Sharif Digital Repository

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... 

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... 

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  

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... 

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... 

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... 

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... 

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... 

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... 

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...