Cholesterol Biosynthesis in the Nervous System with an Emphasis on Desmosterolosis

Cholesterol biosynthesis is integral to proper neurodevelopment due to the reliance on de novo synthesis of cholesterol in the brain. Disruptions in this process have devastating outcomes for human life characterized by several phenotypic manifestations concomitant with developmental delay. The cholesterol biosynthesis disorder desmosterolosis is an extremely rare disorder with a severe clinical phenotype, however, the models used to study this disease are not well characterized. In addition to genetic disruptions in cholesterol biosynthesis, pharmacological perturbation is an understudied side effect of many commonly prescribed drugs. Here we present a characterization of the sterol profile of the mouse model of desmosterolosis followed by an examination of one such pharmacological inhibitor of cholesterol biosynthesis, amiodarone. Amiodarone is a commonly prescribed medication used to treat life-threatening atrial and ventricular arrhythmias with the primary target being potassium channels and beta adrenergic receptors. We show that amiodarone is also a potent inhibitor of several cholesterol biosynthesis enzymes in various cell culture models, affecting the enzymes 24-dehydrocholesterol reductase (Dhcr24) and emopamil binding protein (Ebp). Additionally we show that the serum of amiodarone users have elevated levels of desmosterol, zymosterol, zymostenol and 8-dehydrocholesterol. Our study provides evidence that the use of various medications, unrelated to cholesterol metabolism, may lead to potentially severe clinical consequences related to the inhibition of sterol biosynthetic enzymes

Neuroimaging of Sudden Unexpected Death in Epilepsy (SUDEP)

BACKGROUND: Sudden unexpected death in epilepsy (SUDEP) is the leading cause of premature death among people with epilepsy. The precise mechanisms underlying SUDEP remain elusive, though work so far demonstrates a potential centrally mediated event in which autonomic, respiratory and/or arousal processes fail to recover following a significant seizure. Neuroimaging enables non-invasive assessment of the structural and functional architecture among sites and networks involved in regulating such processes; damage or alterations may indicate a central predisposition in those at high-risk and who suffer SUDEP, and provide non-invasive biomarkers. // METHODS: In this thesis, structural and functional imaging techniques were employed to address this possibility. Both retrospective investigations of those who succumbed to SUDEP, and prospective studies of those at high-risk, were performed. Voxel-based morphometry, volumetry and resting-state functional magnetic resonance imaging (RS-fMRI) network analysis techniques were utilised to identify and characterise brain structural and functional alterations relative to low-risk subjects and controls. // RESULTS: Brain morphometric and volumetric alterations among sites involved in cardiorespiratory regulation and recovery were found in those who later suffered SUDEP and in matched, living individuals at high risk. Prospective work revealed similar, and additional, structural alterations in those at high-risk which were associated with the extent of seizure-related hypoxemia; notably among the thalamus, periaqueductal grey (PAG), medulla, vermis and hippocampus. Network analysis of functional imaging data revealed disturbed patterns of connectivity in high-risk temporal lobe epilepsy (TLE) patients, and altered functional organisation in confirmed cases of SUDEP, among regulatory brain sites as well as the whole brain. // CONCLUSIONS: Structural and resting state functional connectivity disturbances were found in patients who suffered SUDEP, and those at elevated risk. Injury and connectivity disturbances may indicate damage or dysfunction within sites and networks involved central regulatory processes, which could facilitate SUDEP. However, further work is required to elucidate the precise mechanisms of volume and functional connectivity alterations, and to provide firm links between centrally mediated autonomic and respiratory dysfunction, SUDEP and related imaging findings. A more immediate use for the imaging outcomes revealed here may rest with the development of non-invasive biomarkers, which may one day assist in identifying those at risk and evaluating individual risk for SUDEP based on injury to brain sites or altered functional networks

Jominy Hardenability Tester with In-Situ Heating

This project centers on building a Jominy Hardenability tester with In-Situ heating for the manufacturing lab at the University of Akron. A new process and setup will be designed using engineering concepts in order to make the testing more efficient and safer for the teaching and testing of metal hardness. The current Jominy testing setup has efficiency issues within the transfer of specimen from induction heater to testing rig. Our design will simplify the design by creating a test rig that removes the traveling aspect of the specimen which will limit the amount of premature cooling done and will be much safer for whom ever undergoes the test. The possibility of dropping a red-hot specimen onto the ground endangering those around is too great to be overlooked. A new process and design must be done to improve the existing model

The coronavirus outbreak: the central role of primary care in emergency preparedness and response

On the last day of 2019, a cluster of cases of a pneumonia with unknown cause were reported by the Chinese authorities to the World Health Organization (WHO), believed to be connected to a seafood market in Wuhan, China. This market was closed the following day. On 7 January 2020, a novel coronavirus was isolated, and known pathogens were ruled out.1 Coronaviruses usually cause respiratory illness ranging from the common cold to severe acute respiratory syndrome (SARS). Clinical symptoms and signs of the Wuhan coronavirus include fever, with some sufferers experiencing difficulty breathing and bilateral pulmonary infiltrates seen on chest X-ray. WHO are referring to it as ‘2019-nCov’. At the time of writing, there have been over 4,500 confirmed cases and 106 deaths, including among healthcare workers. Over 98% of these cases are within mainland China, but cases have also been confirmed in tens of other countries

Quantifying entrainment and dilution in numerical simulations of developing thunderstorms

Entrainment is the process by which turbulent clouds draw environmental air inward, and this process has long been understood to dilute the cloud, i.e., reduce the cloud liquid water content, buoyancy, and updraft velocity. In cumuli, entrainment results from overturning thermal circulations near cloud top. Past observational and numerical modeling studies have shown that in environments with significant vertical wind shear, the down-shear circulation is stronger. It has been hypothesized that greater entrainment (and thus dilution) occurs in stronger shear environments, but this relationship has not been suitably demonstrated with direct calculations of entrainment. This lack of understanding has consequences on the numerical weather prediction of convective initiation and development, as well as climate modeling. Here, entrainment is quantified within six different high-resolution numerical simulations of developing thunderstorms in environments with different wind profiles to understand the role of vertical wind shear in modulating cumulus entrainment. Entrainment is directly quantified using the mass flux across a defined cloud core surface. Greater entrainment consistently occurs in simulated storms developing in environments with greater vertical wind shear, due to stronger overturning thermal circulations near the cloud tops, and greater storm-relative inflow on the down-shear side of the cloud. Evaluations of the dilution produced by entrainment in the developing storms is often obscured by successive thermals in the sheared environments, often rising through the remains of previous thermals that modified the air entrained by the later thermals. The storms growing in strong-shear environments are also broader, so a smaller fraction of the cloud is affected by each individual entrainment event. Precipitation production appeared to be more related to the time the cloud had been present, and the aid of successive thermals, than entrainment and dilution. Thus, while more entrainment occurs in the higher-shear environments, and stronger forcing is required for the storms to develop, the enhanced interaction of successive thermals in such environments, as well as their enhanced core widths, can enable the development of deep convective storms

Effectiveness of conservation education at the Chattanooga Zoo

Conservation is the central focus of many modern zoos and aquariums. These zoos incorporate guest education to facilitate a connection between zoo guests and animal conservation. I conducted a study at the Chattanooga Zoo and the University of Tennessee at Chattanooga which examined two modern zoo education approaches. The two approaches utilized in the study are currently used in keeper chats at the Chattanooga Zoo. The first approach is an emotional appeal (an appeal to the personalities of the chimps at the zoo) and the second approach is a utilization of a take-action initiative (recycling cell phones to reduce mining in chimpanzee habitat). Both approaches were placed at the beginning of the same chimpanzee presentation which exclusively involved facts about chimpanzees. These two approaches were tested against a control presentation that involved only the chimpanzee facts and no educational approaches. All three presentations were given to two populations, zoo guests and UTC students in front of the chimpanzee exhibit at the zoo and in various lecture halls at UTC. My goal was to examine the effects of these approaches on retention of chimpanzee related information. I hypothesized that incorporating an emotional appeal in an informational chat increases guest retention more than using a take-action initiative. The response data collected from the Chattanooga Zoo revealed no significant differences in guest retention of information between any of the three zoo chats (presentations) due to small sample size. The results from the UTC student population did yield statistically significant differences. The group exposed to the emotional appeal scored the highest on average, followed by the control group, and finally the take-action initiative group. My study may serve as a starting point for future research involving effectiveness of conservation messaging at the Chattanooga Zoo

COMPARISON OF MUSCLE ACTIVATION AND KINEMATICS DURING THE DEADLIFT USING A DOUBLE‐PRONATED AND OVERHAND/UNDERHAND GRIP

This study examined muscle activation and relative joint angles during a conventional deadlift while using either a double‐pronated or overhand/underhand (OU) grip. Ten weight‐trained individuals performed the deadlift with 60% and 80% of their 1‐repetition maximum, with three different grip variations. EMG recordings were taken of the left and right biceps brachii, brachioradialis, upper trapezius, and upper latissimus dorsi. Motion capture was used to measure angles of the wrist, elbow, knee, and hip. With an OU grip, significant bilateral asymmetry was seen in EMG activity of biceps brachii and brachioradialis. Mean wrist and elbow angle also showed significant bilateral asymmetry when using an OU grip. Training recommendations for the OU grip deadlift should emphasize the need to vary which hand is supinated/pronated to avoid muscle imbalances and possible injury. Furthermore, it may be preferential to use a double‐pronated grip to avoid asymmetric training altogether

Lies Behind Bars: An Analysis of the Problematic Reliance on Jailhouse Informant Testimony in the Criminal Justice System and a Texas-Sized Attempt to Address the Issue

The advent of DNA technology in the late 1980s led to a wave of exonerations in the United States, shedding light on major problems with the U.S. criminal justice system. Many of these wrongful convictions were traced back to criminal informants, colloquially referred to as “snitches,” who provided incriminating testimony in exchange for a sentence reduction, leniency, inmate privileges, or some other perk. The correlation between wrongful convictions and informant testimony is a cause for concern, especially in Texas, where more people have been executed and exonerated than anywhere else in the country. This Note analyzes the use of criminal informants with a particular focus on jailhouse informants—inmates that come forward with the “confessions” of fellow inmates. First, this Note discusses the broad use of criminal informants throughout history and the problems that have arisen therefrom. Second, it examines Nolley v. State, the Texas Court of Criminal Appeals case that inspired legislative change in Texas. Third, this Note assesses Texas House Bill 34, which is Texas’s latest legislative effort to regulate the use of jailhouse informants. Finally, this Note proposes a solution to address the problem of unreliable jailhouse informant testimony that requires judges to serve a “gatekeeping role” through which they could filter out unreliable testimony before trial. As part of this solution, this Note recommends giving judges and defense attorneys access to a statewide database containing information on every jailhouse informant ever used so that they do not have to rely on the prosecution to produce that information. Though this solution will add to the workload of judges, it is necessary to prevent prosecutorial misconduct and ensure the integrity of the U.S. criminal justice system