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Articles 1 - 21 of 21
Full-Text Articles in Life Sciences
Quantifying Components Of Protein Translation And Metabolite Heterogeneity In Isogenic Microbial Populations, Alexander Schmitz
Quantifying Components Of Protein Translation And Metabolite Heterogeneity In Isogenic Microbial Populations, Alexander Schmitz
McKelvey School of Engineering Theses & Dissertations
Cell-to-cell variation in gene expression and metabolite levels have a significant impact on ensemble productivity of microbial bioproduction. New metabolic engineering tools and approaches are needed that consider cell cultures as an amalgam of uniquely behaving individuals to improve the slow commercialization of metabolically engineered systems. Stochastic cellular process including gene expression, metabolism, and growth lead to phenotypic variation between genetically identical cells. Understanding and the ability to control microbial phenotypic variation is key to improving microbial bioproduction metrics. During protein translation, codon usage strongly influences ensemble gene expression but the effect on the variation of gene expression was not …
Defining The Role Of Elastic Fibers In Tendon Mechanics, Jeremy D. Eekhoff
Defining The Role Of Elastic Fibers In Tendon Mechanics, Jeremy D. Eekhoff
McKelvey School of Engineering Theses & Dissertations
Tendons serve as a linking component of the musculoskeletal system by transferring forces between muscle and bone. As such, the structural proteins of the tendon extracellular matrix are of vital importance for the tissue to function properly and maintain its mechanical integrity. Collagen is the principal constituent of tendon and makes up its aligned hierarchical organization. Other structural proteins, such as elastin, are in comparison understudied and not well understood in relation to tendon function. Elastin, the main component of elastic fibers, has unique mechanical properties including high extensibility, fatigue resistance, and elasticity; these properties are important for elastin-rich tissues …
Toward Lignin Valorization: Development Of Rhodococcus Opacus Pd630 As A Chassis For Triacylglycerol (Tag) Production From Recalcitrant Aromatic Feedstocks, Rhiannon R. Carr
Toward Lignin Valorization: Development Of Rhodococcus Opacus Pd630 As A Chassis For Triacylglycerol (Tag) Production From Recalcitrant Aromatic Feedstocks, Rhiannon R. Carr
McKelvey School of Engineering Theses & Dissertations
The advent of the industrial era was precipitated by the discovery of fossil fuels, and ushered in unprecedented changes for humanity included but not limited to the development of rapid transit and communications, improvements to food distribution and preservation, the mass production of goods, and a radical rearrangement of communities from relatively small enclaves to metropolises. With all the benefits, however, come considerable costs, especially to the global environment. Greenhouse gas emissions, built up over centuries of unregulated combustion, have precipitated a rate of global temperature change unparalleled in the 4.5 billion-year history of this planet. In order to preserve …
Human Ipsc Tissue-Engineered Cartilage For Disease Modeling Of Skeletal Dysplasia-Causing Trpv4 Mutations, Amanda R. Dicks
Human Ipsc Tissue-Engineered Cartilage For Disease Modeling Of Skeletal Dysplasia-Causing Trpv4 Mutations, Amanda R. Dicks
McKelvey School of Engineering Theses & Dissertations
Cartilage is essential to joint development and function. However, there is a variety of cartilage diseases, ranging from developmental (e.g., skeletal dysplasias) to degenerative (e.g., arthritis), in which treatments and therapeutics are lacking. For example, specific point mutations in the ion channel transient receptor potential vanilloid 4 (TRPV4) prevent proper joint development, leading to mild brachyolmia and severe, neonatally lethal metatropic dysplasia. Tissue-engineered cartilage offers an opportunity to elucidate the underlying mechanisms of these cartilage diseases for the development of treatments. Human induced pluripotent stem cells (hiPSCs) are an improved cell source option for cartilage tissue engineering given their minimal …
Towards The Discovery Of Prognostic Biomarkers For Glioblastoma Using Resting-State Functional Connectivity, Andy G. S. Daniel
Towards The Discovery Of Prognostic Biomarkers For Glioblastoma Using Resting-State Functional Connectivity, Andy G. S. Daniel
McKelvey School of Engineering Theses & Dissertations
Gliomas are highly diffusive, primary brain tumors. The most malignant form, glioblastoma, has a dismal survival rate: 14-17 months following the current standard of care, which consists of surgery, radiation, and chemotherapy. Insights into the molecular, cellular, and microenvironmental components of glioblastoma have revealed a vast array of factors utilized to support its proliferation, infiltration, and resistance to treatment. Recent advancements have also identified diagnostic and prognostic biomarkers that are now being used to guide treatment planning. However, survival has improved only marginally, thus emphasizing the continued need for novel biomarkers and treatment strategies. Given its delicate location in the …
Long-Term Neural Activity Recorders Using Energy-Based Sensing, Compressive Computation And Data Logging, Darshit Mehta
Long-Term Neural Activity Recorders Using Energy-Based Sensing, Compressive Computation And Data Logging, Darshit Mehta
McKelvey School of Engineering Theses & Dissertations
Insects are ideal candidates for developing bio-robotic systems owing to their ability to thrive in almost any environment. For example, neurons in their exquisite olfactory sensory systems can be tapped to create a sensing platform for standoff chemical monitoring. However, for enabling such cyborg systems, it is vital that the neural activity of a freely behaving organism can be measured for long periods of time. The current state-of-the-art neural recording techniques are power-intensive and they either need batteries, which make them too bulky for insects, or they have to maintain a continuous telemetry link to an external power source which …
Mechanisms For Osteoblast And Osteocyte Initiation And Sustainment Of Bone Formation In Young-Adult And Aged Mice, Taylor Lynn Harris
Mechanisms For Osteoblast And Osteocyte Initiation And Sustainment Of Bone Formation In Young-Adult And Aged Mice, Taylor Lynn Harris
McKelvey School of Engineering Theses & Dissertations
The cellular mechanisms for loading-induced bone formation, from osteocyte mechano-sensation to osteoblast-directed bone formation, are not well understood. Elucidating these mechanisms and identifying any processes that are disrupted in aged mice can aide in the development of new anabolic drugs for treating diseases like osteoporosis. This thesis begins by investigating the genes expressed by osteocytes following loading at an early mechanosensitive (4-hr) timepoint, and later at a bone-forming (day 5) timepoint. We demonstrated increases in Ngf and Wnt1 in osteocyte-enriched intracortical bone by laser capture microdissection and microarray analysis. These results were important in demonstrating the presence of Ngf in …
Elucidating And Leveraging Dynamics-Function Relationships In Neural Circuits Through Modeling And Optimal Control, Sruti Mallik
Elucidating And Leveraging Dynamics-Function Relationships In Neural Circuits Through Modeling And Optimal Control, Sruti Mallik
McKelvey School of Engineering Theses & Dissertations
A fundamental research question in neuroscience pertains to understanding how neural networks through their activity encode and decode information. In this research, we build on methods from theoretical domains such as control theory, dynamical systems analysis and reinforcement learning to investigate such questions. Our objective is two-fold: first, to use methods from engineering to identify specific objectives that neural circuits might be optimizing through their spatiotemporal activity patterns, and second, to draw motivation from neuroscience to formulate new engineering principles such as synthesis of dynamical networks for decentralized control applications. We specifically take a top-down, optimization driven approach in our …
Disentangling Glial Diversity In Peripheral Nerves At Single Nuclei Resolution, Aldrin Kay Yuen Yim
Disentangling Glial Diversity In Peripheral Nerves At Single Nuclei Resolution, Aldrin Kay Yuen Yim
Arts & Sciences Electronic Theses and Dissertations
The ability to discern gene expression at single cell level is revolutionizing our understanding of both basic biology and human health. Peripheral nerves are essential communicators between the outside world and the CNS, as evidenced by the devastating effects of diseases that disrupt them, such as ALS, Charcot-Marie-Tooth Syndrome and diabetic neuropathy. Understanding peripheral nerve dysfunction at a mechanistic level is of considerable interest due to the increasing prevalence and associated patient care costs of these disorders. Although most research of the peripheral nerve has focused on glial-axonal interactions, the important contributions of other cell types besides Schwann cells, such …
Cortical Organization In Humans And Nonhuman Primates: The Evolution Of Cognitive Areas And Circuits, Chad Joseph Donahue
Cortical Organization In Humans And Nonhuman Primates: The Evolution Of Cognitive Areas And Circuits, Chad Joseph Donahue
McKelvey School of Engineering Theses & Dissertations
Similarities in organization of cerebral cortex in humans and nonhuman primates offer the promise of leveraging data from invasive animal studies to better understand the complexities of the human brain, particularly those related to higher cognitive function (e.g. attention, working memory, language). Such comparisons necessitate the identification of convincing cortical homologues (areas or regions presumed to have derived from a common ancestor), requiring an accurate interspecies mapping of cortical areas and features. To this end, I describe (i) a survey of connectivity and its measures across primate species, particularly retrograde tracing and diffusion tractography, (ii) a morphometric analysis of cognitive …
Synthetic Gene Circuits For Self-Regulating And Temporal Delivery Of Anti-Inflammatory Biologic Drugs In Engineered Tissues, Lara Pferdehirt
Synthetic Gene Circuits For Self-Regulating And Temporal Delivery Of Anti-Inflammatory Biologic Drugs In Engineered Tissues, Lara Pferdehirt
McKelvey School of Engineering Theses & Dissertations
The recent advances in the fields of synthetic biology and genome engineering open up new possibilities for creating cell-based therapies. We combined these tools to target repair of articular cartilage, a tissue that lacks a natural ability to regenerate, in the presence of arthritic diseases. To this end, we developed cell-based therapies that harness disease pathways and the unique properties of articular cartilage for prescribed, localized, and controlled delivery of biologics, creating the next generation of cell therapies and new classes of synthetic circuits. We created tissue engineered cartilage from murine induced pluripotent stem cells that had the ability to …
Subject-Specific Musculoskeletal Modeling Of Hip Dysplasia Biomechanics, Ke Song
Subject-Specific Musculoskeletal Modeling Of Hip Dysplasia Biomechanics, Ke Song
McKelvey School of Engineering Theses & Dissertations
Developmental dysplasia of the hip (DDH) is characterized by abnormal bony anatomy, causes pain and functional limitations, and is a prominent risk factor for premature hip osteoarthritis. Although the pathology of DDH is believed to be mechanically-induced, little is known about how DDH anatomy alters hip biomechanics during activities of daily living, partly due to the difficulties with measuring hip muscle and joint forces. Musculoskeletal models (MSMs) are useful for dynamic simulations of joint mechanics, but the reliability of MSMs for DDH research is limited by an accurate model representation of the unique hip anatomy. To address such challenges, this …
Autologous Stem Cell-Derived Β Cells For Diabetes Cell Replacement Therapy, Kristina G. Maxwell
Autologous Stem Cell-Derived Β Cells For Diabetes Cell Replacement Therapy, Kristina G. Maxwell
McKelvey School of Engineering Theses & Dissertations
Autologous stem cell therapy is a promising treatment for patients with diabetes worldwide. Previous stem cell-derived β (SC-β) cell protocols were unable to efficiently differentiate multiple patient induced pluripotent stem cells (iPSCs) into stem cell-derived islets (SC-islets), containing insulin-secreting SC-β cells. Recent updates targeting the actin cytoskeleton have enabled the differentiation of 14 diabetic and nondiabetic stem cell lines into SC-islets. We used genetic engineering, specifically CRISPR/Cas9, to correct the diabetes-causing mutation in stem cells from patients with Wolfram Syndrome. The genetically engineered SC-β cells functioned and had a composition similar to nondiabetic SC-β cells, unlike the unedited SC-β cells …
Evaluating The Structural And Functional Consequences Of Traumatic Joint Injury And Their Relation To Nf-Κb In A Non-Invasive Model Of Post-Traumatic Osteoarthritis, Ian Matthew Berke
Evaluating The Structural And Functional Consequences Of Traumatic Joint Injury And Their Relation To Nf-Κb In A Non-Invasive Model Of Post-Traumatic Osteoarthritis, Ian Matthew Berke
McKelvey School of Engineering Theses & Dissertations
Post-traumatic osteoarthritis (PTOA) is a painful and debilitating disease of the synovial joint, characterized by degenerative changes to various joint tissues following traumatic joint injury. While several risk factors have been identified in the symptomatic progression of PTOA following injury, inflammation and NF-κB mediated changes are believed to significantly contribute to symptomatic joint dysfunction and pain. However, the temporal presentation of these pro-inflammatory signals following clinically relevant injury and their relationship to the development of symptomatic disease have not been thoroughly investigated. Therefore, there exists a critical need to better understand how these early inflammatory events following injury may contribute …
Uncovering The Roles And Evolved Sequence Grammar Of Hypervariable Intrinsically Disordered Proteins In Bacterial Cell Division, Megan Cohan
McKelvey School of Engineering Theses & Dissertations
Across all domains of life, a defining hallmark of the onset of cell division is the formation of a cytokinetic ring at the center of the cell. Cell division is a tightly controlled process that involves various regulatory factors that modulate the assembly of the cytokinetic ring. In rod-shaped bacteria, the ring is termed the Z-ring after the protein FtsZ, which is foundational to ring formation and is the bacterial homolog of tubulin. Like tubulin, FtsZ is an assembling GTPase, where GTP binding promotes the cooperative assembly into FtsZ polymers that laterally associate to form bundles. While the GTPase domain …
Neural Coding And Organization Principles In The Drosophila Olfactory System, Haoyang Rong
Neural Coding And Organization Principles In The Drosophila Olfactory System, Haoyang Rong
McKelvey School of Engineering Theses & Dissertations
Sensory systems receive and process external stimuli to allow an organism to perceive and react to the environment. How is sensory information subsequently represented, transformed, and interpreted in the neural system? In this dissertation, I have investigated this fundamental question using the fruit fly (Drosophila melanogaster) olfactory system.Chemical cues are transduced into neural signals in the insect antenna by the olfactory receptor neurons (ORNs). The ORNs send their axons to the antennal lobe (AL), with each ORN type innervating a specific neuropil (glomerulus), where they synapse onto excitatory and inhibitory projection neurons (ePNs and iPNs). The ePNs project their axons …
Neural Dynamics, Adaptive Computations, And Sensory Invariance In An Olfactory System, Srinath Nizampatnam
Neural Dynamics, Adaptive Computations, And Sensory Invariance In An Olfactory System, Srinath Nizampatnam
McKelvey School of Engineering Theses & Dissertations
Sensory stimuli evoke spiking activities that are patterned across neurons and time in the early processing stages of olfactory systems. What features of these spatiotemporal neural response patterns encode stimulus-specific information (i.e. ‘neural code’), and how they are translated to generate behavioral output are fundamental questions in systems neuroscience. The objective of this dissertation is to examine this issue in the locust olfactory system. In the locust antennal lobe (analogous to the vertebrate olfactory bulb), a neural circuit directly downstream to the olfactory sensory neurons, even simple stimuli evoke neural responses that are complex and dynamic. We found each odorant …
Constructing And Analyzing Neural Network Dynamics For Information Objectives And Working Memory, Elham Ghazizadeh Ahsaei
Constructing And Analyzing Neural Network Dynamics For Information Objectives And Working Memory, Elham Ghazizadeh Ahsaei
McKelvey School of Engineering Theses & Dissertations
Creation of quantitative models of neural functions and discovery of underlying principles of how neural circuits learn and compute are long-standing challenges in the field of neuroscience. In this work, we blend ideas from computational neuroscience, information and control theories with machine learning to shed light on how certain key functions are encoded through the dynamics of neural circuits. In this regard, we pursue the ‘top-down’ modeling approach of engineering neuroscience to relate brain functions to basic generative dynamical mechanisms. Our approach encapsulates two distinct paradigms in which ‘function’ is understood. In the first part of this research, we explore …
Differentiating Human Embryonic Stem Cells In Micropatterns To Study Cell Fate Specification And Morphogenetic Events During Gastrulation, Kyaw Thu Minn
McKelvey School of Engineering Theses & Dissertations
During mammalian embryogenesis, the first major lineage segregation occurs when embryonic epiblast, and extraembryonic trophectoderm and hypoblast arise in the blastocyst. In the next fundamental and conserved phase of animal embryogenesis known as gastrulation, extraembryonic cells provide signals to epiblast to instruct embryonic patterning, and epiblast gives rise to germ layers ectoderm, mesoderm, and endoderm, that will establish all embryonic tissues. Proper specification and morphogenesis of germ layers during gastrulation is vital for correct embryonic development. Due to ethical and legal restrictions limiting human embryo studies, human gastrulation is poorly understood. Our knowledge of human gastrulation has largely been derived …
Relating Spontaneous Activity And Cognitive States Via Neurodynamic Modeling, Matthew Singh
Relating Spontaneous Activity And Cognitive States Via Neurodynamic Modeling, Matthew Singh
Arts & Sciences Electronic Theses and Dissertations
Stimulus-free brain dynamics form the basis of current knowledge concerning functional integration and segregation within the human brain. These relationships are typically described in terms of resting-state brain networks—regions which spontaneously coactivate. However, despite the interest in the anatomical mechanisms and biobehavioral correlates of stimulus-free brain dynamics, little is known regarding the relation between spontaneous brain dynamics and task-evoked activity. In particular, no computational framework has been previously proposed to unite spontaneous and task dynamics under a single, data-driven model. Model development in this domain will provide new insight regarding the mechanisms by which exogeneous stimuli and intrinsic neural circuitry …
Midfoot And Ankle Movement Dysfunction In People With Diabetes Mellitus And Peripheral Neuropathy, Hyo Jung Jeong
Midfoot And Ankle Movement Dysfunction In People With Diabetes Mellitus And Peripheral Neuropathy, Hyo Jung Jeong
Arts & Sciences Electronic Theses and Dissertations
People with diabetes mellitus and peripheral neuropathy (DMPN) have midfoot and ankle musculoskeletal problems, including limited joint mobility and weakness and atrophy of foot intrinsic and calf muscles. Impaired foot structures and function could lead to midfoot and ankle movement dysfunction, measured by a heel rise task. A repeated movement dysfunction during weightbearing tasks (e.g., heel rise, walking) could cause excessive stress on the plantar tissue, which is a leading cause of plantar ulceration in people with DMPN. Understanding heel rise performance and the underlying mechanisms could help prevent the sequence of events associated with plantar ulcer development in people …