Engineering Commons^™

The Role Of The Neurodevelopmental Disorder Gene Myt1l In Mammalian Brain Development, Jiayang Chen

Arts & Sciences Electronic Theses and Dissertations

Recent human genetic studies have associated mutations in a gene called Myelin Transcription Factor 1 Like (MYT1L) with neurodevelopmental disorders (NDDs). Patients with MYT1L loss of function (LoF) mutations (MYT1L Syndrome patients) demonstrate shared symptoms such as microcephaly, attention deficit and hyperactivity disorder (ADHD), and obesity. Despite prior studies showing MYT1L overexpression facilitates neuronal differentiation in vitro, its functions in vivo, especially in the mammalian brain, and how its mutation leads to human disease pathology remains poorly understood. Here, I established the first mouse model of MYT1L Syndrome mimicking a patient specific LoF mutation. I found mice with Myt1l heterozygous …

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 …

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 …

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 …

Pathophysiology And Proteogenomics Of Post-Infectious And Post-Hemorrhagic Hydrocephalus In Infants, Albert M. Isaacs

Arts & Sciences Electronic Theses and Dissertations

Post-infectious (PIH) and post-hemorrhagic (PHH) hydrocephalus occur as sequalae of neonatal sepsis or intraventricular hemorrhage (IVH) of prematurity, respectively. Together, PIH and PHH represent the most common form of infantile hydrocephalus, the most common indication for neurosurgery in children globally, and the leading cause of neurological morbidity and mortality worldwide. The lack of understanding of the pathophysiology of PIH and PHH, particularly with regards to the host central nervous system response to the antecedent infection and hemorrhage, perturbation of differentiating neural stems in the ventricular (VZ) and subventricular (SVZ) zones, and damage to periventricular white matter (PVWM) tracts carrying sensorimotor …

Joint Estimation Of Perceptual, Cognitive, And Neural Processes, Katherine Heisey

Arts & Sciences Electronic Theses and Dissertations

Humans are remarkable in their ability to perform highly complicated behaviors with ease and little conscious thought. Successful speech comprehension, for example, requires the collaboration of multiple sensory, perceptual, and cognitive processes to focus attention on the speaker, disregard competing cues, correctly process incoming audio stimuli, and attach meaning and context to what is heard. Investigating these phenomena can help unravel crucial aspects of human behavior as well as how the brain works in health and disease. However, traditional methods typically involve isolating individual variables and evaluating their decontextualized contribution to an outcome variable of interest. While rigorous and more …

Phantoms To Placentas: Mr Methods For Oxygen Quantification, Kelsey Meinerz

Arts & Sciences Electronic Theses and Dissertations

Molecular oxygen (O2) is vital for efficient energy production and improper oxygenation is a hallmark of disease or metabolic dysfunction. In many pathologies, knowledge of tissue oxygen levels (pO2) could aid in diagnosis and treatment planning. The gold standard for pO2 measures in tissue are implantable probes, which are invasive, require surgery for placement, and are inaccessible to certain regions of the body. Methods for determining pO2 both non-invasively and quantitatively are lacking. The slight paramagnetic nature of O2 provides opportunities to non-invasively characterize pO2 in tissue via magnetic resonance (MR) techniques. As such, O2 can be treated as a …

Genetic Interactions And Maternal Genes Modulate Congenital Heart Disease Risk, Ehiole Ogboma Akhirome

Arts & Sciences Electronic Theses and Dissertations

Congenital heart disease (CHD) is the most common congenital anomaly, which makes it a leading cause of infant mortality. Congenital heart defects are a cluster of distinct developmental malformations that affect the vasculature, musculature and organization of the heart, each with varying clinical severity. Although medical and surgical advances have reduced CHD mortality in newborns and children, these patients grow up and many experience serious morbidity and early mortality. The first step toward reducing this burden is to understand the causes of CHD. Surprisingly, environmental insults and de novo mutations are estimated to explain less than one-third of CHD cases. …

Wheelchair Propulsion For Everyday Manual Wheelchair Users: Repetition Training And Machine Learning-Based Monitoring, Pin-Wei Chen

Arts & Sciences Electronic Theses and Dissertations

Upper limb pain and injuries are prevalent among manual wheelchair users and can restrict their participation and daily activities. Due to the high repetition and force in wheelchair propulsion, chronic wheelchair propulsion has been linked to the risk of upper limb pain and injury. Prevention of upper limb pain and injury is a high priority in wheelchair-related research. Decades of research in wheelchair propulsion biomechanics have led to clinical practice guidelines (CPG). Unfortunately, a decade after the publication of the CPG, CPG-recommended propulsion is still uncommon. Hence, for the first aim, a randomized controlled trial pilot study with two groups …

Quantitatively Studying Tissue Damage In Multiple Sclerosis Using Gradient Recalled Echo Mri Sequences, Biao Xiang

Arts & Sciences Electronic Theses and Dissertations

Multiple Sclerosis (MS) is an unpredictable, often disabling disease of the central nervous system (CNS) that disrupts the flow of information within the brain, and between the brain the body. MS is the most common progressive neurologic disease of young adults, affecting approximately 2.3 million people worldwide. It is estimated that more than 700,000 individuals are affected by MS in United States. While MS has been studied for decades, the cause of it is still not definite and a fully effective treatment for MS is not yet available.

Magnetic resonance imaging (MRI) has been used extensively in MS diagnosis and …

Quantitatively Studying Tissue Damage In Multiple Sclerosis Using Gradient Recalled Echo Mri Sequences, Biao Xiang

Arts & Sciences Electronic Theses and Dissertations

Multiple Sclerosis (MS) is an unpredictable, often disabling disease of the central nervous system (CNS) that disrupts the flow of information within the brain, and between the brain the body. MS is the most common progressive neurologic disease of young adults, affecting approximately 2.3 million people worldwide. It is estimated that more than 700,000 individuals are affected by MS in United States. While MS has been studied for decades, the cause of it is still not definite and a fully effective treatment for MS is not yet available. Magnetic resonance imaging (MRI) has been used extensively in MS diagnosis and …

Modeling Mechanisms Behind Force Generation By Actin Polymerization, Seyed Fowad Motahari

Arts & Sciences Electronic Theses and Dissertations

Actin polymerization is the primary mechanism for overcoming the large turgor pressure that opposes endocytosis in yeast. While generation of pushing forces by actin polymerization is fairly well understood, it is not clear how actin polymerization produces pulling forces. In order to understand this process, it is necessary to simulate polymerization of filaments having various types of interactions with the membrane. Since existing methodologies in the literature do not treat such problems correctly, we develop a thermodynamically consistent methodology for treating polymerization of filaments having arbitrary interaction potentials with the membrane. Then I perform stochastic simulations for a system of …

Vrshape: A Virtual Reality Tool For Shaping Movement Compensation, Matthew Hale Foreman

Arts & Sciences Electronic Theses and Dissertations

The majority of persons living with chronic stroke experience some form of upper extremity motor impairment that affects their functional movement, performance of meaningful activities, and participation in the flow of daily life. Stroke survivors often compensate for these impairments by adapting their movement patterns to incorporate additional degrees of freedom at new joints and body segments. One of the most common compensatory movements is the recruitment of excessive trunk flexion when reaching with the affected upper extremity. Long-term use of these compensations may lead to suboptimal motor recovery and chronic pain or injury due to overuse. Rehabilitation focuses on …