superstructure design not only on this individual bioreactor but also more generally on bioprocess optimisation.

Journal article

Chang H, Krieger A, Astolfi A, Pistikopoulos ENet al., 2014, Robust multi-parametric model predictive control for LPV systems with application to anaesthesia, JOURNAL OF PROCESS CONTROL, Vol: 24, Pages: 1538-1547, ISSN: 0959-1524

Journal article

Velliou E, Fuentes-Gari M, Misener R, Pefani E, Rende M, Panoskaltsis N, Mantalaris A, Pistikopoulos E Net al., 2014, A framework for the design, modeling and optimization of biomedical systems

We present an overview of the key building blocks of a design framework for modeling and optimization of biomedical systems with main focus on leukemia, that we have been developing in the Biological Systems Engineering Laboratory and the Centre for Process Systems Engineering at Imperial College. The framework features the following areas: (i) a three-dimensional, biomimetic, in vitro platform for culturing both healthy and diseased blood; (ii) a novel, hollow fiber bioreactor that upgrades this in vitro platform to enable expansion and continuous harvesting of healthy and diseased blood; (iii) a global optimization-based approach for the design and operation of the aforementioned bioreactor; (iv) a pharmacokinetic / pharmacodynamic model representing patient response to Acute Myeloid Leukemia treatment; (v) an experimental framework for cell cycle modeling and quantitative analysis of environmental stress. This manuscript recapitulates the progress made in the different areas as well as the way in which these areas are connected, finally leading to a hybrid in vitro/in silico platform which allows the optimization of the ex vivo expansion of healthy and diseased blood.

Journal article

Pefani E, Panoskaltsis N, Mantalaris A, Georgiadis MC, Pistikopoulos ENet al., 2014, Chemotherapy Drug Scheduling for the Induction Treatment of Patients With Acute Myeloid Leukemia, IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, Vol: 61, Pages: 2049-2056, ISSN: 0018-9294

Journal article

Marzinek JK, Bond PJ, Lian G, Zhao Y, Han L, Noro MG, Pistikopoulos EN, Mantalaris Aet al., 2014, Free Energy Predictions of Ligand Binding to an α-Helix Using Steered Molecular Dynamics and Umbrella Sampling Simulations, JOURNAL OF CHEMICAL INFORMATION AND MODELING, Vol: 54, Pages: 2093-2104, ISSN: 1549-9596

Journal article

Diangelakis NA, Panos C, Pistikopoulos EN, 2014, Design optimization of an internal combustion engine powered CHP system for residential scale application, Computational Management Science, Vol: 11, Pages: 237-266, ISSN: 1619-697X

We present an analytical dynamic mathematical model and a design optimization of a residential scale combined heat and power system. The mathematical model features a detailed description of the internal combustion engine based on a mean value approach, and simplified sub-models for the throttle valve, the intake and exhaust manifolds, and the external circuit. The validated zero-dimensional dynamic mathematical model of the system is implemented in gPROMS®, and used for simulation and optimization studies. The objective of the design optimization is to estimate the optimum displacement volume of the internal combustion engine that minimizes the operational costs while satisfying the electrical and heating demand of a residential 10-house district. The simulation results show that the mathematical model can accurately predict the behavior of the actual system while the design optimization will later be the basis for advanced control studies. © 2014 Springer-Verlag Berlin Heidelberg.

Journal article

Diangelakis NA, Panos C, Pistikopoulos EN, 2014, Design optimization of an internal combustion engine powered CHP system for residential scale application, Computational Management Science, ISSN: 1619-697X

We present an analytical dynamic mathematical model and a design optimization of a residential scale combined heat and power system. The mathematical model features a detailed description of the internal combustion engine based on a mean value approach, and simplified sub-models for the throttle valve, the intake and exhaust manifolds, and the external circuit. The validated zero-dimensional dynamic mathematical model of the system is implemented in gPROMS(Formula presented.), and used for simulation and optimization studies. The objective of the design optimization is to estimate the optimum displacement volume of the internal combustion engine that minimizes the operational costs while satisfying the electrical and heating demand of a residential 10-house district. The simulation results show that the mathematical model can accurately predict the behavior of the actual system while the design optimization will later be the basis for advanced control studies. © 2014 Springer-Verlag Berlin Heidelberg.

Journal article

Fuentes-Gari M, Misener R, Garcia-Munzer D, Velliou E, Georgiadis M, Kostoglou M, Panoskaltsis N, Pistikopoulos S, Mantalaris Set al., 2014, Development and experimental validation of a cyclin-based population balance model of the cell cycle in leukemia cell lines, JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Vol: 8, Pages: 489-489, ISSN: 1932-6254

Journal article

Misener R, Allenby M, Gari MF, Rende M, Velliou E, Panoskaltsis N, Pistikopoulos S, Mantalaris Aet al., 2014, Optimisation under uncertainty for a bioreactor that produces red blood cells

Poster

Kiparissides A, Georgakis C, Mantalaris A, Pistikopoulos ENet al., 2014, Design of In Silico Experiments as a Tool for Nonlinear Sensitivity Analysis of Knowledge-Driven Models, INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH, Vol: 53, Pages: 7517-7525, ISSN: 0888-5885

Journal article

Zhao Y, Marzinek JK, Bond PJ, Chen L, Li Q, Mantalaris A, Pistikopoulos EN, Noro MG, Han L, Lian Get al., 2014, A Study on Fe<SUP>2+</SUP> - α-Helical-Rich Keratin Complex Formation Using Isothermal Titration Calorimetry and Molecular Dynamics Simulation, JOURNAL OF PHARMACEUTICAL SCIENCES, Vol: 103, Pages: 1224-1232, ISSN: 0022-3549

Journal article

Kopanos GM, Pistikopoulos EN, 2014, Reactive Scheduling by a Multiparametric Programming Rolling Horizon Framework: A Case of a Network of Combined Heat and Power Units, INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH, Vol: 53, Pages: 4366-4386, ISSN: 0888-5885

Journal article

Koltsaklis NE, Dagoumas AS, Kopanos GM, Pistikopoulos EN, Georgiadis MCet al., 2014, A Spatial multi-period long-term energy planning model: A case study of the Greek power system, APPLIED ENERGY, Vol: 115, Pages: 456-482, ISSN: 0306-2619

Journal article

Wittmann-Hohlbein M, Pistikopoulos EN, 2014, Approximate solution of mp-MILP problems using piecewise affine relaxation of bilinear terms, COMPUTERS & CHEMICAL ENGINEERING, Vol: 61, Pages: 136-155, ISSN: 0098-1354

Journal article

Krieger A, Panoskaltsis N, Mantalaris A, Georgiadis MC, Pistikopoulos ENet al., 2014, Modeling and Analysis of Individualized Pharmacokinetics and Pharmacodynamics for Volatile Anesthesia, IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, Vol: 61, Pages: 25-34, ISSN: 0018-9294

Journal article

Muenzer DGG, Kostoglou M, Georgiadis MC, Pistikopoulos EN, Mantalaris Aet al., 2014, A Cyclin Distributed Cell Cycle Model in GS-NS0, 24TH EUROPEAN SYMPOSIUM ON COMPUTER AIDED PROCESS ENGINEERING, PTS A AND B, Vol: 33, Pages: 19-24, ISSN: 1570-7946

Journal article

Nascu I, Lambert RSC, Krieger A, Pistikopoulos ENet al., 2014, Simultaneous Multi-Parametric Model Predictive Control and State Estimation with Application to Distillation Column and Intravenous Anaesthesia, 24TH EUROPEAN SYMPOSIUM ON COMPUTER AIDED PROCESS ENGINEERING, PTS A AND B, Vol: 33, Pages: 541-546, ISSN: 1570-7946

Journal article

Diangelakis NA, Manthanwar AM, Pistikopoulos EN, 2014, A Framework for Design and Control Optimisation: Application on a CHP System, PROCEEDINGS OF THE 8TH INTERNATIONAL CONFERENCE ON FOUNDATIONS OF COMPUTER-AIDED PROCESS DESIGN, Vol: 34, Pages: 765-770, ISSN: 1570-7946

Journal article

Zavitsanou S, Mantalaris A, Georgiadis MC, Pistikopoulos ENet al., 2014, Optimization of Insulin Dosing in Patients with Type 1 Diabetes Mellitus, 24TH EUROPEAN SYMPOSIUM ON COMPUTER AIDED PROCESS ENGINEERING, PTS A AND B, Vol: 33, Pages: 1459-1464, ISSN: 1570-7946

Journal article

Misener R, Chin J, Lai M, Gari MF, Velliou E, Panoskaltsis N, Pistikopoulos EN, Mantalaris Aet al., 2014, Robust Superstructure Optimisation of a Bioreactor that Produces Red Blood Cells, 24TH EUROPEAN SYMPOSIUM ON COMPUTER AIDED PROCESS ENGINEERING, PTS A AND B, Vol: 33, Pages: 91-96, ISSN: 1570-7946

Journal article

Oberdieck R, Wittmann-Hohlbein M, Pistikopoulos E, 2014, A branch and bound method for the solution of multiparametric mixed integer linear programming problems, Journal of Global Optimization, Vol: 59, Pages: 527-543, ISSN: 0925-5001

Journal article

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