Digital Commons Network^™

Discovery Of Pyrimidine-Based Heterocycles As Single Agents With Combination Chemotherapy Potential And As Inhibitors Of Purine Nucleotide Biosynthesis For The Treatment Of Cancer, Rishabh Mohan

Electronic Theses and Dissertations

This dissertation describes the design, synthesis and biological evaluation of monocyclic and bicyclic pyrimidine-base heterocycles as single agents with combination chemotherapy potential having both antiangiogenic effects and cytotoxic effects. This dissertation also describes selective tumor targeting with 5-substituted pyrrolo[2,3-d]pyrimidines analogs with heteroatom bridge substitution as GARFTase inhibitors.

The work in this dissertation is centered on identifying structural features that are necessary for inhibition of tubulin polymerization as well as for inhibition of one or more of the receptor tyrosine kinases (RTKs)- vascular endothelial growth factor receptor-2 (VEGFR2), platelet derived growth factor receptor-β (PDGFRβ) and epidermal growth factor receptor …

Target Based Design And Synthesis Of Heterocycles In The Potential Treatment Of Cancer And Opportunistic Infection, Shruti Choudhary

Electronic Theses and Dissertations

Dose limiting toxicity and development of multidrug resistance by the tumors are the major limitations of current cancer chemotherapy. Microtubule targeting agents (MTAs) are a structurally diverse set of compounds that disrupt microtubule dynamics and exert their anticancer effect. Among the various classes of such agents, the colchicine site binding agents are particularly important as they circumvent the Pgp and β-III tubulin mediated clinical resistance. These resistance mechanisms, when manifested, are a major reason for the failure of clinically used agents such as taxanes and vinca alkaloids. A series of monocyclic pyrimidine analogs were designed and synthesized as colchicine site …

Modeling The Binding Of Neurotransmitter Transporter Inhibitors With Molecular Dynamics And Free Energy Calculations, Bernandie Jean

Electronic Theses and Dissertations

The monoamine transporter (MAT) proteins responsible for the reuptake of the neurotransmitter substrates, dopamine, serotonin, and norepinephrine, are drug targets for the treatment of psychiatric disorders including depression, anxiety, and attention deficit hyperactivity disorder. Small molecules that inhibit these proteins can serve as useful therapeutic agents. However, some dopamine transporter (DAT) inhibitors, such as cocaine and methamphetamine, are highly addictive and abusable. Efforts have been made to develop small molecules that will inhibit the transporters and elucidate specific binding site interactions. This work provides knowledge of molecular interactions associated with MAT inhibitors by offering an atomistic perspective that can guide …

Target Based Design And Synthesis Of Fused Pyrimidines In The Potential Treatment Of Cancer And Opportunistic Infection, Khushbu Shah

Electronic Theses and Dissertations

This dissertation describes an introduction, background and research progress in the areas of agents designed as (a) selective Pneumocystis jirovecii dihydrofolate reductase (pjDHFR) inhibitors for pneumocystis pneumonia (PCP) infection; (b) inhibitors of microtubule polymerization and multiple receptor tyrosine kinase (RTK) for potential treatment of cancer; and (c) substrates for tumor-targeted therapy for cancer.

PCP is a host species-specific infection. Most of the drugs, synthesized and evaluated so far, have been tested against Pneumocystis carinii dihydrofolate reductase (the causative organism in rats), which would not necessarily be effective against pjDHFR (the causative organism in humans). Trimethoprim-sulfamethoxazole (TMP-SMX) combination, which has been …

Nitric Oxide Release From Poly(Lactic-Co-Glycolic Acid) Nanoparticles And Titanium Alloy, Nina A. Reger

Electronic Theses and Dissertations

Current methods for the treatment of bacterial infection involve the use of systemic antibiotics, which are high concentrations of antibiotics delivered over a long period time. Unfortunately, the use of systemic antibiotics can cause harmful side effects to the patient and increases the possibility for antibiotic resistance. The delivery of antibiotics or alternative antimicrobial compounds, such as nitric oxide, directly to the site of infection would decrease the amount of antibiotic necessary to treat a bacterial infection.

Poly (lactic-co-glycolic acid)/polyvinyl alcohol nanoparticles and a titanium- aluminum-vanadium metal oxide alloy implant were surface functionalized to deliver nitric oxide. Polymer nanoparticles can …

Distribution Changes, Genetic Population Structure, And A Novel Environmental Dna (Edna) Detection Method For Darters (Subgenus Nothonotus) In The Upper Ohio River Watershed, Anthony S. Honick

Electronic Theses and Dissertations

In the upper Ohio River watershed three species of small-bodied benthic fish the Bluebreast Darter, Etheostoma (Nothonotus) camurum (Cope), the Tippecanoe Darter, Etheostoma (Nothonotus) tippecanoe Jordan and Evermann, and the Spotted Darter, Etheostoma (Nothonotus) maculatum Kirtland previously existed in disjunct distributions due to poor water quality and habitat degradation. Signs of recovery indicated that these species were moving from areas of refugia into the deeper mainstem waters of the Allegheny and Ohio rivers and expanding their distributions. To provide information for the proper conservation management of these species this dissertation was divided into three stages: 1) distribution records were updated …

Marine Biology (Bsc 4312) Curation Workshop Presentation, Linda Walters

Curating across the Curriculum Workshops

Can “puncept”, digital storytelling, or other engaging form of curation save my beloved Florida photo-organism collection class project?

Understanding Zoonotic Enteric Disease In Minnesota: A Spatio Temporal Analysis And Causal Theory Approach, Suchismita Swain

All Graduate Theses, Dissertations, and Other Capstone Projects

With 75 percent of diseases in humans having origin in animals or animal products, zoonotic diseases have an enormous impact on the global disease burden. A significant portion of this can be attributed to bacterial zoonotic enteric pathogens. This study was designed to locate clusters of bacterial zoonotic enteric outbreaks in the State of Minnesota and study the seasonality of these outbreaks. In addition to identifying hot spots for zoonotic enteric outbreaks in Minnesota, the study also aimed to design a causal model to improve understanding of risk factors. This thesis considered only the bacterial zoonotic pathogens with significant disease …

Attic Salt, 2017, Loyola Marymount University, The Honors Program

Attic Salt

No abstract provided.

Measuring Community And University Impacts Of Critical Civic Geography: Insights From Chicago, Daniel R. Block, Euan Hague, Winifred Curran, Howard Rosing

Faculty Publications - Geography Department

No abstract provided.

Using Mixed Methods To Identify Delirium Bundle Care In The Intensive Care Unit, Jama Goers

MUSC Theses and Dissertations

Delirium is a serious complication experienced by patients in the intensive care unit (ICU). Over the past 15 years, researchers have identified risk factors, assessment techniques, pharmacological, and nonpharmacological interventions. Despite the current literature, there is a gap regarding delirium bundle care provided by an interprofessional team. This dissertation, a compendium of three manuscripts, delineates delirium bundle care by the interprofessional team in the ICU. The first manuscript details Rodgers’ Evolutionary Concept Analysis to identify attributes, antecedents, consequences, surrogate concepts, and related terms of bundled delirium care in the ICU. The second manuscript utilized the Social Ecological Model to identify …

The Role Of The 5-Hydroxytrptamine 1f Receptor In Mitochondrial Biogenesis And Acute Kidney Injury, Whitney Sharee Gibbs

MUSC Theses and Dissertations

Mitochondrial dysfunction exacerbates cellular injury, impairs energy-dependent repair, and leads to kidney damage and failure following acute kidney injury (AKI). Mitochondrial dysfunction and impaired mitochondrial biogenesis correlate with decreased in peroxisome proliferator-activated receptor coactivator 1-α (PGC-1α), the reported master regulator of mitochondrial biogenesis, and its downstream targets following I/R-induced AKI. Furthermore, recovery of renal function and tubular injury is accelerated following pharmacological induction of mitochondrial biogenesis following I/R-induced AKI. These results suggest that recovery of mitochondrial number and function may be an effective therapeutic strategy in restoring renal function following AKI. We recently made the novel observation that agonists of …

Investigating The Sub-Lethal Effects Of Mercury Exposure Using Environmental Sentinels, Frances M. Nilsen

MUSC Theses and Dissertations

Mercury (Hg) is a ubiquitous environmental contaminant that is bioaccumulative and toxic. Ecosystems accumulate high mercury concentrations throughout their food web based on their unique environmental characteristics, exposing predators in these environments to mercury concentrations that elicit toxic effects, which are rarely observed outside of the laboratory. These predators provide the opportunity to investigate the sub-lethal effects of chronic mercury exposure that occur prior to the onset of toxic effects. Here the American alligator is thoroughly assessed for use as a sentinel of human dietary mercury exposure. We find that wild healthy alligators from the southeastern Atlantic coast of the …

The Impact Of Sugar Derived Metabolites (Ages) On Pubertal Mammary Gland Development, Bradley Krisanits

MUSC Theses and Dissertations

The mammary gland is one of few organs that continues to develop postnatally, through puberty, pregnancy, lactation and involution. Interestingly, these times of development are also considered windows of susceptibility for future development of breast cancer. Studies have shown that processes important in mammary gland development are often deregulated during breast cancer tumorigenesis. Advanced glycation end products (AGEs) are highly reactive metabolites produced during normal metabolism. AGE content in the Western Diet has consistently increased over the years and accumulation of AGEs in the body leads to pro- inflammatory and pro-oxidant effects. Diet, including a diet high in fat has …

Prevalence And Potential Reproductive Health Impacts Of Phthalates And Phthalate Alternatives In Pregnant Women In Charleston, South Carolina, Abby Goodson Wenzel

MUSC Theses and Dissertations

Phthalates are plasticizers commonly detected in humans due to widespread exposure from PVC plastics, food packaging, and personal care products. Several phthalates are known antiandrogens, raising concern for prenatal exposures during critical windows of fetal development. The goal of the research presented here is to 1) Determine if certain demographics have greater or lesser phthalate concentrations, 2) Evaluate associations between prenatal phthalate exposure and AGD, a marker of in utero androgen exposure, in newborns, and 3) Investigate the prevalence and bioactivity of a novel phthalate replacement, DINCH. We sampled urine from 378 pregnant women during the second trimester of pregnancy …

Tristetraprolin In Human Periodontal Health And Disease, Michael Khoa Nguyen

MUSC Theses and Dissertations

Background: Tristetraprolin (TTP) is an RNA binding protein that tightly regulates target mRNA stability and translation through specific interactions with AU-rich regions of target mRNA 3’ untranslated region (UTR). TTP has been shown to play an important role involving decreased translation of important inflammatory cytokines in periodontal disease including TNF- , IL-6 and other immune mediators. The role of TTP was initially demonstrated in TTP knock- out mice that displayed systemic inflammatory conditions, including rheumatoid arthritis and dermatitis. The p38 MAPK cascade that is activated by bacterial-derived lipopolysaccharide (LPS) has been demonstrated to be part of the deactivation process of …

Cd26 As A Novel Marker For Identifying T Cells With Potent Antitumor Activity, Stefanie Renae Bailey

MUSC Theses and Dissertations

Cancer immunotherapies engage the immune system to elicit antitumor responses. The discovery of cell-intrinsic inhibitory pathways and cancer-specific antigens has allowed for the advancement of immune checkpoint blockades and a cellular therapy called adoptive cell transfer (ACT), respectively. ACT is an innovative therapy that entails the acquisition, expansion and infusion of autologous T cells back into the patient to eradicate tumors. The development of this field has yielded exciting results for patients with advanced malignancies, particularly blood-based cancers. Defined as a living drug, ACT has the unique potential to elicit long-term responses if transferred T cells are capable of persisting. …

Using Blubber To Assess Steroid Hormone Homeostasis In Bottlenose Dolphins (Tursiops Truncatus) Exposed To Organochlorine Pesticides, Thomas Matthew Galligan

MUSC Theses and Dissertations

The purpose of this dissertation is to examine the impacts of dichlorodiphenyltrichloroethane (DDT) and its metabolites (collectively DDTs or DDx) on steroid hormone homeostasis in the bottlenose dolphin (Tursiops truncatus) using only remotely collected blubber. First, I examined whether blubber is a suitable proxy for blood in the assessment of steroid hormone homeostasis in dolphins. To do so, I developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for the simultaneous measurement of multi-class steroid hormones in dolphin blood matrices. Then I quantified steroids in matched blood and blubber samples collected from reference populations, and modeled the relationships between the hormones …

Annual Report 2016-2017: Student Life & Development, Denise Mcdowell, Brian Jicinsky, Sarah Curtin, Sue Eckerson, Kendra Weber, Alex Kromminga, Karen Johnson, Jeff Reinardy, Connie Kamara, Paula Scheevel, Bruno Borsari, Kate Noelke, Mark Bambenek, Tracy Rahim, Nhia Yang, Joseph E. Reed, Lori Beseler, Mari Livingston, Tania Schmidt, Paul Stern, Barbara Oertel, Ron Strege

Annual Reports

Student Life and Development (SLD) professionals at Winona State University (WSU) deliver programs, services, and activities that support students' academic achievement, social development, and well-being in the timely pursuit of their educational goals. The 2016-2017 SLD Annual Report provides information from the following departments: Admissions, Community Engagement, Conduct & Citizenship, Counseling & Wellness, Dean of Students, Fitness & Wellness, Health & Wellness Services, Housing & Residence Life, Inclusion & Diversity Office, Integrative Wellness, Intramurals, Student Activities & Leadership, TRIO Student Support Services, the Student Union, the Warrior Hub, and the Warrior Success Center.

Principles Of Stable Isotope Geochemistry, 2nd Edition, Zachary Sharp

Open Textbooks

Principles of Stable Isotope Geochemistry is written as a textbook to accompany a one semester course in Stable Isotope Geochemistry. There are 13 chapters, each dealing with a specific subtopic of the field. Other than Chapters 1 and 2 – introduction and definitions – most of the remaining chapters can be read without reliance on the preceding ones. It is also hoped that the book will serve as a general reference volume for researchers in the field.

Principles of Stable Isotope Geochemistry has been organized in such a way that major concepts are explained and accompanied by numerous examples. In …

Cerebral Reorganization In Subacute Stroke Survivors After Virtual Reality-Based Training: A Preliminary Study, Xiang Xiao, Qiang Lin, Wai-Leung Lo, Yu-Rong Mao, Ryan S. Cates, Shu-Feng Zhou, Dong-Feng Huang, Le Li

Pharmacy Faculty Publications

Background. Functional magnetic resonance imaging (fMRI) is a promising method for quantifying brain recovery and investigating the intervention-induced changes in corticomotor excitability after stroke. This study aimed to evaluate cortical reorganization subsequent to virtual reality-enhanced treadmill (VRET) training in subacute stroke survivors. Methods. Eight participants with ischemic stroke underwent VRET for 5 sections per week and for 3 weeks. fMRI was conducted to quantify the activity of selected brain regions when the subject performed ankle dorsiflexion. Gait speed and clinical scales were also measured before and after intervention. Results. Increased activation in the primary sensorimotor cortex of …

Tumor Exome Sequencing And Copy Number Alterations Reveal Potential Predictors Of Intrinsic Resistance To Multi-Targeted Tyrosine Kinase Inhibitors, Nancy K. Gillis, Daniel M. Rotroff, Tania E. Mesa, Jiqiang Yao, Michael A. Carulli, Sean J. Yoder, Christine M. Walko, Jamie K. Teer, Howard L. Mcleod

Pharmacy Faculty Publications

Multi-targeted tyrosine kinase inhibitors (TKIs) have broad efficacy and similar FDA-approved indications, suggesting shared molecular drug targets across cancer types. Irrespective of tumor type, 20-30% of patients treated with multi-targeted TKIs demonstrate intrinsic resistance, with progressive disease as a best response. We conducted a retrospective cohort study to identify tumor (somatic) point mutations, insertion/deletions, and copy number alterations (CNA) associated with intrinsic resistance to multi-targeted TKIs. Using a candidate gene approach (n=243), tumor next-generation sequencing and CNA data was associated with resistant and non-resistant outcomes. Resistant individuals (n=11) more commonly harbored somatic point mutations in NTRK1, KDR, TGFBR2 …

Mir-200c Is A Cmyc-Activated Mirna That Promotes Nasopharyngeal Carcinoma By Downregulating Pten, Pan Chen, Xiaofang Guo, Liming Zhang, Wenling Zhang, Qingyu Zhou, Zhi Tian, Ying Zheng, Qianjin Liao, Heran Wang, Guiyuan Li, Jin Huang, Xiayu Li

Pharmacy Faculty Publications

The c-Myc transcription factor regulates a complex transcriptional program that leads to cellular transformation by targeting a large number of protein-encoding genes and non-coding RNAs. In this study, we show that a microRNA, miR-200c, is a novel c-Myc target that promotes cellular transformation and metastasis in nasopharyngeal carcinoma. MiR-200c achieves this oncogenic effect, at least in part, by targeting and inhibiting the tumor suppressor gene PTEN (phosphatase and tensin homolog), which is a key inhibitor of the AKT kinase signaling that promotes tumorigenesis in nasopharyngeal carcinoma. Our study thus identifies cMyc-miR-200c-PTEN-AKT as a functional module that promotes cellular transformation in …

Can Coloring Pre-Structured Designs That Have Complexity Aid In Reducing Anxiety In Those Greater Than 17 Years Of Age?, Kaitlyn P. Probasco

PCOM Physician Assistant Studies Student Scholarship

Objective: The objective of this selective evidence based medicine (EBM) review is to determine whether or not coloring mandalas or designs that have complexity and structure can aid in reducing anxiety in those greater than 17 years of age.

Study Design: Review of three English language randomized controlled trials (RCTs), published in 2007, 2012, and 2015.

Data Sources: Three randomized controlled trials published in peer-reviewed journals obtained using PubMed and EBSCOhost.

Outcomes Measured: The Curry and Kasser study and the van dV and Serice7study both used the State Anxiety Inventory (SAI) to record anxiety. The Henderson …

Self-Efficacy And Gender In Stem Majors, Katie Jordan, Randy Carden

Modern Psychological Studies

This study investigated self-efficacy in men and women studying STEM (science, technology, engineering, and mathematics) majors at a small private university in order to determine whether women had lower self-efficacy scores than men, as has been suggested by previous research. The study also investigated the possibility of a negative correlation between femininity and self-efficacy. The participants (N=67) were evaluated using the College Academic Self-Efficacy Survey created by Owen and Froman (1988) to find self-efficacy scores, and the women (N=37) were also given the Bem Sex Role Inventory (Bem,1974) to determine femininity scores. The results found no relationship between gender and …

2017 Supplement Vol. 1, American Dental Association

ADA Transactions

This item is part of the Supplements subtitle of The ADA Transactions, a serial publication of the annual activities of the ADA House of Delegates (HOD)/Board of Trustees (BOT) made up of three separate subtitles: Annual Reports and Resolutions, Supplements, and the Transactions. Generally, The ADA Transactions are published in multiple volumes throughout the year. The Supplements function like an appendix and are, in more recent editions, numbered separately with page numbers determined by HOD reference committee assignation. Items are described variously as "Supplement #", "Volume #", etc. throughout the series but have been labeled here as Vol. # for …

Anthropology Discipline Assessment Pslo's Spring 2017, Anthropology Discipline

Assessment of Student Learning Reports

No abstract provided.

Biology Discipline Assessment Pslo's Spring 2017, Biology Discipline

Assessment of Student Learning Reports

No abstract provided.

Foraging Behavior Of The Variegated Flycatcher (Empidonomus Varius) At Two North American Vagrancy Sites In The Context Of Foraging In Its Native Range, Jon S. Greenlaw

Florida Field Naturalist

No abstract provided.

Defensive Behavior Of Ospreys (Pandion Haliaetus) At Natural And Artificial Nest Sites, Cierra Braga

Florida Field Naturalist

No abstract provided.