Physical Sciences and Mathematics Commons^™

Liposome-Coated Magnesium Phosphate Nanoparticle For Delivery Of Cytochrome C Into Lung Cancer Cells A549, Weizhou Yue

University of the Pacific Theses and Dissertations

Proteins are large biomolecules that have great therapeutic potential in treating many human diseases. However, chemical/enzymatic degradation, denaturation, and poor penetration into cells are some of the challenges for clinical use of intracellular proteins.

Previously, our group has developed cationic lipid-coated magnesium phosphate nanoparticle (LP MgP NP-CAT) formulations to enhance the intracellular delivery of the negatively charged protein catalase. The goal of the current research is to develop a formulation to deliver cytochrome c (CytC), a positively charged protein into lung cancer cells A549. Specifically, this thesis research prepares and tests liposome-coated magnesium phosphate nanoparticle for delivery of cytochrome c …

A Rational Design Of A Selective Inhibitor For Kv1.1 Channels Prevalent In Demyelinated Nerves That Improves Their Impaired Axonal Conduction, Ahmed Al-Sabi, Declan Daly, Patrick Hoefer, Gemma K. Kinsella, Charles Metais, Mark Pickering, Caroline Herron, Seshu Kumar Kaza, Kieran Nolan, J. Oliver Dolly

Articles

K+ channels containing Kv1.1 α subunits, which become prevalent at internodes in demyelinated axons, may underlie their dysfunctional conduction akin to muscle weakness in multiple sclerosis. Small inhibitors were sought with selectivity for the culpable hyper-polarizing K+ currents. Modeling of interactions with the extracellular pore in a Kv1.1-deduced structure identified diaryldi(2-pyrrolyl)methane as a suitable scaffold with optimized alkyl ammonium side chains. The resultant synthesized candidate [2,2′-((5,5′(di-p-topyldiaryldi(2-pyrrolyl)methane)bis(2,2′carbonyl)bis(azanediyl)) diethaneamine·2HCl] (8) selectively blocked Kv1.1 channels (IC50 ≈ 15 μM) recombinantly expressed in mammalian cells, induced a positive shift in the voltage dependency of K+ current activation, and slowed its kinetics. It …

Geospatial Drivers Of The Groundwater Δ18o Isoscape In A Temperate Maritime Climate (Republic Of Ireland), S. Regan, R. Goodhue, O. Naughton, Paul Hynds

Articles

In recent years, the concept of “isoscapes” has been used to describe spatiotemporal stable isotope distributions within natural environments including groundwater systems at multiple scales. This study presents an updated groundwater δ18O isoscape for the Republic of Ireland and describes the climatic and geological drivers influencing 18O composition. In all, 142 geographically and geologically representative groundwater installations were sampled and analysed, in addition to 35 samples from six nested boreholes. Geospatially, Irish groundwater exhibits high δ18O values in southern and western coastal regions, becoming progressively depleted inland before reaching lowest measured values along the eastern coast, equating to a national …

An Iterative Bézier Method For Fitting Beta-Sheet Component Of A Cryo-Em Density Map, Michael Poteat, Jing He

Computer Science Faculty Publications

Cryo-electron microscopy (Cryo-EM) is a powerful technique to produce 3-dimensional density maps for large molecular complexes. Although many atomic structures have been solved from cryo-EM density maps, it is challenging to derive atomic structures when the resolution of density maps is not sufficiently high. Geometrical shape representation of secondary structural components in a medium-resolution density map enhances modeling of atomic structures. We compare two methods in producing surface representation of the β-sheet component of a density map. Given a 3-dimensional volume of β-sheet that is segmented from a density map, the performance of a polynomial fitting was compared with that …

Infusion Of Essentail Oils In Agarose Gels To Create Antimicrobial Surfaces, Simran Guron

Honors College Theses

The current use of antibiotics is very excessive in multiple settings, from treating patients to being present in cleaning products. This overuse of antibiotics is resulting in multiple consequences, ranging from having a negative impact on human health to breeding antibiotic-resistant strains of microorganisms. Antimicrobial surfaces are useful today to aid in sterilization, especially in the medical setting. This would help prevent the spread of infection of microorganisms in these settings. In our research, agarose acts as the antimicrobial surface and essential oils would act as the solution incorporated into the surface that has the antimicrobial properties. Agarose is a …

Biofunctionalized Capillary Flow Channel Platform Integrated With 3d Nanostructured Matrix To Capture Circulating Tumor Cells, Shashwat Banerjee, Ganesh Khutale, Vrushali Khobragade, Narendra Kale, Milind Pore, Govind Chate, Archana Jalota-Badhwar, Manoj Dongare, Jayant Khandare

Articles

Circulating tumor cells (CTCs) from peripheral blood account genetic information for cancer diagnosis and overall disease monitoring. Analysis of “liquid biopsy” holds immense promise as it may lead to new approaches for cancer treatment. The study reports effective and continuous flow microchannel system for isolating CTCs using transferrin conjugated 3D matrix synthesized by crosslinking polyethylene glycol-Fe3O4 nanostructures for rapid and efficient capturing of CTCs. The platform provides option of using multiple microchannel units in series that can influence higher cell-capture efficiency due to increasing cell-substrate contact frequency. CTCs are captured with high efficiency even at low concentration of target cells …

Thermostability Of The Coating, Antigen And Immunostimulator In An Adjuvanted Oral Capsule Vaccine Formulation, Stephanie Longet, Vincenzo Aversa, Daire O'Donnell, Joshua Tobias, Monica Rosa, Jan Holmgren, Ivan Coulter, Ed Lavelle

Articles

Oral vaccines present an attractive alternative to injectable vaccines for enteric diseases due to ease of delivery and the induction of intestinal immunity at the site of infection. However, susceptibility to gastrointestinal proteolysis, limited transepithelial uptake and a lack of clinically acceptable adjuvants present significant challenges. A further challenge to mass vaccination in developing countries is the very expensive requirement to maintain the cold chain. We recently described the effectiveness of a Single Multiple Pill® (SmPill®) adjuvanted capsule approach to enhance the effectiveness of a candidate enterotoxigenic Escherichia coli (ETEC) oral vaccine. Here it was demonstrated that this delivery system …

Quantification Of Trace Metals In Infant Formula Premixes Using Laser-Induced Breakdown Spectroscopy, Raquel Cama-Moncunill, Maria Piedad Casado-Gavalda, Xavier Cama-Moncunill, Maria Markiewicz-Keszycka, Yash Dixit, Patrick J. Cullen, Carl Sullivan

Articles

Infant formula is a human milk substitute generally based upon fortified cow milk components. In order to mimic the composition of breast milk, trace elements such as copper, iron and zinc are usually added in a single operation using a premix. The correct addition of premixes must be verified to ensure that the target levels in infant formulae are achieved. In this study, a laser-induced breakdown spectroscopy (LIBS) system was assessed as a fast validation tool for trace element premixes. LIBS is a promising emission spectroscopic technique for elemental analysis, which offers real-time analyses, little to no sample preparation and …

Impact Of Atmospheric Pressure Nonequilibrium Plasma Discharge On Polymer Surface Metrology, Laurence Scally, James Lalor, Patrick J. Cullen, Vladimir Milosavljevic

Articles

Due to the attraction of plasma technologies as a clean and efficient means of surface modification, significant research has gone into the physical and chemical aspects of polymer functionalization. In this study, it was shown that the use of an atmospheric plasma jet can efficiently modify the surface of polyethylene terephthalate samples and change their hydrophobic properties to more hydrophilic characteristics. The dependence on the changes with respect to time, distance, and atomic oxygen (O I) intensity were considered as factors. It was found that with closer proximity to the plasma source (without causing thermal degradation) and with increasing levels …

A Multi-Model Approach In Developing An Intelligent Assistant For Diagnosis Recommendation In Clinical Health Systems, Christian E. Pulmano, Ma. Regina Justina E. Estuar

Department of Information Systems & Computer Science Faculty Publications

Clinical health information systems capture massive amounts of unstructured data from various health and medical facilities. This study utilizes unstructured patient clinical text data to develop an intelligent assistant that can identify possible related diagnoses based on a given text input. The approach applies a one-vs-rest binary classification technique wherein given an input text data, it is identified whether it can be positively or negatively classified for a given diagnosis. Multi-layer Feed-Forward Neural Network models were developed for each individual diagnosis case. The task of the intelligent assistant is to iterate over all the different models and return those that …

Bayesian Exponential Random Graph Modelling Of Interhospital Patient Referral Networks, Alberto Caimo, Francesca Pallotti, Alessandro Lomi

Articles

Using original data that we have collected on referral relations between 110 hospitals serving a large regional community, we show how recently derived Bayesian exponential random graph models may be adopted to illuminate core empirical issues in research on relational coordination among healthcare organisations. We show how a rigorous Bayesian computation approach supports a fully probabilistic analytical framework that alleviates well-known problems in the estimation of model parameters of exponential random graph models. We also show how the main structural features of interhospital patient referral networks that prior studies have described can be reproduced with accuracy by specifying the system …

Silencing Science.Pptx, Kai Hung

Faculty Research & Creative Activity

This is a non-peer reviewed teaching resource.

Oxidative Stress And Proteomic Studies Of Mammalian Models Of Age-Related Metabolic Dysfunction In Neurodegenerative Disorders, Aaron M. Swomley

Theses and Dissertations--Chemistry

Expression proteomics is the field of science wherein proteins that make up the cellular proteome are identified both by name and by fold-change. Depending on the application of proteomics, this change in level could be due to internal cellular stressors or introduction of xenobiotics. Global oxidative stress measures use immunohistochemistry to determine the relative level of oxidative stress of macromolecules within the cell. In this dissertation, both global oxidative stress measures and expression proteomics were used in a variety of mammalian models in order to determine the effects of protein upregulation, intranasal insulin administration, and resveratrol supplementation on the cellular …

Micro-Spectroscopy Of Bio-Assemblies At The Single Cell Level, Jeslin Kera

Honors Undergraduate Theses

In this thesis, we investigate biological molecules on a micron scale in the ultraviolet spectral region through the non-destructive confocal absorption microscopy. The setup involves a combination of confocal microscope with a UV light excitation beam to measure the optical absorption spectra with spatial resolution of 1.4 μm in the lateral and 3.6 μm in the axial direction. Confocal absorption microscopy has the benefits of requiring no labels and only low light intensity for excitation while providing a strong signal from the contrast generated by the attenuation of propagating light due to absorption. This enables spatially resolved measurements of single …

Assessing Patient And Caregiver Intent To Use Mobile Device Videoconferencing For Remote Mechanically-Ventilated Patient Management, Brian R. Smith

Master's Theses and Doctoral Dissertations

The Michigan Medicine adult Assisted Ventilation Clinic (AVC) supports patients with neuromuscular disorders and spinal cord injuries and their caregivers at home, helping them avoid expensive emergency department visits, hospitalization, and unnecessary or excessive treatments. Mobile device videoconferencing provides an effective capability for remote mechanically-ventilated patient management but must rely upon an unknown infrastructure comprising patient and caregiver mobile device ownership, connectivity, and experience—and intent to use the service if provided. The purpose of this study was to measure the extent of this infrastructure and the perceived ease of use, perceived usefulness, and intent to use this mobile device …

Multi-Scale Cardiovascular Flow Analysis By An Integrated Meshless-Lumped Parameter Model, Leonardo A. Bueno, Eduardo A. Divo, Alain J. Kassab

Publications

A computational tool that integrates a Radial basis function (RBF)-based Meshless solver with a Lumped Parameter model (LPM) is developed to analyze the multi-scale and multi-physics interaction between the cardiovascular flow hemodynamics, the cardiac function, and the peripheral circulation. The Meshless solver is based on localized RBF collocations at scattered data points which allows for automation of the model generation via CAD integration. The time-accurate incompressible flow hemodynamics are addressed via a pressure-velocity correction scheme where the ensuing Poisson equations are accurately and efficiently solved at each time step by a Dual-Reciprocity Boundary Element method (DRBEM) formulation that takes advantage …

Visualizing Morphogenesis With The Processing Programming Language, Avik Patel, Amar Bains, Richard Millet, Tamira Elul

Faculty Publications & Research of the TUC College of Osteopathic Medicine

We used Processing, a visual artists’ programming language developed at MIT Media Lab, to simulate cellular mechanisms of morphogenesis – the generation of form and shape in embryonic tissues. Based on observations of in vivo time-lapse image sequences, we created animations of neural cell motility responsible for elongating the spinal cord, and of optic axon branching dynamics that establish primary visual connectivity. These visual models underscore the significance of the computational decomposition of cellular dynamics underlying morphogenesis.

Synthesis Of Ag10 Analogs And Optimization Of Ttr Ligands For Half-Life Enhancement (Tlhe) Of Peptides, Raghavendra Jampala

University of the Pacific Theses and Dissertations

The misassembly of soluble proteins into toxic aggregates, including amyloid fibrils, underlies a large number of human degenerative diseases. Cardiac amyloidosis, which is most commonly, caused by aggregation of Immunoglobulin (Ig) light chains or transthyretin (TTR) in the cardiac muscle, represent an important and often underdiagnosed cause of heart failure. TTR-mediated amyloid cardiomyopathies are chronic and progressive conditions that lead to arrhythmias, biventricular heart failure, and death. As no Food and Drug Administration-approved drugs are currently available for treatment of these diseases, the development of therapeutic agents that prevent TTR-mediated cardiotoxicity is desired. AG10 is a potent and selective kinetic …

Fragment-Based Excitonic Coupled-Cluster Theory For Large Chemical Systems, Yuhong Liu

University of the Pacific Theses and Dissertations

Accurate energetic modeling of large molecular systems is always desired by chemists. For example, ligand-protein binding simulations and enzymatic catalysis studies all involve with a small energy difference. The energetic accuracy depends largely on a proper handling of electronic correlations. Molecular mechanics (MM) methods deliver a parameterized Newtonian treatment to these problems. They show great capability in handling large calculations but give only qualitatively good results. Quantum mechanics (QM) methods solve Schrödinger equations and exhibit much better energy accuracy, though the computational cost can be prohibitive if directly applied to very large systems.

Fragment-based methods have been developed to decompose …

Investigating Secondary Structure Features Of Yap1 Protein Fragments Using Molecular Dynamics (Md) And Steered Molecular Dynamics (Smd) Simulations, Ferdiemar Cardenas Guinto Jr.

University of the Pacific Theses and Dissertations

Molecular dynamics (MD) is a powerful tool that can be applied to protein folding and protein structure. MD allows for the calculation of movement, and final position, of atoms in a biomolecule. These movements can be used to investigate the pathways that allow proteins to fold into energetically favorable structures. While MD is very useful, it still has its limitations. Most notable, computing power and time are of constant concern.

Protein structure is inherently important due to the direct link between the structure of a protein and its function. One of the four levels of protein structure, the secondary structure, …

The Rational Investigation Of Anti-Cancer Peptide Specificity Using The Knob-Socket Model, Shivarni Patel

University of the Pacific Theses and Dissertations

Cancer has been a pervasive and deadly problem for many years. No treatments have been developed that effectively destroy cancer cells while also keeping healthy cells safe. In this work, the knob-socket construct is used to analyze two systems involved in cancer pathways, the PDZ domain and the Bcl-BH3 complex. Application of the knob-socket model in mapping the packing surface topology (PST) allows a direct analysis of the residue groups important for peptide specificity and affinity in both of these systems. PDZ domains are regulatory proteins that bind the C-terminus of peptides involved in the signaling pathway of cancer progression. …

Clinical Factors Associated With Hepatitis C Treatment Selection In A Veterans Affairs Population, Carly Anne Ranson

University of the Pacific Theses and Dissertations

Background: Hepatitis C virus is currently the most common chronic blood borne pathogen in the United States, with only half of those infected aware of their condition. The cost for treatment is higher with Harvoni® (ledipasvir/sofosbuvir) than Viekira Pak® (ombitasvir/paritaprevir/ritonavir and dasabuvir). With finite resources available to treat patients, it is important to understand which clinical factors may influence treatment selection decisions.

Methods: The study is a 12-month medical record review within the Veterans Affairs (VA) system to evaluate significant relationships between selected clinical and sociodemographic factors and HCV treatment selection with either Harvoni® or Viekira Pak®. Clinical and demographic …

Solubility Enhancement Of Model Compounds, Lavanya Pitani

University of the Pacific Theses and Dissertations

Solubility is the amount of solute in the solvent system at phase equilibrium with certain temperature and pressure. Many of the new chemical entities are lipophilic molecules that require techniques to enhance solubility. Solubility enhancement can be achieved by either physical and/or chemical modification of the drug. Various techniques are available for solubility enhancement of poorly soluble drugs include particle size reduction, salt formation, solid dispersions, use of surfactants, prodrug, crystal modification, etc.

In this study, the three model drugs belong to BCS class II and IV having low solubility with a certain range of physicochemical properties were studies in …

Research Strategies For Biomedical And Health Informatics: Some Thought-Provoking And Critical Proposals To Encourage Scientific Debate On The Nature Of Good Research In Medical Informatics, Reinhold Haux, Et Al.

Research Collection School Of Computing and Information Systems

Medical informatics, or biomedical and health informatics (BMHI), has become an established scientific discipline. In all such disciplines there is a certain inertia to persist in focusing on well-established research areas and to hold on to well-known research methodologies rather than adopting new ones, which may be more appropriate. To search for answers to the following questions: What are research fields in informatics, which are not being currently adequately addressed, and which methodological approaches might be insufficiently used? Do we know about reasons? What could be consequences of change for research and for education? Outstanding informatics scientists were invited to …

Comparison Of Atypical Bacteriophages That Infect Caulobacter Crescentus, Doreen Nguyen

Theses and Dissertations

Several Caulobacter bacterial genomes have been recently sequenced, and all of the genomes contained one or more clusters of genes with phage origins. This observation indicates that bacteriophages contribute to the Caulobacter gene pool, so in order to understand bacteria genomes we will need to understand phage genomes as well. As part of understanding the phage genomes, we want to isolate novel bacteriophages and study their genomics. This study resulted in the isolation of 12 new phages, including four that differ from the well-studied CbKlike phages. Two of these novel phages are Podoviruses with icosahedral heads and small tails, and …

Marginal Structural Cox Model For Survival Data With Treatment-Confounder Feedback, Yanan Zhang

Theses and Dissertations

In an observational longitudinal study, there can be time-varying exposure/treatment and time-varying confounders. When the confounders affect the exposure and prior exposure also has an impact on levels of confounders, there is treatment confounder feedback. To admit estimation of unbiased causal effects, these conditions need to be hold, exchangeability, positivity, consistency. The traditional method of conditioning on potential confounders does not meet these 3 conditions. Therefore, parameter estimates from traditional Cox model are biased casual effect estimates when the treatment confounder feedback exists. The marginal structural Cox model can be used to address this issue. By calculating and including inverse …

Remote Sensing Observation Of Annual Dust Cycles And Possible Causality Of Kawasaki Disease Outbreaks In Japan, Hesham El-Askary, Nick Lahaye, Erik J. Linstead, William A. Sprigg, Magdi Yacoub

Mathematics, Physics, and Computer Science Faculty Articles and Research

Kawasaki disease (KD) is a rare vascular disease that, if left untreated, can result in irreparable cardiac damage in children. While the symptoms of KD are well-known, as are best practices for treatment, the etiology of the disease and the factors contributing to KD outbreaks remain puzzling to both medical practitioners and scientists alike. Recently, a fungus known as Candida, originating in the farmlands of China, has been blamed for outbreaks in China and Japan, with the hypothesis that it can be transported over long ranges via different wind mechanisms. This paper provides evidence to understand the transport mechanisms …

Simulating Foodborne Pathogens In Poultry Production And Processing To Defend Against Intentional Contamination, S. Lankford, D. R. Thompson, S. C. Ricke

Journal of the Arkansas Academy of Science

There is a lack of data in recent history of food terrorism attacks, and as such, it is difficult to predict its impact. The food supply industry is one of the most vulnerable industries for terrorist threats while the poultry industry is one of the largest food industries in the United States. A small food terrorism attack against a single poultry processing center has the potential to affect a much larger human population than its immediate consumers. In this work, the spread of foodborne pathogens is simulated in a poultry production and processing system to defend against intentional contamination. An …

Linking Atr-Ftir And Raman Features To Phenolic Extractability And Other Attributes In Grape Skin, Hugh Byrne, Abigain Rooney, Julio Nogales-Bueno, Jose Miguel Hernandez-Hierro, Francisco Jose Heredia

Articles

The importance of wine phenolics on the sensory characteristic of red wines is well-known. Therefore, it is necessary to control the extractability of phenolic compounds from grape skins, which depends significantly on grape ripeness and hence, on cell wall degradation.

In the present study, attenuated total reflectance Fourier transform infrared (ATR-FTIR) and Raman spectra of grape skin have been recorded. Then, these spectral matrices have been studied and the main spectral features have been linked to extractabilities of phenolic compounds (anthocyanins, flavanols and total phenols). Moreover, spectral differences between external and internal grape skin surfaces also have been studied.

It …

Determination Of Spectral Markers Of Cytotoxicity And Genotoxicity Using In Vitro Raman Microspectroscopy: Cellular Responses To Polyamidoamine Dendrimer Exposure, Esen Efeoglu, Alan Casey, Hugh Byrne

Articles

Although consumer exposure to nanomaterials is ever increasing, with potential increased applications in areas such as drug and/or gene delivery, contrast agents and diagnosis, determination of cyto- and geno- toxic effect of nanomaterials on human health and the environment still remains challenging. Although many techniques have been established and adapted to determine the cytotoxicity and genotoxicity of nano-sized materials, these techniques remain limited by the number of assays required, total cost, use of labels and they struggle to explain the underlying interaction mechanisms. In this study, Raman microspectroscopy is employed as an in vitro label free high content screening technique …