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Synthesis And In-Vitro Cell Viability/Cytotoxicity Studies Of Novel Pyrrolobenzodiazepine Derivatives, John M. Jarrett 2017 East Tennessee State University

Synthesis And In-Vitro Cell Viability/Cytotoxicity Studies Of Novel Pyrrolobenzodiazepine Derivatives, John M. Jarrett

Undergraduate Honors Theses

Pyrrolobenzodiazepines (PBDs) are a group of naturally occurring compounds that were discovered in the cultures of Streptomyces in the 1960s. Some natural PBDs discovered in these cultures, such as anthramycin and sibiromycin, were shown to possess a broad spectrum of anti-tumor activity. Since cancer is still a leading cause of death globally, the development of novel anti-proliferative derivatives of PBDs is essential for human welfare worldwide. Further synthesis and structure-activity relationship (SAR) studies of the parent natural products and their tetracyclic analogs will lead to the discovery of drug candidates. In this work, thirteen PBD analogues were synthesized using no ...


Metastatic Biomarkers In Synovial Sarcoma, Rosalia de Necochea-Campion, Lee M. Zuckerman, Hamid R. Mirshahidi, Shahrzad Khosrowpour, Chien-Shing Chen, Saied Mirshahidi 2017 Loma Linda University

Metastatic Biomarkers In Synovial Sarcoma, Rosalia De Necochea-Campion, Lee M. Zuckerman, Hamid R. Mirshahidi, Shahrzad Khosrowpour, Chien-Shing Chen, Saied Mirshahidi

Library Articles and Research

Synovial sarcoma (SS) is an aggressive soft tissue sarcoma (STS) that typically occurs in the extremities near a joint. Metastatic disease is common and usually occurs in the lungs and lymph nodes. Surgical management is the mainstay of treatment with chemotherapy and radiation typically used as adjuvant treatment. Although chemotherapy has a positive impact on survival, the prognosis is poor if metastatic disease occurs. The biology of sarcoma invasion and metastasis remain poorly understood. Chromosomal translocation with fusion of the SYT and SSX genes has been described and is currently used as a diagnostic marker, although the full impact of ...


Cocoa Procyanidin And Β-Cell Proliferation, Whitney Harris, Alonzo Cook PhD, Michael Scott Brashaw III, Jeffrey Brown, Kyril Cole, Kody Hasebi, Ysabella Del Rosario, Sara Werner, Bryan Samuel Witt 2017 Brigham Young University

Cocoa Procyanidin And Β-Cell Proliferation, Whitney Harris, Alonzo Cook Phd, Michael Scott Brashaw Iii, Jeffrey Brown, Kyril Cole, Kody Hasebi, Ysabella Del Rosario, Sara Werner, Bryan Samuel Witt

Biomedical Engineering Western Regional Conference

This presentation explains an experiment that attempts to provide a more thorough understanding on the effect of cocoa procyanidin on β-Cell proliferation in diabetic rats in order to advance the treatment of diabetes.


Longitudinal Changes In Neurodevelopmental Outcomes Between 18 And 36 Months In Children With Prenatal Triptan Exposure: Findings From The Norwegian Mother And Child Cohort Study, Mollie E. Wood, Jean A. Frazier, Hedvig M.E. Nordeng, Kate L. Lapane 2017 University of Massachusetts Medical School

Longitudinal Changes In Neurodevelopmental Outcomes Between 18 And 36 Months In Children With Prenatal Triptan Exposure: Findings From The Norwegian Mother And Child Cohort Study, Mollie E. Wood, Jean A. Frazier, Hedvig M.E. Nordeng, Kate L. Lapane

Jean A. Frazier

OBJECTIVE: This study sought to determine whether changes in neurodevelopmental outcomes between 18 and 36 months of age were associated with prenatal exposure to triptan medications, a class of 5-HT receptor agonists used in the treatment of migraine. METHOD: Using data from the Norwegian Mother and Child Cohort Study, a prospective birth cohort that includes nearly 40% of all pregnancies in Norway from 1999 to 2008, we identified 50 469 mother-child dyads who met inclusion criteria and were present for at least one follow-up assessment at 18 or 36 months postpartum. Neurodevelopment was assessed using the Child Behaviour Checklist, the ...


A Case For Caution: An Evaluation Of Calabrese And Baldwin's Studies Of Chemical Hormesis, Kevin C. Elliott 2017 University of New Hampshire

A Case For Caution: An Evaluation Of Calabrese And Baldwin's Studies Of Chemical Hormesis, Kevin C. Elliott

RISK: Health, Safety & Environment

Suggesting a need for more research, Mr. Elliott argues that it is too soon for risk-assessment policy to account for recent challenges to a toxicological linear dose-response assumption.


Comparing The Epa Indoor Air Quality Personal Computer Model And Field Data, Arash Behravesh, Wilbur A. Spaul 2017 University of New Hampshire

Comparing The Epa Indoor Air Quality Personal Computer Model And Field Data, Arash Behravesh, Wilbur A. Spaul

RISK: Health, Safety & Environment

The authors recommend caution in using an EPA model for reconstructing past exposure events as well as for predicting future exposures.


Tricresyl Phosphate Neurotoxicity Potential, George William Sherk 2017 University of New Hampshire

Tricresyl Phosphate Neurotoxicity Potential, George William Sherk

RISK: Health, Safety & Environment

Mr. Sherk discusses the potential effects of ongoing human exposure to ordinary doses of neurotoxicants.


Computational Analysis Of Residue Interaction Networks And Coevolutionary Relationships In The Hsp70 Chaperones: A Community- Hopping Model Of Allosteric Regulation And Communication, Gabrielle Stetz, Gennady M. Verkhivker 2017 Chapman University

Computational Analysis Of Residue Interaction Networks And Coevolutionary Relationships In The Hsp70 Chaperones: A Community- Hopping Model Of Allosteric Regulation And Communication, Gabrielle Stetz, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Allosteric interactions in the Hsp70 proteins are linked with their regulatory mechanisms and cellular functions. Despite significant progress in structural and functional characterization of the Hsp70 proteins fundamental questions concerning modularity of the allosteric interaction networks and hierarchy of signaling pathways in the Hsp70 chaperones remained largely unexplored and poorly understood. In this work, we proposed an integrated computational strategy that combined atomistic and coarse-grained simulations with coevolutionary analysis and network modeling of the residue interactions. A novel aspect of this work is the incorporation of dynamic residue correlations and coevolutionary residue dependencies in the construction of allosteric interaction networks ...


Maysin And Its Flavonoid Derivative From Centipedegrass Attenuates Amyloid Plaques By Inducting Humoral Immune Response With Th2 Skewed Cytokine Response In The Tg (Appswe, Ps1de9) Alzheimer's Mouse Model, Yuno Song, Hong-Duck Kim, Min-Kwon Lee, Il-Hwa Hong, Chung-Kil Won, Seung Sik Lee, Jae-Hyeon Cho 2017 New York Medical College

Maysin And Its Flavonoid Derivative From Centipedegrass Attenuates Amyloid Plaques By Inducting Humoral Immune Response With Th2 Skewed Cytokine Response In The Tg (Appswe, Ps1de9) Alzheimer's Mouse Model, Yuno Song, Hong-Duck Kim, Min-Kwon Lee, Il-Hwa Hong, Chung-Kil Won, Seung Sik Lee, Jae-Hyeon Cho

NYMC Faculty Publications

Alzheimer's disease (AD) is a slow, progressive neurodegenerative disease and the most common type of dementia in the elderly. The etiology of AD and its underlying mechanism are still not clear. In a previous study, we found that an ethyl acetate extract of Centipedegrass (CG) (i.e., EA-CG) contained 4 types of Maysin derivatives, including Luteolin, Isoorientin, Rhamnosylisoorientin, and Derhamnosylmaysin, and showed protective effects against Amyloid beta (Aβ) by inhibiting oligomeric Aβ in cellular and in vitro models. Here, we examined the preventative effects of EA-CG treatment on the Aβ burden in the Tg (Mo/Hu APPswe PS1dE9) AD ...


Risk Of Gastrointestinal Bleeding Among Dabigatran Users – A Self Controlled Case Series Analysis, Wenze Tang, Hsien-Yen Chang, Meijia Zhou, Sonal Singh 2017 George Washington University

Risk Of Gastrointestinal Bleeding Among Dabigatran Users – A Self Controlled Case Series Analysis, Wenze Tang, Hsien-Yen Chang, Meijia Zhou, Sonal Singh

Epidemiology and Biostatistics Faculty Publications

This article aims to evaluate the real world risk of gastrointestinal bleeding among users naïve to dabigatran. We adopted a self-controlled case series design. We sampled 1215 eligible adult participants who were continuous insured users between July 1, 2010 and March 31, 2012 with use of dabigatran and at least one gastrointestinal bleeding episode. We used a conditional Poisson regression to estimate incidence rate ratios. The population consisted of 64.69% of male and 60.25% patients equal to or greater than age 65 at start of observation. After adjustment for time-variant confounders, the incidence rate of gastrointestinal bleeding was ...


Cyclic Ac253, A Novel Amylin Receptor Antagonist, Improves Cognitive Deficits In A Mouse Model Of Alzheimer’S Disease, Rania Soudy, Aarti Patel, Wen Fu, Kamaljit Kaur, David MacTavish, David Westaway, Rachel Davey, Jeffrey Zajac, Jack Jhamandas 2017 University of Alberta

Cyclic Ac253, A Novel Amylin Receptor Antagonist, Improves Cognitive Deficits In A Mouse Model Of Alzheimer’S Disease, Rania Soudy, Aarti Patel, Wen Fu, Kamaljit Kaur, David Mactavish, David Westaway, Rachel Davey, Jeffrey Zajac, Jack Jhamandas

Pharmacy Faculty Articles and Research

Introduction: Amylin receptor serves as a portal for the expression of deleterious effects of amyloid b-protein (Ab), a key pathologic hallmark of Alzheimer’s disease. Previously, we showed that AC253, an amylin receptor antagonist, is neuroprotective against Ab toxicity in vitro and abrogates Ab-induced impairment of hippocampal long-term potentiation.

Methods: Amyloid precursor protein–overexpressing TgCRND8 mice received intracerebroventricularly AC253 for 5 months. New cyclized peptide cAC253 was synthesized and administered intraperitoneally three times a week for 10 weeks in the same mouse model. Cognitive functions were monitored, and pathologic changes were quantified biochemically and immunohistochemically.

Results: AC253, when administered intracerebroventricularly ...


Characterization Of Physicochemical And Thermal Properties Of Biofield Treated Ethyl Cellulose And Methyl Cellulose, Mahendra Trivedi 2016 Trivedi Global Inc.

Characterization Of Physicochemical And Thermal Properties Of Biofield Treated Ethyl Cellulose And Methyl Cellulose, Mahendra Trivedi

Mahendra Kumar Trivedi

Cellulose and its derivatives are used as potential matrices for biomaterials and tissue engineering applications. The objective of present research was to investigate the influence of biofield treatment on physical, chemical and thermal properties of ethyl cellulose (EC) and methyl cellulose (MC). The study was performed in two groups (control and treated). The control group remained as untreated, and biofield treatment was given to treated group. The biofield treated polymers are characterized by Fourier transform infrared spectroscopy (FT-IR), CHNSO analysis, X-ray diffraction study (XRD), Differential Scanning calorimetry (DSC), and thermogravimetric analysis (TGA). FT-IR analysis of treated EC showed downward shifting ...


Characterization Of Physicochemical And Thermal Properties Of Biofield Treated Ethyl Cellulose And Methyl Cellulose, Mahendra Trivedi, Dahryn Trivedi 2016 Trivedi Global Inc.

Characterization Of Physicochemical And Thermal Properties Of Biofield Treated Ethyl Cellulose And Methyl Cellulose, Mahendra Trivedi, Dahryn Trivedi

Mahendra Kumar Trivedi

Cellulose and its derivatives are used as potential matrices for biomaterials and tissue engineering applications. The objective of present research was to investigate the influence of biofield treatment on physical, chemical and thermal properties of ethyl cellulose (EC) and methyl cellulose (MC). The study was performed in two groups (control and treated). The control group remained as untreated, and biofield treatment was given to treated group. The biofield treated polymers are characterized by Fourier transform infrared spectroscopy (FT-IR), CHNSO analysis, X-ray diffraction study (XRD), Differential Scanning calorimetry (DSC), and thermogravimetric analysis (TGA). FT-IR analysis of treated EC showed downward shifting ...


Il-15 Activates The Jak3/Stat3 Signaling Pathway To Mediate Glucose Uptake In Skeletal Muscle Cells, James E. Krolopp, Shantaé M. Thornton, Marcia J. Abbott 2016 Chapman University

Il-15 Activates The Jak3/Stat3 Signaling Pathway To Mediate Glucose Uptake In Skeletal Muscle Cells, James E. Krolopp, Shantaé M. Thornton, Marcia J. Abbott

Health Sciences and Kinesiology Faculty Articles

Myokines are specialized cytokines that are secreted from skeletal muscle (SKM) in response to metabolic stimuli, such as exercise. Interleukin-15 (IL-15) is a myokine with potential to reduce obesity and increase lean mass through induction of metabolic processes. It has been previously shown that IL-15 acts to increase glucose uptake in SKM cells. However, the downstream signals orchestrating the link between IL-15 signaling and glucose uptake have not been fully explored. Here we employed the mouse SKM C2C12 cell line to examine potential downstream targets of IL-15-induced alterations in glucose uptake. Following differentiation, C2C12 cells were treated overnight with 100 ...


The Effects Of Tranexamic Acid On Mortality Rate In Trauma Patients Compared To Trauma Patients With No Tranexamic Acid Treatment, Bradley Earl Tolar 2016 University of Southern Mississippi

The Effects Of Tranexamic Acid On Mortality Rate In Trauma Patients Compared To Trauma Patients With No Tranexamic Acid Treatment, Bradley Earl Tolar

Doctoral Nursing Capstone Projects

Traumatic injury is the leading cause of death for many age groups. Traumatic accidents caused over 130,000 deaths in the United States in 2014. This DNP project studied the effects of Tranexamic acid on mortality rate in trauma patients. After the completion of a needs assessment at a local level II trauma center, a literature review was performed. The literature showed a decrease in mortality rate when patients were administered Tranexamic acid within 3 hours of injury with statistically significant statistics. Also, the data from the literature showed no correlation between vascular occlusive events and Tranexamic acid use in ...


The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., Glenn Ward Vicary 2016 University of Louisville

The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., Glenn Ward Vicary

Electronic Theses and Dissertations

The median survival for idiopathic pulmonary fibrosis (IPF) patients from diagnosis is a dismal 3 years. This condition is characterized by pulmonary fibroproliferation and excess production and disordered deposition of extracellular matrix (ECM) proteins resulting in obliteration of the original tissue architecture, loss of lung function and eventual death due to respiratory failure. The main hindrance to the development of effective treatments against pulmonary fibrosis is the late detection of its progression and is often of unknown cause. Tobacco smoke represents the most important environmental factor linked to the development of pulmonary fibrosis, with over 60% of IPF patients current ...


The Oncolytic Potential Of Tanapoxvirus To Treat Retinoblastoma, John D. Christie 2016 Western Michigan University

The Oncolytic Potential Of Tanapoxvirus To Treat Retinoblastoma, John D. Christie

Master's Theses

Retinoblastoma is the leading cause of intraocular malignancy in children under 2 years of age. Current treatments, while generally effective in eliminating the tumor, have many negative side effects. Oncolytic virotherapy is the use of either wild type or recombinant viruses, to destroy tumor cells. There are currently several viruses being engineered as potential therapeutics for a wide range of cancers. They offer tumor specific alternative to current therapies with lesser toxicity. This study looked at the oncolytic efficacy of multiple tanapoxviruses (TPV) recombinants in an in vitro retinoblastoma. Here we have tested recombinants of TPV for their ability to ...


Partial Amino Acid Sequence Of Lipid Transfer Protein From Fennel (Foeniculum Vulgare) Seeds, Hasan Al-Shiyab, Caroline Aziz 2016 Chapman University

Partial Amino Acid Sequence Of Lipid Transfer Protein From Fennel (Foeniculum Vulgare) Seeds, Hasan Al-Shiyab, Caroline Aziz

Student Research Day Abstracts and Posters

Fennel (Foeniculum vulgare) is a biennial Egyptian medicinal plant with an aromatic odor that belongs to the family Apiaceae (Umbelliferae). Fennel seeds are commonly used in traditional medicine, as they are known to have anti-inflammatory, anti-fungal and anti-cancerous activities. The major constituents of the fennel plant are sugars, minerals, essential fatty acids, proteins and fibers. Although, there are numerous studies on the medicinal properties of essential oils of the fennel seeds, but there is limited data reported on the proteins and peptides. The aims of this project are to fully characterize the primary structure of proteins and to determine their ...


Exploring Molecular Mechanisms Of Paradoxical Activation In The Braf Kinase Dimers: Atomistic Simulations Of Conformational Dynamics And Modeling Of Allosteric Communication Networks And Signaling Pathways, Amanda Tse, Gennady M. Verkhivker 2016 Chapman University

Exploring Molecular Mechanisms Of Paradoxical Activation In The Braf Kinase Dimers: Atomistic Simulations Of Conformational Dynamics And Modeling Of Allosteric Communication Networks And Signaling Pathways, Amanda Tse, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

The recent studies have revealed that most BRAF inhibitors can paradoxically induce kinase activation by promoting dimerization and enzyme transactivation. Despite rapidly growing number of structural and functional studies about the BRAF dimer complexes, the molecular basis of paradoxical activation phenomenon is poorly understood and remains largely hypothetical. In this work, we have explored the relationships between inhibitor binding, protein dynamics and allosteric signaling in the BRAF dimers using a network-centric approach. Using this theoretical framework, we have combined molecular dynamics simulations with coevolutionary analysis and modeling of the residue interaction networks to determine molecular determinants of paradoxical activation. We ...


Network Inference Driven Drug Discovery, Gergely Zahoránszky-Kőhalmi, Tudor I. Oprea MD, PhD, Cristian G. Bologa PhD, Subramani Mani MD, PhD, Oleg Ursu PhD 2016 University of New Mexico School of Medicine

Network Inference Driven Drug Discovery, Gergely Zahoránszky-Kőhalmi, Tudor I. Oprea Md, Phd, Cristian G. Bologa Phd, Subramani Mani Md, Phd, Oleg Ursu Phd

Biomedical Sciences ETDs

The application of rational drug design principles in the era of network-pharmacology requires the investigation of drug-target and target-target interactions in order to design new drugs. The presented research was aimed at developing novel computational methods that enable the efficient analysis of complex biomedical data and to promote the hypothesis generation in the context of translational research. The three chapters of the Dissertation relate to various segments of drug discovery and development process.

The first chapter introduces the integrated predictive drug discovery platform „SmartGraph”. The novel collaborative-filtering based algorithm „Target Based Recommender (TBR)” was developed in the framework of this ...


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