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STUDIES OF ENANTIOSPECIFIC INTERACTION BETWEEN CHIRAL MOLECULES AND MAGNETIZED SURFACES
No full textThe chiral induced spin selectivity (CISS) effect describes the spin-dependent transport of electrons through chiral molecules, in which the preferred spin orientation is determined by the handedness of the molecule and the direction of motion. The CISS effect has attracted considerable research interest due to its important implications across a wide range of scientific fields, including enantiomeric resolution, spin controlled chemical reactions, biorecognition, among others. In this dissertation, fundamental studies on the enantiospecific spin exchange interaction between chiral molecules and magnetized ferromagnetic substrates are investigated and leveraged for enantioseparation, enantiorecognition and enantiospecific polymerization studies. In the first study, the enantiospecific adsorption of cysteine on a ferromagnetic electrode was shown to arise from a kinetically controlled process and not from a thermodynamic stabilization. In the second study, the enantiospecific adsorption of cysteine on a ferromagnetic electrode at different pHs was investigated. Here, the kinetics for enantiospecific adsorption were found to depend strongly on the charge state and geometry of the adsorbate. In the third study, the effects of spin on the enantioselective binding of amino acids with N-acetyl-cysteine coated ferromagnetic electrodes was probed. These studies revealed that the intermolecular interactions between the amino acids and the chiral ferromagnetic surface depend on the electron spin. In the fourth study, Two enantioselective electrochemical reactions that have used polarized electron spins as a chiral reagent are described; enantioselective electroreduction to resolve an enantiomer from a racemic mixture and an oxidative electropolymerization to generate a chiral polymer from achiral monomers. These studies provide a more fundamental understanding of the CISS effect, identify the key contributions necessary for using the CISS effect in enantioseparations, and shed new light on enantiorecognition
Analysis of Somatic Mutations in the Brain Regions of Alzheimer Disease Cases Using Whole-genome Sequencing
No full textAlzheimer’s disease (AD) is the seventh leading cause of death worldwide and the most prevalent dementia . Age is the most significant risk factor for AD. With the shift in global demographics from younger to older adults, the age-related diseases such as AD will pose a huge public health burden. Genetic studies using human populations have identified the risk and protective genes, and cell and animal models have illustrated the pathways and the underlying biology of the AD. However, these findings do not offer a complete understanding of genetic susceptibility to AD. Somatic mutations, the well-known causative risk factors of neoplasm, have also been implicated in non-cancerous diseases and these somatic mutations could contribute to liability of AD. We explored the burden of somatic mutations in four brain regions (hippocampus, entorhinal cortex, cingulate gyrus and cerebellum) of 6 AD cases along with their corresponding blood as the control. We found that somatic mutations were mostly present in intergenic and intronic regions with the greatest number of mutations present in an immune related gene, LILBR1 and a synaptic vesicle related gene , SYN3. We observed several pathogenic mutations in the MMP9, CALCR1, and NPAP1. Gene set-enrichment analysis showed that these genes are involved in response to amyloid beta . Our study shows that pathogenic mutations in the AD brain could increase the risk of developing AD. Future studies in cell models might help in understanding the precise role of these pathogenic somatic variants in AD
Examining the relationships between psychosocial stress exposure, glucocorticoid resistance in immune cells and cardiometabolic risk
No full textThe present study examined the relationships between chronic stress, glucocorticoid resistance in immune cells and cardiometabolic risk factors. 247 adults completed measures of psychological stress and underwent a blood draw and anthropometric assessment. Glucocorticoid resistance was measured as the concentration of dexamethasone required to reduce IL-6 concentration in half after mitogen exposure, and cardiometabolic risk consisted of a composite score of blood pressure, triglycerides, glucose scores, HDL, and waist circumference. Linear regression analyses revealed largely null results. Stress was not found to be associated with glucocorticoid resistance or cardiometabolic risk across 3 of 4 measures of psychological stress. A small, negative association between a novel measure of chronic stress and glucocorticoid resistance was observed. Results suggest need for further research into the conditions under which stress alters immune and cardiometabolic functioning
Assessing COVID-19 Transmission Risk: Roommate and Unit Mate Exposures at an Inpatient Behavioral Health Facility
No full textAbstract/Objective: The COVID-19 pandemic caused an upsurge in demand for inpatient mental healthcare. Inpatient psychiatric facilities have an inherently increased risk of infection transmission and a heightened possibility of adverse outcomes among patients. This study aimed to evaluate the impact of roommate and unit mate exposures on COVID-19 transmission by index cases to inform on the safest isolation practices at an inpatient behavioral health facility.
Methods: This retrospective study evaluated post-exposure COVID-19 test results for roommates and unit mates of patient index cases from July 2020 through August 2023. Electronic health records provided demographics, roommate assignments, unit locations, and testing results. Only inpatient test results recorded during the expected testing timeframe were included in this study. Units and index case exposures where no roommate exposure occurred and exposures with test refusals or discharges before testing during the study period were excluded. Contingency tables were created, stratified by unit location, to display post-exposure test results and relation to the index case. Fisher’s exact or Chi-square tests were conducted for each unit separately.
Results: During the 38-month study period, comprising 139,194 patient days, there were 208 COVID-19 positive patient index cases resulting in 2,594 total exposure events. The conversion rate overall was 10.05%, 24.4% for roommates, and 9.3% for unit mates, with an infection odds ratio of 3.14 (1.42, 6.92). For the unit-stratified analysis, 5 of the 6 included units had higher conversion rates among roommates, with a range of differences in conversion rates ranging from -5.6% to 34.2%. The difference in conversion rates was significant in one unit (Unit K) where the conversion rate for roommates was 33.3% and 7.3% for unit mates (Chi-squared p-value <.0001).
Conclusion: Roommates were observed to have a higher frequency of conversion that was statistically significant in one hospital unit that primarily treats older adults. Additional exposure event observations are needed to ascertain whether this pattern persists across other units, improving the generalizability of the study. Hospital-wide, those who tested positive post-exposure were likelier to be a roommate. Understanding how to care for the greatest number of patients possible safely is of utmost public health importance
Fostering Social and Co-Curricular Engagement with Commuter Students at a Regional University Campus
No full textAt the University of Pittsburgh at Greensburg, commuter students make up the majority of the currently enrolled student population. The majority population has expressed their dissatisfaction about co-curricular and social activities and a diminished sense of belonging and inclusion. The focus of this dissertation is on the Greensburg Experiences More Program (GEM), and the central idea that the program is not inclusive nor engaging to commuter students and that there has not been a redesigned or evaluation of the program within the past five years to promote more buy in for the social and co-curricular experiences it provides. By interviewing ten higher education professionals and explore how they engage their commuter student population could provide ways that the GEM program could be changed or adapted. The ten semi-structured interviews consisted of professionals from both public and private institutions from five different states. The interviews were recorded and then transcribed resulting in three different themes, which are as follows a. Time is of the Essence b. Linear Level of Social and Co-Curricular Events and c. Free Everything: From Food to Fun. These overall findings show that the campus needs to make a considerable effort in working with their commuter student as much if not more than their non-commuter student for them to become engaged in social and co-curricular activities. These findings also examine that the best time to engage their commuter students was between the hours of 8:00am to 6:00 pm, to provide more than just an experience by enhancing events with incentives such as food or additional giveaways, and the creation and implementation of the common hour
Enantio- and regioselective propargylic and allylic functionalization
No full textThe rapid development of enantioselective allylic or propargylic C − H functionalization methods offers great opportunities for introducing functional groups to readily available starting materials in a stereodefined manner. In this dissertation, we synthesized N-heterocyclic molecules from simple alkynes with good regioselectivity utilizing stoichiometric Fe intermediates. The achievement of highly enantioselective allylic functionalization of non-activated alkenes was realized through the synergistic combination of Fe and Ir catalysts. In addition, we systematically investigated the enantioselective propargylic functionalization with Ir catalysis, thereby expanding the scope pf propargylic functionalization. A wide range of alkynes underwent successful propargylic allylation and silylation, enabling the formation of 1,5-dienes, propargylsilanes and allenylsilanes with good enantioselective and stereoselective control
Genetic Variability of EDIL3 in Aneurysmal Subarachnoid Hemorrhage
No full textAneurysmal subarachnoid hemorrhage (aSAH) results from a ruptured brain aneurysm leading to severe stroke with varying outcomes, ranging from cognitive decline to long-term disability, and death. The study used existing genome-wide association and DNA methylome data from an aSAH cohort to address the hypothesis that Epidermal Growth Factor-like repeats and Discoidin I-like Domains 3 (EDIL3) single nucleotide polymorphisms (SNPs) and DNA methylation will be associated with delayed cerebral ischemia (DCI), Glasgow Outcome Scale (GOS) and Modified Rankin Scale (mRS).
Aim 1 evaluated the relationship between EDIL3 SNPs and patient outcomes (n=197) using logistic regression analysis. Significant associations were observed between DCI and three SNPs: rs16901000 (OR: 0.385, CI: 0.147 – 0.891, p= 0.036), rs16901053 (OR: 0.343, CI: 0.137 – 0.774, p= 0.014), and rs16901061 (OR: 0.325. CI: 0.136 – 0.709, p= 0.007). Similarly, GOS was associated with SNPs, rs4612038 at 3 months (OR: 1.819, CI: 1.009 – 3.366, p= 0.049), rs2301103 at both 3 (OR: 2.857, CI: 1.233 – 6.908, p= 0.016) and 12 months (OR: 2.539, CI: 1.053 – 6.306, p= 0.039), and rs13165263 at 12 months (OR: 2.382, CI: 1.086 – 5.277, p= 0.03). No associations were observed with mRS at 3 or 12 months, including the methylation sites.
Aim 2 involved collapsing the DNA methylation data from cerebrospinal fluid samples collected longitudinally (n=260) at five cross-sectional time points using logistic regression analysis. Three CpG sites showed significant association with DCI, and eleven sites with GOS at 3 and/or 12 months. These CpG sites mainly showed protective effects for both short- and long-term outcomes, except for cg07690181, which conferred an increased risk of developing DCI.
Finally, Aim 3 evaluated whether the outcome-associated lead SNP (from Aim 1) was a potential Methylation Quantitative Trait Locus (meQTL) by performing linear regression analysis in 117 subjects for whom both the SNP and methylation data were available. The most significant (lead) SNP from Aim 1, rs16901061, was found to function as an meQTL.
The results suggest that EDIL3 could be a potential target for public health intervention, focusing on the polymorphisms and the DNA methylation sites to manage short- and long-term outcomes
Pivoting Priorities Post-pandemic: How Pitt realigned ETD Support services for students
No full textDuring 2020 the University of Pittsburgh was tasked with realigning ETD Support services to meet the needs of our students in lockdown. Those changes allowed us to continue making process changes to eliminate inefficiencies, create more learning opportunities, and set standards for process evaluation for the future. This talk will speak to the successes and roadblocks we encountered in this on-going process
AI and the Everyday Writer
No full textBased on a qualitative study of workplace writers, we argue that theories of language and AI must account for the activity of uptake and implementation on the ground, which, at least in the near future, will be messy, incomplete, uneven, chaotic, and perhaps even boring
Evaluation and application of computational strategies for exploring the dynamics and small-molecule binding properties of proteins
No full textProtein functions are determined by their intrinsic dynamics. In order to affect the functions of certain proteins many drugs impact the dynamics of their target protein, either through their interactions directly or by altering interactions with other binding partners. Allosteric drugs, those that target sites on proteins distal from their active sites, provide a way to finely tune the dynamics of proteins of interest without directly competing with endogenous ligands while also generally being less promiscuous due to the lower evolutionary conservation of allosteric sites compared to orthosteric sites. A crucial step for the development of allosteric drugs is the understanding of the intrinsic dynamics of proteins of interest. In this dissertation I show the application of protein dynamics analysis using Gaussian Network Models (GNMs) at the domain and family level in order to characterize the dynamics of PDZ domain and Class A G Protein Coupled Receptors (GPCRs). I also present my work evaluating virtual screening strategies as part of the 2016 Drug Design Data Resource (D3R) competition, a community-wide virtual screening competition funded by the NIH. And lastly, I apply dynamics analysis and virtual screening methods towards the goal of developing novel Poly [ADP-ribose] polymerase 1 (PARP1) inhibitors for the treatment of traumatic brain injury