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Design and Synthesis of Novel Cannabinoid Receptor Modulators
Get PDFCannabinoid (CB) receptors are validated drug targets in the endocannabinoid signaling system associated with a number of human pathologies, and the development of novel and selective small molecule CB ligands is warranted. A lead molecule HL-010, a member of the 4H-thieno[3,2-b]pyrrole-5-carboxamide class of compounds, was previously identified through CB homology modeling and virtual screening protocols as a potential high affinity ligand for cannabinoid receptors. Validation of the in silico data was realized with the evaluation of both CB1 and CB2 receptor binding and functional activity assessment: HL-010 was found to be a potent (~10 nM) and selective CB2 receptor agonist with more than 100-fold selectivity over CB1 receptors. Unfortunately, its high lipophilicity limited its aqueous solubility, and prevented further evaluation in animal models. The bioisostere, RS-DFA-6-2 containing the 4H-furo[3,2-b]pyrrole-5-carboxamide scaffold, was synthesized and preliminary data showed similar CB2 binding affinity (~18 nM) with modest selectivity (40 fold) compared to HL-010, with slightly improved aqueous solubility. This thesis research discloses the design and synthesis of four additional analogs modified at the carboyxamide group (7a-d) using RS-DFA-6-2 as the parent scaffold. These compounds were tested against both CB receptor and opioid receptors using established radioligand displacement assays. Additionally, compound 7a was determined to be a CB2 agonist based on functional assay data
Attitudinal Changes in Experiential Learning via Poverty Simulation
Get PDFMore than 10% of people living in the United States are impoverished. These human beings are subjected to poor living conditions, experience increased mental and emotional stress, lack basic necessities, and are more susceptible to many health conditions. Lack of poverty awareness and understanding has contributed to the spread of misconceptions, the majority of which are damaging to the impoverished community. These misconceptions affect how impoverished individuals are viewed by health care professionals and influence the quality of medical treatment they receive. The Missouri Community Action Poverty Simulation (CAPS) is an experiential learning tool that requires participants role-play a low-income individual and attempt to survive a month (four 15-minute periods) in poverty. CAPS was held on both March 30, 2017 and February 25, 2018 at the University of Mississippi in partnership with Student Housing and the McLean Institute for Community Action. This project served to measure whether beliefs and attitudes about poverty may be influenced by participation in CAPS. Results show that CAPS is a successful pedagogical tool, and based on its ability to increase understanding of poverty, this project suggests that other experiential learning processes be integrated into curricula for health profession students. By requiring health professionals to engage in CAPS, it is expected that they will be better equipped to provide quality and access care to their low-income patients
A Comprehensive Collection of Accounting Methods and Principles: A Case by Case Analysis
Get PDFThe purpose of this thesis is to address the most commonly accepted accounting methods and principles used in practice and apply them to companies’ financial statements. This thesis uses examples from companies’ financial statements, management discussion and analysis, 10k reports, quarterly reports, and various other statements in conjunction with a particular topic of financial accounting. This thesis begins by applying accounting principles to specific companies. Certain topics include revenue recognition, the time value of money, tradeable securities, pension plans, and various other topics. Each topic is broken down by a section. Inside these sections will be supporting data, journal entries, and calculations. The format of this thesis is broken down on a case by case application to these specific accounting topics
The Israeli Druze: "Neither Here nor There"
Get PDFDruze scholar Rabah Halabi describes the Druze standing in Israel as “neither here nor there.” This thesis asks the question: How do the Druze fit into a society created to house and defend the Jewish people? To answer this question, Druze identity is examined from the Jewish-Israeli and Arab-Israeli perspectives regarding the Druze community based on their service in the Israel Defense Forces (IDF) through a case study of media reactions to the July 2017 fatal shooting of two on-duty Druze policemen by three Arab-Israeli shooters at Islamic holy site al-Aqsa Mosque in the Old City in Jerusalem. Three preliminary questions are explored to preface the case study: Who are the Israeli Druze? What is the IDF? and What is the Druze role in the IDF? Analysis of Jewish-Israeli media and Arab-Israeli media of reactions to the fatal shooting confirms Halabi’s conclusion, reflecting the indifference both sides feel toward the Druze community. Because Arabs living inside the borders of Israel sympathize so closely with Palestinians, Arab-Israelis feel a similar sense of detachment from the Druze, even though they are all Arabs, a link that was forcefully removed from memory through Israel’s divide-and-rule policy. The Israelis succeeded in their attempt to break the non-Jewish minority into even smaller groups. They further succeeded by turning those minorities against one another and ensured that relations between the Arab-Israeli and Druze minorities were so hostile that the two
groups never would unite to fight against the Jews and the State of Israel. Arab-Israeli media articles’ use of the word “martyr” to describe only the three Arab-Israeli shooters and not the fallen Druze policemen demonstrates Arab-Israelis’ sentiments toward the the Druze population. The Arab-Israeli shooters were martyrs because they
were defending their Arab brethren from the tyranny of Israel. The Druze are not because, like the Jews, they are the enemy. Stuck in the middle of the larger Palestinian-Israeli conflict, the Druze are “neither here nor there” in Israeli society
The Effects of Mutations in the ATH1 and STM Genes on Sepal, Petal, and Stamen Abscission in Arabidopsis thaliana Plants
Get PDFFloral organ boundaries are areas that allow distinct organs within a flower to differentiate from each other and the underlying stem. Boundary regions are also where abscission zones (AZs) can form, which allow floral organs to abscise, or detach, from the plant. This study takes a look into a pair of genes, ARABIDOPSIS THALIANA HOMEOBOX GENE1 (ATH1) and SHOOT MERISTEMLESS (STM), which code for transcription factors found in Arabidopsis thaliana that are responsible for proper boundary formation and AZ specification. Mutations in one or both of these genes affect AZ formation of specific floral organs. The ATH1 and STM transcription factors belong to the BELL and KNOX homeodomain families respectively. Heterodimerization of these transcriptions factors is necessary for STM to enter into cell nuclei; therefore mutations in any of the BELL-type partners that STM interacts with will affect its ability to regulate gene expression.
I investigated the effect of ath1-3 and stm mutations on stamen, petal, and sepal abscission in Arabidopsis flowers. A device consisting of two soft bristled paintbrushes was used to release floral organs if AZs were present and cell separation had already initiated. Data were collected from WT, ath1-3, and stm flowers and from ath1-3/stm double mutant flowers. While all of the outer floral organs were abscised in wild-type flowers, the ath1-3 and stm single mutants retained many of their stamens. In addition to their stamens, the ath1-3/stm double mutants also retained significantly more sepals and petals than wild-type flowers. These results supported my hypothesis that the ATH1 and STM transcription factors are able to play redundant roles in sepal and petal AZ formation
Application of Accounting Principles in a Collection of Case Studies
Get PDFThis thesis is a compilation of case studies that I have conducted within the period of 6 months. Each case study is independent from one another. The main purpose of these case studies is to investigate complex accounting issues that are very common in real practice.
In each case I did my best to understand accounting principles that are applied in a specific situation and further investigate the issue. In order to identify the problematic areas, I analyzed the facts that were given to me and then implemented solutions based on my accounting knowledge and extensive research I have conducted.
The whole thesis writing process taught me to be more analytical. It also gave me a new set of skills that I used during my internship that I have done after the completion of my thesis.
There is far more to accounting that it may seem like, it is more than just numbers and calculations. Accounting is a whole new world of principles and rules that one should be able to apply and understand, in order to be able to call oneself an accountant
Stress in College Students: Associations with Anxiety and Perfectionism
Get PDFPsychosocial stressors are prevalent in the workplace and academic environment largely due to emotional responses from rising conflict, unattainable demands, or a decreased sense of control. An individual’s perception of stress is interrelated to the characteristic of perfectionism and the level of anxiety one possesses. Stress is commonly associated with adverse circumstances, and perfectionism is characterized by the setting of unrealistically high standards accompanied by a personal and social standard, attitude, or philosophy. Anxiety is characterized by increased physiological arousal, inhibition of ongoing activities, and a change in individual priorities. Previous studies have examined
anxiety’s relation to stress-invoking stimuli, but none to date have studied perfectionism as the potential mediator between these constructs. The primary objective of the study is to assess whether perfectionism mediates the relationship between stress and anxiety.
Participants included 150 undergraduate students from the University of Mississippi campus (77.33% Caucasian, 72.67% female, SD=1.523, M=20) with age ranging from 18 to 23, who were predominantly unemployed (60.67%). Upon arrival to the lab, participants reviewed an information sheet explaining the proposed study and completed a demographics form. Subjects then completed self-report measures, including the Perceived Stress Scale (PSS;Cohen et al., 1983); Depression, Anxiety, and Stress Scale-21 (DASS-21; Lovibond et al., 1995); and the Multidimensional Perfectionism Scale (MPS; Hewitt, P.L., & Flettt, G.L., 1990).
As hypothesized, results indicated a significant positive correlation between the three constructs of interest (stress, anxiety, and perfectionism). Also in line with the hypotheses, findings from the primary analysis demonstrated perfectionism to mediate the relationship between stress and anxiety in college students.
Overall, this study contributes to the literature replicating a significant association between stress and anxiety symptoms but is unique in that the trait of perfectionism moderates said relationship. Further research is needed to determine other possible predictors of stress so that its potentially negative effects can be controlled and minimized among the college population
All That Glitters Is Not Gold: Media Coverage of the Golden State Killer
Get PDFThis thesis focused on the media’s extensive coverage of serial killers and, thus, how it
could propel them to a state of fame. It discusses that no matter a serial killer’s circumstance, the
media typically finds a story. For example, a serial killer can be on a rampage or can be dormant,
but in subsequent stories, the media will center a story around the killer’s first and/or recent
crimes, his identity, or his possible next move.
The New York Times and Los Angeles Times coverage of the Golden State Killer frames
the analysis of this manuscript. The purpose was to recognize the connection between extensive
coverage and a serial killer’s state of fame while evaluating how journalists draw readers in and
keep their attention with the weighted topic of serial murder. Furthermore, the goal was to
identify common themes of serial homicide coverage across two news publications and
recognize a journalist’s ethical dilemma in focusing on the serial killer rather than the victims.
Based on an examination of more than two dozen articles, the research indicates that
journalists bait readers with an entertaining aspect about a serial killer or an important fact
readers want to know. Once the readers are pulled in, they, unwillingly, begin to identify with the
killers. Empathy was found as the overall tone as well as the most common theme in the majority
of articles. More often than not, readers never know the names or lives of the victim, but end up
knowing everything there is to know about the killer, which puts the killer in a spotlight for
years.
Yet and still, the media must cover serial crime to keep the public informed or to remind
the public of horrific crimes of the past. As media practitioners, journalists must not shrink from
revealing the truths of society
Alternative Strategies for Solving Subtraction Problems Generated by Third Grade Students Proficient with the Standard Algorithm
Get PDFThis study explores third grade students’ mathematical understandings by examining the strategies they generate to solve subtraction word problems. Ten students proficient with the standard subtraction and addition algorithms were individually observed and interviewed while using as many different methods as they could to solve three multi-digit subtraction and addition word problems. The students were found to rely excessively on algorithms and class-taught methods, even when inappropriate, and were divided in the sophistication of their modeling strategies, with half only using direct modeling with ones, while four successfully modeled with grouping. The creativity of the strategies used by some students, the prevalence of direct modeling with ones, and the misconceptions of many students provide insight into ways elementary teachers can promote students’ present and future mathematical success
Heterobifunctional Linear Dendritic Block Co-Polymers (LDBCS) as Multifunctional Carriers for Targeted Drug Delivery
Get PDFDespite current research towards applications of polymeric drug delivery systems (DDSs) in biomedical research, significant limitations—specifically in synthetic accessibility, bio compatibility, and principles of molecular self-assembly—have been discerned. To address these drawbacks, we will investigate the synthesis and characterization of heterobifunctional linear-dendritic block copolymers (LDBCs), which combine the advantageous properties of both linear and dendritic blocks to afford nanomaterials with superior mechanical properties. Our LDBC systems contain two differing functional constituents, namely a hydrophilic polyamidoamine (PAMAM) dendron covalently linked to a hydrophobic polyester (polylactic acid, or PLA), and can self-assemble to form nanoparticles of various morphologies that serve as the vehicles for drug delivery. The initial amine-terminated PAMAM is not ideal in biological systems due to a high positive surface charge yielding concerns over cytotoxicity, so various functional groups were incorporated at the hydrophilic block to not only investigate biocompatibility, but also to discern interfacial surface behavior of these nanoparticles. These additional structural modifications are important as they provide several biological advantages such as resistance against plasma proteins and efficient cell penetrating ability. The synthesis of well-defined PAMAM-polyester LDBCs was confirmed via spectroscopic and chromatographic analysis. Microscopy and light scattering techniques afford evidence of nanoparticle formation. The results of the study regarding terminal group alteration demonstrated observable differences in parameters related to biocompatibility and confirm that these materials are indeed applicable for targeted drug delivery