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Computational simulations of tumor growth and treatment response: Benefits of high-frequency, low-dose drug regimens and concurrent vascular normalization
, Article PLoS Computational Biology ; Volume 19, Issue 6 June , 2023 ; 1553734X (ISSN) ; Jain, R. K ; Munn, L. L ; Sharif University of Technology
Public Library of Science
2023
Abstract
Implementation of effective cancer treatment strategies requires consideration of how the spatiotemporal heterogeneities within the tumor microenvironment (TME) influence tumor progression and treatment response. Here, we developed a multi-scale three-dimensional mathematical model of the TME to simulate tumor growth and angiogenesis and then employed the model to evaluate an array of single and combination therapy approaches. Treatments included maximum tolerated dose or metronomic (i.e., frequent low doses) scheduling of anti-cancer drugs combined with anti-angiogenic therapy. The results show that metronomic therapy normalizes the tumor vasculature to improve drug delivery, modulates...
Investigation of cancer response to chemotherapy: a hybrid multi-scale mathematical and computational model of the tumor microenvironment
, Article Biomechanics and Modeling in Mechanobiology ; Volume 21, Issue 4 , 2022 , Pages 1233-1249 ; 16177959 (ISSN) ; Firoozabadi, B ; Sharif University of Technology
Springer Science and Business Media Deutschland GmbH
2022
Abstract
Tumor microenvironment (TME) is a multi-scale biological environment that can control tumor dynamics with many biomechanical and biochemical factors. Investigating the physiology of TME with a heterogeneous structure and abnormal functions not only can achieve a deeper understanding of tumor behavior but also can help develop more efficient anti-cancer strategies. In this work, we develop a hybrid multi-scale mathematical model of TME to simulate the progression of a three-dimensional tumor and elucidate its response to different chemotherapy approaches. The chemotherapy approaches include multiple low dose (MLD) of anti-cancer drug, maximum tolerated dose (MTD) of anti-cancer drug,...
Continuum model of actin-myosin flow
, Article 2013 20th Iranian Conference on Biomedical Engineering, ICBME 2013 ; December , 2013 , Pages 98-102 ; Firoozabadi, B ; Saidi, M. S ; Sharif University of Technology
IEEE Computer Society
2013
Abstract
The front part of a cell is divided to two regions called lamellum and lamellipodium (lamellipodial). This part plays an essential role for cell migration. Indeed, there are many protein filaments called actin in lamellum and lamellipodium, which induce the cell motion with polymerization in the leading edge of the cell. The actin filaments adhere to the extracellular matrix (ECM) by means of focal adhesions and they have contact by myosin motor proteins. The myosin motor proteins cause actin retrograde and anterograde flow exerted contractile stress on them. The focal adhesions exert frictional stress on the actin filaments. In this work, we developed a two-dimensional continuum model of...
Two-phase acto-cytosolic fluid flow in a moving keratocyte: a 2d continuum model
, Article Bulletin of Mathematical Biology ; Volume 77, Issue 9 , September , 2015 , Pages 1813-1832 ; 00928240 (ISSN) ; Firoozabadi, B ; Saidi, M. S ; Sharif University of Technology
Springer New York LLC
2015
Abstract
The F-actin network and cytosol in the lamellipodia of crawling cells flow in a centripetal pattern and spout-like form, respectively. We have numerically studied this two-phase flow in the realistic geometry of a moving keratocyte. Cytosol has been treated as a low viscosity Newtonian fluid flowing through the high viscosity porous medium of F-actin network. Other involved phenomena including myosin activity, adhesion friction, and interphase interaction are also discussed to provide an overall view of this problem. Adopting a two-phase coupled model by myosin concentration, we have found new accurate perspectives of acto-cytosolic flow and pressure fields, myosin distribution, as well as...
Fully-coupled mathematical modeling of actomyosin-cytosolic two-phase flow in a highly deformable moving Keratocyte cell
, Article Journal of Biomechanics ; 2017 ; 00219290 (ISSN) ; Firoozabadi, B ; Saidi, M. S ; Sharif University of Technology
Elsevier Ltd
2017
Abstract
Interaction between intracellular dynamics and extracellular matrix (ECM) generally occurred into very thin fragment of moving cell, namely lamellipodia, enables all movable cells to crawl on ECM. In fast-moving cells such as fish Keratocytes, Lamellipodia including most cell area finds a fan-like shape during migration, with a variety of aspect ratio function of fish type. In this work, our purpose is to present a novel and more complete two-dimensional continuum mathematical model of actomyosin-cytosolic two-phase flow of a self-deforming Keratocyte with circular spreaded to steady fan-like shape. In the new approach, in addition to the two-phase flow of the F-actin and cytosol, the...
Fully-coupled mathematical modeling of actomyosin-cytosolic two-phase flow in a highly deformable moving Keratocyte cell
, Article Journal of Biomechanics ; Volume 67 , January , 2018 , Pages 37-45 ; 00219290 (ISSN) ; Firoozabadi, B ; Saidi, M. S ; Sharif University of Technology
Elsevier Ltd
2018
Abstract
Interaction between intracellular dynamics and extracellular matrix (ECM) generally occurred into very thin fragment of moving cell, namely lamellipodia, enables all movable cells to crawl on ECM. In fast-moving cells such as fish Keratocytes, Lamellipodia including most cell area finds a fan-like shape during migration, with a variety of aspect ratio function of fish type. In this work, our purpose is to present a novel and more complete two-dimensional continuum mathematical model of actomyosin-cytosolic two-phase flow of a self-deforming Keratocyte with circular spreaded to steady fan-like shape. In the new approach, in addition to the two-phase flow of the F-actin and cytosol, the...
Chemo-mechanistic multi-scale model of a three-dimensional tumor microenvironment to quantify the chemotherapy response of cancer
, Article Biotechnology and Bioengineering ; Volume 118, Issue 10 , 2021 , Pages 3871-3887 ; 00063592 (ISSN) ; Firoozabadi, B ; Mozafari, A ; Sharif University of Technology
John Wiley and Sons Inc
2021
Abstract
Exploring efficient chemotherapy would benefit from a deeper understanding of the tumor microenvironment (TME) and its role in tumor progression. As in vivo experimental methods are unable to isolate or control individual factors of the TME, and in vitro models often cannot include all the contributing factors, some questions are best addressed with mathematical models of systems biology. In this study, we establish a multi-scale mathematical model of the TME to simulate three-dimensional tumor growth and angiogenesis and then implement the model for an array of chemotherapy approaches to elucidate the effect of TME conditions and drug scheduling on controlling tumor progression. The...
A mechanobiological mathematical model of liver metabolism
, Article Biotechnology and Bioengineering ; Volume 117, Issue 9 , 5 June , 2020 , Pages 2861-2874 ; Firoozabadi, B ; Munn, L. L ; Sharif University of Technology
John Wiley and Sons Inc
2020
Abstract
The liver plays a complex role in metabolism and detoxification, and better tools are needed to understand its function and to develop liver-targeted therapies. In this study, we establish a mechanobiological model of liver transport and hepatocyte biology to elucidate the metabolism of urea and albumin, the production/detoxification of ammonia, and consumption of oxygen and nutrients. Since hepatocellular shear stress (SS) can influence the enzymatic activities of liver, the effect of SS on the urea and albumin synthesis are empirically modeled through the mechanotransduction mechanisms. The results demonstrate that the rheology and dynamics of the sinusoid flow can significantly affect...
A multi-scale model for determining the effects of pathophysiology and metabolic disorders on tumor growth
, Article Scientific Reports ; Volume 10, Issue 1 , 20 February , 2020 ; Firoozabadi, B ; Mozafari, A ; Munn, L. L ; Sharif University of Technology
Nature Research
2020
Abstract
The search for efficient chemotherapy drugs and other anti-cancer treatments would benefit from a deeper understanding of the tumor microenvironment (TME) and its role in tumor progression. Because in vivo experimental methods are unable to isolate or control individual factors of the TME and in vitro models often do not include all the contributing factors, some questions are best addressed with systems biology mathematical models. In this work, we present a new fully-coupled, agent-based, multi-scale mathematical model of tumor growth, angiogenesis and metabolism that includes important aspects of the TME spanning subcellular-, cellular- and tissue-level scales. The mathematical model is...
Mechanistic model for booster doses effectiveness in healthy, cancer, and immunosuppressed patients infected with SARS-CoV-2
, Article Proceedings of the National Academy of Sciences of the United States of America ; Volume 120, Issue 3 , 2023 ; 00278424 (ISSN) ; Hardin, C. C ; Naranbhai, V ; Nikmaneshi, M. R ; Khandekar, M. J ; Gainor, J. F ; Stylianopoulos, T ; Munn, L. L ; Jain, R. K ; Sharif University of Technology
National Academy of Sciences
2023
Abstract
SARS-CoV-2 vaccines are effective at limiting disease severity, but effectiveness is lower among patients with cancer or immunosuppression. Effectiveness wanes with time and varies by vaccine type. Moreover, previously prescribed vaccines were based on the ancestral SARS-CoV-2 spike-protein that emerging variants may evade. Here, we describe a mechanistic mathematical model for vaccination-induced immunity. We validate it with available clinical data and use it to simulate the effectiveness of vaccines against viral variants with lower antigenicity, increased virulence, or enhanced cell binding for various vaccine platforms. The analysis includes the omicron variant as well as hypothetical...
Fluids Flow Simulation in the Cell Influenced the Focal Adhesions
, Ph.D. Dissertation Sharif University of Technology ; Firoozabadi, Bahar (Supervisor) ; saidi, Mohammad said (Co-Advisor)
Abstract
In the present thesis, intracellular fluid flows have investigated for study cell motions. It is due to firmly relation between the cell motion and these flows. Generally, the cell firstly adheres to a surface, then, moves forward with the effects of the internal fluid flows. In this study, the cell structure is invided to two general parts; the front part of the cell and the cell body. The front part of the cell plays a essential roles in the cell motion, however, the cell body is considered as a extra cargo that is carried by the front of the cell. Therefor, in the present modellings, the front part is only considered. Here, using four different models for the front part of the cell, many...
Multi-scale Simulation of Tumor Microenvironment
, M.Sc. Thesis Sharif University of Technology ; Firoozabadi, Bahar (Supervisor) ; Mozafari, Ali Asghar (Co-Supervisor)
Abstract
Search for effective methods for treating cancer requires a deep understanding of the tumor microenvironment and its role in cancerous tumor growth and progression. Mathematical modeling methods, which have fewer limitations than experimental methods for examining the microcirculation of cancer in detail, are suggested to answer many questions about the behavior and dynamics of cancerous tumors. In the present study, a multi-scale mathematical model of the three-dimensional tumor microenvironment, including molecular, cellular, and tissue scales, is presented. In this model, important aspects of tumor microenvironmental dynamics including tumor growth, angiogenesis, cancer metabolism, and...
Analysis of porosity distribution of large-scale porous media and their reconstruction by Langevin equation
, Article Physical Review E - Statistical, Nonlinear, and Soft Matter Physics ; Volume 83, Issue 2 , February , 2011 ; 15393755 (ISSN) ; Sahimi, M ; Rasaei, M. R ; Tabar, M. R. R ; Sharif University of Technology
2011
Abstract
Several methods have been developed in the past for analyzing the porosity and other types of well logs for large-scale porous media, such as oil reservoirs, as well as their permeability distributions. We developed a method for analyzing the porosity logs φ(h) (where h is the depth) and similar data that are often nonstationary stochastic series. In this method one first generates a new stationary series based on the original data, and then analyzes the resulting series. It is shown that the series based on the successive increments of the log y(h)=φ(h+δh)-φ(h) is a stationary and Markov process, characterized by a Markov length scale hM. The coefficients of the Kramers-Moyal expansion for...
Attacks on a lightweight mutual authentication protocol under EPC C-1 G-2 standard
, Article Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics), 1 June 2011 through 3 June 2011 ; Volume 6633 LNCS , June , 2011 , Pages 254-263 ; 03029743 (ISSN) ; 9783642210396 (ISBN) ; Alagheband, M. R ; Aref, M. R ; Sharif University of Technology
2011
Abstract
Yeh et al. have recently proposed a mutual authentication protocol based on EPC Class-1 Gen.-2 standard. They claim their protocol is secure against adversarial attacks and also provides forward secrecy. In this paper we show that the proposed protocol does not have cited security features properly. A powerful and practical attack is presented on this protocol whereby the whole security of the protocol is broken. Furthermore, Yeh et al.'s protocol does not assure the untraceabilitiy and backwarduntraceabilitiy attributes. We also will propose our revision to safeguard the Yeh et al.'s protocol against cited attacks
Time-Sharing improves dynamic index coding delay
, Article 2019 Iran Workshop on Communication and Information Theory, IWCIT 2019, 24 April 2019 through 25 April 2019 ; 2019 ; 9781728105840 (ISBN) ; Mojahedian, M. M ; Aref, M. R ; Pakravan, M. R ; Sharif University of Technology
Institute of Electrical and Electronics Engineers Inc
2019
Abstract
In this paper, we show how time-sharing method may reduce transmission delay in the dynamic index coding scenario. We propose a novel time-shared dynamic index coding transmission scheme that achieves the maximum index coding gain for a complete bi-directional side information graph and formulate a constrained optimization problem to tune the transmission scheme for the minimum transmission delay. A closed-form solution is presented for the special case of two-user. We also use analytical and simulation results to provide graphical intuition for the obtained results
Strategies for Optimal Transmission and Delay Reduction in Dynamic Index Coding Problem
, Article IEEE Transactions on Communications ; Volume 71, Issue 8 , 2023 , Pages 4694-4706 ; 00906778 (ISSN) ; Mojahedian, M. M ; Aref, M. R ; Pakravan, M. R ; Sharif University of Technology
Institute of Electrical and Electronics Engineers Inc
2023
Abstract
Dynamic index coding is a practical generalization of conventional index coding that deals with real dynamic traffic streams. We identify the code-constrained capacity region of a dynamic index coding problem with a complete bi-directional side information graph and introduce the performance metric of dynamic index coding gain to measure how dynamic index coding reduces the required data transmissions. A greedy dynamic index coding scheme is proposed that achieves the maximum coding gain almost everywhere in the identified capacity region. Although the greedy scheme attains the maximum coding gain, its selfish nature may unacceptably increase transmission delay. To address this issue, a...
Efficiency improvement of a high step up high efficiency converter for photovoltaic applications based on three-state switching cell
, Article PEDSTC 2013 - 4th Annual International Power Electronics, Drive Systems and Technologies Conference ; 2013 , Pages 454-458 ; 9781467344845 (ISBN) ; Zolghadri, M. R ; Hajimoradi, M. R ; Sharif University of Technology
2013
Abstract
This paper suggests methods for improving efficiency of a high step up high efficiency converter based on three state commutation cells. A loss analysis has been performed to identify the source of power loss. Based on this analysis, methods are presented to reduce losses in the most power dissipating elements. These methods include replacing some power diodes with large conduction losses with MOSFETs having small on-state resistance. Efficiency improvement up to %1.25 percent is verified in simulation and experimental results
Locally multipath adaptive routing protocol resilient to selfishness and wormholes
, Article Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics), 12 May 2010 through 13 May 2010 ; Volume 6047 LNCS , May , 2010 , Pages 187-200 ; 03029743 (ISSN) ; 9783642128264 (ISBN) ; Pakravan, M. R ; Salmasizadeh, M ; Aref, M. R ; Sharif University of Technology
2010
Abstract
Locally multipath adaptive routing (LMAR) protocol, classified as a new reactive distance vector routing protocol for MANETs is proposed in this paper. LMAR can find an ad-hoc path without selfish nodes and wormholes using a random search algorithm in polynomial-time. Also when the primary path fails, it discovers an alternative safe path if network graph remains connected after eliminating selfish/malicious nodes. The main feature of LMAR to seek safe route free of selfish and malicious nodes in polynomial time is its searching algorithm and flooding stage that its generated traffic is equiloaded compared to single-path routing protocols but its ability to bypass the attacks is much better...
Cooperation within von Willebrand factors enhances adsorption mechanism
, Article Journal of the Royal Society Interface ; Volume 12, Issue 109 , 2015 ; 17425689 (ISSN) ; Mehrbod, M ; Ejtehadi, M. R ; Mofrad, M. R ; Sharif University of Technology
Royal Society of London
2015
Abstract
von Willebrand factor (VWF) is a naturally collapsed protein that participates in primary haemostasis and coagulation events. The clotting process is triggered by the adsorption and conformational changes of the plasma VWFs localized to the collagen fibres found near the site of injury. We develop coarse-grained models to simulate the adsorption dynamics of VWF flowing near the adhesive collagen fibres at different shear rates and investigate the effect of factors such as interaction and cooperativity of VWFs on the success of adsorption events. The adsorption probability of a flowing VWF confined to the receptor field is enhanced when it encounters an adhered VWF in proximity to the...
Liquid-liquid coaxial swirl injector performance prediction using general regression neural network
, Article Particle and Particle Systems Characterization ; Volume 25, Issue 5-6 , 2009 , Pages 454-464 ; 09340866 (ISSN) ; Soltani, M. R ; Ashjaee, M ; Morad, M. R ; Sharif University of Technology
2009
Abstract
A general regression neural network technique was applied to design optimization of a liquid-liquid coaxial swirl injector. Phase Doppler Anemometry measurements were used to train the neural network. A general regression neural network was employed to predict droplet velocity and Sauter mean diameter at any axial or radial position for the operating range of a liquid-liquid coaxial swirl injector. The results predicted by neural network agreed satisfactorily with the experimental data. A general performance map of the liquid-liquid coaxial swirl (LLCS) injector was generated by converting the predicted result to actual fuel/oxidizer ratios. © 2008 WILEY-VCH Verlag GmbH & Co. KGaA