+publisher:"Virginia Tech" +contributor:("Sriranganathan, Nammalwar")

Virginia Tech

1. Rushin, Tiffany Patricia. Prevalence and Identity of Tissue Cyst Forming Apicomplexan Parasites in the Muscles of Raptors.

Degree: MS, Biomedical and Veterinary Sciences, 2014, Virginia Tech

URL: http://hdl.handle.net/10919/48900

► There is little information on the distribution and diversity of Apicomplexan protozoal infections in the tissues of raptors in the United States. Protozoan encephalitis caused… (more)

▼ There is little information on the distribution and diversity of Apicomplexan protozoal infections in the tissues of raptors in the United States. Protozoan encephalitis caused by Sarcocystis species and Toxoplasma gondii is being increasingly reported in raptors from various locations in the United States. To better determine the exposure of raptors to these Apicomplexan parasites, we examined breast and heart muscle tissue of raptors from the Carolina Raptor Center for the presence of Sarcocystis species, T. gondii and Neospora caninum via histology, Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) using DraI and HinfI enzymes (Sarocystis only). Of 187 available HandE stained tissue sections, 33 contained sarcocysts. Nineteen of these slides had a matching DNA sample to compare via PCR. Nine of these 19 were positive for Sarcocystis via ITS PCR. Using ITS PCR, we detected Sarcocystis DNA in 24 of 114 birds (21.1%). Further molecular differentiation using JNB primers showed that 9 of the 24 birds were positive for either S. neurona or S. falcatula. RFLP analysis of these 9 indicated that 4 were S. falcatula samples, and 3 were S. falcatula Arg samples that cut with both enzymes. Our Sarcocystis positive samples were also tested for S. calchasi, S. columbae and Sarcocystis sp. Ex. A. nisus using PCR primers designed for these species. These species are emerging in Europe and have already shown an expansion of their distribution. Two samples (14567 and 15203) suggestive of Sarcocystis sp. Ex. A. nisus were identified, as well as one sample (14567), which suggested the presence of S. columbae. None of these samples were confirmed by sequencing the amplicons and the other 22 samples were all negative for these parasites. Recent reports have demonstrated DNA of S. falcatula in the brain and muscles of great horned owls (Bubo virginianus), golden eagles (Aquila chrysaetos), and bald eagles (Haliaeetus leucocephalus) with encephalitis in rehabilitation centers in Indiana, Minnesota, and Virginia using PCR. DNA of S. calchasi has been found in CNS tissue of several species of birds suffering encephalitis in an aviary in California. Hawks (Accipiter species) are believed to be the source of infection. The prevalence of T. gondii was 18.4% (21 of 114) in these birds by PCR, but none were positive by histopathology. N. caninum prevalence in raptors has been poorly discussed in the literature. This parasite uses canids as the definitive host in its life cycle, and is considered to have a much more restricted host range than T. gondii. Thirty-five of 114 birds (30.7%) were found to be PCR positive for N. caninum, but no tissue cysts of N. caninum were observed in histological sections. Co-infection of 2 or all 3 species was detected in 16 of 114 birds (14%). This study demonstrates that there may be a higher prevalence of S. falcatula in raptors than was previously known, including more, as yet unknown, species of Sarcocystis capable of infecting raptors as intermediate hosts. Our PCR… Advisors/Committee Members: Lindsay, David S. (committeechair), Sriranganathan, Nammalwar (committee member), Zajac, Anne M. (committee member).

Subjects/Keywords: Sarcocystis; Sarcocystis falcatula; Toxoplasma gondii; Neospora caninum; raptors; Apicomplexa

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APA (6^th Edition):

Rushin, T. P. (2014). Prevalence and Identity of Tissue Cyst Forming Apicomplexan Parasites in the Muscles of Raptors. (Masters Thesis). Virginia Tech. Retrieved from http://hdl.handle.net/10919/48900

Chicago Manual of Style (16^th Edition):

Rushin, Tiffany Patricia. “Prevalence and Identity of Tissue Cyst Forming Apicomplexan Parasites in the Muscles of Raptors.” 2014. Masters Thesis, Virginia Tech. Accessed April 13, 2021. http://hdl.handle.net/10919/48900.

MLA Handbook (7^th Edition):

Rushin, Tiffany Patricia. “Prevalence and Identity of Tissue Cyst Forming Apicomplexan Parasites in the Muscles of Raptors.” 2014. Web. 13 Apr 2021.

Vancouver:

Rushin TP. Prevalence and Identity of Tissue Cyst Forming Apicomplexan Parasites in the Muscles of Raptors. [Internet] [Masters thesis]. Virginia Tech; 2014. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10919/48900.

Council of Science Editors:

Rushin TP. Prevalence and Identity of Tissue Cyst Forming Apicomplexan Parasites in the Muscles of Raptors. [Masters Thesis]. Virginia Tech; 2014. Available from: http://hdl.handle.net/10919/48900

Virginia Tech

2. Casterlow, Samantha Alexandra. Characterization and Pharmacokinetics of Rifampicin Laden Carboxymethylcellulose Acetate Butyrate Particles.

Degree: MS, Biomedical and Veterinary Sciences, 2012, Virginia Tech

URL: http://hdl.handle.net/10919/42659

► Tuberculosis, caused by Mycobacterium tuberculosis (MTB), is a common and potentially lethal infectious human disease. Rifampicin is a front line anti-tuberculosis drug usually prescribed in… (more)

Subjects/Keywords: characterization; carboxymethylcellulose acetate butyrate; pharmacokinetics; rifampicin; particles

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APA (6^th Edition):

Casterlow, S. A. (2012). Characterization and Pharmacokinetics of Rifampicin Laden Carboxymethylcellulose Acetate Butyrate Particles. (Masters Thesis). Virginia Tech. Retrieved from http://hdl.handle.net/10919/42659

Chicago Manual of Style (16^th Edition):

Casterlow, Samantha Alexandra. “Characterization and Pharmacokinetics of Rifampicin Laden Carboxymethylcellulose Acetate Butyrate Particles.” 2012. Masters Thesis, Virginia Tech. Accessed April 13, 2021. http://hdl.handle.net/10919/42659.

MLA Handbook (7^th Edition):

Casterlow, Samantha Alexandra. “Characterization and Pharmacokinetics of Rifampicin Laden Carboxymethylcellulose Acetate Butyrate Particles.” 2012. Web. 13 Apr 2021.

Vancouver:

Casterlow SA. Characterization and Pharmacokinetics of Rifampicin Laden Carboxymethylcellulose Acetate Butyrate Particles. [Internet] [Masters thesis]. Virginia Tech; 2012. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10919/42659.

Council of Science Editors:

Casterlow SA. Characterization and Pharmacokinetics of Rifampicin Laden Carboxymethylcellulose Acetate Butyrate Particles. [Masters Thesis]. Virginia Tech; 2012. Available from: http://hdl.handle.net/10919/42659

Virginia Tech

3. Arca, Hale Cigdem. Cellulose Esters and Cellulose Ether Esters for Oral Drug Delivery Systems.

Degree: PhD, Macromolecular Science and Engineering, 2016, Virginia Tech

URL: http://hdl.handle.net/10919/82920

► Amorphous solid dispersion (ASD) is a popular method to increase drug solubility and consequently poor drug bioavailability. Cellulose ω-carboxyesters were designed and synthesized specifically for… (more)

▼ Amorphous solid dispersion (ASD) is a popular method to increase drug solubility and consequently poor drug bioavailability. Cellulose ω-carboxyesters were designed and synthesized specifically for ASD preparations in Edgar lab that can meet the ASD expectations such as high Tg, recrystallization prevention and pH-triggered release due to the free -COOH groups. Rifampicin (Rif), Ritonavir (Rit), Efavirenz (Efa), Etravirine (Etra) and Quercetin (Que) cellulose ester ASDs were investigated in order to increase drug solubility, prevent release at low pH and controlled release of the drug at small intestine pH that can improve drug bioavailability, decrease needed drug content and medication price to make it affordable in third world countries, and extent pill efficiency period to improve patient quality of life and adherence to the treatment schedule. The studies were compared with cellulose based commercial polymers to prove the impact of the investigation and potential for the application. Furthermore, the in vitro results obtained were further supported by in vivo studies to prove the significant increase in bioavailability and show the extended release. The need of new cellulose derivatives for ASD applications extended the research area, the design and synthesis of a new class of polymers, alkyl cellulose ω-carboxyesters for ASD formulations investigated and the efficiency of the polymers were summarized to show that they have the anticipated properties. The polymers were synthesized by the reaction of commercial cellulose alkyl ethers with benzyl ester protected, monofunctional hydrocarbon chain acid chlorides, followed by removal of protecting group using palladium hydroxide catalyzed hydrogenolysis to form the alkyl cellulose wcarboxyalkanoate. Having been tested for ASD preparation, it was proven that the polymers were efficient in maintaining the drug in amorphous solid state, release the drug at neutral pH and prevent the recrystallization for hours, as predicted. Advisors/Committee Members: Edgar, Kevin J. (committeechair), Davis, Richey M. (committee member), Turner, S. Richard (committee member), Sriranganathan, Nammalwar (committee member), Taylor, Lynne S. (committee member).

Subjects/Keywords: Cellulose esters; cellulose ether esters; Amorphous solid dispersions; structure-property relationship; anti-HIV; rifampicin; quercetin solubility enhancement

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APA (6^th Edition):

Arca, H. C. (2016). Cellulose Esters and Cellulose Ether Esters for Oral Drug Delivery Systems. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/82920

Chicago Manual of Style (16^th Edition):

Arca, Hale Cigdem. “Cellulose Esters and Cellulose Ether Esters for Oral Drug Delivery Systems.” 2016. Doctoral Dissertation, Virginia Tech. Accessed April 13, 2021. http://hdl.handle.net/10919/82920.

MLA Handbook (7^th Edition):

Arca, Hale Cigdem. “Cellulose Esters and Cellulose Ether Esters for Oral Drug Delivery Systems.” 2016. Web. 13 Apr 2021.

Vancouver:

Arca HC. Cellulose Esters and Cellulose Ether Esters for Oral Drug Delivery Systems. [Internet] [Doctoral dissertation]. Virginia Tech; 2016. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10919/82920.

Council of Science Editors:

Arca HC. Cellulose Esters and Cellulose Ether Esters for Oral Drug Delivery Systems. [Doctoral Dissertation]. Virginia Tech; 2016. Available from: http://hdl.handle.net/10919/82920

Virginia Tech

4. Ernst, Marigold Ellen Bethany. Characterization, toxicity, and biological activities of organometallic compounds and peptide nucleic acids for potential use as antimicrobials.

Degree: PhD, Biomedical and Veterinary Sciences, 2019, Virginia Tech

URL: http://hdl.handle.net/10919/100634

► Bacterial antibiotic resistance is a globally recognized problem that has prompted extensive research into novel antimicrobial compounds. This dissertation describes research focusing on two types… (more)

▼ Bacterial antibiotic resistance is a globally recognized problem that has prompted extensive research into novel antimicrobial compounds. This dissertation describes research focusing on two types of potential antimicrobial molecules, organometallic compounds (OMC) and peptide nucleic acids (PNA). Organometallic compounds show promise as antimicrobial drugs because of their structural difference from conventional antibiotics and antimicrobials, and because of the ability to "tune" their chemical and biological properties by varying ligand attachments. Peptide nucleic acids, when linked to a cell-penetrating peptide (CPP), can suppress bacterial gene expression by an antisense mechanism and are attractive candidates for antimicrobial drugs because they bind strongly to target nucleic acids and are resistant to nucleases. Chapters 1 and 2 of the dissertation provide an introduction and broad literature review to frame the experimental questions addressed. Chapter 3 describes work to test the cytotoxicity and cellular penetration capabilities of novel OMCs by evaluating their effects on J774A.1 murine macrophage-like cells that were either uninfected or were infected with Mycobacterium bovis BCG. Results indicate that OMCs with an iridium (Ir) metal center and an amino acid ligand show minimal cytotoxicity against eukaryotic cells but likely do not penetrate the intracellular compartment in significant amounts. Chapter 4 presents research into in vitro effects of CPP-PNAs targeting the tetA and tetR antibiotic resistance genes (CPP-anti-tetA PNA and CPP-anti-tetR PNA, respectively) in tetracycline-resistant Salmonella enterica ssp. enterica serovar Typhimurium DT104 (DT104). Through the use of modified minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays it was shown that both the CPP-anti-tetA PNA and CPP-anti-tetR PNA increase tetracycline susceptibility in DT104. Chapter 5 explores the molecular mechanism of the CPP-anti-tetA PNA and CPP-anti-tetR PNA through the use of reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). Results indicate good specificity of the CPP-anti-tetA PNA for its nucleic acid target as evidenced by suppression of tetA mRNA expression in DT104 cultures treated with a combination of tetracycline and the PNA. Chapter 6 describes the development of a mouse model of DT104 infection using BALB/c mice, followed by implementation of that model to test in vivo antimicrobial effects of the CPP-anti-tetA PNA and the CPP-Sal-tsf PNA, which targets expression of the essential tsf gene. An optimal dose of DT104 was identified that causes clinical illness within 2-4 days. At the doses tested, concurrent treatment of infected mice with tetracycline and the CPP-anti-tetA PNA or with the CPP-Sal-tsf PNA alone did not have a protective effect. Final conclusions are 1) that further research with the OMCs should focus on compounds with an Ir center and an amino acid ligand, and should explore ways to enhance intracellular penetration, 2) that the in vitro… Advisors/Committee Members: Merola, Joseph S. (committeechair), Sriranganathan, Nammalwar (committeechair), Ehrich, Marion F. (committee member), Boes, Katie Mae (committee member).

Subjects/Keywords: drug discovery; RT-qPCR; tetracycline; TetA efflux pump

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ernst, M. E. B. (2019). Characterization, toxicity, and biological activities of organometallic compounds and peptide nucleic acids for potential use as antimicrobials. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/100634

Chicago Manual of Style (16^th Edition):

Ernst, Marigold Ellen Bethany. “Characterization, toxicity, and biological activities of organometallic compounds and peptide nucleic acids for potential use as antimicrobials.” 2019. Doctoral Dissertation, Virginia Tech. Accessed April 13, 2021. http://hdl.handle.net/10919/100634.

MLA Handbook (7^th Edition):

Ernst, Marigold Ellen Bethany. “Characterization, toxicity, and biological activities of organometallic compounds and peptide nucleic acids for potential use as antimicrobials.” 2019. Web. 13 Apr 2021.

Vancouver:

Ernst MEB. Characterization, toxicity, and biological activities of organometallic compounds and peptide nucleic acids for potential use as antimicrobials. [Internet] [Doctoral dissertation]. Virginia Tech; 2019. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10919/100634.

Council of Science Editors:

Ernst MEB. Characterization, toxicity, and biological activities of organometallic compounds and peptide nucleic acids for potential use as antimicrobials. [Doctoral Dissertation]. Virginia Tech; 2019. Available from: http://hdl.handle.net/10919/100634

Virginia Tech

5. Pothayee, Nipon. Development of Polymeric Nanocarriers for Dual Magnetic Resonance Imaging and Drug Delivery.

Degree: PhD, Macromolecular Science and Engineering, 2013, Virginia Tech

URL: http://hdl.handle.net/10919/24355

► Two types of (polymer-imaging agent-drug) complexes were prepared and characterized. These included block and graft copolymer complexes with magnetite nanoparticles and manganese ions. Magnetite block… (more)

▼ Two types of (polymer-imaging agent-drug) complexes were prepared and characterized. These included block and graft copolymer complexes with magnetite nanoparticles and manganese ions. Magnetite block ionomer complexes (MBICs) were formed through binding of a portion of the anionic segment of poly(ethylene oxide)-b-poly(acrylic acid) (PEO-b-PAA) block copolymers with the magnetite nanoparticle surfaces. The remainder of the carboxylic acids were utilized to bind with high concentrations of the cationic antibiotic gentamicin (31 wt%). A near zero-order release of gentamicin (pH 7.4 in PBS) that reached ~35 wt% of the initial gentamicin within 10 hours was observed, and this was followed by slower release of another 7 % by 18 hours. These nanoparticles were efficiently taken up by macrophages and appeared to enhance intracellular antimicrobial activities of gentamicin. To increase the complex sizes and NMR T2 relaxivities, amine functional MBICs (MBICs-NH2) were first assembled by adsorbing the polyacrylate block of an aminofunctional poly(ethylene oxide)-b-poly(acrylic acid)) (H2N-PEO-b-PAA) copolymer onto magnetite nanoparticles. Amines at the tips of the H2N-PEO corona were then linked through reaction with a PEO diacrylate oligomer to yield MBIClusters where the metal oxides in the precursor nanoparticles were distinctly separated by the hydrophilic polymer. These MBIClusters with hydrophilic intra-cluster space had transverse relaxivities (r2's) that increased from 190 to 604 s-1 mM Fe-1 measured at 1.4 T and 37°C as their average sizes increased. The clusters were loaded with up to ~38 wt% of the multi-cationic drug gentamicin. MRI scans focused on the livers of mice demonstrated that these MBIClusters are very sensitive contrast agents. These results indicate that these complexes could be potential theranostic agents for dual imaging and drug delivery. Manganese graft ionomer complexes (MaGICs) comprised of Mn ions and a novel polyaminobisphosphonate-g-PEO copolymer were developed for use as T1 weighted MRI positive contrast agents. The graft copolymers were prepared by free radical copolymerization of ammonium bisphosphonate methacrylate monomers with PEO-acrylate macromonomers. The complexes exhibited good colloidal stability without release of free manganese and did not show any in vitro toxicity against mouse hepatocytes. The T1 relaxivities of the MaGICs were 2-10 times higher than that of a commercial manganese based contrast agent MnDPDP. These MaGICs with encapsulated anticancer drugs including doxorubicin, cisplatin and carboplatin have encapsulation efficiencies of 80-100 %. Drug release was sustained and depended on environmental pH, drug structure and drug concentration in the MaGICs. Moreover, these drug-loaded complexes exhibited high anticancer efficacy against MCF-7 breast cancer cells. The prominent MRI relaxivities and high anticancer efficacy suggest that these MaGICs have potential as effective dual imaging and chemotherapeutic agents. Advisors/Committee Members: Riffle, Judy S. (committeechair), Edgar, Kevin J. (committee member), Davis, Richey M. (committee member), Sriranganathan, Nammalwar (committee member), Turner, S. Richard (committee member).

Subjects/Keywords: magnetite; manganese; block; graft ionomers; contrast agents; drug delivery

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Pothayee, N. (2013). Development of Polymeric Nanocarriers for Dual Magnetic Resonance Imaging and Drug Delivery. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/24355

Chicago Manual of Style (16^th Edition):

Pothayee, Nipon. “Development of Polymeric Nanocarriers for Dual Magnetic Resonance Imaging and Drug Delivery.” 2013. Doctoral Dissertation, Virginia Tech. Accessed April 13, 2021. http://hdl.handle.net/10919/24355.

MLA Handbook (7^th Edition):

Pothayee, Nipon. “Development of Polymeric Nanocarriers for Dual Magnetic Resonance Imaging and Drug Delivery.” 2013. Web. 13 Apr 2021.

Vancouver:

Pothayee N. Development of Polymeric Nanocarriers for Dual Magnetic Resonance Imaging and Drug Delivery. [Internet] [Doctoral dissertation]. Virginia Tech; 2013. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10919/24355.

Council of Science Editors:

Pothayee N. Development of Polymeric Nanocarriers for Dual Magnetic Resonance Imaging and Drug Delivery. [Doctoral Dissertation]. Virginia Tech; 2013. Available from: http://hdl.handle.net/10919/24355

Virginia Tech

6. Balasubramaniam, Sharavanan. Synthesis, Characterization and Structure-Property Relationships of Polymer-Stabilized Nanoparticles Containing Imaging and Therapeutic Agents.

Degree: PhD, Macromolecular Science and Engineering, 2014, Virginia Tech

URL: http://hdl.handle.net/10919/55119

► The controllable design of magnetic nanocarriers is essential for advanced in vivo applications such as magnetic resonance image-guided therapeutic delivery and alternating magnetic field-induced remote… (more)

▼ The controllable design of magnetic nanocarriers is essential for advanced in vivo applications such as magnetic resonance image-guided therapeutic delivery and alternating magnetic field-induced remote release of drugs. This work describes the fabrication of polymer-stabilized nanoparticles encapsulating imaging and therapeutic agents and delineates relationships among materials parameters and response. The effect of aggregation of magnetic iron oxide nanoparticles in aqueous suspension was characterized using a well-defined core-corona complex comprised of a superparamagnetic magnetite nanoparticle stabilized by terminally-anchored poly(N-isopropylacrylamide) (PNIPAM) corona. The modified Vagberg density distribution model was employed to verify that the complexes were individually dispersed prior to aggregation and was found to accurately predict the intensity-weighted hydrodynamic diameter in water. Aggregation of the complexes was systematically induced by heating the suspension above the lower critical solution temperature (LCST) of the polymer, and substantial increase in the NMR transverse relaxation rates was noted. Controlled clusters of primary iron oxide nanoparticles stabilized by the biodegradable block copolymer, poly(ethylene oxide-b-D,L-lactide) were fabricated by a scalable, rapid precipitation technique using a multi-inlet vortex mixer. Quantitative control over iron oxide loading, up to 40 wt%, was achieved. Correlations between particle parameters and transverse relaxivities were studied within the framework of the analytical models of transverse relaxivity. The experimental relaxivities typically agreed to within 15% with the values predicted using the analytical models and cluster size distributions derived from cryo-transmission electron microscopy. Hydrophilic-core particles assembled using the poly(ethylene oxide-b-acrylate) copolymer and at similar primary nanoparticle sizes and loadings had considerably higher transverse (r2) and longitudinal (r1) relaxivities, with r2s approaching the theoretical limit for ~ 8 nm magnetite. Block copolymer nanoparticles comprised of poly(D,L-lactide) and poly(butylene oxide) cores were utilized to encapsulate the poorly water-soluble antiretroviral drug, ritonavir, at therapeutically-useful loadings. Controlled size distributions were achieved by incorporation of homopolymer additives, poly(L-lactide) or poly(butylene oxide) during the nanoparticle preparation process. Nanoparticles either co-encapsulating a highly hydrophobic polyester poly(oxy-2,2,4,4-tetramethyl-1,3-cyclobutanediyloxy-1,4-cyclohexanedicarbonyl) within the core or possessing crosslinkable groups around the core were also successfully fabricated for potential sustained release of ritonavir from block copolymer carriers. Advisors/Committee Members: Davis, Richey M. (committeechair), Sriranganathan, Nammalwar (committee member), Riffle, Judy S. (committee member), Turner, S. Richard (committee member), Madsen, Louis A. (committee member).

Subjects/Keywords: magnetic nanoparticle; controlled clusters; relaxivity; MRI contrast; polylactide; poly(ethylene oxide); poly(butylene oxide); poly(N-isopropylacrylamide); block copolymers; ritonavir; drug delivery

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Balasubramaniam, S. (2014). Synthesis, Characterization and Structure-Property Relationships of Polymer-Stabilized Nanoparticles Containing Imaging and Therapeutic Agents. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/55119

Chicago Manual of Style (16^th Edition):

Balasubramaniam, Sharavanan. “Synthesis, Characterization and Structure-Property Relationships of Polymer-Stabilized Nanoparticles Containing Imaging and Therapeutic Agents.” 2014. Doctoral Dissertation, Virginia Tech. Accessed April 13, 2021. http://hdl.handle.net/10919/55119.

MLA Handbook (7^th Edition):

Balasubramaniam, Sharavanan. “Synthesis, Characterization and Structure-Property Relationships of Polymer-Stabilized Nanoparticles Containing Imaging and Therapeutic Agents.” 2014. Web. 13 Apr 2021.

Vancouver:

Balasubramaniam S. Synthesis, Characterization and Structure-Property Relationships of Polymer-Stabilized Nanoparticles Containing Imaging and Therapeutic Agents. [Internet] [Doctoral dissertation]. Virginia Tech; 2014. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10919/55119.

Council of Science Editors:

Balasubramaniam S. Synthesis, Characterization and Structure-Property Relationships of Polymer-Stabilized Nanoparticles Containing Imaging and Therapeutic Agents. [Doctoral Dissertation]. Virginia Tech; 2014. Available from: http://hdl.handle.net/10919/55119

Virginia Tech

7. Dev Kumar, Govindaraj. Role of airborne soil particulate in transfer of Salmonella spp. to tomato blossoms and consequential fruit contamination.

Degree: PhD, Food Science and Technology, 2011, Virginia Tech

URL: http://hdl.handle.net/10919/40421

► Contaminated tomatoes have become a commonly implicated vehicle of Salmonella outbreaks. Exposure of tomatoes to pathogen could occur in the field. Blossom inoculation with Salmonella… (more)

▼ Contaminated tomatoes have become a commonly implicated vehicle of Salmonella outbreaks. Exposure of tomatoes to pathogen could occur in the field. Blossom inoculation with Salmonella can result in contaminated fruit but natural routes of blossom contamination are not well known. Salmonellae have been known to survive in agricultural soil. Since dispersal of soil particulate by wind is a common phenomenon, the potential of airborne soil particulate as a vehicle of Salmonella contamination in tomato blossoms was examined. It was determined that Salmonella enterica serotype Anatum, Baildon, Braenderup, Montevideo, Newport, Javiana had similar survival patterns in both soil and water. At the end of 40 days, populations of Salmonella in soil dropped by 2.59 log CFU/g and 5.11 log CFU/g when enumerated on Tryptic Soy Agar Yeast Extract (TSAYE) and xylose lysine Tergitol 4 (XLT4) agar respectively. Salmonella populations in water reduced by 2.55 log CFU/ml (TSAYE, enumeration) and 2.94 log CFU/ml (XLT4, enumeration). Blossom to fruit formation takes 20-30 days in tomatoes hence the introduction or presence of the pathogen in agricultural soil and water could increase risk of blossom contamination. Also, it was determined that all Salmonella serotypes tested were capable of biofilm production on glass coverslips and quartz particles. Biofilm based attachment of Salmonella to sand might aid in its dispersal. To visualize transfer of pathogen from soil particulate to blossom in real-time, bioluminescent S. Baildon, S. Braenderup, S. Newport, S. Javiana and S. Anatum were created.Heat shock procedure was developed to improve electrotransformation efficiency in Salmonella. Transformed strains were compared for bioluminescence production and plasmid stability. S. Newport had the best bioluminescence properties but no difference was observed between strains for plasmid stability. Imaging of soil particulate - S. Newport mixture inoculated blossoms, indicated that the event led to pathogen transfer to blossom. It was also determined that S. Newport â soil particulate contaminated blossoms developed into fruits that were positive for S. Newport. S. Newport presence in blossom, fruit surface and internal tissue indicates that contaminated soil particulate could serve as a vehicle of tomato contamination. Advisors/Committee Members: Williams, Robert C. (committeechair), Boyer, Renee R. (committee member), Eifert, Joseph D. (committee member), Sriranganathan, Nammalwar (committee member).

Subjects/Keywords: tomato; dust; soil; bioluminescence; Salmonella

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Dev Kumar, G. (2011). Role of airborne soil particulate in transfer of Salmonella spp. to tomato blossoms and consequential fruit contamination. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/40421

Chicago Manual of Style (16^th Edition):

Dev Kumar, Govindaraj. “Role of airborne soil particulate in transfer of Salmonella spp. to tomato blossoms and consequential fruit contamination.” 2011. Doctoral Dissertation, Virginia Tech. Accessed April 13, 2021. http://hdl.handle.net/10919/40421.

MLA Handbook (7^th Edition):

Dev Kumar, Govindaraj. “Role of airborne soil particulate in transfer of Salmonella spp. to tomato blossoms and consequential fruit contamination.” 2011. Web. 13 Apr 2021.

Vancouver:

Dev Kumar G. Role of airborne soil particulate in transfer of Salmonella spp. to tomato blossoms and consequential fruit contamination. [Internet] [Doctoral dissertation]. Virginia Tech; 2011. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10919/40421.

Council of Science Editors:

Dev Kumar G. Role of airborne soil particulate in transfer of Salmonella spp. to tomato blossoms and consequential fruit contamination. [Doctoral Dissertation]. Virginia Tech; 2011. Available from: http://hdl.handle.net/10919/40421

Virginia Tech

8. Budnick, James Andrew. Characterization of the VtlR regulons in Brucella abortus and Agrobacterium tumefaciens.

Degree: PhD, Biomedical and Veterinary Sciences, 2019, Virginia Tech

URL: http://hdl.handle.net/10919/100598

► Brucella abortus and Agrobacterium tumefaciens are pathogenic bacteria that infect animals and plants, respectively. These bacteria are genetically similar and are found within the same… (more)

▼ Brucella abortus and Agrobacterium tumefaciens are pathogenic bacteria that infect animals and plants, respectively. These bacteria are genetically similar and are found within the same Class, Alphaproteobacteria, and Order, Rhizobiales, of the domain Eubacteria; however, they survive and replicate in vastly different environmental niches. In Order to adapt to different environments, bacteria utilize several mechanisms of gene regulation to tightly control gene expression. Two of these mechanisms include transcriptional regulators and small regulatory RNAs (sRNAs), which can activate and repress gene expression through various interactions with DNA, mRNA, and proteins. A well-conserved transcriptional regulator among the Rhizobiales is VtlR, a virulence-associated transcriptional LysR regulator. The objectives of this dissertation were three fold: 1) characterize the known regulon of VtlR in B. abortus with regards to gene regulatory function and virulence, 2) determine the regulon of VtlR in A. tumefaciens and define the mechanism by which this regulation occurs, and 3) define the role of an ABC-type transport system indirectly regulated by VtlR in B. abortus that putatively imports the non-proteinogenic amino acid gamma-aminobutyric acid (GABA). VtlR was characterized in B. abortus as a virulence-associated transcriptional regulator that directly activates four genes: the sRNA AbcR2, and the three small hypothetical proteins BAB1_0914, BAB2_0512, and BAB2_0574; and deletion of vtlR led to a significant defect in the ability of B. abortus to cause infection in vitro and in vivo. Since dysregulation of abcR2 alone could not account for the defect in virulence, it was hypothesized that one or all three hypothetical proteins could be responsible for a virulence phenotype observed in ΔvtlR. This turned out to not be the case, as a deletion of the entire VtlR regulon displayed no difference in virulence compared to the parental strain. Further characterization of the small hypothetical proteins is outlined in Chapter 2 and the data revealed bona fide translation of each small protein, and the deletion strain of the VtlR regulon displayed a growth defect when grown in the presence of the sugar fucose. This phenotype was subsequently observed in ΔvtlR as well. This led to the identification of a putative fucose transport and metabolism locus in B. abortus that has yet to be studied. In A. tumefaciens, VtlR is necessary for proper attachment to plant cells and biofilm formation and regulates over 200 genes, significantly more than the four genes VtlR regulates in B. abortus. The mechanism by which this occurs was unknown, and the relationship between VtlR and AbcR1 or AbcR2 was uncharacterized. The data in Chapter 3 outline the VtlR network by showing that VtlR regulation of myriad genes in A. tumefaciens is primarily indirect via the direct regulation of a few sRNAs. This direct interaction was shown experimentally and a VtlR binding box was identified in the A. tumefaciens genome. This project outlines the divergence… Advisors/Committee Members: Caswell, Clayton Christopher (committeechair), Sriranganathan, Nammalwar (committee member), Inzana, Thomas Joseph (committee member), Scharf, Birgit (committee member).

Subjects/Keywords: Brucella abortus; Agrobacterium tumefaciens; transcriptional regulon; small protein; GABA

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APA (6^th Edition):

Budnick, J. A. (2019). Characterization of the VtlR regulons in Brucella abortus and Agrobacterium tumefaciens. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/100598

Chicago Manual of Style (16^th Edition):

Budnick, James Andrew. “Characterization of the VtlR regulons in Brucella abortus and Agrobacterium tumefaciens.” 2019. Doctoral Dissertation, Virginia Tech. Accessed April 13, 2021. http://hdl.handle.net/10919/100598.

MLA Handbook (7^th Edition):

Budnick, James Andrew. “Characterization of the VtlR regulons in Brucella abortus and Agrobacterium tumefaciens.” 2019. Web. 13 Apr 2021.

Vancouver:

Budnick JA. Characterization of the VtlR regulons in Brucella abortus and Agrobacterium tumefaciens. [Internet] [Doctoral dissertation]. Virginia Tech; 2019. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10919/100598.

Council of Science Editors:

Budnick JA. Characterization of the VtlR regulons in Brucella abortus and Agrobacterium tumefaciens. [Doctoral Dissertation]. Virginia Tech; 2019. Available from: http://hdl.handle.net/10919/100598

Virginia Tech

9. Smith, Garrett Paul. Immunocontraceptive vaccines against brucellosis and population growth in feral swine.

Degree: PhD, Veterinary Medical Sciences, 2016, Virginia Tech

URL: http://hdl.handle.net/10919/77987

► Feral swine are a nuisance species across the United States that costs around $1.5 billion each year in agricultural, environmental, and personal property damages. In… (more)

▼ Feral swine are a nuisance species across the United States that costs around $1.5 billion each year in agricultural, environmental, and personal property damages. In the last ten years the population of feral swine is estimated to have quadrupled and novel population control methods are needed. Furthermore, feral swine are known carriers of zoonotic diseases such as brucellosis, which threatens both livestock biosecurity and public health. Recombinant multimeric gonadotropin-releasing hormone (mGnRH) has been previously used as a subunit vaccine to induce immunocontraception in feral pigs. However, potent adjuvants and large amounts of purified antigen are needed to elicit a robust anti-GnRH immune response and current delivery methods are limited. Brucella suis strain VTRS2 can be used as a novel platform to deliver mGnRH without the use of antibiotic resistant markers. Strain VTRS2 was created by deletion of the LPS biosynthesis gene wboA as well as the leuB gene required for leucine biosynthesis inside the nutrient-depleted intracellular environment occupied by Brucella. Mutations in wboA are known to attenuate Brucella strains such as the vaccine strain B. abortus RB51, however strain RB51 is rifampin resistant and has poor efficacy in swine. Strain VTRS2 confers significant protection against B. suis challenge in mice and additionally shows evidence of protection in feral swine. Furthermore, the mGnRH antigen can be delivered using the pNS4 plasmid (which expresses leuB under its native promoter) thus maintaining the plasmid in strain VTRS2 under leucine-deficient conditions while expressing recombinant antigen in the host. The murine model was used to determine the clearance kinetics of strain VTRS2-mGnRH and to measure vaccine efficacy against challenge by virulent B. suis 1330. Subsequently the effects of the VTRS2-mGnRH vaccine on fertility were assessed in breeding trials in mice. Strains VTRS2 and VTRS2-mGnRH were found to be protective against virulent Brucella suis challenge. Strain VTRS2-mGnRH elicited an anti-mGnRH antibody response in vaccinated mice, though an effect on fertility was not observed. An improved vaccine against brucellosis in swine, which also confers immunocontraception without the introduction of antibiotic resistance, could become an important tool in the management of this nuisance invasive species. Advisors/Committee Members: Sriranganathan, Nammalwar (committeechair), Boyle, Stephen M. (committee member), Clark-Deener, Sherrie (committee member), Larson, Timothy (committee member).

Subjects/Keywords: immunocontraception; vaccine; brucellosis; Brucella; feral swine; mouse model; mGnRH; infertility

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Smith, G. P. (2016). Immunocontraceptive vaccines against brucellosis and population growth in feral swine. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/77987

Chicago Manual of Style (16^th Edition):

Smith, Garrett Paul. “Immunocontraceptive vaccines against brucellosis and population growth in feral swine.” 2016. Doctoral Dissertation, Virginia Tech. Accessed April 13, 2021. http://hdl.handle.net/10919/77987.

MLA Handbook (7^th Edition):

Smith, Garrett Paul. “Immunocontraceptive vaccines against brucellosis and population growth in feral swine.” 2016. Web. 13 Apr 2021.

Vancouver:

Smith GP. Immunocontraceptive vaccines against brucellosis and population growth in feral swine. [Internet] [Doctoral dissertation]. Virginia Tech; 2016. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10919/77987.

Council of Science Editors:

Smith GP. Immunocontraceptive vaccines against brucellosis and population growth in feral swine. [Doctoral Dissertation]. Virginia Tech; 2016. Available from: http://hdl.handle.net/10919/77987

Virginia Tech

10. Lighty, Megan Elizabeth Folk. Epidemiology and Pathophysiology of Clostridial Dermatitis (Cellulitis) in Turkeys.

Degree: PhD, Biomedical and Veterinary Sciences, 2015, Virginia Tech

URL: http://hdl.handle.net/10919/76677

► Clostridial dermatitis (CD) is a multifactorial disease of rapidly-growing turkeys. Clostridium septicum (Cs) has been identified as the primary cause, although C. perfringens (Cp) has… (more)

▼ Clostridial dermatitis (CD) is a multifactorial disease of rapidly-growing turkeys. Clostridium septicum (Cs) has been identified as the primary cause, although C. perfringens (Cp) has also been implicated. Pathogenesis is not fully understood; however, it is hypothesized that Clostridia translocate from the gastrointestinal tract and spread hematogenously to capillary beds of skeletal muscles. Intense genetic selection has produced a rapidly growing bird that is heavier and less active. This may predispose birds to development of CD due to positional restriction of blood flow to the caudal breast and medial thigh. Subsequent reduction in oxygen tension within these tissues produces conditions conducive to germination, proliferation, and toxin production by previously trapped, non-replicative Clostridia. Studies were undertaken to investigate the epidemiology and pathophysiology of CD. Retrospective epidemiologic investigations evaluated incidence, risk factors, and economic impact of CD. Cs and Cp qPCR were performed on blood and tissue samples to demonstrate hematogenous spread in asymptomatic birds. Studies assessed the effect of prolonged recumbency by measuring oxygen saturation and surface temperature in dependent tissues. Tissues from CD cases were evaluated for Cs and Cp alpha toxin mRNA (CsA and CpA). Analyses were conducted to determine associations between these toxins and severity of histopathologic lesions. Whole genome sequencing was performed on the Cs type strain to identify other toxin genes. Flock type, breed, weight at time of processing, and stocking density affected disease incidence. Detection of Clostridium spp. in intestine, liver, and muscle from asymptomatic turkeys without cutaneous trauma implies hematogenous spread from an endogenous source. Focal polyphasic myonecrosis in dependent muscles of asymptomatic turkeys suggests an underlying predisposition to development of CD. Recumbency appeared to be associated with decreased perfusion to these tissues. Cs DNA was present in asymptomatic birds without corresponding CsA mRNA expression suggesting that organisms were present in a quiescent form. CsA was associated with CD while CpA did not appear to be involved in pathogenesis. Genome sequencing identified several coding regions which may correspond to other potentially active Cs toxins. These results support the proposed mechanism of pathogenesis and provide targets for further investigation of disease pathophysiology and vaccine development. Advisors/Committee Members: Pierson, Frank William|LeRoith, Tanya (committeechair), Sriranganathan, Nammalwar (committee member), Evans, Robert D. (committee member), Elvinger, Francois C. (committee member).

Subjects/Keywords: clostridial dermatitis; cellulitis; turkeys; Clostridium

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lighty, M. E. F. (2015). Epidemiology and Pathophysiology of Clostridial Dermatitis (Cellulitis) in Turkeys. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/76677

Chicago Manual of Style (16^th Edition):

Lighty, Megan Elizabeth Folk. “Epidemiology and Pathophysiology of Clostridial Dermatitis (Cellulitis) in Turkeys.” 2015. Doctoral Dissertation, Virginia Tech. Accessed April 13, 2021. http://hdl.handle.net/10919/76677.

MLA Handbook (7^th Edition):

Lighty, Megan Elizabeth Folk. “Epidemiology and Pathophysiology of Clostridial Dermatitis (Cellulitis) in Turkeys.” 2015. Web. 13 Apr 2021.

Vancouver:

Lighty MEF. Epidemiology and Pathophysiology of Clostridial Dermatitis (Cellulitis) in Turkeys. [Internet] [Doctoral dissertation]. Virginia Tech; 2015. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10919/76677.

Council of Science Editors:

Lighty MEF. Epidemiology and Pathophysiology of Clostridial Dermatitis (Cellulitis) in Turkeys. [Doctoral Dissertation]. Virginia Tech; 2015. Available from: http://hdl.handle.net/10919/76677

Virginia Tech

11. Tyler, Ronald Dale Jr. Evaluation of a Paratuberculosis Quantitative Polymerase Chain Reaction Assay with Microscopic Correlation.

Degree: MS, Veterinary Medical Sciences, 2012, Virginia Tech

URL: http://hdl.handle.net/10919/41736

► Paratuberculosis is an intestinal condition in ruminants infected with Mycobacterium avium subspecies paratuberculosis (MAP) and precedes Johneâ s disease, a chronic enteric disorder in ruminants… (more)

Subjects/Keywords: Johneâ s disease; paratuberculosis; histopathology; qPCR

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APA (6^th Edition):

Tyler, R. D. J. (2012). Evaluation of a Paratuberculosis Quantitative Polymerase Chain Reaction Assay with Microscopic Correlation. (Masters Thesis). Virginia Tech. Retrieved from http://hdl.handle.net/10919/41736

Chicago Manual of Style (16^th Edition):

Tyler, Ronald Dale Jr. “Evaluation of a Paratuberculosis Quantitative Polymerase Chain Reaction Assay with Microscopic Correlation.” 2012. Masters Thesis, Virginia Tech. Accessed April 13, 2021. http://hdl.handle.net/10919/41736.

MLA Handbook (7^th Edition):

Tyler, Ronald Dale Jr. “Evaluation of a Paratuberculosis Quantitative Polymerase Chain Reaction Assay with Microscopic Correlation.” 2012. Web. 13 Apr 2021.

Vancouver:

Tyler RDJ. Evaluation of a Paratuberculosis Quantitative Polymerase Chain Reaction Assay with Microscopic Correlation. [Internet] [Masters thesis]. Virginia Tech; 2012. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10919/41736.

Council of Science Editors:

Tyler RDJ. Evaluation of a Paratuberculosis Quantitative Polymerase Chain Reaction Assay with Microscopic Correlation. [Masters Thesis]. Virginia Tech; 2012. Available from: http://hdl.handle.net/10919/41736

Virginia Tech

12. Walters, Jessica Nicole. Characterization of Atypical Hemolytic Ornithobacterium rhinotracheale Isolates and Comparison with the Normal Non-Hemolytic Phenotype.

Degree: PhD, Veterinary Medical Sciences, 2014, Virginia Tech

URL: http://hdl.handle.net/10919/77251

► Ornithobacterium rhinotracheale (ORT) is a Gram-negative bacterium that causes respiratory disease in poultry characterized by rhinitis, tracheitis, and pneumonia with mortality averaging 2-3%. In the… (more)

▼ Ornithobacterium rhinotracheale (ORT) is a Gram-negative bacterium that causes respiratory disease in poultry characterized by rhinitis, tracheitis, and pneumonia with mortality averaging 2-3%. In the Shenandoah Valley of Virginia, the seroprevalence for ORT among turkey flocks as determined by enzyme-linked immunosorbent assay (ELISA) was found to be 70.9% (n=175). Additionally, the seroprevalence for hemorrhagic enteritis virus (vaccine induced), Bordetella avium, and paramyxovirus-1 was 100%, 74.8%, and 6.3% respectively. No significant interactions were detected. The type strain of ORT is characteristically non-hemolytic at least for 96 hours at 37°C on Columbia Blood Agar. In recent years, atypical isolates that rapidly produce hemolysis have been isolated with increasing frequency. A variety of in vitro tests were used to determine differences between representative isolates of the hemolytic (H) and non-hemolytic (NH) phenotypes. Findings suggest that the H isolate contains a 4 kb plasmid similar to that found in Reimerella anatipestifer. No plasmid was found in the NH isolate. Differences in growth characteristics and resistance to tetracyclines were also noted. No differences in proteins, biochemical characteristics or 16S rRNA sequences were found, the latter serving as confirmation that the isolates were both ORT. Embryo inoculation was used to assess virulence. No significant differences were observed and most embryos survived through to the day of hatch (pip) despite the fact that ORT could be re-isolated. In turkey poults however, the H phenotype did appear less virulent. A significant depression in weight gain was noted for birds inoculated intratracheally with the NH isolate at 7 days post-inoculation (dpi). NH inoculates also had significantly higher antibody levels on ELISA at 14 and 21 dpi and histopathological lesion scores for lung at 7, 14, and 21 dpi. The NH isolate could be re-isolated from NH-inoculated poults through 21 dpi; whereas the H isolate could only be re-isolated through 14 dpi. In conclusion, there are numerous differences between the NH and H isolates found in the field with the H isolate appearing less virulent and as such, making it a potential vaccine candidate. The phenotypic difference appears to correlate with this, but may not suffice to explain it. Advisors/Committee Members: Pierson, Frank William (committeechair), McElroy, Audrey (committee member), Evans, Robert (committee member), Sriranganathan, Nammalwar (committee member), LeRoith, Tanya (committee member).

Subjects/Keywords: Ornithobacterium rhinotracheale; hemolysis; ELISA; plasmid; turkeys

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Walters, J. N. (2014). Characterization of Atypical Hemolytic Ornithobacterium rhinotracheale Isolates and Comparison with the Normal Non-Hemolytic Phenotype. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/77251

Chicago Manual of Style (16^th Edition):

Walters, Jessica Nicole. “Characterization of Atypical Hemolytic Ornithobacterium rhinotracheale Isolates and Comparison with the Normal Non-Hemolytic Phenotype.” 2014. Doctoral Dissertation, Virginia Tech. Accessed April 13, 2021. http://hdl.handle.net/10919/77251.

MLA Handbook (7^th Edition):

Walters, Jessica Nicole. “Characterization of Atypical Hemolytic Ornithobacterium rhinotracheale Isolates and Comparison with the Normal Non-Hemolytic Phenotype.” 2014. Web. 13 Apr 2021.

Vancouver:

Walters JN. Characterization of Atypical Hemolytic Ornithobacterium rhinotracheale Isolates and Comparison with the Normal Non-Hemolytic Phenotype. [Internet] [Doctoral dissertation]. Virginia Tech; 2014. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10919/77251.

Council of Science Editors:

Walters JN. Characterization of Atypical Hemolytic Ornithobacterium rhinotracheale Isolates and Comparison with the Normal Non-Hemolytic Phenotype. [Doctoral Dissertation]. Virginia Tech; 2014. Available from: http://hdl.handle.net/10919/77251

Virginia Tech

13. Houk-Miles, Alice Elizabeth. Characterizing Cystoisospora canis as a Model of Apicomplexan Tissue Cyst Formation and Reactivation.

Degree: PhD, Biomedical and Veterinary Sciences, 2015, Virginia Tech

URL: http://hdl.handle.net/10919/53999

► Cystoisospora canis is an Apicomplexan parasite of the small intestine of dogs. C. canis produces monozoic tissue cysts (MZT) that are similar to the polyzoic… (more)

▼ Cystoisospora canis is an Apicomplexan parasite of the small intestine of dogs. C. canis produces monozoic tissue cysts (MZT) that are similar to the polyzoic tissue cysts (PZT) of Toxoplasma gondii, a parasite of medical and veterinary importance, which can reactivate and cause toxoplasmic encephalitis. We hypothesized that C. canis is similar biologically and genetically enough to T. gondii to be a novel model for studying tissue cyst biology. We examined the pathogenesis of C. canis in beagles and quantified the oocysts shed. We found this isolate had similar infection patterns to other C. canis isolates studied. We were able to superinfect beagles that came with natural infections of Cystoisospora ohioensis-like oocysts indicating that little protection against C. canis infection occurred in these beagles. The C. canis oocysts collected were purified and used for future studies. We demonstrated in vitro that C. canis could infect 8 mammalian cell lines and produce MZT. The MZT were able to persist in cell culture for at least 60 days. We were able to induce reactivation of MZT treated with bile-trypsin solution. In molecular studies, we characterized C. canis genetically using ITS1 and CO1 to build phylogenetic trees and found C. canis was most similar to C. ohioensis-like with ITS1 and more similar to T. gondii than any other coccidia using ITS1 and CO1. We identified genes and proteins involved with virulence, cyst wall structure, and immune evasion of T. gondii and examined the DNA of C. canis for orthologs. C. canis had orthologs with 8 of 20 T. gondii genes examined. Monoclonal and polyclonal antibody and lectin studies demonstrated similar tissue cyst wall proteins on C. canis MZT and T. gondii PZT. Our findings in vitro and using genetic characterization of C. canis indicated the presence of similar genes and proteins, and its close phylogenetic location with T. gondii demonstrate that C. canis may serve as a model to examine tissue cyst biology. The system we described provides a simple model to produce tissue cysts and to study host factors that cause reactivation of tissue cysts. Advisors/Committee Members: Lindsay, David S. (committeechair), Zajac, Anne M. (committee member), Strobl, Jeannine Susan (committee member), Sriranganathan, Nammalwar (committee member).

Subjects/Keywords: Cystoisospora canis; Toxoplasma gondii; characterization; tissue cyst reactivation; model

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Houk-Miles, A. E. (2015). Characterizing Cystoisospora canis as a Model of Apicomplexan Tissue Cyst Formation and Reactivation. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/53999

Chicago Manual of Style (16^th Edition):

Houk-Miles, Alice Elizabeth. “Characterizing Cystoisospora canis as a Model of Apicomplexan Tissue Cyst Formation and Reactivation.” 2015. Doctoral Dissertation, Virginia Tech. Accessed April 13, 2021. http://hdl.handle.net/10919/53999.

MLA Handbook (7^th Edition):

Houk-Miles, Alice Elizabeth. “Characterizing Cystoisospora canis as a Model of Apicomplexan Tissue Cyst Formation and Reactivation.” 2015. Web. 13 Apr 2021.

Vancouver:

Houk-Miles AE. Characterizing Cystoisospora canis as a Model of Apicomplexan Tissue Cyst Formation and Reactivation. [Internet] [Doctoral dissertation]. Virginia Tech; 2015. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10919/53999.

Council of Science Editors:

Houk-Miles AE. Characterizing Cystoisospora canis as a Model of Apicomplexan Tissue Cyst Formation and Reactivation. [Doctoral Dissertation]. Virginia Tech; 2015. Available from: http://hdl.handle.net/10919/53999

Virginia Tech

14. Schroeder, Betsy. Finding Typhoid Mary: Identifying Latent Carriers of Salmonella enterica serovar Typhimurium.

Degree: PhD, Biomedical and Veterinary Sciences, 2020, Virginia Tech

URL: http://hdl.handle.net/10919/99979

► Salmonella enterica serovar Typhimurium (S. Typhimurium) is an important human pathogen. Determining the true number of cases of salmonellosis is made more difficult because of… (more)

Subjects/Keywords: Salmonella; latency; detection

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APA (6^th Edition):

Schroeder, B. (2020). Finding Typhoid Mary: Identifying Latent Carriers of Salmonella enterica serovar Typhimurium. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/99979

Chicago Manual of Style (16^th Edition):

Schroeder, Betsy. “Finding Typhoid Mary: Identifying Latent Carriers of Salmonella enterica serovar Typhimurium.” 2020. Doctoral Dissertation, Virginia Tech. Accessed April 13, 2021. http://hdl.handle.net/10919/99979.

MLA Handbook (7^th Edition):

Schroeder, Betsy. “Finding Typhoid Mary: Identifying Latent Carriers of Salmonella enterica serovar Typhimurium.” 2020. Web. 13 Apr 2021.

Vancouver:

Schroeder B. Finding Typhoid Mary: Identifying Latent Carriers of Salmonella enterica serovar Typhimurium. [Internet] [Doctoral dissertation]. Virginia Tech; 2020. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10919/99979.

Council of Science Editors:

Schroeder B. Finding Typhoid Mary: Identifying Latent Carriers of Salmonella enterica serovar Typhimurium. [Doctoral Dissertation]. Virginia Tech; 2020. Available from: http://hdl.handle.net/10919/99979

Virginia Tech

15. Jain, Neeta. Approaches towards therapeutic development against chronic brucellosis in a mouse model.

Degree: PhD, Veterinary Medical Sciences, 2012, Virginia Tech

URL: http://hdl.handle.net/10919/77039

► Brucellosis is the most common zoonotic disease worldwide. The intracellular localization of Brucella hinders the action of drugs that poorly cross cell membrane barriers. Additionally,… (more)

▼ Brucellosis is the most common zoonotic disease worldwide. The intracellular localization of Brucella hinders the action of drugs that poorly cross cell membrane barriers. Additionally, when the immune response fails to clear the infection, chronic brucellosis ensues that becomes more challenging to treat with antibiotics. Therefore, two approaches, intracellular drug delivery and immunostimulation, have been explored in this dissertation, with an aim to develop a better therapeutic against Brucella infection in mice. First, to overcome the cell membrane barriers, drug loaded nanoparticles were tested to treat B. melitensis infection in mice. Gentamicin loaded block-ionomer complexes (BICs) and magnetite block-ionomer complexes (MBICs) were tested in vitro and along with clusters of MBICs (MBIClusters) were tested in vivo as tools to deliver gentamicin intracellularly. While these complexes showed very high efficacy compared to free gentamicin against Brucella in macrophage cell culture, they failed to show similar efficacies in mice. Histopathological examination of kidneys from mice treated with MBICs or MBIClusters showed deposition of brown pigment-laden macrophages in peri-renal adipose tissue and the pigment was confirmed as MBICs or MBIClusters based on special staining for iron. Additionally, it was found that doxycycline-gentamicin (DG) treatment results in better clearance of Brucella from infected mice compared to doxycycline alone. Secondly, two vaccine candidates, irradiated B. neotomae (IBN) and outer membrane vesicles (OMVs), were tested as immunostimulants to treat chronic B. melitensis infection in mice in combination with antibiotics. The non-ionic block co-polymer Pluronic P85, when mixed with OMVs as an adjuvant showed significantly higher protection against B. melitensis challenge in vaccinated mice compared to those vaccinated with OMVs alone. When tested as immunostimulants, there was no additive effect of vaccines and antibiotics on Brucella clearance from mice. However, IBN enhanced the production of IFN-γ while OMVs were associated with enhanced antibody production. This enhancement in the immune system resulted in the control of Brucella growth after the end of treatment. When given without antibiotics, vaccine alone failed to clear any Brucella from infected mice. The use of these vaccine candidates in combination with antibiotics shows a potential to prevent relapses in cases of brucellosis. Advisors/Committee Members: Sriranganathan, Nammalwar (committeechair), Huckle, William R. (committee member), Riffle, Judy S. (committee member), Boyle, Stephen M. (committee member).

Subjects/Keywords: Brucella; Brucella neotomae; antibiotics; nanoparticles; Brucella melitensis; adjuvants; subunit vaccines; immunotherapy

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Jain, N. (2012). Approaches towards therapeutic development against chronic brucellosis in a mouse model. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/77039

Chicago Manual of Style (16^th Edition):

Jain, Neeta. “Approaches towards therapeutic development against chronic brucellosis in a mouse model.” 2012. Doctoral Dissertation, Virginia Tech. Accessed April 13, 2021. http://hdl.handle.net/10919/77039.

MLA Handbook (7^th Edition):

Jain, Neeta. “Approaches towards therapeutic development against chronic brucellosis in a mouse model.” 2012. Web. 13 Apr 2021.

Vancouver:

Jain N. Approaches towards therapeutic development against chronic brucellosis in a mouse model. [Internet] [Doctoral dissertation]. Virginia Tech; 2012. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10919/77039.

Council of Science Editors:

Jain N. Approaches towards therapeutic development against chronic brucellosis in a mouse model. [Doctoral Dissertation]. Virginia Tech; 2012. Available from: http://hdl.handle.net/10919/77039

Virginia Tech

16. Walker, Michelle Kay. The ability of TLR agonists to upregulate Brucella abortus strain RB51 mediated protection in a murine respiratory model.

Degree: MS, Biomedical and Veterinary Sciences, 2014, Virginia Tech

URL: http://hdl.handle.net/10919/54564

► Brucella abortus is amongst the top 5 zoonotic diseases worldwide. The overall goal of this research is to generate a safe and effective vaccine for… (more)

Subjects/Keywords: Brucella abortus; innate immunity; dendritic cells; vaccine strains RB51; toll-like receptors; intranasal vaccination

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Walker, M. K. (2014). The ability of TLR agonists to upregulate Brucella abortus strain RB51 mediated protection in a murine respiratory model. (Masters Thesis). Virginia Tech. Retrieved from http://hdl.handle.net/10919/54564

Chicago Manual of Style (16^th Edition):

Walker, Michelle Kay. “The ability of TLR agonists to upregulate Brucella abortus strain RB51 mediated protection in a murine respiratory model.” 2014. Masters Thesis, Virginia Tech. Accessed April 13, 2021. http://hdl.handle.net/10919/54564.

MLA Handbook (7^th Edition):

Walker, Michelle Kay. “The ability of TLR agonists to upregulate Brucella abortus strain RB51 mediated protection in a murine respiratory model.” 2014. Web. 13 Apr 2021.

Vancouver:

Walker MK. The ability of TLR agonists to upregulate Brucella abortus strain RB51 mediated protection in a murine respiratory model. [Internet] [Masters thesis]. Virginia Tech; 2014. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10919/54564.

Council of Science Editors:

Walker MK. The ability of TLR agonists to upregulate Brucella abortus strain RB51 mediated protection in a murine respiratory model. [Masters Thesis]. Virginia Tech; 2014. Available from: http://hdl.handle.net/10919/54564

17. Pereira, Junia M. Synthesis of New Pullulan Derivatives for Drug Delivery.

Degree: PhD, Macromolecular Science and Engineering, 2013, Virginia Tech

URL: http://hdl.handle.net/10919/23884

► Pullulan is a non-ionic water-soluble polysaccharide which is produced from starch by the yeast-like fungus Aureobasidium pullulans. Pullulan is known for its non-toxicity and biocompatibility.… (more)

▼ Pullulan is a non-ionic water-soluble polysaccharide which is produced from starch by the yeast-like fungus Aureobasidium pullulans. Pullulan is known for its non-toxicity and biocompatibility. Most pullulan modifications are intended to reduce its water solubility or to introduce charged or reactive groups for functionality. Polysaccharides that have been hydrophobically modified and contain carboxyl groups are commonly used in drug delivery systems because of their ability to provide pH-controlled drug release. We demonstrated in this dissertation the regioselective synthesis of a range of 6-carboxypullulan ethers that are promising anionic derivatives for drug delivery applications. These compounds have also shown impressive surfactant properties. Another class of pullulan derivatives was synthesized by regioselective introduction of amine and amide groups to the pullulan backbone. These chemical groups are known to play a fundamental role in the biological activity of important polysaccharides, such as chitin and chitosan, therefore, the pullulan derivatives synthesized herein, which are structural isomers of those polymers, possess great potential for biomedical applications. Clarithromycin (CLA) is an aminomacrolide antibiotic whose physical properties are fascinating and challenging. It has very poor solubility at neutral intestinal pH, but much higher solubility under acidic conditions. Therefore, CLA dissolves better in the stomach than in the small intestine; but CLA is also quite labile towards acid-catalyzed degradation. We report herein a study on amorphous solid dispersion (ASD) of CLA with promising carboxyl-containing cellulose derivatives, both as macro and nanoparticles. This approach was intended to improve CLA solubility in neutral media, to protect it from acid degradation, and thereby increase its uptake from the small intestine and ultimately its bioavailability. We have also prepared ASDs of selected anti-HIV drugs, ritonavir (RTV), efavirenz (EFV) and etravirine (ETR) with the cellulosic derivative carboxymethyl cellulose acetate butyrate (CMCAB). This polymer was efficient in stabilizing RTV and EFV in their amorphous form in the solid phase and all ASDs provided significant enhancement of drug solution concentration. Advisors/Committee Members: Edgar, Kevin J. (committeechair), Taylor, Lynne S. (committee member), Roman, Maren (committee member), Riffle, Judy S. (committee member), Sriranganathan, Nammalwar (committee member).

Subjects/Keywords: polysaccharides; regioselective; oxidation; amphiphilic; Staudinger reaction; amorphous solid dispersion; clarithromycin; HIV drugs

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APA (6^th Edition):

Pereira, J. M. (2013). Synthesis of New Pullulan Derivatives for Drug Delivery. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/23884

Chicago Manual of Style (16^th Edition):

Pereira, Junia M. “Synthesis of New Pullulan Derivatives for Drug Delivery.” 2013. Doctoral Dissertation, Virginia Tech. Accessed April 13, 2021. http://hdl.handle.net/10919/23884.

MLA Handbook (7^th Edition):

Pereira, Junia M. “Synthesis of New Pullulan Derivatives for Drug Delivery.” 2013. Web. 13 Apr 2021.

Vancouver:

Pereira JM. Synthesis of New Pullulan Derivatives for Drug Delivery. [Internet] [Doctoral dissertation]. Virginia Tech; 2013. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10919/23884.

Council of Science Editors:

Pereira JM. Synthesis of New Pullulan Derivatives for Drug Delivery. [Doctoral Dissertation]. Virginia Tech; 2013. Available from: http://hdl.handle.net/10919/23884

Virginia Tech

18. Kimsawatde, Gade Carolyn. Establishment of a Long Term Cell Culture Model for Testing Anti-Infectives against Mycobacterium avium subsp. paratuberculosis.

Degree: PhD, Biomedical and Veterinary Sciences, 2015, Virginia Tech

URL: http://hdl.handle.net/10919/73329

► Mycobacterium avium subsp. paratuberculosis (MAP) is a very slow growing bacterium that is the causative agent of Johne's disease (JD) in ruminants and has long… (more)

▼ Mycobacterium avium subsp. paratuberculosis (MAP) is a very slow growing bacterium that is the causative agent of Johne's disease (JD) in ruminants and has long been suggested to be associated with complications of Crohn's disease (CD) in humans. Although there is no direct evidence that MAP is the primary etiological agent for CD, most CD patients are found to have MAP in their intestinal tissues. The current control measures for JD in cattle, sheep, and goats have only been minimally effective, and there are only medications to treat the symptoms of mycobacterial infections associated with CD in humans. Along with not being able to cure MAP infections, there is no established laboratory animal model for testing therapeutics. When mice are infected with MAP they develop systemic infection and do not mimic disease observed in ruminants. J774A.1 murine macrophages typically have a very short lifespan of about 4-6 days, however MAP infected cell cultures can survive up to about 10 days. Using a modified protocol of Estrella et al. (2011), we have been able to establish a 45-60 day long-term MAP infected J774A.1 murine macrophage cell culture model. With the addition of retinoic acid (RA), vitamin D (VD), and phorbol myristate acetate (PMA) in combination in cell culture, we were able to screen novel therapeutics before embarking on in vivo testing in animals. This is a significant step forward in Crohn's and Johne's disease treatment research. We are not only able to test various drugs against specific strains of MAP to determine susceptibility, but we are also able to test a wide variety of drugs at the same time, with relatively minimal cost. We have evaluated the efficacy of clarithromycin, azithromycin, isoniazid, amikacin, ethambutol, ciprofloxacin, levofloxacin, rifampicin, clofazimine, as well as a combination of clarithromycin, rifampicin, and clofazimine using our MAP infected macrophage cell culture model. We were able to determine the drugs' differential ability to kill intracellular MAP in the early stages of infection, versus chronic stages of infection, and against two different strains of MAP, 43015 and 19698 that affect humans and cattle respectively. The minimal inhibitory concentration (MIC) of each drug was determined as per NCCLS protocol in vitro, and the drugs were tested at the MIC value, along with one concentration above and below the MIC in our cell culture model. The antimicrobials were found to be effective at different stages of cell culture infection and in different strains of MAP. Some drugs were more effective at early stages of MAP infection, whereas others were more effective in chronic or latent stages of infections. It is important to note that although a drug may be effective at a certain stage of infection, it may not necessarily be effective against all strains of MAP. The most promising results were seen with a combination of clarithromycin, clofazimine, and rifampicin, which was effective at all stages of infection with both strains of MAP tested. This long… Advisors/Committee Members: Sriranganathan, Nammalwar (committeechair), Riffle, Judy S. (committee member), Edgar, Kevin J. (committee member), Lahmers, Kevin K. (committee member).

Subjects/Keywords: Mycobacterium avium subsp. paratuberculosis; retinoic acid; vitamin D; phorbol myristate acetate; J774A.1 murine macrophages; peptide nucleic acids

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kimsawatde, G. C. (2015). Establishment of a Long Term Cell Culture Model for Testing Anti-Infectives against Mycobacterium avium subsp. paratuberculosis. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/73329

Chicago Manual of Style (16^th Edition):

Kimsawatde, Gade Carolyn. “Establishment of a Long Term Cell Culture Model for Testing Anti-Infectives against Mycobacterium avium subsp. paratuberculosis.” 2015. Doctoral Dissertation, Virginia Tech. Accessed April 13, 2021. http://hdl.handle.net/10919/73329.

MLA Handbook (7^th Edition):

Kimsawatde, Gade Carolyn. “Establishment of a Long Term Cell Culture Model for Testing Anti-Infectives against Mycobacterium avium subsp. paratuberculosis.” 2015. Web. 13 Apr 2021.

Vancouver:

Kimsawatde GC. Establishment of a Long Term Cell Culture Model for Testing Anti-Infectives against Mycobacterium avium subsp. paratuberculosis. [Internet] [Doctoral dissertation]. Virginia Tech; 2015. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10919/73329.

Council of Science Editors:

Kimsawatde GC. Establishment of a Long Term Cell Culture Model for Testing Anti-Infectives against Mycobacterium avium subsp. paratuberculosis. [Doctoral Dissertation]. Virginia Tech; 2015. Available from: http://hdl.handle.net/10919/73329

Virginia Tech

19. Settle, Lori L. Characterization of the Bacteriophage Felix O1 Endolysin and Potential Application for Salmonella Bioremediation.

Degree: PhD, Biomedical and Veterinary Sciences, 2012, Virginia Tech

URL: http://hdl.handle.net/10919/39222

► There is an increasing incidence of antimicrobial-resistant organisms isolated from food and food products. Coupled with that rising incidence is increased media scrutiny and coverage… (more)

▼ There is an increasing incidence of antimicrobial-resistant organisms isolated from food and food products. Coupled with that rising incidence is increased media scrutiny and coverage of outbreaks of foodborne illnesses. Consequently, consumers increasingly demand safer food, and that the antimicrobial measures used be other than antimicrobial drugs. A possible solution is to use bacteriophages, or the purified holin and endolysin proteins that make them lethal and lytic, as antimicrobial food treatments or additives. The bacteriophage Felix O1 is a promising candidate for development as an anti-Salmonella food treatment. This dissertation describes the work done to determine if these proteins could be of value as bioremedial agents. Endolysin treatments of Gram negative bacteria require two agents: the lytic endolysin, and a second agent to permeabilize the outer membrane of the bacterium. The holin protein was proposed as an outer membrane permeabilization agent. Methods used to locate the holin gene included BLAST analysis, analysis of putative Felix O1 proteins for transmembrane domains, and examination of the lysin sequence for an N-terminal signal sequence. Analyses did not reveal a promising candidate. Cloning of rIIA as a potential holin was attempted without success. Results of various analyses are discussed, as are chemical alternatives to the use of purified holin as a permeabilization agent. The endolysin, LysO1, was successfully cloned and characterized. PHYRE analysis predicted that the enzyme structure is composed of Î± helices arranged into two lobes, with the active site in a cleft between them. The enzyme lysed all tested strains of Salmonella and a tested strain of the foodborne pathogen Escherichia coli. Campylobacter jejuni susceptibility remains ambiguous, and the enzyme had no effect on Listeria monocytogenes or Micrococcus luteus. LysO1 was most active at alkaline pH and low ionic strength; optimal activity was observed in 25 mM buffer at pH 10. If removed from frozen storage, the enzyme was most thermostable at 30 Â°C. Lytic activity was adversely affected by the presence of the divalent cations calcium, magnesium, and zinc, and by high ionic strength. Considerable time was devoted to development of the activity assay used to further characterize the enzyme, and details of those experiments are provided. Logical extensions of the research project, such as further characterization and testing needed to obtain government approval for widespread use of the treatment, and possible pursuit of treatment based on an enzyme derivative such as an antimicrobial peptide, are discussed. Advisors/Committee Members: Larson, Timothy J. (committee member), Meng, Xiang-Jin (committee member), Pierson, Frank William (committeecochair), Sriranganathan, Nammalwar (committeecochair).

Subjects/Keywords: Felix O1; endolysin; holin; Salmonella; bacteriophage

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Settle, L. L. (2012). Characterization of the Bacteriophage Felix O1 Endolysin and Potential Application for Salmonella Bioremediation. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/39222

Chicago Manual of Style (16^th Edition):

Settle, Lori L. “Characterization of the Bacteriophage Felix O1 Endolysin and Potential Application for Salmonella Bioremediation.” 2012. Doctoral Dissertation, Virginia Tech. Accessed April 13, 2021. http://hdl.handle.net/10919/39222.

MLA Handbook (7^th Edition):

Settle, Lori L. “Characterization of the Bacteriophage Felix O1 Endolysin and Potential Application for Salmonella Bioremediation.” 2012. Web. 13 Apr 2021.

Vancouver:

Settle LL. Characterization of the Bacteriophage Felix O1 Endolysin and Potential Application for Salmonella Bioremediation. [Internet] [Doctoral dissertation]. Virginia Tech; 2012. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10919/39222.

Council of Science Editors:

Settle LL. Characterization of the Bacteriophage Felix O1 Endolysin and Potential Application for Salmonella Bioremediation. [Doctoral Dissertation]. Virginia Tech; 2012. Available from: http://hdl.handle.net/10919/39222

Virginia Tech

20. Mazumder, Sonal. Synthesis and Characterization of Drug-Containing, Polysaccharide-Based Nanoparticles for Applications in Oral Drug Delivery.

Degree: PhD, Macromolecular Science and Engineering, 2013, Virginia Tech

URL: http://hdl.handle.net/10919/23692

► Amorphous solid dispersions of polysaccharide-drug nanoparticles were produced by a rapid precipitation process known as flash nanoprecipitation and the formulation process and properties of nanoparticles… (more)

▼ Amorphous solid dispersions of polysaccharide-drug nanoparticles were produced by a rapid precipitation process known as flash nanoprecipitation and the formulation process and properties of nanoparticles were investigated. In this thesis, several novel cellulose derivatives and a pullulan derivative were studied. Among these polymers, carboxymethyl cellulose acetate butyrate (CMCAB)-drug nanoparticles were investigated in detail. Previous work has shown that the presence of different chemical groups in CMCAB could aid in complexation with hydrophobic drugs with low solubility, forming an amorphous matrix which can increase the effective solubility and, hence, bioavailability of the drug in physiological conditions. An antibacterial drug and two less soluble anti-viral drugs were selected as model drugs for this study. A separate study was conducted with several other cellulose derivatives like cellulose acetate propionate adipates with two different degree of substitution 0.33 and 0.85 (CAP-Adp 0.33 and CAP-Adp 0.85), cellulose acetate sebacate (CA-320S Se) and butyl pullulan-6-carboxylate (BPC) polymers. The effect of polymer interaction with drug molecule on release of antiviral drugs was studied with these latter polymers. The purpose of this research was two-fold. First, the methodology for producing drug-polymer nanoparticles with well-defined particle size distributions was developed. Second, the factors affecting drug loading and release properties of these nanoparticles were investigated. The nanoparticles were processed using two methods of solvent removal and drying to investigate their effects on drug loading and particle size: (a) various combinations of rotary vacuum evaporation (rotavap) and acid-induced flocculation were used and (b), dialysis followed by freeze drying. Dynamic light scattering showed particle sizes were between 150-400 nm with polydispersity index values as low as 0.12. The antibiotic drug loading efficiencies ranged from 14-40%, whereas drug loading efficiency as high as 85 % was attained with the antiviral drug. The dissolution studies showed an increase in the solution concentration and release of the amorphous drug nanoparticles. The high glass transition temperature helped to stabilize the drug in an amorphous form, thus increasing the effective solution concentration of the drug in an aqueous medium. Advisors/Committee Members: Davis, Richey M. (committeechair), Sriranganathan, Nammalwar (committee member), Edgar, Kevin J. (committee member), Joseph, Eugene Gregory (committee member), Riffle, Judy S. (committee member).

Subjects/Keywords: polysaccharides; mixing; nanoprecipitation; cellulose derivatives; antibacterial; antiviral; nanoparticle; self-assembly; parti

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Mazumder, S. (2013). Synthesis and Characterization of Drug-Containing, Polysaccharide-Based Nanoparticles for Applications in Oral Drug Delivery. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/23692

Chicago Manual of Style (16^th Edition):

Mazumder, Sonal. “Synthesis and Characterization of Drug-Containing, Polysaccharide-Based Nanoparticles for Applications in Oral Drug Delivery.” 2013. Doctoral Dissertation, Virginia Tech. Accessed April 13, 2021. http://hdl.handle.net/10919/23692.

MLA Handbook (7^th Edition):

Mazumder, Sonal. “Synthesis and Characterization of Drug-Containing, Polysaccharide-Based Nanoparticles for Applications in Oral Drug Delivery.” 2013. Web. 13 Apr 2021.

Vancouver:

Mazumder S. Synthesis and Characterization of Drug-Containing, Polysaccharide-Based Nanoparticles for Applications in Oral Drug Delivery. [Internet] [Doctoral dissertation]. Virginia Tech; 2013. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10919/23692.

Council of Science Editors:

Mazumder S. Synthesis and Characterization of Drug-Containing, Polysaccharide-Based Nanoparticles for Applications in Oral Drug Delivery. [Doctoral Dissertation]. Virginia Tech; 2013. Available from: http://hdl.handle.net/10919/23692

Virginia Tech

21. Pudupakam, Raghavendra Sumanth Kumar. Understanding the Role of the Hypervariable Region in the Open Reading Frame 1 of the Hepatitis E virus in Viral Replication.

Degree: PhD, Veterinary Medical Sciences, 2011, Virginia Tech

URL: http://hdl.handle.net/10919/77083

► Hepatitis E virus (HEV) is a major cause of enterically transmitted acute viral hepatitis in developing countries that lack proper hygienic infrastructure. Hepatitis E is… (more)

▼ Hepatitis E virus (HEV) is a major cause of enterically transmitted acute viral hepatitis in developing countries that lack proper hygienic infrastructure. Hepatitis E is globally distributed and has emerged as an important public health disease in both developing and industrialized countries. HEV is a non-enveloped virus carrying a single-stranded positive-sense RNA genome of approximately 7.200 bp in length. The life cycle of HEV is poorly understood due to the lack of an efficient cell culture system. Animal model systems, including non-human primates, swine, and chickens are being used to study some fundamental aspects of the HEV biology. Recently, novel animal strains of rat and rabbit HEV have been discovered, and whose usage as animal model systems needs to be established. HEV infections in pigs and chickens provide excellent model systems to study the replication and pathogenesis aspects of HEV. Recently, we identified a hypervariable region (HVR) in the open reading frame 1 (ORF1) of HEV. The objectives of this dissertation were to utilize chicken and swine model systems to study the role of HVR in HEV infection in vivo, to determine the effects of HVR on replication of HEV in vitro, and to analyze the effect of exchange of HVR among different genotypes on the replication-competency and virion production in vitro. Extensive sequence variability in the HVR among HEV strains of different genotypes prompted us to study the dispensability of this region. Initially we constructed two partial deletion mutants of genotype 1 human HEV, hHVRd1 and hHVRd2, with in-frame deletion of amino acids (aa) 711 to 777 and 747 to 761 in the HVR of a sub-genomic GFP HEV replicon. Expression of enhanced green fluorescent protein by the mutant hHVRd2 confirmed the dispensability of amino acid residues 747-761 of the HVR. To confirm our in vitro results, specific-pathogen-free (SPF) chickens were intra-hepatically inoculated with capped RNA transcripts from three avian HEV HVR-deletion mutants: mutants aHVRd1 (Δ557-585), aHVRd2 (Δ612-641), and aHVRd3 (Δ557-641). Chickens intra-hepatically inoculated with the mutants, aHVRd1 and aHVRd2, developed active viral infection as evidenced by seroconversion, viremia, and fecal virus shedding. Mutant aHVRd3, with a larger HVR deletion, was apparently attenuated in chickens. Additionally, we used the swine model system to further verify our results from the chicken study. The infectivity of four genotype 3 swine HEV HVR-deletion mutants, sHVRd1 (Δ712-790), sHVRd2 (Δ722-781), sHVRd3 (Δ735-765), and sHVRd4 (Δ712-765) constructed using the genotype 3 swine HEV as the backbone was determined in SPF pigs. Pigs intra-hepatically inoculated with capped RNA transcripts from the mutants sHVRd2, sHVRd3, and sHVRd4 developed active viral infection, whereas mutant sHVRd1 (Δ712-790), with a nearly complete HVR deletion, exhibited an attenuation phenotype. The data from these studies indicate that deletions in HVR do not abolish HEV infectivity in vitro or in vivo, although evidence for attenuation was… Advisors/Committee Members: Meng, Xiang-Jin (committeechair), Boyle, Stephen M. (committee member), Myles, Kevin M. (committee member), Sriranganathan, Nammalwar (committee member), Avery, Roger J. (committee member).

Subjects/Keywords: hepatitis E virus; hypervariable region; HVR; subgenomic replicon; HEV; swine HEV; human HEV; avian HEV; hepatitis–splenomegaly syndrome; BLSD; big liver and spleen disease; HS syndrome

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Pudupakam, R. S. K. (2011). Understanding the Role of the Hypervariable Region in the Open Reading Frame 1 of the Hepatitis E virus in Viral Replication. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/77083

Chicago Manual of Style (16^th Edition):

Pudupakam, Raghavendra Sumanth Kumar. “Understanding the Role of the Hypervariable Region in the Open Reading Frame 1 of the Hepatitis E virus in Viral Replication.” 2011. Doctoral Dissertation, Virginia Tech. Accessed April 13, 2021. http://hdl.handle.net/10919/77083.

MLA Handbook (7^th Edition):

Pudupakam, Raghavendra Sumanth Kumar. “Understanding the Role of the Hypervariable Region in the Open Reading Frame 1 of the Hepatitis E virus in Viral Replication.” 2011. Web. 13 Apr 2021.

Vancouver:

Pudupakam RSK. Understanding the Role of the Hypervariable Region in the Open Reading Frame 1 of the Hepatitis E virus in Viral Replication. [Internet] [Doctoral dissertation]. Virginia Tech; 2011. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10919/77083.

Council of Science Editors:

Pudupakam RSK. Understanding the Role of the Hypervariable Region in the Open Reading Frame 1 of the Hepatitis E virus in Viral Replication. [Doctoral Dissertation]. Virginia Tech; 2011. Available from: http://hdl.handle.net/10919/77083

Virginia Tech

22. Restis, Eva Marie. Development of Drug Loaded Nanoparticles for Treatment of Mycobacterium avium Infection.

Degree: PhD, Biomedical and Veterinary Sciences, 2014, Virginia Tech

URL: http://hdl.handle.net/10919/52565

► Currently, about one third of the world's population is latently infected with Mycobacterium tuberculosis and about 4 million people die from the disease annually worldwide.… (more)

▼ Currently, about one third of the world's population is latently infected with Mycobacterium tuberculosis and about 4 million people die from the disease annually worldwide. Although treatment with antimicrobials can be curative, many people fail to complete the prescribed therapeutic regimen which can increase the risk of disease re-emergence, spread of infection to others and development of drug resistance. An improved approach is urgently needed for patient compliance. Development of safe and effective colloidal drug delivery systems may reduce the amount and frequency of antimicrobial therapy needed. The major goal of this research effort is to explore the safety and efficacy of antimicrobial loaded nanoparticles against M. avium. Various in vitro efficacy studies were done with a) amikacin-loaded nanoparticles, b) clarithromycin-loaded nanoparticles, and c) with aerogel nanoparticles loaded with rifampicin, clarithromycin and ethambutol. Clarithromycin (CLA) and amikacin (AMK) loaded nanoparticles showed a significant reduction in viable M. avium compared to free antibiotics and untreated controls. Cytotoxicity assays revealed that all types of drug-laden nanoparticles were non-toxic to J774A.1 mouse macrophage cells at therapeutic doses. In vivo efficacy studies showed that only amikacin-loaded polymeric nanoparticles improved clearance compared to free amikacin in M. avium infected BALB/c mice. In general, none of the nanoparticle formulations elicited any significant microscopic lesions in the organs of infected mice at tested doses. Each nanoparticle formulation was analyzed physicochemically for size, zeta potential, amount of drug load, minimum inhibitory concentration (MIC) and stability. Both the AMK and CLA polymeric nanoparticles were below 200 nm in size and had a slightly negative overall surface charge, aerogel nanoparticles were somewhat larger in size. The amount of drug load varied between all three nanoparticles and is largely dependent on the chemical structure and interactions between the nanoparticle and drug. The AMK and CLA nanoparticles were relatively stable under varying environmental conditions and time points and had MIC ranges equivalent to the respective free drugs. Advisors/Committee Members: Sriranganathan, Nammalwar (committeechair), Riffle, Judy S. (committee member), Falkinham, Joseph O. III (committee member), Subbiah, Elankumaran (committee member).

Subjects/Keywords: tuberculosis; nanoparticle; Mycobacterium avium

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Restis, E. M. (2014). Development of Drug Loaded Nanoparticles for Treatment of Mycobacterium avium Infection. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/52565

Chicago Manual of Style (16^th Edition):

Restis, Eva Marie. “Development of Drug Loaded Nanoparticles for Treatment of Mycobacterium avium Infection.” 2014. Doctoral Dissertation, Virginia Tech. Accessed April 13, 2021. http://hdl.handle.net/10919/52565.

MLA Handbook (7^th Edition):

Restis, Eva Marie. “Development of Drug Loaded Nanoparticles for Treatment of Mycobacterium avium Infection.” 2014. Web. 13 Apr 2021.

Vancouver:

Restis EM. Development of Drug Loaded Nanoparticles for Treatment of Mycobacterium avium Infection. [Internet] [Doctoral dissertation]. Virginia Tech; 2014. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10919/52565.

Council of Science Editors:

Restis EM. Development of Drug Loaded Nanoparticles for Treatment of Mycobacterium avium Infection. [Doctoral Dissertation]. Virginia Tech; 2014. Available from: http://hdl.handle.net/10919/52565

Virginia Tech

23. Zheng, Yi. Biological Agent Sensing Integrated Circuit (BASIC): A New Complementary Metal-oxide-semiconductor (CMOS) Magnetic Biosensor System.

Degree: PhD, Computer Engineering, 2014, Virginia Tech

URL: http://hdl.handle.net/10919/48892

► Fast and accurate diagnosis is always in demand by modern medical professionals and in the area of national defense. At present, limitations of testing speed,… (more)

Subjects/Keywords: Biohazard; Antibody and antigen; Pathogen; Iron nanoparticle; CMOS; Integrated circuit; Conical-shaped inductor; Uniform magnetic field; Magnetic sensor; LC oscillator; Frequency counter; Prototype; Antenna effect

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Zheng, Y. (2014). Biological Agent Sensing Integrated Circuit (BASIC): A New Complementary Metal-oxide-semiconductor (CMOS) Magnetic Biosensor System. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/48892

Chicago Manual of Style (16^th Edition):

Zheng, Yi. “Biological Agent Sensing Integrated Circuit (BASIC): A New Complementary Metal-oxide-semiconductor (CMOS) Magnetic Biosensor System.” 2014. Doctoral Dissertation, Virginia Tech. Accessed April 13, 2021. http://hdl.handle.net/10919/48892.

MLA Handbook (7^th Edition):

Zheng, Yi. “Biological Agent Sensing Integrated Circuit (BASIC): A New Complementary Metal-oxide-semiconductor (CMOS) Magnetic Biosensor System.” 2014. Web. 13 Apr 2021.

Vancouver:

Zheng Y. Biological Agent Sensing Integrated Circuit (BASIC): A New Complementary Metal-oxide-semiconductor (CMOS) Magnetic Biosensor System. [Internet] [Doctoral dissertation]. Virginia Tech; 2014. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10919/48892.

Council of Science Editors:

Zheng Y. Biological Agent Sensing Integrated Circuit (BASIC): A New Complementary Metal-oxide-semiconductor (CMOS) Magnetic Biosensor System. [Doctoral Dissertation]. Virginia Tech; 2014. Available from: http://hdl.handle.net/10919/48892

Virginia Tech

24. Raghunath, Shobana. Targeted Oncolytic Virotherapy Using Newcastle Disease Virus Against Prostate Cancer.

Degree: PhD, Biomedical and Veterinary Sciences, 2012, Virginia Tech

URL: http://hdl.handle.net/10919/77985

► Prostate cancer (CaP) is the second leading cause of cancer related deaths in men in the United States. Currently, androgen depletion is an essential strategy… (more)

▼ Prostate cancer (CaP) is the second leading cause of cancer related deaths in men in the United States. Currently, androgen depletion is an essential strategy for CaP combined with surgery, chemotherapy and radiation. Hormone independent cancer stem cells escaping conventional therapy present a major therapeutic challenge. The available treatment regimens for hormone resistant CaP are only palliative and marginally increase survival. Therefore, novel strategies to eradicate CaP including stem cells are imperative. Oncolytic virus (OV) therapy is a novel approach that overcomes the limitations posed by radiation and chemotherapy. Oncolytic virotherapy of cancer is based on the use of replication competent, tumor selective viruses with limited toxicity. Newcastle Disease Virus (NDV), an avian paramyxovirus, is a safe and promising OV successfully used in many clinical trials. NDV is inherently tumor selective and cytotoxic but replication restricted in normal cells. But, systemically delivered NDV fails to reach solid tumors in therapeutic concentrations and also spreads poorly within the tumors due to barriers including complement, innate immunity and extracellular matrix. Overcoming these hurdles is paramount to realize the exceptional oncolytic efficacy of NDV. Therefore, we engineered the fusion (F) glycoprotein of NDV and generated a recombinant NDV (rNDV) cleavable exclusively by prostate specific antigen (PSA). The rNDV replicated efficiently and specifically only in prostate cancer (CaP) cells but failed to replicate in the absence of PSA. Further, PSA-cleavable rNDV caused specific lysis of androgen independent and dependent/responsive CaP cells with a mean effective concentration (EC50) ranging from 0.01 to 0.1 multiplicity of infection (MOI). PSA retargeted rNDV efficiently lysed three-dimensional prostaspheres, suggesting efficacy in vivo. Also, PSA-cleavable NDV failed to replicate in chicken embryos, indicating absence of pathogenicity to its natural host, chickens. Prostaspheres generated from DU-145 CaP cell line derived xenografts showed self-renewal, proliferative and clonogenic potential in vitro, and exhibited increased tumorigenicity in vivo. Embryonic stem and progenitor cell markers like Nanog, Nestin and CD44 were overexpressed in spheres as compared to the cell line suggesting prostaspheres comprise tumor-initiating cells from CaP. Xenograft and cell line derived prostaspheres were permissive for rNDV replication, when the fusion protein was activated by exogenous PSA. The EC50 against tumor initiating cells was 0.11-0.14 MOI, suggesting an excellent therapeutic margin for in vivo studies. PSA retargeting is likely to enhance the therapeutic index of rNDV owing to tumor restricted replication and enhanced fusogenicity. Our results suggest PSA retargeted rNDV selectively replicates and lyse PSA producing CaP cells including tumor-initiating cells and is a promising candidate for immediate Phase I/II clinical trials. Advisors/Committee Members: Subbiah, Elankumaran (committeechair), Yuan, Lijuan (committee member), Parks, Griffin D. (committee member), Sriranganathan, Nammalwar (committee member), Meng, Xiang-Jin (committee member).

Subjects/Keywords: Tumor initiating cells; Prostate cancer stem cells; Oncolytic virotherapy; Newcastle disease virus; Re targeting; Prostate specific antigen

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APA (6^th Edition):

Raghunath, S. (2012). Targeted Oncolytic Virotherapy Using Newcastle Disease Virus Against Prostate Cancer. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/77985

Chicago Manual of Style (16^th Edition):

Raghunath, Shobana. “Targeted Oncolytic Virotherapy Using Newcastle Disease Virus Against Prostate Cancer.” 2012. Doctoral Dissertation, Virginia Tech. Accessed April 13, 2021. http://hdl.handle.net/10919/77985.

MLA Handbook (7^th Edition):

Raghunath, Shobana. “Targeted Oncolytic Virotherapy Using Newcastle Disease Virus Against Prostate Cancer.” 2012. Web. 13 Apr 2021.

Vancouver:

Raghunath S. Targeted Oncolytic Virotherapy Using Newcastle Disease Virus Against Prostate Cancer. [Internet] [Doctoral dissertation]. Virginia Tech; 2012. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10919/77985.

Council of Science Editors:

Raghunath S. Targeted Oncolytic Virotherapy Using Newcastle Disease Virus Against Prostate Cancer. [Doctoral Dissertation]. Virginia Tech; 2012. Available from: http://hdl.handle.net/10919/77985

Virginia Tech

25. Sheehan, Lauren Marie. Characterizing the AbcR/VtlR system in the Rhizobiales.

Degree: PhD, Biomedical and Veterinary Sciences, 2018, Virginia Tech

URL: http://hdl.handle.net/10919/96536

► Rhizobiales encompass a diverse group of microbes, ranging from free-living, soil-dwelling bacteria to disease-causing, intracellular pathogens. Although the lifestyle of these organisms vary, many genetic… (more)

▼ Rhizobiales encompass a diverse group of microbes, ranging from free-living, soil-dwelling bacteria to disease-causing, intracellular pathogens. Although the lifestyle of these organisms vary, many genetic systems are well conserved. One system, named the AbcR/VtlR system, is found throughout rhizobiales, and even extends to bacteria in other orders within the Alphaproteobacteria. The AbcR sRNAs are an example of sibling sRNAs, where two copies of the abcR gene are typically present in the genome. The AbcRs are involved in the negative regulation of ABC-type transport systems, which are important components for nutrient acquisition. Although the AbcRs share several features amongst organisms, major differences can be found in their functional and regulatory redundancy, the targets they regulate and how they regulate them. Specifically, one major difference in the AbcRs lies in the nucleotide sequences utilized by the sRNAs to bind mRNA targets. In the present studies, the regulatory mechanisms of the AbcR sRNAs were further characterized in the mammalian pathogen Brucella abortus, and the full regulatory profiles of the AbcRs were defined in the plant pathogen Agrobacterium tumefaciens. As mentioned above, the AbcR sRNAs are important for the proper regulation of nutrient-acquiring transport systems in the Rhizobiales. Since these sRNAs are critical to the lifestyle of a bacterium, proper regulation of this system is key to survival. A LysR-type transcriptional regulator, named VtlR, was found to be the bonefide transcriptional activator of abcR1 in B. abortus. Furthermore, VtlR has been shown to be a key component in host interactions in several rhizobiales. The preset work has shed light on the evolutionary divergence of this regulator in bacteria, and further defined the regulatory capacity of VtlR in Agrobacterium. Overall, the studies described here have made significant advances in our knowledge of the AbcR/VtlR-regulatory systems in the Rhizobiales, and have further defined this system as being a vital part of host-microbe interactions. Advisors/Committee Members: Caswell, Clayton Christopher (committeechair), Inzana, Thomas Joseph (committee member), Sriranganathan, Nammalwar (committee member), Scharf, Birgit (committee member).

Subjects/Keywords: Brucella; LysR-type transcriptional regulators; small RNAs

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APA (6^th Edition):

Sheehan, L. M. (2018). Characterizing the AbcR/VtlR system in the Rhizobiales. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/96536

Chicago Manual of Style (16^th Edition):

Sheehan, Lauren Marie. “Characterizing the AbcR/VtlR system in the Rhizobiales.” 2018. Doctoral Dissertation, Virginia Tech. Accessed April 13, 2021. http://hdl.handle.net/10919/96536.

MLA Handbook (7^th Edition):

Sheehan, Lauren Marie. “Characterizing the AbcR/VtlR system in the Rhizobiales.” 2018. Web. 13 Apr 2021.

Vancouver:

Sheehan LM. Characterizing the AbcR/VtlR system in the Rhizobiales. [Internet] [Doctoral dissertation]. Virginia Tech; 2018. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10919/96536.

Council of Science Editors:

Sheehan LM. Characterizing the AbcR/VtlR system in the Rhizobiales. [Doctoral Dissertation]. Virginia Tech; 2018. Available from: http://hdl.handle.net/10919/96536

26. Alexander, Jeffry Chanen. Considerations for Automating Salmonella Serovar Identification within an Electronic Public Health Reporting Environment.

Degree: PhD, Biomedical and Veterinary Sciences, 2015, Virginia Tech

URL: http://hdl.handle.net/10919/75211

► CDC's requirements for Salmonella surveillance reporting include submission of serovars from the recognized naming scheme, Kauffmann-White (K-W), using identifiers curated by the Systematized Nomenclature of… (more)

▼ CDC's requirements for Salmonella surveillance reporting include submission of serovars from the recognized naming scheme, Kauffmann-White (K-W), using identifiers curated by the Systematized Nomenclature of Medicine-Clinical Terms (SNOMED CT®). Translating the serotype formula of a Salmonella isolate to the correct identifier has been a multistep manual process for users. Our goal was to determine whether a degree of automation could be achieved using an ontology based on K-W. We investigated information artifacts presently available, namely K-W, SNOMED CT and CDC's Public Health Information Network - Vocabulary Access and Distribution System (PHIN-VADS). As SNOMED CT creates identifiers and associates them with serovar names, we performed detailed analysis on its coverage of K-W. An overall error rate of 13.1% included simple omissions and transcription errors. We limited our assessment of K-W and PHIN-VADS to the functional characteristics of the resources they distribute. K-W creates serovar names but does not provide identifiers. PHIN-VADS includes the identifiers but not antigenic formulae for most isolates. In summary, neither K-W nor PHIN-VADS contained all information users require. Two different ontology prototypes were developed. Prototype I placed K-W serovars as terminal nodes in the hierarchy and these were given logic-based definitions. Prototype II added isolate classes as serovar subtypes. Only the isolate classes had complete logical definitions. Both prototypes were logically sound and functioned as expected. Prototype I paralleled existing SNOMED CT content but required more robust description logic than currently employed in SNOMED CT. Prototype II was more compatible with current functionality of SNOMED CT but created identifiers that would not meet current requirements for public health reporting. Prototype I was fully populated as the Salmonella Serotype Designation Ontology (SSDO). As it stands, SSDO reliably places isolates in the appropriate classes, with few and predictable exceptions. Although SNOMED CT cannot accommodate its functionality at this time, SSDO can serve as the basis for a stand-alone application. Ultimately whether by improving functionality of existing systems or providing a framework for an ancillary automated system, this work should facilitate real-time reporting and analysis of surveillance data that will prevent new or reduce severity of infectious disease outbreaks. Advisors/Committee Members: Wilcke, Jeffrey R. (committeechair), Green, Julie Meadows (committee member), Sriranganathan, Nammalwar (committee member), Martin, Michael K. (committee member).

Subjects/Keywords: Public Health; Salmonella; serovar; terminology; ontology; SNOMED CT; Kauffmann-White

…Virginia Tech. (VTSL, 2012) A specific issue from VDCLS was that SNOMED FSNs only…

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APA (6^th Edition):

Alexander, J. C. (2015). Considerations for Automating Salmonella Serovar Identification within an Electronic Public Health Reporting Environment. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/75211

Chicago Manual of Style (16^th Edition):

Alexander, Jeffry Chanen. “Considerations for Automating Salmonella Serovar Identification within an Electronic Public Health Reporting Environment.” 2015. Doctoral Dissertation, Virginia Tech. Accessed April 13, 2021. http://hdl.handle.net/10919/75211.

MLA Handbook (7^th Edition):

Alexander, Jeffry Chanen. “Considerations for Automating Salmonella Serovar Identification within an Electronic Public Health Reporting Environment.” 2015. Web. 13 Apr 2021.

Vancouver:

Alexander JC. Considerations for Automating Salmonella Serovar Identification within an Electronic Public Health Reporting Environment. [Internet] [Doctoral dissertation]. Virginia Tech; 2015. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10919/75211.

Council of Science Editors:

Alexander JC. Considerations for Automating Salmonella Serovar Identification within an Electronic Public Health Reporting Environment. [Doctoral Dissertation]. Virginia Tech; 2015. Available from: http://hdl.handle.net/10919/75211

27. Al Qublan, Hamzeh. Development and testing of recombinant B. abortus RB51 vaccine strains carrying M. tuberculosis protective antigens.

Degree: PhD, Biomedical and Veterinary Sciences, 2015, Virginia Tech

URL: http://hdl.handle.net/10919/73696

► Tuberculosis, caused by Mycobacterium tuberculosis, is one of the most prevalent infectious diseases inflicting humankind. The World Health Organization estimates that one third of the… (more)

▼ Tuberculosis, caused by Mycobacterium tuberculosis, is one of the most prevalent infectious diseases inflicting humankind. The World Health Organization estimates that one third of the world's population, approximately 2.2 billion people, is infected with TB with a mortality of 1.7 million people annually. Currently, the WHO estimates that each year more than 9 million people develop TB. Bacille Calmette-Guérin (BCG), an attenuated strain of M. bovis, is the only licensed TB vaccine in the world. Clinical studies have shown childhood vaccination with BCG to be protective against disseminating and meningeal forms of TB. However, the efficacy of BCG against pulmonary TB in adults has been variable and inconsistent (0-80%). The objective of this study is to develop and test the efficacy of the B. abortus vaccine strain RB51 as a platform for expression of M. tuberculosis antigens (Ag85B, ESAT6 and Rv2660c) and induction of a protective immune response against M. tuberculosis and B. abortus challenge in mice. Here we report the construction of two recombinant strains of B. abortus vaccine strain RB51 capable of expressing mycobacterial antigens Ag85B, ESAT6 and Rv2660c. Our studies show that expression of mycobacterial antigens in strain RB51 lead to induction of antigen-specific immune responses characterized by secretion of IgG2a antibodies as well as of IFN- and TNF-α. Mice immunized with a combination of two strains of RB51 in equal numbers, one carrying Rv2660c-ESAT6 and another carrying Ag85B, led to a 0.90 log reduction in CFU burden with significance nearly reaching borderline (p = 0.052). However, when mice were primed with the same strains of RB51 and boosted with proteins Ag85B and ESAT6, a significant level of protection (1 log reduction) compared to the PBS vaccinated group was achieved. The protection levels conferred by this vaccination strategy was similar to that conferred by BCG vaccine. In conclusion, we have shown that recombinant RB51 strains expressing mycobacterial protective antigens result in stimulation of antigen specific immune response without altering the vaccine efficacy in protecting against the more virulent strain of B. abortus 2308. These recombinant vaccines could potentially be used to protect against M. tuberculosis infection. Advisors/Committee Members: Sriranganathan, Nammalwar (committeechair), Huckle, William Rupert (committee member), Prater, Mary R. (committee member), Boyle, Stephen M. (committee member).

Subjects/Keywords: Vaccine; TB; Brucella

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APA (6^th Edition):

Al Qublan, H. (2015). Development and testing of recombinant B. abortus RB51 vaccine strains carrying M. tuberculosis protective antigens. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/73696

Chicago Manual of Style (16^th Edition):

Al Qublan, Hamzeh. “Development and testing of recombinant B. abortus RB51 vaccine strains carrying M. tuberculosis protective antigens.” 2015. Doctoral Dissertation, Virginia Tech. Accessed April 13, 2021. http://hdl.handle.net/10919/73696.

MLA Handbook (7^th Edition):

Al Qublan, Hamzeh. “Development and testing of recombinant B. abortus RB51 vaccine strains carrying M. tuberculosis protective antigens.” 2015. Web. 13 Apr 2021.

Vancouver:

Al Qublan H. Development and testing of recombinant B. abortus RB51 vaccine strains carrying M. tuberculosis protective antigens. [Internet] [Doctoral dissertation]. Virginia Tech; 2015. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10919/73696.

Council of Science Editors:

Al Qublan H. Development and testing of recombinant B. abortus RB51 vaccine strains carrying M. tuberculosis protective antigens. [Doctoral Dissertation]. Virginia Tech; 2015. Available from: http://hdl.handle.net/10919/73696

Virginia Tech

28. Whichard, Jean Marie. Bacteriophage Felix O1: Genetic Characterization and Bioremedial Application.

Degree: PhD, Veterinary Medical Sciences, 2000, Virginia Tech

URL: http://hdl.handle.net/10919/29591

► Bacteriophage Felix O1 was studied for applicability as a Salmonella intervention. Felix O1's potential as a Salmonella therapeutic was explored, as was its utility as… (more)

▼ Bacteriophage Felix O1 was studied for applicability as a Salmonella intervention. Felix O1's potential as a Salmonella therapeutic was explored, as was its utility as a food application. Felix O1 is specific for and infects most serovars within the genus Salmonella. The entire 86.155-kb sequence of the phage's linear, double-stranded chromosome was determined. 213 open reading frames (ORFs) were found, including 23 homologues of phage genes (e<0.008). Homology searches do not indicate genes that would be expected to increase virulence of Salmonella. Thirteen T4 homologues were found, including rIIA and rIIB, rapid lysis genes of T-even phages. Site-directed mutagenesis of the rIIB region was attempted by homologous recombination with plasmids containing luxAB of Vibrio harveyi. No DrIIB luxAB+ recombinants resulted from the methods tried. Serial in vivo passage was used to select for a longer-circulating Felix O1 mutant using the modified methods of Merril et al., (1996). No difference was found in the clearance of wild-type (WT) and Felix O1 following nine serial passages. Injection of 10⁹pfus yielded 24-hour concentrations of 6.5 and 4.9 log10 pfus/ml plasma for WT and 9th passage, respectively. Both isolates were undetectable in plasma by 72 hours, but remained in spleens at 96 hours. A large-plaque Felix O1 variant (LP) isolated during in vivo serial passage was compared with WT for Salmonella growth suppression. Spectrophotometric measurement of BHI cultures indicated greater suppression of S. typhi by LP than by WT, a difference not seen with S. typhimurium DT104. Both isolates suppressed 24-hour S. typhimurium DT104 growth on experimentally-contaminated chicken frankfurters at 22Â°C. Untreated frankfurters yielded 6.81 log10 Salmonella cfus/g, whereas WT and LP-treated samples yielded 5.01 and 4.70 log10 cfus/g, respectively. Both phages suppressed the Salmonella typhimurium DT104 growth (p<0.0001), but the isolates did not perform differently (p=0.5088). Presence of Salmonella caused a higher yield of WT phage than from the uninoculated group (p=0.0011), but did not affect LP yield (p=0.4416). With Salmonella present, the 24-hour LP concentration was lower than WT concentration. This supports the surmised LP rapid-lysis phenotype since T4 rapid-lysis mutants typically exhibit lower burst sizes than wild-type phage. Advisors/Committee Members: Pierson, Frank William (committeecochair), Sriranganathan, Nammalwar (committeecochair).

Subjects/Keywords: Salmonella; Felix O1; poultry; bacteriophage

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Whichard, J. M. (2000). Bacteriophage Felix O1: Genetic Characterization and Bioremedial Application. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/29591

Chicago Manual of Style (16^th Edition):

Whichard, Jean Marie. “Bacteriophage Felix O1: Genetic Characterization and Bioremedial Application.” 2000. Doctoral Dissertation, Virginia Tech. Accessed April 13, 2021. http://hdl.handle.net/10919/29591.

MLA Handbook (7^th Edition):

Whichard, Jean Marie. “Bacteriophage Felix O1: Genetic Characterization and Bioremedial Application.” 2000. Web. 13 Apr 2021.

Vancouver:

Whichard JM. Bacteriophage Felix O1: Genetic Characterization and Bioremedial Application. [Internet] [Doctoral dissertation]. Virginia Tech; 2000. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10919/29591.

Council of Science Editors:

Whichard JM. Bacteriophage Felix O1: Genetic Characterization and Bioremedial Application. [Doctoral Dissertation]. Virginia Tech; 2000. Available from: http://hdl.handle.net/10919/29591

Virginia Tech

29. Hirst, Suzanne Marie. Anti-inflammatory Effects and Biodistribution of Cerium Oxide Nanoparticles.

Degree: MS, Veterinary Medical Sciences, 2010, Virginia Tech

URL: http://hdl.handle.net/10919/76806

► Cerium oxide nanoparticles have the unique ability to accept and donate electrons, making them powerful antioxidants. Their redox nature is due to oxygen defects in… (more)

Subjects/Keywords: inflammation; oxygen defect; reactive oxygen species (ROS); free radical; nanoparticle; cerium oxide; iNOS

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APA (6^th Edition):

Hirst, S. M. (2010). Anti-inflammatory Effects and Biodistribution of Cerium Oxide Nanoparticles. (Masters Thesis). Virginia Tech. Retrieved from http://hdl.handle.net/10919/76806

Chicago Manual of Style (16^th Edition):

Hirst, Suzanne Marie. “Anti-inflammatory Effects and Biodistribution of Cerium Oxide Nanoparticles.” 2010. Masters Thesis, Virginia Tech. Accessed April 13, 2021. http://hdl.handle.net/10919/76806.

MLA Handbook (7^th Edition):

Hirst, Suzanne Marie. “Anti-inflammatory Effects and Biodistribution of Cerium Oxide Nanoparticles.” 2010. Web. 13 Apr 2021.

Vancouver:

Hirst SM. Anti-inflammatory Effects and Biodistribution of Cerium Oxide Nanoparticles. [Internet] [Masters thesis]. Virginia Tech; 2010. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10919/76806.

Council of Science Editors:

Hirst SM. Anti-inflammatory Effects and Biodistribution of Cerium Oxide Nanoparticles. [Masters Thesis]. Virginia Tech; 2010. Available from: http://hdl.handle.net/10919/76806

Virginia Tech

30. Dyer, John Gilbert. Curli Production and ERIC-PCR Fingerprinting of Escherichia coli from Clinical Cases of Bovine Mastitis.

Degree: MS, Biomedical and Veterinary Sciences, 2005, Virginia Tech

URL: http://hdl.handle.net/10919/31401

► Mastitis caused by Escherichia coli is among the most common and severe forms of environmental mastitis. Currently, the severity of E. coli mastitis is thought… (more)

Subjects/Keywords: Escherichia coli; mastitis; ERIC-PCR; bovine; curli; dairy

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APA (6^th Edition):

Dyer, J. G. (2005). Curli Production and ERIC-PCR Fingerprinting of Escherichia coli from Clinical Cases of Bovine Mastitis. (Masters Thesis). Virginia Tech. Retrieved from http://hdl.handle.net/10919/31401

Chicago Manual of Style (16^th Edition):

Dyer, John Gilbert. “Curli Production and ERIC-PCR Fingerprinting of Escherichia coli from Clinical Cases of Bovine Mastitis.” 2005. Masters Thesis, Virginia Tech. Accessed April 13, 2021. http://hdl.handle.net/10919/31401.

MLA Handbook (7^th Edition):

Dyer, John Gilbert. “Curli Production and ERIC-PCR Fingerprinting of Escherichia coli from Clinical Cases of Bovine Mastitis.” 2005. Web. 13 Apr 2021.

Vancouver:

Dyer JG. Curli Production and ERIC-PCR Fingerprinting of Escherichia coli from Clinical Cases of Bovine Mastitis. [Internet] [Masters thesis]. Virginia Tech; 2005. [cited 2021 Apr 13]. Available from: http://hdl.handle.net/10919/31401.

Council of Science Editors:

Dyer JG. Curli Production and ERIC-PCR Fingerprinting of Escherichia coli from Clinical Cases of Bovine Mastitis. [Masters Thesis]. Virginia Tech; 2005. Available from: http://hdl.handle.net/10919/31401

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