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Synthesis and Evaluation of Novel Biologically Active Compounds
Get PDFSCP-1, a potent derivative of acetaminophen, exhibits significantly diminished hepatotoxicity and nephrotoxicity relative to acetaminophen and nitrate ester derivatives of acetaminophen. It was therefore of interest to explore the development of nitric oxide donor analogs of SCP-1 to identify compounds that could have enhanced analgesic and/or antipyretic activity while taking advantage of the very low liver and kidney toxicity inherent to SCP-1. In this project, a series of nitrate ester analogues of the SCP-1 were prepared as potential nitric oxide donors. The synthesis of SCP analogs was achieved by triflic acid catalyzed O-acylation of SCP-1 with chloroalkanoyl chlorides followed by nitration with silver nitrate. The chloroesters and corresponding nitrate esters were obtained in high yields (\u3e90%). Preliminary hepatotoxicity studies revealed the nitrate esters to be well tolerated by human hepatocytes and had little effect on the three cytochrome P450 enzymes tested (CYP3A4, CYP2E1 and CYP2D6). In addition, the nitrate esters exhibited antipyretic activity similar to acetaminophen.
With the emerging interest in 3,3-diarylazetidines as novel motifs in drug discovery programs, an easy, efficient, scalable synthetic method that could accommodate the introduction of both electron-rich and electron-deficient aryl groups for preparation of diversely substituted 3,3-diarylazetidines would be valuable to medicinal chemists. In this second project, a versatile synthesis of 3,3-diaryl azetidines from N-Boc-3-aryl-3-azetidinols using Friedel-Crafts arylation conditions with AlCl3 is described. A series of substituted diaryl azetidines were readily prepared and isolated as the oxalate salts in high yield and high purity. The 3,3-diaryl azetidine oxalates were then easily converted into N-alkyl and N-acyl analogues in high overall yields (\u3e85%).
In the last project, A general synthesis of pyruvate esters was developed. Using this method, a series of alkyl pyruvate esters were synthesized in moderate to high yields (56-93%). This was achieved in four steps starting from the readily available triethyl-2-phosphonopropionate which was converted to the alkene ethyl 2,3-dimethyl-2-butenoate using Horner-Wadsworth-Emmons reaction. The ethyl ester was hydrolyzed to the corresponding carboxylic acid after which a series of esters were prepared using Steglich esterification. The esters were then converted to their corresponding pyruvate esters via ozonolysis
Physiological and behavioral correlates of HIF-1 alpha protein levels in the Gulf killifish, Fundulus grandis
Get PDFAlthough the hypoxia-inducible transcription factor (HIF) orchestrates molecular responses to low oxygen, the amount of HIF-1α protein expressed during hypoxia varies among species, individuals, and tissues. This study measured HIF-1α protein levels along with several physiological and behavioral variables in the estuarine fish Fundulus grandis under normoxia (\u3e 7 mg l-1 dissolved oxygen) and hypoxia (1 mg l-1 dissolved oxygen). Fish under hypoxic conditions had higher tissue levels of HIF-1α, hematocrit, blood glucose, blood lactate, frequency of aquatic surface respiration (ASR), and lower activity than normoxic controls. Under hypoxia, HIF-1α abundance in gill was positively correlated with body mass, HIF-1α abundance in liver was positively correlated with blood lactate, and HIF-1α abundance in brain was negatively correlated with time the fish was quiescent. Therefore, this work reveals that heterogeneity in HIF-1ɑ protein in tissues of fish is related to select physiological and behavioral variables under hypoxia
The First Cut is the Deepest: George H.W. Bush and CHIREP at the U.N. 1970-1971
Get PDFScholarship on George H.W. Bush tends to regard his career with the State Department in the context of traditional presidential biography. His tenure as Ambassador to the United Nations thus becomes a line-item on a presidential resume with little significance beyond its usefulness as a political credential. This paper situates Bush’s voice as it appears in his personal diary into one of the widescreen events of Sino-American rapprochement, the conclusion in 1971 of the long-simmering conflict over Chinese representation at the U.N. (CHIREP) between the People’s Republic of China (PRC) and the American-backed Republic of China (ROC). As chief of the U.S. Mission to the U.N. (USUN) in 1971 the fight over CHIREP represents George H.W. Bush’s “first bleeding,” a baptism into both the ecology of international diplomacy and a sustained, imbricate relationship with the People’s Republic of China
Dictation from the Moon
Get PDFMuch of my poetry concerns twelve-step recovery, brushes with suicide, and other related incidents. With more poetry coming out, there was more recovery and other influences. Some manifested themselves through imitation. Sometimes they came through form. Sometimes inspiration manifested through language. Some came from goodness knows where. An accumulation of all of it, each poem follows one or more of these guiding principles
A Story-Centered Approach to AP English Literature, Curriculum, and Assessment
Get PDFAdvanced Placement and Literature and Composition is the pinnacle of literary studies in the secondary school classroom. However, the content of the course and its primary mode of assessment equally damage the reputation of literary analysis as a purposeful academic field and threaten to further stigmatize the humanities in a moment when their usefulness is under scrutiny. Students should be shown how stories, and not literature, can be better appreciated in the AP literature classroom through a biocultural, and evolutionary approach to fiction and storytelling
To Cement the Bond of Friendship :The Joan of Arc Statue in New Orleans, 1958-2020
Get PDFThis thesis presents a study of the importance of statuary related to historical memory and influence focusing on the Joan of Arc Statue in New Orleans, Louisiana. Gifted to the city in 1958 and installed in 1972 officially in the wake of Charles de Gaulle’s visit, the Joan of Arc Statue has been the subject of controversy and a costly reinstallation in the French Quarter. This thesis, using primary evidence from court cases, interviews, and newspapers, traces Joan’s significance and use as a site of memory and link between France and the City of New Orleans
Worlds Inside Worlds Inside Drawings
Get PDFI make drawings about memory and identity.
I make drawings about drawings.
I sew because I love sewing.
I paint because I have to.
I explore the parallel universes and realities that exist in me alongside reality.
I make marks intuitively and leave the analysis for later.
I wonder if magic is real.
I wonder if everyone has something like a religion that they cling to.
I like truth in my work.
I never want to trick anybody.
I like to say it simply
“New Orleans never was tighter”: Jim Garrison’s Gendered Vice Campaign in New Orleans, 1962-1966
Get PDFMost historical writing and research on Jim Garrison’s political career focus on his investigation of President John F. Kennedy’s assassination and Garrison’s prosecution of Clay Shaw. Few scholars examine the years prior to the investigation when Garrison served as District Attorney of New Orleans. In 1962, Garrison won the election for District Attorney in part for his pledge to clean up the French Quarter of its lurid reputation. Garrison’s vice crusade targeted mostly women who symbolized the city\u27s colorful reputation. Aided by his office and the vice squad, he raided the French Quarter to arrest prostitutes, strippers, and anyone associated with these women’s work. This thesis argues that Jim Garrison utilized his political power in a gendered anti-vice campaign to target and unjustly arrest some of the women in the vice industry to gain publicity and fame. While Garrison publicly fought against women in the vice world, his vice crusade masked his own misconduct as a District Attorney
Analysis of Human Affect and Bug Patterns to Improve Software Quality and Security
Get PDFThe impact of software is ever increasing as more and more systems are being software operated. Despite the usefulness of software, many instances software failures have been causing tremendous losses in lives and dollars. Software failures take place because of bugs (i.e., faults) in the software systems. These bugs cause the program to malfunction or crash and expose security vulnerabilities exploitable by malicious hackers.
Studies confirm that software defects and vulnerabilities appear in source code largely due to the human mistakes and errors of the developers. Human performance is impacted by the underlying development process and human affects, such as sentiment and emotion. This thesis examines these human affects of software developers, which have drawn recent interests in the community. For capturing developers’ sentimental and emotional states, we have developed several software tools (i.e., SentiStrength-SE, DEVA, and MarValous). These are novel tools facilitating automatic detection of sentiments and emotions from the software engineering textual artifacts.
Using such an automated tool, the developers’ sentimental variations are studied with respect to the underlying development tasks (e.g., bug-fixing, bug-introducing), development periods (i.e., days and times), team sizes and project sizes. We expose opportunities for exploiting developers’ sentiments for higher productivity and improved software quality.
While developers’ sentiments and emotions can be leveraged for proactive and active safeguard in identifying and minimizing software bugs, this dissertation also includes in-depth studies of the relationship among various bug patterns, such as software defects, security vulnerabilities, and code smells to find actionable insights in minimizing software bugs and improving software quality and security. Bug patterns are exposed through mining software repositories and bug databases. These bug patterns are crucial in localizing bugs and security vulnerabilities in software codebase for fixing them, predicting portions of software susceptible to failure or exploitation by hackers, devising techniques for automated program repair, and avoiding code constructs and coding idioms that are bug-prone.
The software tools produced from this thesis are empirically evaluated using standard measurement metrics (e.g., precision, recall). The findings of all the studies are validated with appropriate tests for statistical significance. Finally, based on our experience and in-depth analysis of the present state of the art, we expose avenues for further research and development towards a holistic approach for developing improved and secure software systems
Classification of Prostate Cancer Patients into Indolent and Aggressive Using Machine Learning
Get PDFProstate cancer (PCa) is the second most common cancer in men in the US. Many Prostate cancers are Indolent and don’t result in cancer mortality, even without treatment. However, a significant proportion of patients with Prostate cancer have aggressive tumors that progress rapidly to metastatic disease and are often dangerous. Currently, treatment decisions for PCa patients are guided by various stratification algorithms. Among these parameters, the most important predictor of PCa mortality is the Gleason Grade (ranges from 6 to 10). Although current risk stratification tools are moderately effective, limitation remains in their ability to distinguish truly Indolent from aggressive and potentially lethal disease. Here we propose the use of Machine Learning (ML) for the classification of PC patients as having either indolent or aggressive using transcriptome data. We hypothesize that genomic alterations could lead to measurable changes distinguishing indolent from aggressive tumors. We also trained a Stacking-based model with a different set of combinations of classifiers. The highest overall accuracy of our stacking model (all samples with Gleason Grade: 6, 7, 8, 9, and 10) is 95.758% and (samples with Gleason Grade: 6, 8, 9, and 10) is 97.19%