Characterization of theala16val manganese superoxide dismutase polymorphism

McAtee, Britt Marie The Johns Hopkins University 2007 해외박사(DDOD)

The ala16val polymorphism, found in the mitochondrial targeting signal of manganese superoxide dismutase (MnSOD), has been associated with a number of diseases, including breast cancer. MnSOD is an important antioxidant enzyme that functions in the mitochondrial matrix to dismutate superoxide to hydrogen peroxide. A single nucleotide polymorphism causes a change in the amino acid sequence from alanine (ala) to valine (val) at the 16th amino acid and is referred to as the alal6val polymorphism. Previous studies have reported that the polymorphism may cause an increase in import of MnSOD to the mitochondrial matrix in vitro. Altered levels of MnSOD due to the polymorphism are hypothesized to disrupt the oxidative balance in the cell, making the cell more susceptible to oxidative stress. We hypothesized that the alal6val polymorphism alters MnSOD protein levels and investigated this hypothesis in human breast epithelial cell lines and human cryopreserved hepatocytes. In the hepatocytes, we found no association between MnSOD protein, activity, or mRNA levels and the alal6val polymorphism. The breast epithelial cell lines showed that some, but not all, of the ala/ala lines had increased levels of MnSOD protein, activity, or protein per unit mRNA compared to the val/val cell lines. In order to assess the role of this polymorphism in situ, human MnSOD was cloned into the pcDNA3.1/Zeo expression vector and stably transfected into mouse embryonic fibroblasts (MEF) developed from the MnSOD knockout mouse. Six cell lines were established, 3 that express MnSOD-ala protein, and 3 that express MnSOD-val. MnSOD enzymatic activity correlated fairly well with MnSOD protein levels determined by Western blot. MnSOD mRNA expression, evaluated by TaqMan(TM) real-time PCR, was significantly lower in MnSOD-ala lines versus MnSOD-val lines (p<0.05). The MnSOD-ala lines produced significantly more MnSOD protein per unit mRNA than the MnSOD-val lines (p<0.05). This suggests that the MnSOD-ala lines are more efficient in their production of MnSOD protein than are MnSOD-val lines. MnSOD-val lines had significantly higher copy numbers of MnSOD DNA than did the MnSOD-ala lines. There was no association between the amount of MnSOD activity and production of superoxide or hydrogen peroxide, as detected by flow cytometry.

Estimating demand with attitude: How opinions and feelings affect consumer choice

McAtee, Gregory M The University of North Carolina at Chapel Hill 2013 해외박사(DDOD)

A consumer's mood, opinions, and general disposition can influence her demand for a product. While an empirical specification that models the correlation between attitudes and purchasing decisions will allow for a more accurate prediction of demand, there is disagreement among researchers over the role of attitudinal responses in estimation. This paper examines the relationship between the consumer's responses to questions about attitudes and demand for goods in order to demonstrate the most appropriate use of attitudinal data in empirical work. A theoretical model of consumer behavior identifies several latent factors that simultaneously influence the individual's purchasing decisions and responses to attitudinal questions. This correlation, driven by unobserved heterogeneity such as the individual's mood, opinions, discount factor, expectations over future outcomes, and unreported experiences, causes a simultaneity bias in specifications that include attitudinal responses as explanatory variables. Instead, I jointly estimate purchases and attitudinal responses using a random effects model to accurately capture the relationship between both observed outcomes. An econometric proof, a Monte Carlo experiment, and a data application show that, compared to commonly-used specifications, this jointly-estimated model improves the accuracy and efficiency of the estimated response parameters of the covariates that explain consumer demand.

C(2) smooth knots of constant curvature

McAtee, Jenelle Marie The University of Iowa 2005 해외박사(DDOD)

Since the curvature of a space curve is a key factor in the determination of a curve's shape, curvature constraints impact the set of allowable curve conformations. In this thesis, we study knots with constant curvature, and we prove that this geometric constraint does not inhibit any type of knotting. That is, we show that every knot type can be represented by a C 2 smooth curve of constant curvature.

A method for analyzing the financial viability of a rural geriatric provider-based outpatient clinic

McAtee, Robin E University of Arkansas for Medical Sciences 2005 해외박사(DDOD)

Older adults living in rural areas lack access to geriatric specialty care. A geriatric provider-based outpatient clinic is a unique primary care venue that meets this need for access. The specialized clinic assembles geriatric professional experts from multiple disciplines to work as a team to provide comprehensive care for the older adult. However, little is known about the financial viability of geriatric provider-based outpatient clinics, especially those associated with a rural hospital. Therefore, the purpose of this study was to develop a method for analyzing the financial viability of a geriatric provider-based outpatient clinic within the context of its owner hospital. The three research questions developed to address the purpose were: (1) What is the net profit or loss of the rural geriatric provider-based outpatient clinic? (2) What is the identifiable downstream net profit or loss resulting from business generated by geriatric provider-based outpatient clinic patients to the owner hospital? (3) What is the overall profit or loss of the geriatric provider-based outpatient clinic when combined with the related hospital downstream net profit or loss?. A descriptive case-study approach was used in which data were collected for a 12-month retrospective period regarding a geriatric provider-based outpatient clinic and the associated downstream revenue. The data were obtained from the hospital's financial management system using a unique clinic identifier to obtain specific clinic and financial data. Data revealed 5411 patient visits were made to the practitioners of the provider-based geriatric clinic, 2607 visits were made by the geriatric practitioners to inpatients and 1328 visits were made to nursing home residents. The results of the financial analysis revealed a $112,270 loss for the clinic itself and an overall loss of $326,871 when the downstream net impact was added. Although, the study was limited by the inability to track referrals through the rural healthcare system, the case study revealed valuable areas in which further refinement could improve areas of operations and financial accountability.

Innovations in Photochemical C-C and C-N Bond Forming Reactions

McAtee, Rory Christopher ProQuest Dissertations & Theses University of Mich 2019 해외박사(DDOD)

Over the past decade, photoredox catalysis has risen to the forefront of synthetic organic chemistry as an indispensable tool for selective small-molecule activation and chemical-bond formation. New bond forming strategies have the potential to impact a variety of synthetic endeavors including, pharmaceuticals, natural product synthesis, and material sciences. This cutting-edge platform allows photosensitizers to convert visible light into chemical energy, prompting generation of reactive radical intermediates. In particular, the formation of new C−C and C−N bonds is fundamental to organic synthesis. This thesis describes some of our contributions to the design, optimization, implementation, and mechanistic underpinnings of novel C−C and C−N bond forming reactions mediated by photoredox catalysis. Chapter 1 provides a detailed summary of the importance of photoredox catalysis in organic synthesis and its appeal as an enabling technology for free radical generation. The history. key contributions in the field, the impact of light arrays on reactivity, aliphatic amine functionalization, designing complementary mechanistic paradigms, and applications of photoredox catalysis in industry is reviewed. Chapter 2 focuses on a method for the radical chlorodifluoromethylation of (hetero)arenes using chlorodifluoroacetic anhydride. A historical perspective on (hetero)arene functionalization via the classic Minisci reaction, along with strategies for radical (perfluoro)alkylation, are presented. Optimization studies, elucidation of scope, and product diversification of chlorodifluoromethylated (hetero)arenes is described. Chapter 3 describes our efforts in the area of alkene aminoarylation using simple bifunctional arylsulfonylacetamide reagents to synthesize 2,2-diarylethylamines. In this process, single-electron alkene oxidation enables C−N bond formation to provide a key benzylic radical poised for a Smiles-Truce 1,5-aryl shift. This reaction is redox-neutral, exhibits broad functional group compatibility, and occurs at room temperature with loss of sulfur dioxide. The ability of photoredox catalysis to mediate the formation C−C and C−N bonds in a single operation is established in this Chapter. Chapter 4 continues to explore the utility of bifunctional arylsulfonylacetamide reagents; now in the context of arene dearomatization. Arene dearomatization reactions are an important class of synthetic technologies for the rapid assembly of unique chemical architectures. Here, we describe a catalytic protocol to initiate a carboamination/dearomatization cascade that proceeds through transient sulfonamidyl radical intermediates formed from strong N−H bonds leading to 1,4-cyclohexadiene-fused sultams. Reaction optimization, substrate scope, and mechanistic features of this transformation are presented. Additionally, several new substrate classes are identified which undergo N-radical aryl transfer reactivity with electron-neutral olefins leading to functionalized arylethylamine products in good yields.

Sculptured Thin Films as a Platform for Machine-Learning Based Optical Sensing of Analytes

Mcatee, Patrick D. ProQuest Dissertations & Theses The Pennsylvania S 2022 해외박사(DDOD)

A surface plasmon-polariton (SPP) wave can propagate along the planar interface of a homogeneous metal and a homogeneous dielectric material. Furthermore, the metal layer in a metal/dielectric combination can provide binding sites for analytes of interest. Binding changes the electromagnetic properties of the dielectric material within the region where the electric field of a SPP wave is maximum in magnitude. Therefore, SPP waves can be used for sensing.If the dielectric material is also periodically nonhomogeneous in the direction perpendicular to the metal/dielectric interface, then several SPP waves may be excited. An example of such a periodically nonhomogenous material is a type of sculptured thin film (STF) called a chiral sculptured thin film (CSTF). A CSTF comprises closely nested nano-helixes which are grown on a substrate by a process called physical vapor deposition. STFs are porous and can be infiltrated by fluids containing analytes.Many problems arise in the discipline of sensing. The obvious goal is to sense ever diminishing concentrations of the analyte. This results in ever smaller changes in reflectance of light in a prism-coupled apparatus. When analyzing reflectance data, a human will have a bias towards identifying only those features which arise due to known phenomena. It is wise to assume that there are phenomena which have not yet been identified. Also, the theory describing known phenomena may be incomplete. The solution to these problems is to use machine-learning algorithms, such as artificial neural networks (ANNs) and support vector machines (SVMs). Another problem is sensing multiple analytes simultaneously. STFs can help in this regard by utilizing vertical multiplexing of binding sites.This work addressed the use of STFs with machine learning to sense analytes. First, the correct type of STF, a CSTF, was chosen based on uniform porosity and electromagnetic periodicity. Next, using ANNs and varying incidence conditions, it was verified that the efficacy of this CSTF sensor is comparable to that of basic plasmonic sensors. This was done theoretically and experimentally. Also, a multi-analyte sensing scheme using vertical multiplexing was investigated. Finally, the capabilities of sensing an analyte in solution were compared between two types of CSTF sensors and a basic plasmonic sensor.It was found that (1) a CSTF is better suited for sensing purposes than other structurally periodic STFs because of uniform porosity; (2) p-polarized light is best for sensing using CSTFs; (3) experimentally, the statistical measures of the ANN performance from CSTF sensors are comparable to that of basic plasmonic sensors for predicting the refractive index of a homogeneous liquid; (4) calculated reflectance data from a CSTF in a prism-coupled configuration can be used to train an ANN to identify solutions with different concentrations of two analytes with high accuracy, in which the non-SPP features are important for ensuring high accuracy of classification; (5) measured reflectance data from CSTF sensors with an embedded metallic nanoparticle layer can be used to train an SVM to identify solutions with different concentrations of a single analyte with high accuracy, the CSTF sensors performing better than basic plasmonic sensors.

Nickel-catalyzed reactions of nontraditional electrophiles to set stereogenic centers

Shacklady McAtee, Danielle Maria University of Delaware 2014 해외박사(DDOD)

This dissertation focuses on investigations of nickel-catalyzed reactions of nontraditional electrophiles to set stereogenic centers. Chapter 1 describes a novel nickel(0)-catalyzed cyclization of N-benzoylaminals for isoindolinone synthesis. This method enables preparation of a variety of isoindolinones with substitution on the benzoyl fragment and C-3 carbon. This reaction likely proceeds via an &agr;-amidoalkylnickel(II) intermediate, which then may cyclize via either an electrophilic aromatic substitution or an insertion pathway. Chapter 2 describes the development of a nickel-catalyzed cross coupling of benzylic ammonium triflates with aryl boronic acids to afford diarylmethanes and diarylethanes. This reaction proceeds under mild reaction conditions and with exceptional functional group tolerance. Further, it transforms branched benzylic ammonium salts to diarylethanes with excellent chirality transfer. A second-generation catalyst system is also discussed for the activation of benzylic ammonium triflates. This method relies on the use of Ni(cod) 2 without ancillary phosphine or N-heterocyclic carbene ligands as catalyst. Preliminary mechanistic studies have been undertaken to probe the identity of the active catalyst for the second-generation phosphine-less catalyst system for both the napthyl and phenyl substituted ammonium salts. Chapter 3 focuses on the progress towards activating the C--N bond of amino acids. Preliminary results have been obtained for activating the C--N bond of beta-amino acids, which represents the first example of non-benzylic C--N activation for our group. Synthesis of a new model substrate that includes a chelating group to help aid in the activation of the C--N bond of &agr;-amino acids is also discussed.