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    A Library For Developing Optimization Algorithms In Metabolic Network Analysis

    , M.Sc. Thesis Sharif University of Technology Ghadimi Deylami, Iman (Author) ; Tefagh, Mojtaba (Supervisor)
    Abstract
    In systems biology, one of the most important biological systems that is analyzed and investigated is the metabolic network. A metabolic network is a complete set of metabolic and physical processes that determine the physiological and biochemical characteristics of a cell. These networks encompass metabolic chemical reactions, metabolic pathways, and regulatory interactions that govern these reactions. Therefore, metabolic networks at the genome scale are immensely large, making even efficient algorithms time-consuming for their analysis. To address this issue, reducing metabolic networks is crucial, as it significantly decreases the execution time of algorithms and enhances computational... 

    Numerical Simulation of Glucose Metabolism and Hepatocyte Viability within a Microfluidic

    , M.Sc. Thesis Sharif University of Technology Nejadnasrollah, Farzam (Author) ; Firoozabadi, Bahar (Supervisor)
    Abstract
    The advent of microfluidics as suitable environments for culturing cells is associated with some challenges such as shear stresses applied on the cells. In fact, hepatocytes lose their function as exposed to high shear stresses similar to other cell types. Moreover, among all factors needed for cell viability, feeding hepatocytes with adequate oxygen is of great importance due to their high demand for oxygen compared the other cells. In this thesis, different types of cultures including 2D and 3D has been used in order that shear stresses would be in allowed range and provision of hepatocytes with sufficient oxygen concentrations has been ensured as well. In addition to supplying hepatocytes... 

    Investigation of Anticancer Drug Metabolism in Saccharomyces Cerevisiae as a Drug Resistance Model

    , M.Sc. Thesis Sharif University of Technology Hamed Rahimi, Reza (Author) ; Yaghmaei, Soheila (Supervisor) ; Sardari, Soroush (Supervisor)
    Abstract
    Cancer is a life-threatening group of diseases that arises from the uncontrolled growth and division of cells in the body. Treatment options for cancer include surgery, chemotherapy, radiation therapy, immunotherapy, targeted therapy, and hormone therapy. However, resistance to anticancer drugs can develop through a variety of mechanisms, such as the upregulation of drug efflux pumps and alterations in DNA repair mechanisms. One common mechanism of drug resistance is through changes in metabolism, where cancer cells switch to alternative metabolic pathways to survive and evade the effects of anticancer drugs. The development of new drugs targeting specific molecules and pathways involved in... 

    Metabolic Engineering of Yeast Saccharomyces Cerevisiae for Production of Fatty Acids and Its Derivatives

    , M.Sc. Thesis Sharif University of Technology Homayoonfar, Mohammad (Author) ; Roosta Azad, Reza (Supervisor) ; Sardari, Soroush (Supervisor)
    Abstract
    With the increasing emphasis on production of various chemicals by biotechnology industry, the establishment of optimal cell factories for the maximum production of a specific chemical product will be a serious challenge in large-scale production in this industry. Metabolic engineering is a branch of biochemical engineering that has been developed to achieve this and the approaches in it seek to address this challenge. In this study, focusing on increasing production of fatty acids by yeast cells of Saccharomyces cerevisiae, and using a combination of computational and laboratory methods to present a methodology for the optimal design of culture media. Thus, using the constraint-based... 

    Dynamic Simulation and Control of Reactive Systems Involving Metabolic Pathways

    , M.Sc. Thesis Sharif University of Technology Aghaee Foroushani, Mohammad (Author) ; Bozorgmehry Bozarjomehry, Ramin (Supervisor) ; Setoodeh, Payam (Co-Supervisor)
    Abstract
    In this project, modeling, simulation, and control of the Saccharomyces Cerevisiae were studied. In the first section, simulation and control of a structural model of saccharomyces Cerevisiae were performed. Fuzzy Logic Controller (FLC) as a model-independent controller and Global Linearization Controller (GLC) as a model-based controller were designed. Additionally, two types of Kalman filters were designed to predict all states of the structural model: 1-Extended Kalman Filter (EKF), 2- Unscented Kalman Filter (UKF). As a concise explanation, the control action of the GLC is a function of all states of the model, and since that measuring all metabolites is not practical, the EKF and UKF... 

    Ontological Study of Metabolic Networks to Develop an Identification Software for Metabolic Networks

    , M.Sc. Thesis Sharif University of Technology Mohammadi Peyhani, Homa (Author) ; Bozorgmehry Boozarjomehry, Ramin (Supervisor)
    Abstract
    Simulation of biological behaviors as the pre requirement for control and optimization, especially for recognition and treating diseases, requires studying involved reactions which may or may not be accessible. In the other side, finding the correct network structures and related mathematical expressions to simulate biological behaviors is a complicated problem due to multi aspect interactions among biological reactions, which imply an approach that integrate the knowledge coming from multiple discipline including biological concepts, mathematical modelling, bioinformatics and advanced programming. In this study we aim to analyze this problem using ontological inference to develop a... 

    Simulation of Optimum Nutrition in Bioreactors

    , M.Sc. Thesis Sharif University of Technology Radfar, Marjan (Author) ; Abdekhodaie, Mohammad Jafar (Supervisor) ; Mehrvar, Mehrab (Supervisor)
    Abstract
    In this study, a semi-structured model for the growth and production of lactase in an aerated bioreactor by Kluyveromyces marxianus, growing on cheese whey, was developed. Three modes of culture, consisting of batch, fed-batch and a controlled-release system were investigated. Modeling was based on three metabolic pathways, representing the growth of Kluyveromyces marxianus. Lactose and oxygen consumption, cell growth, and also lactase and ethanol production rates were determined in the model. Induction was considered as the governing mechanism for enzyme production. The model showed good agreement with the experimental data in batch and fed-batch cultures. Controlled-release system is a... 

    Modeling the Endothelial Function in the Brachial Artery Using Photoplethysmography

    , M.Sc. Thesis Sharif University of Technology Mashayekhi, Ghoncheh (Author) ; Zahedi, Edmond (Supervisor) ; Jahed, Mehran (Supervisor)
    Abstract
    Flow Mediated Dilation (FMD) is a non-invasive method for endothelial function assessment providing an index extracted from ultrasonic B-mode images. Although utilized in the research community, the difficulty of its application and high cost of ultrasonic device prevent it from being widely used in clinical settings. In this study we show that substituting the ultrasonic device with more easily handled and low cost photoplethysmography and electrocardiography is possible. We introduce new indices based on the photoplethysmogram (PPG) and electrocardiogram (ECG) and show that they are correlated with the ultrasound-based FMD index. To this end, conventional ultrasound FMD test was carried... 

    Context-Specific Reconstruction and Gap-Filling of Metabolic Networks by Sparse Reconciliation of Data Inconsistencies

    , M.Sc. Thesis Sharif University of Technology Fathi, Ali (Author) ; Tefagh, Mojtaba (Supervisor)
    Abstract
    With the increasingly collected biological data, appropriate usage of this data is of great importance for understanding and predicting biological systems and has been the aim of experiments and data collections. A famous category of biological data is known as “omics” which refers to transcriptomics, proteomics, metabolomics, and fluxomics, from different cells or tissues in various media and conditions. This set of data is regularly used for tasks such as studying cells and organisms, understanding cell states, cancer prediction, etc. and is of great importance in Systems Biology.In this thesis, we concentrate on studying cells or organisms using such data, where during that process, we... 

    Hyperbolic and Metabolic Forms and Involutions

    , Ph.D. Dissertation Sharif University of Technology Nokhodkar Hassan Abadi, Amir Hossein (Author) ; Gholamzadeh Mahmoudi, Mohammad (Supervisor) ; Mahdavi-Hezavehi, Mohammad (Supervisor)
    Abstract
    In this thesis, we investigate the involutions of a Clifford algebra induced by involutions of orthogonal group in characteristic two. Several properties of these involutions, such as the relations between their invariants and their decompositions are studied. Also it is shown that a tensor product of quaternion algebras with involution can be expressed as the Clifford algebra of a suitable quadratic form with an involution induced by an involution of orthogonal group. Finally, in connection with the Pfister factor conjecture formulated by D. B. Shapiro, split tensor products of quaternion algebras with involution over a field of characteristic two are investigated  

    Possible role for growth hormone in suppressing acylated ghrelin and hunger ratings during and after intermittent exercise of different intensities in obese individuals

    , Article Acta Medica Iranica ; Vol. 52, Issue. 1 , 2014 , pp. 29-37 ; ISSN: 1735-9694 Gholipour, M ; Kordi, M. R ; Taghikhani, M ; Ravasi, A. A ; Gaeini, A. A ; Tabrizi, A ; Sharif University of Technology
    Abstract
    Body weight is influenced by both food intake and energy expenditure. Acylated ghrelin enhances appetite, and its circulating level is suppressed by Growth Hormone. Data on the acylated ghrelin responses to exercise of different intensities in obese individuals are currently not available. This study examined the effects of an intermittent exercise protocol on acylated ghrelin levels and hunger ratings in obese people. Nine inactive male ran on the treadmill at 0900 with progressive intensities of 50, 60, 70, and 80% of VO2max for 10, 10, 5, and 2 min respectively. Blood samples were collected before the exercise at 0845 (-15 min as the resting values), after each workload (10, 23, 31, and... 

    Cyto and genotoxicities of graphene oxide and reduced graphene oxide sheets on spermatozoa

    , Article RSC Advances ; Vol. 4, issue. 52 , May , 2014 , pp. 27213-27223 ; ISSN: 20462069 Hashemi, E ; Akhavan, O ; Shamsara, M ; Rahighi, R ; Esfandiar, A ; Tayefeh, A. R ; Sharif University of Technology
    Abstract
    Concentration-dependent cyto and genotoxicities of graphene oxide (GO) and reduced GO (rGO) sheets on spermatozoa were studied. rGO sheets with various surface chemical states were achieved using hydrazine (N2H 4) hydrothermal (HT) reactions and green tea polyphenols (GTPs). Although 0.1 μg mL-1 graphene could not change sperm viability and kinetic parameters, <40% and 20% of spermatozoa were viable and progressively motile, after 2 h incubation with 400 μg mL-1 GO or rGO, respectively. All the graphene nanomaterials induced concentration- dependent reductions of adenosine triphosphate and NAD+/NADH produced by spermatozoa for motility and metabolic activity. While GO, N 2H4-rGO, and HT-rGO... 

    The Differential Diagnosis of Crohn's Disease and Celiac Disease Using Nuclear Magnetic Resonance Spectroscopy

    , Article Applied Magnetic Resonance ; Volume 45, Issue 5 , May , 2014 , Pages 451-459 Fathi, F ; Kasmaee, L. M ; Sohrabzadeh, K ; Nejad, M. R ; Tafazzoli, M ; Oskouie, A. A ; Sharif University of Technology
    Abstract
    Crohn's disease and celiac disease belong to a group of autoimmune conditions that affect the digestive system, specifically the small intestine. They both attack the digestive tract and share many symptoms. Thus, the discovery of proper methods would be a major step toward differentiating celiac disease from Crohn's disease. The aim of this study was to search for the metabolic biomarkers to differentiate between these two diseases. Proton nuclear magnetic resonance spectroscopy (1H NMR) was employed as the metabolic profiling method to look for serum metabolites that differentiate between celiac disease and Crohn's disease. Classification of celiac disease and Crohn's disease was done... 

    1H NMR based metabolic profiling in Crohn's disease by random forest methodology

    , Article Magnetic Resonance in Chemistry ; Vol. 52, issue. 7 , July , 2014 , p. 370-376 Fathi, F ; Majari-Kasmaee, L ; Mani-Varnosfaderani, A ; Kyani, A ; Rostami-Nejad, M ; Sohrabzadeh, K ; Naderi, N ; Zali, M. R ; Rezaei-Tavirani, M ; Tafazzoli, M ; Arefi-Oskouie, A ; Sharif University of Technology
    Abstract
    The present study was designed to search for metabolic biomarkers and their correlation with serum zinc in Crohn's disease patients. Crohn's disease (CD) is a form of inflammatory bowel disease that may affect any part of the gastrointestinal tract and can be difficult to diagnose using the clinical tests. Thus, introduction of a novel diagnostic method would be a major step towards CD treatment.Proton nuclear magnetic resonance spectroscopy ( 1H NMR) was employed for metabolic profiling to find out which metabolites in the serum have meaningful significance in the diagnosis of CD. CD and healthy subjects were correctly classified using random forest methodology. The classification model for... 

    Disc size markedly influences concentration profiles of intravenously administered solutes in the intervertebral disc: A computational study on glucosamine as a model solute

    , Article European Spine Journal ; Vol. 23, issue. 4 , April , 2014 , p. 715-723 Motaghinasab, S ; Shirazi-Adl, A ; Parnianpour, M ; Urban, J. P. G ; Sharif University of Technology
    Abstract
    Purpose: Tests on animals of different species with large differences in intervertebral disc size are commonly used to investigate the therapeutic efficacy of intravenously injected solutes in the disc. We hypothesize that disc size markedly affects outcome. Methods: Here, using a small non-metabolized molecule, glucosamine (GL) as a model solute, we calculate the influence of disc size on transport of GL into rat, rabbit, dog and human discs for 10 h post intravenous-injection. We used transient finite element models and considered an identical GL supply for all animals. Results: Huge effects of disc size on GL concentration profiles were found. Post-injection GL concentration in the rat... 

    Flash photo stimulation of human neural stem cells on graphene/TiO 2 heterojunction for differentiation into neurons

    , Article Nanoscale ; Volume 5, Issue 21 , 2013 , Pages 10316-10326 ; 20403364 (ISSN) Akhavan, O ; Ghaderi, E ; Sharif University of Technology
    2013
    Abstract
    For the application of human neural stem cells (hNSCs) in neural regeneration and brain repair, it is necessary to stimulate hNSC differentiation towards neurons rather than glia. Due to the unique properties of graphene in stem cell differentiation, here we introduce reduced graphene oxide (rGO)/TiO2 heterojunction film as a biocompatible flash photo stimulator for effective differentiation of hNSCs into neurons. Using the stimulation, the number of cell nuclei on rGO/TiO2 increased by a factor of ∼1.5, while on GO/TiO2 and TiO2 it increased only ∼48 and 24%, respectively. Moreover, under optimum conditions of flash photo stimulation (10 mW cm-2 flash intensity and 15.0 mM ascorbic acid in... 

    Discovering dominant pathways and signal-response relationships in signaling networks through nonparametric approaches

    , Article Genomics ; Volume 102, Issue 4 , October , 2013 , Pages 195-201 ; 08887543 (ISSN) Nassiri, I ; Masoudi Nejad, A ; Jalili, M ; Moeini, A ; Sharif University of Technology
    2013
    Abstract
    A signaling pathway is a sequence of proteins and passenger molecules that transmits information from the cell surface to target molecules. Understanding signal transduction process requires detailed description of the involved pathways. Several methods and tools resolved this problem by incorporating genomic and proteomic data. However, the difficulty of obtaining prior knowledge of complex signaling networks limited the applicability of these tools. In this study, based on the simulation of signal flow in signaling network, we introduce a method for determining dominant pathways and signal response to stimulations. The model uses topology-weighted transit compartment approach and comprises... 

    Functional analyses of recombinant mouse hepcidin-1 in cell culture and animal model

    , Article Biotechnology Letters ; Volume 35, Issue 8 , August , 2013 , Pages 1191-1197 ; 01415492 (ISSN) Yazdani, Y ; Keyhanvar, N ; Kalhor, H. R ; Rezaei, A ; Sharif University of Technology
    2013
    Abstract
    Hepcidin is a peptide hormone that plays an important role in iron metabolism. We have produced a recombinant mouse hepcidin-1 by using baculovirus expression system. Its expression yield was 25 μg/ml when cell culture media were supplemented with a protease inhibitor cocktail. The recombinant mouse hepcidin-1 and synthetic human hepcidin-25 had similar effects on reducing ferroportin expression in J774A cell line and in peritoneal macrophages. However, synthetic human hepcidin-25 was more efficient than recombinant mouse hepcidin-1 in reducing iron concentration in blood circulation (p < 0.01)  

    NETAL: A new graph-based method for global alignment of protein-protein interaction networks

    , Article Bioinformatics ; Volume 29, Issue 13 , 2013 , Pages 1654-1662 ; 13674803 (ISSN) Neyshabur, B ; Khadem, A ; Hashemifar, S ; Arab, S. S ; Sharif University of Technology
    2013
    Abstract
    Motivation: The interactions among proteins and the resulting networks of such interactions have a central role in cell biology. Aligning these networks gives us important information, such as conserved complexes and evolutionary relationships. Although there have been several publications on the global alignment of protein networks; however, none of proposed methods are able to produce a highly conserved and meaningful alignment. Moreover, time complexity of current algorithms makes them impossible to use for multiple alignment of several large networks together.Results: We present a novel algorithm for the global alignment of protein-protein interaction networks. It uses a greedy method,... 

    Relationship between serum level of selenium and metabolites using 1hnmr-based metabonomics in parkinson's disease

    , Article Applied Magnetic Resonance ; Volume 44, Issue 6 , January , 2013 , Pages 721-734 ; 09379347 (ISSN) Fathi, F ; Kyani, A ; Darvizeh, F ; Mehrpour, M ; Tafazzoli, M ; Shahidi, G ; Sharif University of Technology
    2013
    Abstract
    Parkinson's disease (PD) is a neurodegenerative disease, which is not easily diagnosed using clinical tests and the discovery of proper methods would be a major step towards a successful diagnosis. In the present study, we employed metabolic profiling using proton nuclear magnetic resonance spectroscopy to find metabolites in serum, which are helpful for the diagnosis of PD. Classification of PD and healthy subject was done using random forest. Serum levels of selenium measured by atomic absorption spectrometry in PD group were lower than the serum selenium levels in the control group. The metabolites causing selenium changes in PD patients were identified using random forest, and a model...