Systems Biology Commons^™

Dynamic Metabolic Flux Analysis Amidst Data Variability: Sphingolipid Biosynthesis Case Study In Arabidopsis Thaliana Cell Cultures, Abraham Boluwatife Osinuga

Department of Chemical and Biomolecular Engineering: Dissertations, Theses, and Student Research

Sphingolipids are pivotal for plant development and stress responses. Growing interest has been directed towards fully comprehending the regulatory mechanisms of the sphingolipid pathway. In this study, we explore its de novo biosynthesis and homeostasis in Arabidopsis thaliana cell cultures, shedding light on fundamental metabolic mechanisms. Employing ¹⁵N isotope labeling and quantitative dynamic modeling approach, we obtained data with notable variations and developed a regularized and constraint-based Dynamic Metabolic Flux Analysis (r-DMFA) framework to predict metabolic shifts due to enzymatic changes. Our analysis revealed key enzymes such as sphingoid-base hydroxylase (SBH) and long-chain-base kinase …

Leveraging Redundancy As A Link Between Spreading Dynamics On And Of Networks, Felipe Xavier Costa

Electronic Theses & Dissertations (2024 - present)

A constant quest in network science has been in the development of methods to identify the most relevant components in a dynamical system solely via the interaction structure amongst its subsystems. This information allows the development of control and intervention strategies in biochemical signaling and epidemic spreading. We highlight the relevant components in heterogeneous dynamical system by their patterns of redundancy, which can connect how dynamics affect network topology and which pathways are necessary to spreading phenomena on networks. In order to measure the redundancies in a large class of empirical systems, we develop the backbone of directed networks methodology, …

Determining The Effects Of Glycocalyx Modifications On The Electrophysical Properties Of Human Mesenchymal Stem Cells, Rominna E. Valentine Ico

Electronic Theses, Projects, and Dissertations

Human mesenchymal stem cells (hMSCs) have gained popularity in clinical trials due to their multipotent differentiation characteristics, ability to secrete bioactive molecules, migrate into diseased or damaged tissues, and their immunosuppressive properties. HMSC cultures are heterogeneous, containing stem cells, partially differentiated progenitor cells, and fully differentiated cells. One of the major challenges with hMSCs therapeutic potential is the inability to select specific cell subpopulations due to an insufficient number of biomarkers. Often the biomarkers used, like those for fluorescence-activated cell sorting, are not sufficient to define hMSCs because they overlap with other cell types. Consequently, there is a need to …

Do Plants Have The Cognitive Complexity For Sentience?, Ricard V. Solé

Animal Sentience

Are plants sentient? Like other aspects of the cognitive potential of plants, this is a controversial issue, often driven by analogies and seldom supported on solid theoretical grounds. Sentience is understood in cognitive sciences as the capacity to feel. I suggest that because of plants’ evolved adaptations to morphological plasticity, sessile nature and ecological constraints, they are unlikely to have the requisite cognitive complexity for sentience.

Histological Evidence For The Therapeutic Effect Of Chitosan Nanofibrous Dressing On Acute Skin Wounds In A Rat Model, Mahboubeh Ghanbari, Sayed Ahmadreza Razian, Sara Cartwright, Yury Salkovskiy, Jason Mactaggart, Mark A. Carlson

UNO Student Research and Creative Activity Fair

Introduction: Large-area skin traumas, such as thermal burns, are among the most severe health issues that decrease patients’ quality of life and burden healthcare systems. The CDC estimates that there are 1.1 million burns requiring medical attention each year, with more than 20,000 cases involving at least 25% of the body surface, resulting in 4,500 deaths. In addition, about 10,000 people die from burn-related infections. A promising solution to alleviate this problem is using wound dressings based on biopolymers with inherent wound healing properties and biodegradability. One of these biopolymers is chitosan, which is derived from arthropod shells and exhibits …

The Effects Of Host-Like Environmental Signals And Gene Expression On Capsule Growth In Cryptococcus Neoformans, Yu Min Jung

McKelvey School of Engineering Theses & Dissertations

Cryptococcus neoformans is a fungal pathogen that causes cryptococcosis, a disease that kills almost 200,000 people worldwide each year. A unique feature of this deadly yeast is its polysaccharide capsule, which is known to be associated with its virulence. Here, we systematically explore the effects of all possible combinations of 4 capsule-inducing signals on gene expression, cell size, and capsule size. These signals are medium (YPD, DMEM or RPMI), temperature (30°C or 37°C), CO₂ (room air or 5%), cAMP (0 mM or 20 mM), and pH buffer (HEPES/no HEPES). We explore the effects of exogenous cAMP at a range …

Convergence Properties Of Solutions Of A Length-Structured Density-Dependent Model For Fish, Geigh Zollicoffer

Rose-Hulman Undergraduate Mathematics Journal

We numerically study solutions to a length-structured matrix model for fish populations in which the probability that a fish grows into the next length class is a decreasing nonlinear function of the total biomass of the population. We make conjectures about the convergence properties of solutions to this equation, and give numerical simulations which support these conjectures. We also study the distribution of biomass in the different age classes as a function of the total biomass.

Engineering Modularity Of Ester Biosynthesis Across Biological Scales, Hyeongmin Seo

Doctoral Dissertations

Metabolic engineering and synthetic biology enable controlled manipulation of whole-cell biocatalysts to produce valuable chemicals from renewable feedstocks in a rapid and efficient manner, helping reduce our reliance on the conventional petroleum-based chemical synthesis. However, strain engineering process is costly and time-consuming that developing economically competitive bioprocess at industrial scale is still challenging. To accelerate the strain engineering process, modular cell engineering has been proposed as an innovative approach that harnesses modularity of metabolism for designing microbial cell factories. It is important to understand biological modularity and to develop design principles for effective implementation of modular cell engineering. In this …

A New Mathematical Theory For The Dynamics Of Large Tumor Populations, A Potential Mechanism For Cancer Dormancy & Recurrence And Experimental Observation Of Melanoma Progression In Zebrafish, Adeyinka A. Lesi

Dissertations and Theses

Cancer, a family of over a hundred disease varieties, results in 600,000 deaths in the U.S. alone. Yet, improvements in imaging technology to detect disease earlier, pharmaceutical developments to shrink or eliminate tumors, and modeling of biological interactions to guide treatment have prevented millions of deaths. Cancer patients with initially similar disease can experience vastly different outcomes, including sustained recovery, refractory disease or, remarkably, recurrence years after apparently successful treatment. The current understanding of such recurrences is that they depend on the random occurrence of critical mutations. Clearly, these biological changes appear to be sufficient for recurrence, but are they …

Metabolic Network Analysis Of Filamentous Cyanobacteria, Daniel Alexis Norena-Caro

LSU Doctoral Dissertations

Cyanobacteria were the first organisms to use oxygenic photosynthesis, converting CO₂ into useful organic chemicals. However, the chemical industry has historically relied on fossil raw materials to produce organic precursors, which has contributed to global warming. Thus, cyanobacteria have emerged as sustainable stakeholders for biotechnological production. The filamentous cyanobacterium Anabaena sp. UTEX 2576 can metabolize multiple sources of Nitrogen and was studied as a platform for biotechnological production of high-value chemicals (i.e., pigments, antioxidants, vitamins and secondary metabolites). From a Chemical engineering perspective, the biomass generation in this organism was thoroughly studied by interpreting the cell as a microbial …

Computational Analysis Of Oxidative Stress In Endothelial Dysfunction: Insights On The Role Of Tetrahydrobiopterin, Ascorbate And Glutathione, Sheetal Kedar Panday

Wayne State University Dissertations

Oxidative stress and endothelial dysfunction are reported in the cardiovascular and neurovascular diseases. Oxidative stress is caused due to an increase in the generation of reactive oxygen (ROS) and nitrogen species (RNS) and incapacity of antioxidant systems to eliminate ROS and RNS. Endothelial dysfunction is characterized by a reduction in nitric oxide (NO) bioavailability. NO is constitutively produced by enzyme endothelial nitric oxide synthase (eNOS). A reduction in tetrahydrobiopterin (BH4), which is an essential cofactor of eNOS, can lead to eNOS uncoupling. There is complex interplay between the ROS/RNS and antioxidant system underlying pathophysiologies of vascular diseases, however our quantitative …

Validating The Accuracy Of Neatwork, A Rural Gravity Fed Water Distribution System Design Program, Using Field Data In The Comarca Ngöbe-Bugle, Panama, Maria Briones

USF Tampa Graduate Theses and Dissertations

Despite the sustainable development goals to increase access to improved water there are still 884 million people in the world without access to an improved water source (WHO, 2017). One method to improve access to water in rural, mountainous areas, is through construction of gravity fed water distribution systems. These systems should be designed based upon fundamental principles of hydraulics. One method of doing so in a time efficient manner with minimal engineering knowledge is to utilize a downloadable computer program such as Neatwork, which aids in design of rural, gravity fed water distribution systems and has been used by …

Radical Social Ecology As Deep Pragmatism: A Call To The Abolition Of Systemic Dissonance And The Minimization Of Entropic Chaos, Arielle Brender

Student Theses 2015-Present

This paper aims to shed light on the dissonance caused by the superimposition of Dominant Human Systems on Natural Systems. I highlight the synthetic nature of Dominant Human Systems as egoic and linguistic phenomenon manufactured by a mere portion of the human population, which renders them inherently oppressive unto peoples and landscapes whose wisdom were barred from the design process. In pursuing a radical pragmatic approach to mending the simultaneous oppression and destruction of the human being and the earth, I highlight the necessity of minimizing entropic chaos caused by excess energy expenditure, an essential feature of systems that aim …

Investigating Smoke Exposure And Chronic Obstructive Pulmonary Disease (Copd) With A Calibrated Agent Based Model (Abm) Of In Vitro Fibroblast Wound Healing., James A. Ratti

Theses and Dissertations

COPD is characterized by tissue inflammation and impaired remodeling that suggests fibroblast maintenance of structural homeostasis is dysregulated. Thus, we performed in vitro wound healing experiments on normal and diseased human lung fibroblasts and developed an ABM of fibroblasts closing a scratched monolayer using NetLogo to evaluate differences due to COPD or cigarette smoke condensate exposure. This ABM consists of a rule-set governing the healing response, accounting for cell migration, proliferation, death, activation and senescence rates; along with the effects of heterogeneous activation, phenotypic changes, serum deprivation and exposure to cigarette smoke condensate or bFGF. Simulations were performed to calibrate …

Managing Exoelectrogenic Microbial Community Development Through Bioprocess Control For Conversion Of Biomass-Derived Streams, Alex James Lewis

Doctoral Dissertations

Bioelectrochemical systems are an emerging technology capable of utilizing aqueous waste streams generated during biomass conversion of lignocellulosic feedstocks to produce valuable co-products and thus, have potential to be integrated into biorefineries. In a microbial electrolysis cell, organic compounds are converted to electrons, protons, and CO₂ by fermentative and exoelectrogenic bacteria in the anode compartment. By having the ability to extract electrons from waste streams, these systems can treat water while also producing hydrogen, and thus can improve the efficiency of biomass to fuel production by minimizing external hydrogen requirement and enabling water recycle. The overall goal of this …

Catalyzed Synthesis Of Zinc Clays By Prebiotic Central Metabolites, Marcelo I. Guzman, Ruixin Zhou, Kaustuv Basu, Hyman Hartman, Christopher J. Matocha, S. Kelly Sears, Hajatollah Vali

Chemistry Faculty Publications

How primordial metabolic networks such as the reverse tricarboxylic acid (rTCA) cycle and clay mineral catalysts coevolved remains a mystery in the puzzle to understand the origin of life. While prebiotic reactions from the rTCA cycle were accomplished via photochemistry on semiconductor minerals, the synthesis of clays was demonstrated at low temperature and ambient pressure catalyzed by oxalate. Herein, the crystallization of clay minerals is catalyzed by succinate, an example of a photoproduced intermediate from central metabolism. The experiments connect the synthesis of sauconite, a model for clay minerals, to prebiotic photochemistry. We report the temperature, pH, and concentration dependence …

Biosimp: Using Software Testing Techniques For Sampling And Inference In Biological Organisms, Mikaela Cashman, Jennie L. Catlett, Myra B. Cohen, Nicole R. Buan, Zahmeeth Sakkaff, Massimiliano Pierobon, Christine A. Kelley

CSE Conference and Workshop Papers

Years of research in software engineering have given us novel ways to reason about, test, and predict the behavior of complex software systems that contain hundreds of thousands of lines of code. Many of these techniques have been inspired by nature such as genetic algorithms, swarm intelligence, and ant colony optimization. In this paper we reverse the direction and present BioSIMP, a process that models and predicts the behavior of biological organisms to aid in the emerging field of systems biology. It utilizes techniques from testing and modeling of highly-configurable software systems. Using both experimental and simulation data we show …

Prospective Doctoral Statement For The University Of Southern California's School Of Cinematic Arts Media Arts + Practice Program, Gabriel Leiner

Gabriel Leiner

After visiting L.A. again and seeing the beautiful fountains on the University of Southern California's campus I am filled with all kinds of ideas about the future and brimming with energy. To all those at the University of Southern California's Cinematic Arts Department, thanks for reading my ideas over the past couple years and helping me to evolve and become a better person and a better writer. Starting a position as a doctoral student in the Media Arts + Practice Program in 2016 is an exciting opportunity. I've got a really positive outlook about Kiss The Water.

In Silico Driven Metabolic Engineering Towards Enhancing Biofuel And Biochemical Production, Richard Adam Thompson

Doctoral Dissertations

The development of a secure and sustainable energy economy is likely to require the production of fuels and commodity chemicals in a renewable manner. There has been renewed interest in biological commodity chemical production recently, in particular focusing on non-edible feedstocks. The fields of metabolic engineering and synthetic biology have arisen in the past 20 years to address the challenge of chemical production from biological feedstocks. Metabolic modeling is a powerful tool for studying the metabolism of an organism and predicting the effects of metabolic engineering strategies. Various techniques have been developed for modeling cellular metabolism, with the underlying principle …

Theoretical Investigation Of Intra- And Inter-Cellular Spatiotemporal Calcium Patterns In Microcirculation, Jaimit B. Parikh

FIU Electronic Theses and Dissertations

Microcirculatory vessels are lined by endothelial cells (ECs) which are surrounded by a single or multiple layer of smooth muscle cells (SMCs). Spontaneous and agonist induced spatiotemporal calcium (Ca²⁺) events are generated in ECs and SMCs, and regulated by complex bi-directional signaling between the two layers which ultimately determines the vessel tone. The contractile state of microcirculatory vessels is an important factor in the determination of vascular resistance, blood flow and blood pressure. This dissertation presents theoretical insights into some of the important and currently unresolved phenomena in microvascular tone regulation. Compartmental and continuum models of isolated EC …

Robust Dynamic Balance Of Ap-1 Transcription Factors In A Neuronal Gene Regulatory Network., Gregory M Miller, Babatunde A Ogunnaike, James S Schwaber, Rajanikanth Vadigepalli

Rajanikanth Vadigepalli

BACKGROUND: The octapeptide Angiotensin II is a key hormone that acts via its receptor AT1R in the brainstem to modulate the blood pressure control circuits and thus plays a central role in the cardiac and respiratory homeostasis. This modulation occurs via activation of a complex network of signaling proteins and transcription factors, leading to changes in levels of key genes and proteins. AT1R initiated activity in the nucleus tractus solitarius (NTS), which regulates blood pressure, has been the subject of extensive molecular analysis. But the adaptive network interactions in the NTS response to AT1R, plausibly related to the development of …

Sprawl Angle In Simplified Models Of Vertical Climbing: Implications For Robots And Roaches, Goran A. Lynch, Lawrence Rome, Daniel E. Koditschek

Daniel E Koditschek

Empirical data taken from fast climbing sprawled posture animals reveals the presence of strong lateral forces with significant pendulous swaying of the mass center trajectory in a manner captured by a recently proposed dynamical template. In this simulation study we explore the potential benefits of pendulous dynamical climbing in animals and in robots by examining the stability and power advantages of variously more and less sprawled limb morphologies when driven by conventional motors in contrast with animal-like muscles. For open loop models of gait generation inspired by the neural-deprived regimes of high stride-frequency animal climbing, our results corroborate earlier hypotheses …

Kinetic Analytical Method For Determination Of Uric Acid In Human Urine Using Analyte Pulse Perturbation Technique, Zeljko D. Cupic

Zeljko D Cupic

No abstract provided.

An Investigation Of Reflective Mulches For Use Over Capillary Mat Systems For Winter-Time Greenhouse Strawberry Production, George E. Meyer, Ellen T. Paparozzi, Elizabeth Walter-Shea, Erin E. Blankenship, Stacy A. Adams

Department of Agronomy and Horticulture: Faculty Publications

Photosynthethically active radiation (PAR) is a principle environmental variable used by horticultural specialists, agronomists and ecosystem modelers to characterize the quantity and quality of light conducive to plant growth and development. Spatial distribution of PAR in a greenhouse can be quite variable and diffuse throughout the day time photoperiod, especially at low sun angles in northern regions of the United States. Four colors of reflective plastic mulches (white, red, olive, and black) were evaluated for winter-time strawberry (Fragaria × ananassa Duch.) production based on their reflectance and transmittance properties in a double-polyethylene, plastic-glazed Quonset greenhouse inNebraska. The spectral properties …

Computer Simulation Of A Hollow-Fiber Bioreactor: Heparan Regulated Growth Factors-Receptors Binding And Dissociation Analysis, Changjiang Zhang

University of Kentucky Doctoral Dissertations

This thesis demonstrates the use of numerical simulation in predicting the behavior of proteins in a flow environment.

A novel convection-diffusion-reaction computational model is first introduced to simulate fibroblast growth factor (FGF-2) binding to its receptor (FGFR) on cell surfaces and regulated by heparan sulfate proteoglycan (HSPG) under flow in a bioreactor. The model includes three parts: (1) the flow of medium using incompressible Navier-Stokes equations; (2) the mass transport of FGF-2 using convection-diffusion equations; and (3) the cell surface binding using chemical kinetics. The model consists of a set of coupled nonlinear partial differential equations (PDEs) for flow and …

Mathematical Modeling Of Clostridium Thermocellum’S Metabolic Responses To Environmental Perturbation, Bless Adotey

Theses and Dissertations--Biosystems and Agricultural Engineering

Clostridium thermocellum is a thermophilic anaerobe that is capable of producing ethanol directly from lignocellulosic compounds, however this organism suffers from low ethanol tolerance and low ethanol yields. In vivo mathematical modeling studies based on steady state traditional metabolic flux analysis, metabolic control analysis, transient and steady states’ flux spectrum analysis (FSA) were conducted on C. thermocellum’s central metabolism. The models were developed in Matrix Laboratory software ( MATLAB^® (The Language of Technical Computing), R2008b, Version 7.7.0.471)) based on known stoichiometry from C. thermocellum pathway and known physical constraints. Growth on cellobiose from Metabolic flux analysis (MFA) and Metabolic …

Improvement Of The Stoichiometric Network Analysis For Determination Of Instability Conditions Of Complex Nonlinear Reaction Systems, Zeljko D. Cupic

Zeljko D Cupic

No abstract provided.

Robust Dynamic Balance Of Ap-1 Transcription Factors In A Neuronal Gene Regulatory Network., Gregory M Miller, Babatunde A Ogunnaike, James S Schwaber, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: The octapeptide Angiotensin II is a key hormone that acts via its receptor AT1R in the brainstem to modulate the blood pressure control circuits and thus plays a central role in the cardiac and respiratory homeostasis. This modulation occurs via activation of a complex network of signaling proteins and transcription factors, leading to changes in levels of key genes and proteins. AT1R initiated activity in the nucleus tractus solitarius (NTS), which regulates blood pressure, has been the subject of extensive molecular analysis. But the adaptive network interactions in the NTS response to AT1R, plausibly related to the development of …

Stoichiometric Network Analysis And Associated Dimensionless Kinetic Equations. Application To A Model Of The Bray-Liebhafsky Reaction, Zeljko D. Cupic

Zeljko D Cupic

No abstract provided.