Digital Commons Network^™

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 …

Synthetic Methods For Ester Bond Formation And Conformational Analysis Of Ester-Containing Carbohydrates, Sven Hackbusch

University of the Pacific Theses and Dissertations

This dissertation encompasses work related to synthetic methods for the formation of ester linkages in organic compounds, as well as the investigation of the conformational influence of the ester functional group on the flexibility of inter-saccharide linkages, specifically, and the solution phase structure of ester-containing carbohydrate derivatives, in general.

Stereoselective reactions are an important part of the field of asymmetric synthesis and an understanding of their underlying mechanistic principles is essential for rational method development. Here, the exploration of a diastereoselective O-acylation reaction on a trans-2-substituted cyclohexanol scaffold is presented, along with possible reasons for the observed reversal of stereoselectivity …

Autonomous Driving With A Simulation Trained Convolutional Neural Network, Cameron Franke

University of the Pacific Theses and Dissertations

Autonomous vehicles will help society if they can easily support a broad range of driving environments, conditions, and vehicles.

Achieving this requires reducing the complexity of the algorithmic system, easing the collection of training data, and verifying operation using real-world experiments. Our work addresses these issues by utilizing a reflexive neural network that translates images into steering and throttle commands. This network is trained using simulation data from Grand Theft Auto V~\cite{gtav}, which we augment to reduce the number of simulation hours driven. We then validate our work using a RC car system through numerous tests. Our system successfully drive …

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 …

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 …

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. …

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 …

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 …

Predicting Aqueous Solubility Of Pharmaceutical Agents By Solid Dispersion Prepared By Solvent Evaporation Method, Karthik Reddy Patlolla

University of the Pacific Theses and Dissertations

Solubility of active pharmaceutical agents is a crucial process that determines drug absorption and ultimately its bioavailability. Many of the new therapeutically beneficial compounds discovered are lipophilic requiring various solubility enhancement strategies to improve their solubility. Among these strategies, solubility enhancement using solid dispersions is a leading method. To obtain a desirable increase in the solubility of a poorly-soluble compound, a good understanding of the molecular descriptors influencing the enhancement of solubility is essential. Therefore, the major research objective was to determine the descriptors which significantly influence the solubility enhancement by solid dispersions. After enhancing the solubility of selected poorly-soluble …

Turning Stealth Liposomes Into Cationic Liposomes For Anticancer Drug Delivery, Vijay Gyanani

University of the Pacific Theses and Dissertations

Targeting the anticancer agents selectively to cancer cells is desirable to improve the efficacy and to reduce the side effects of anticancer therapy. Previously reported passive tumor targeting by PEGylated liposomes (stealth liposomes) have resulted in their higher tumor accumulation. However their interaction with cancer cells has been minimal due to the steric hindrance of the PEG coating. This dissertation reports two approaches to enhance the interaction of stealth liposomes with cancer cells. First, we designed a lipid-hydrazone-PEG conjugate that removes the PEG coating at acidic pH as in the tumor interstitium. However, such a conjugate was highly unstable on …

Glycals : An Extended Study Of The Ferrier-Dimerization, Andreas H. Franz

University of the Pacific Theses and Dissertations

C-linked disaccharides were synthesized from 3,4,6-tri-O-acetyl-D-glucal 1 (1,5- anhydro-3,4,6-tri-O-acetyl-1,2-dideoxy-D-arabino-hex-I-enopyranose), 3,4,6-tri-O- acetyl-D-galactal 2 (1,5-anhydro-3,4,6-tri-O-acetyl-1,2-dideoxy-D-lyxo-hex-1- enopyranose) and 3,4-di-O-acetyl-L-fucal 3 (1,5-anhydro-3,4-di-O-acetyl-1,2,6-tri-deoxy- L-lyxo-hex-1-enopyranose) under Lewis acid catalysis (Scheme 1) and compound 4 was further derivatized at the double bond. Dihydroxylation of the glucose dimer 4 gave high allo-diastereoselectivity. The reactions used in the derivatization of 1 were subsequently applied to 2 and 3. The overall yield of 3 was improved to 70 %. All three glycals (10% solution in toluene) reacted quickly with boron trifluoride to give dimerization products in 40-60% yield. Futile attempts at de-O-acetylation of the 2',3'-unsaturated dimer revealed the necessity of …

Projective And Non-Projective Systems Of First Order Nonlinear Differential Equations, Riad A. Rejoub

University of the Pacific Theses and Dissertations

It is well established that many physical and chemical phenomena such as those in chemical reaction kinetics, laser cavities, rotating fluids, and in plasmas and in solid state physics are governed by nonlinear differential equations whose solutions are of variable character and even may lack regularities. Such systems are usually first studied qualitatively by examining their temporal behavior near singular points of their phase portrait.

In this work we will be concerned with systems governed by the time evolution equations [see PDF for mathematical formulas]

The x_i may generally be considered to be concentrations of species in a chemical …

Ion-Association Complexes Of Thallium And Mercury With Rhodamine 6g In Aqueous Solution, Nasrein El-Masri

University of the Pacific Theses and Dissertations

The present study involves the determination of traces of thallium and mercury in aqueous solution by forming ion-association complexes of these metals with rhodamine 6G (R6G) in the presence of iodide. Thallium(lll) and mercury(Il) are able to quench the fluorescence of R6G in the presence of iodide by forming ion—association complexes, and the degree of quenching correlates with the thallium(III) or mercury(II) concentrations . By using this method, the minimum amount of thallium- (III) that can be determined in aqueous solutions is approximately 4.00 X 10-6m, while the minimum amount of mercury(II) is approximately 3.00 X 10-6m. Thallium(I) cannot be …

Studies On The Effect Of Palmitylcarnitine Chloride On The Solubility Of Etoposide, Lola Kashyap

University of the Pacific Theses and Dissertations

The effect of an endoqenous surfactant, palmitylcarnitine chloride (PCC), on the solubility of etoposide was investigated. Preliminary studies were conducted to establish optimum experimental conditions for subsequent equilibrium solubility determinations. Infrared spectroscopy and thin layer chromatography techniques were used to establish the purity and identity of PCC. PCC was found to undergo rapid hydrolysis in aqueous solutions at 37.0° ± 0.5° C and the degradation was independent of concentration. The effect of pH on the stability of PCC was investigated. These studies revealed that PCC was most stable in the range pH 3.0 - 4.0. Etoposide was found to be …

Use Of Isomerizable N-Alkylmerocyanine Dyes To Robe Molecular Interactions Within Micellar Solubilization Sites, Kim Jason Dennis

University of the Pacific Theses and Dissertations

Effects of aqueous surfactant solutions upon cis/trans isomerization reactions of various N-alkyl-merocyanine dyes (II) were studied. Dramatic rate enhancements were found for all dyes in CTAB and SDS solutions above the CMC. CTAB solutions showed the greatest effect with some dye isomerizations catalyzed in excess of 1000-fold. Increases in either CTAB concentration or dye isomerization rates. N-methyl through N-pentyl dye isomerization rates were measured as a function of CTAB concentration and the data treated according to the pseudophase model for micellar catalysis. K_S values ranged from 198 to 2000 M^-1 for N-methyl to N-pentyl dyes, respectively. Micellar rate …

Tutorials For Software : A Comparison Of The Appleworks Software Tutorial With Pre-Entered Data And An Experimental Tutorial With User Entered Data, Toni L. Steil

University of the Pacific Theses and Dissertations

The attention directed toward computer software research has been sparse which is quite evident in particular facets such as learning methods, specifically towards tutorials. Some authors have identified various important issues which include cognitive factors, reduction of presentation of superfluous information, and the importance of interaction with software and hardware. The present . study examined two tutorials which were similar except in their level of required user behaviors. Tutorial A required only user manipulation of disk stored data. Tutorial B required the user to enter the data into the computer, design the screen format, and then to manipulate it. It …

Group Theoretical Analysis Of In-Shell Interaction In Atoms, Yanfang Ho

University of the Pacific Theses and Dissertations

A group theoretic approach to Layzer's 1/2 expansion method is explored. In part this builds on earlier work of Wulfman(2), of Moshinsky et al(l4), and of Sinanoglu, Herrick(lS), and Kellman (16) on second row atoms.

I investigate atoms with electrons in the 3s-3p-3d shell and find:

1. Wulfman's constant of motion accurately predicts configuration mixing for systems with two to eight electrons in the 3s-3p subshell.

2. The same constant of motion accurately predicts configuration mixing for systems with two electrons in the 3s-3p-3d shell.

3. It accurately predicts configuration mixing in systems of high angular momentum L and of …

Trans Diequatorially Fused 3',3'-Diphenyl-2'-Morpholinone Derivatives Of 2-Amino-2-Deoxy-D-Glucose, Julian Guardado Puentes

University of the Pacific Theses and Dissertations

The chemistry of amino sugar compounds has been studied in the last years in connection with the study of natural products, and many of them have been isolated. ^57,17,18 Amino sugars play an important role in biochemistry, forming blocks of homo- and heteropolymers and complex molecules such as microbial polysaccharides, enzymes, gangliosides, glycoproteins, and antibiotics.

This research project had the purpose of preparing a derivative of 2-amino-2-deoxy-D-glucose, with a free hydroxyl group at the anomeric carbon, with the 4,6-positions blocked with the benzylidene cyclic acetal, and the 2,3-positions being blocked by a 3,3-diphenyl-2-morpholinone ring trans diequatorially fused to the amino …

Setchenov Parameters For Naphthalene, Gerardo Gold Bouchot

University of the Pacific Theses and Dissertations

It is the purpose of this work to study the solubility of naphthalene, the simplest polycyclic aromatic hydrocarbon as a function of the salt content and the temperature, in ranges that span those likely to be found in natural ecosystems. Another goal is to set up a high-pressure generator, to study the effect of pressure on the solubility of hydrocarbons.

Studies On The Biochemical And Antibiotic Patterns Of The Genus Citrobacter, Craig Richard Tanner

University of the Pacific Theses and Dissertations

Today three species are recognized in the genus: C. freundii, C. amalonaticus, and C, diversus. C. freundii is known to occur as three varieties: C. freundii H₂S +, IND -, C. freundii H₂S +, IND +, and C. freundii H₂S -, IND -.

The role of Citrobacter in disease has not been investigated thoroughly. The organism is a normal inhabitant of the human intestine, being as common as Escherichia coli in infants. With age, the child's intestine begins to show a greater ratio of E. coli to Citrobacter (Nahhas, personal communication). Citrobacter has been …

Thermodynamics Of Aqueous Solutions Of 1-Naphthyl Methylcarbamate, Miguel Angel Huerta Diaz

University of the Pacific Theses and Dissertations

Accurate solubility measurements for the pesticide l-naphthyl-N-methylcarbamate (carbaryl) in water, natural and artificial seawater, NaCl, Na₂SO₄, CaCl₂ and (CH₃)₄NBr, at different temperatures covering the range 5-45 °C, were obtained using a combination of the generator column method and absorption spectroscopy techniques. As a rule, it was found that the solubility of carbaryl in water and in the electrolyte solution increased with an increase in temperature.

The thermodynamic parameter ΔG°, ΔH°, ΔS°, and ΔC°_p at 298.15 K, for the dissolution process carbaryl(s) to carbaryl(aq) and carbaryl(s) to carbaryl(aq. elect.), were calculated …

The Synthesis Of Various Substituted 3-Amino-7-Hydroxy-2,2-Dimethyltetralins And Their Opioid-Related Activities, David Alan Lippman

University of the Pacific Theses and Dissertations

A series of aminotetralones and aminotetralins were synthesized from the common intermediate F, 3-amino-2,2-dimethyl-7-methoxy- 1-tetralone. The final compounds derived from F were simple substituted and/or reduced analogues. The products would allow a progressive structure activity relationship to be drawn based on pharmacological testing.

The common intermediate F was synthesized utilizing a six step procedure starting with p-methoxyphenylacetic acid. The overall yield from the precursor to the F:HC1 was 25%. Compound F was either O-demethylated to form 3-amino-2,2-dimethyl-7-hydroxy-l-tetralone (I) or was dimethylated on the amine and subsequently O-demethylated to yield the 3-dimethylamino-7-hydroxy-2,2-dimethyl-l-tetralone (J). The last major modification was the reduction of …

Comparison Of Selected Radiopharmaceutical Chromatographic Quality Control Procedures, Lawrence Ray Andreatta

University of the Pacific Theses and Dissertations

The purpose of this study was to compare the accuracy and reproducibility of two commercially available chromatography kits with Instant Thin Layer Chromatography-Silica Gel (ITLC-SG) and Whatman Chromatography Paper. The two commercial kits evaluated were the- MAC Klt- produced-General Radioisotopes Products, and the TECH Kit by Ackerman Nuclear.

Effect Of Temperature On The Association Constants Of Some Divalent Metal Ions With Chloride In Sea Water-Like Solutions, Jose Vinicio Macias Zamora

University of the Pacific Theses and Dissertations

Association constants for the formation of lead (II) chloride complexes were studies in aqueous solutions also containing copper (II) and cadmium (II) ions.

The ionic strength was adjusted with sodium perchlorate to resemble that of sea water. The temperature was set at fixed values between 5° and 35° C to determine the effect on the equilibria in these systems. The total metal concentration was less than 10^-8 M.

Differential pulse anodic striping voltammetry was used with a conventional three electrode system and a thin-film working electrode of Pt/Hg. Complex formation was followed as a function of the ligand concentration …

Analysis Of Clay Minerals, Other Silicate And Nonsilicate Minerals, And The Grading Of Chrysotile Asbestos By Attenuated Total Reflection Infrared Spectrophotometry (With Atlas), Ashraf Muhammad Chaudhry

University of the Pacific Theses and Dissertations

This study of ATR-IR involved taking spectra of various silicate minerals in powder samples, finding similarities and differences in nature, and locating various bands and intensities of absorption bands for identification and classification purposes. This study is limited to 4000-300 cm^-1 with major emphasis on absorptions in the 2000-300 cm^-1 region.

Flow Injection Atomic Absorption Assay Of Copper And Zinc In The Plasma Of Age Dependent Audiogenic Seizure Susceptible Mice, Neal Dwain Byington

University of the Pacific Theses and Dissertations

Flow injection atomic absorption procedures with less than 10%RSD at 1.0 ppm were developed for the assay of copper and zinc in 10 μL samples of mouse plasma. The flow injection apparatus was designed with a pulseless liquid flow control system, regulated by inert gas pressure. The aspiration liquid is 6% t-butanol in water. After exhaustive parameter optimizations, copper assays were conducted with the conventional air-acetylene flame at 324.754 nm and zinc assays were conducted with the unconventional argon-hydrogen air diffusion flame at 213.856 nm. The argon-hydrogen flame system was chosen because it absorbs very little ultraviolet light.

The developed …

The Reaction Of 4-Vinylcyclohexene With Palladium (Ii), Kathy Ellen Beeler

University of the Pacific Theses and Dissertations

This program of study was concerned with the elucidation of the causes(s) behind the inability of various workers to reproduce the work of Fyre and Kuljian on the rearrangement of 4-vinylcyclohexene to 1,5-cyclooctadiene by the action of palladium (II).

A Spectroscopic Study Of Intramicellar Environment With Merocyanine Dye Probes, Elise Jane Daggs

University of the Pacific Theses and Dissertations

The effects of micelle forming surfactants hexadecyltrimethylammonium bromide, sodium dodecyl sulfate and igepal CA~6JO on the visible spectra of merocyanine dyes of the form 1-alkyl-4-[(3', 5'-alkyl oxocyclohexadienylidene)ethylidene]- 1,4-dihydropyridine were studied. In all cases the visible spectrum shifted to the red when the dye was incorporated into the micelles. The magnitude of the shifts was found to be dependent on the substituted groups and the positioning of the chromophore of the dye in the micelle aggregates. The shifts indicate a highly hydrated environment about the surfactant head groups and an environment equivalent to that of pure ethanol solvent at some undetermined …

The Preparation Of The Coordination Compounds Of Palladium (Ii) And Spermine And Spermidine, Wenli Grace Lee

University of the Pacific Theses and Dissertations

The purpose of this study was to prepare and characterize complexes produced by the reactions of spermine and spermidine with palladium(II) chloride. A first analysis of the problem seemed to indicate that preparation of the complexes should be straightforward and not difficult. Bonding of the nitrogen atoms to the metals allows sterically for formation of two six-membered rings separated by a tetramethylene chain in a spermine complex, and by a six-membered chelate ring in a spermidine complex.

The Effect Of Tungsten(0)Pentacarbonyl On Coordinated Ligands, Janice Imada Byington

University of the Pacific Theses and Dissertations

A series of monosubstituted tungsten(0)pentacarbonyl complexes, W(CO)₅L (L = water, hydrogen sulfide, pyrazine, pyrimidine, 4,4'-bipyridine, 4-cyanopyridine, isonicotinamide, and methanol) were synthesized and characterized. The purpose of this project was to determine the effect of the W(CO)₅ moiety on the coordinated ligand, L.

The visible spectra of the synthesized W(CO)₅L complexes typically exhibited a maximum around 400 nm ((epsilon) (TURN) 4000). The infrared spectra of these complexes exhibited the characteristic three band pattern (2A₁ + E) in the carbonyl region ((TURN)2070 cm^-1, (TURN)1930 cm^-1, (TURN)1900 cm^-1. The pKa's of …