Cisplatin is an antineoplastic drug used to treat malignant tumors in human beings and dogs. Nephrotoxicosis was initially considered dose limiting. The use of saline loading and hypertonic saline administration protocols allowed dose escalation, reduced nephrotoxicosis, and increased remission rates in the treatment previously poorly responsive malignant tumors in human beings. A pilot study was performed to determine efficacy of 4-hour saline loading in providing renal protection for dogs receiving high-dose cisplatin (150 mg/m² IV). Two beagles were saline loaded (25 ml/kg/hr of 0.9% NaCI, IV) for 4 hours and infused with cisplatin (150 mg/m²). We demonstrated that high-dose cisplatin (150 mg/m² IV) can be administered to dogs without biochemical evidence of acute nephrotoxicosis; however gastrointestinal toxicoses (fibrinonecrotic enteritis) and severe myelosuppression (leukopenia) were incompatible with patient survival and therefore, dose limiting. In another study we compared efficacy of hypertonic saline with normal saline in preventing nephrotoxicosis associated with administration of high-dose cisplatin (90 mg/m² IV) to dogs. In this study we demonstrated that a single IV dose of cisplatin (90mg/m²) can be administered to dogs in normal saline (0.9%) or hypertonic saline (7%) in combination with 4 hour saline loading (25 ml/kg/hr) without evidence of reduced renal function as measured by exogenous creatinine clearance. Platelet numbers were significantly increased in dogs that received cisplatin in hypertonic saline. Nephrotoxicosis was not dose limiting in either study. Future studies should attempt to determine the efficacy and toxicoses of multiple doses of cisplatin (90 mg/M² administered in hypertonic saline to tumor bearing dogs. / Master of Science

A three-dimensional finite element model for the analysis of steady state seepage has been presented in this study. The theory of unsaturated flow has been used in the analysis of steady state seepage. The model applies the invariant mesh procedure in the finite element analysis. Galerkin's method is used in the formulation of the finite element equations. The pre and the post processor developed in the generation and viewing of the finite element mesh and the free surface has also been discussed in this study. The study presents the comparison of results obtained from the three-dimensional model with a previously validated two-dimensional model. / Master of Science

The poultry industry, a vital economic force in Virginia, must dispose of vast amounts of waste, mainly litter (PL) , generated during production processes. This study was conducted to investigate the short-term effects of various rates of PL application, i.e., cumulative 2-year totals of 9.8, 19.5, 29.3, 39.0, and 48.8 mt ha⁻¹, to unimproved pasture. Dry matter yield, N recovery and use efficiency, P recovery and use efficiency, and changes in botanical composition were measured on a mixed species, tall fescue (<i>Festuca arundinacea</i>) and bluegrass (<i>Poa pratensis</i>) pasture. Additionally. the accumulation and movement of P was measured in a Starr clay loam (fme-Ioamy mixed thermic Fluventic Dystrochrepts) by the Mehlich 3 (M3) and Bray 1 (Bl) soil tests. Dry matter yields increased curvilinearly with rate of PL application. This yield increase was attributed to correction of N deficiency in pasture by the PL application. Lower levels of PL increased forage yields in 1992 compared with 1991, due to residual effect of unmineralized N from PL applied in 1991. The PL application rate of 11.4 mt ha⁻¹ in 1991, followed by 8.1 mt ha⁻¹ in 1992 was the most environmentally and economically recommendable rate when compared with inorganic N and P recommended fertilizer rates. Forage yields on this treatment were 21.5 mt ha⁻¹ versus 21. 7 mt ha⁻¹ for the inorganic N and P fertilizer treatment. All rates of applied PL increased the percentage of tall fescue (from approximately 50 percent to > 80 percent) and decreased the percentage of bluegrass in this mixed pasture. Phosphorus from both PL and inorganic sources accumulated in the zone of application. In 1992, the highest rates of PL application had increased M3-extractable P levels by 20 fold over the control (192 mg P kg versus 11 mg P kg⁻¹) and caused movement of P into the 10 to 15 cm soil depth. Levels of P extracted by the M3 and Bl soil tests were highly correlated for both years (r² = 0.96 in 1991 and r² = 0.99 in 1992) but the M3 extracted substantially more P from the surface 0 to 5 cm depth (21 percent in 1991 and 23 percent 1992) while the Bl soil test extracted more P from the 5 to 30 cm soil depth (50 to 66 percent more in 1991 and 20 to 57 percent in 1992). Differences in total acidity and F concentrations account for differences of P extracted by the two procedures. Poultry litter is a suitable source of fertilizer for pasture renovation and production in the Piedmont Region of Virginia. / Master of Science

A mathematically one-dimensional model was developed to predict the static response of composite sandwich beams subjected to loads induced by piezoelectric (PZT) actuators. The model was derived using Reddy's (1984) displacement field for a laminated plate which consists of cubic variation of the in-plane displacement through the thickness. In this model, beam deformations include extension, bending, transverse shear, St. Venant torsion, and torsion due to warping of the cross section out of its plane. The PZT actuators can be configurated to induce a bimoment, resulting in twist cf the beam through the warping of the cross section. Hence directionally attached PZT (DAP) actuator elements, which cause twist by inducing tensile and compressive strains at 45° to the longitudinal axis of the beams, are not necessary to actuate twist. For an aluminum beam example, it is shown that the PZT bimomet control produced about 2.7 times more twist than the conventional DAP control. / Master of Science

A field machinery selection model originally developed by Dr. John C. Siemens for Illinois has been fully studied and adapted to Virginia agriculture. The modified version of this model is able to assist farm managers in selecting optimum machinery sets for multiple cropping production systems. The program was written in the C programming language to run on an IBM compatible personal computer. The program input information consists of a list of desired field operations with start date, acres, and hours per day for each operation. Other input includes crop yields, penalty dates for planting and harvesting, availability and cost of labor, and certain economic data such as crop and fuel prices and interest rates. Stored data files contain machine list prices and productivity values, workday probabilities, and equation constants for computing machine costs. For different machinery sets or a specified set of machinery, the program schedules the field operations and computes the total machinery related costs including costs for the machines, labor, and timeliness. Using an optimization process, the lowest cost machinery set is determined and the eight lowest cost sets found during the process are presented. For any of the eight lowest cost sets, or for a specific set of machinery, the output includes a list of the machinery with prices and annual use, the work schedule, the cost for each operation, and total machinery related costs. / Master of Science

The performance of an optical fiber depends to a great extent on the conditions of the process being used to draw the fiber from a glass preform. To get fibers with higher strength and lower transmission loss, the parameters of the draw process must be optimized and the geometric uniformity of the fiber must be maintained with high precision. To increase the geometric uniformity of the fiber the online fiber diameter measuring accuracy must be improved. The coating concentricity and uniformity also play an important role in fabricating quality fiber. As the fiber drawing speed goes higher and higher, which is the trend of modern fiber fabrication processes, the uniformity of fiber diameter and coating concentricity becomes even tougher to maintain. The main objective of this research has been to understand and develop an optical fiber drawing process that produces fiber with improved dimensional uniformity, higher strength and lower transmission loss. Particular emphasis has been given to the accurate measurement of on-line fiber diameter, which is the first and most important step in obtaining uniform fiber. / Master of Science

Disposal of regulated waste has become a major challenge for the generators. Disposal of such waste is regulated by local, state and federal agencies and the problem is intensified because of liability issues, public perception and increasing cost. This document describes the mechanical design, installation and testing of a system that employs bioremediation to disinfect regulated medical waste. Currently marketed treatment systems generally use either heat or extreme pH to disinfect medical waste. The most common and widely accepted of these, incineration, is rapidly losing favor because of undesirable emissions and hazardous by-product. The system described in this document is the first to use a biological process. The advantages of using this system include the absence of harmful effluents or emissions, low cost of operation, reduction of waste volume and disposal directly into landfill and sewers. The evolution of system design from conceptual stage to the design of a system for Lewis-Gale hospital is described. A general overview of the components is presented and the selection and testing criteria are explained. The components used in Lewis-Gale hospital are described with a detailed layout scheme. A detailed failure analysis was done for each component used in Lewis-Gale hospital. This is presented with contingency plans developed for prolonged system failure. Finally, the operators manual developed for the Lewis-Gale hospital is included. / Master of Science

The gram-negative bacterial pathogen Brucella abortus is a zoonotic pathogen causing brucellosis in a variety of animal species including humans. The loss of the O-side chain in the lipopolysaccharide of the outer membrane decreases Brucella virulence. To understand the genetics of O-side chain biosynthesis and its relationship to virulence, studies were initiated to characterize specific O-side chain mutants. B. abortus rough mutant strain RA2 was derived by transposon (Tn5) mutagenesis of smooth B. abortus 2308. The chromosomal region of strain RA2 with the Tn5 and flanking chromosomal region was cloned into the sequencing vector pGEM-3Z to create a suicide plasmid pNW-2. The plasmid pNW-2, or a derivative of it (pNW-3), in which Tn5 was replaced with a Kank gene, were electroporated into wild type smooth B. abortus 2308 in order to assess the phenotypic conversion from smooth to rough. The electroporation parameters such as cell growth stage, pulse field strength and pulse length were optimized. It was determined that using late log phase cells (approximately 70-77 Klett units), 10 ms and 13 KV/cm were the best conditions for achieving transformation by pNW-2 or pNW3. Kanamycin resistant and ampicillin sensitive Brucella were screened for double reciprocal crossovers between the suicide plasmids (pNW-2 and pNW-3) and Brucella chromosomal DNA. The recombinants were checked for their O-side chain by crystal violet uptake and immunoblotting with monoclonal antibody specific for the O-side chain. The locations of Tn5 and the flanking region in the genome of these recombinants were characterized by Southern blot using either a Tn5 probe or a flanking region probe. An analysis of KanR colonies showed that none of the recombinants were rough. The B. abortus DNA in pNW-2 was sequenced and compared with other genes. No Significant homology was found between the Brucella DNA in pNW-2 and gene sequences in the gene bank. Analysis of the recombinants suggests no linkage between the Tn5 element in strain RA2 and the rough phenotype. / Master of Science

Exogenous PGF_2α, (see Appendix I for definitions of abbreviations) is luteolytic in midluteal (1.e., d 9 of a 17 d estrous cycle) sheep. However, the pharmacokinetic responses to PGF_2α-induced luteolysis are not known. This study (Exp. 1 and 2) was conducted to determine several pharmacokinetic responses to two dosing regimens of Lutalyse® (PGF_2α). Experiment 1 was a 2 x 2 factorial design, with Lutalyse and H/Ox as main effects. Lutalyse (15 mg) was injected i.m., and blood samples were collected, relative to the time of injection, from the vena cava at points cranial and caudal to the uteroovarian vein. Progesterone and PGF_2α, were measured in blood plasma. The PGF_2α concentrations were greater in H/Ox and sham H/Ox ewes treated-with Lutalyse® than in control ewes. Peak concentrations of PGF_2α were greatest in sham H/Ox Lutalyse-treated ewes, indicating that the uterus and(or) ovaries secrete PGF_2α, in response to exogenous PGF_2α. In Lutalyse-treated ewes, progesterone concentrations decreased by 50% within 8 h after treatment. The design of Exp. 2 was also a 2 x 2 factorial, with Lutalyse (2 x 5mg at 3 h intervals) and H/Ox as main effects. Prostaglandin F_2α and PGFM were measured in blood plasma collected, relative to the time of injections, from the vena cava at points cranial and caudal to the uteroovarian vein. The PGF_2α concentrations were greater in sham H/Ox ewes treated-with Lutalyse than in control ewes. Peak concentrations of PGF_2α were greater in sham H/Ox than in ewes in all other treatment groups, indicating again that the uterus and(or) ovaries secrete PGF_2α in response to exogenous PGF_2α In general, PGFM concentrations increased in a pattern similar to that of PGF_2α after Lutalyse injection; although there was a short delay of approximately 2 min. Caudal vena caval PGF, concentrations in H/Ox Lutalyse-treated ewes were greater than that after saline injection, which indicates that metabolism may depend on the presence or absence of the uterus and(or) ovaries. In Exp. 1, caudal PGF, concentrations were greater in H/Ox ewes injected with 15 mg of Lutalyse than in ewes in all other treatments . However, in response to 5 mg Lutalyse, caudal PGF_2α concentrations were greater in sham H/Ox ewes than in all other treatment groups. This indicates that the larger dose in H/Ox ewes supersedes the capacity of the lung and kidney to dispose of PGF_2α, and PGF_2α is more tightly regulated in intact ewes. The lungs and kidney are capable of metabolizing the smaller dose of Lutalyse but not the resulting PGF_2α production in intact ewes. A short validation experiment was conducted to determine the effects of sampling location on progesterone, PGF_2α and PGFM concentrations. Sampling location did not affect the mean concentration of progesterone or PGFM. However, location affected the mean PGF_2α concentration. The concentration of PGF_2α, was greater (P < .05) in saphenous vein and caudal vena caval blood plasma than in jugular plasma. In summary, the uterus and(or) ovaries produce and regulate PGF_2α concentration in response to Lutalyse. It is speculated that a threshold PGF_2α concentration or duration of the PGF_2α peak concentration exists because these PGF_2α, responses differed in intact Lutalyse-treated and saline-treated ewes in both experiments. The mean cranial PGF_2α concentration, peak concentration, duration of the peak, increase in PGF_2α and AUC were greater in response to 15 mg of Lutalyse, although the two smaller doses have been shown to be more efficacious in inducing luteolysis. The second dose of PGF_2α may act by mimicking pulses of PGF_2α and initiate the luteolytic cascade two times. / Master of Science

A sensing method that can monitor metallic structures continuously would eventually produce safer metallic structures as well as a more efficient and economic way to monitor corrosion. A secondary focus of this research is the implementation of a fiber optic sensor to measure refractive indices of unknown solutions. The surface plasmon sensor, interrogated with white light resulted in attenuations of light at different wavelengths when solutions of different refractive indices were introduced. This sensor has been shown to respond to the three configurations of polished single mode and multimode, as well as the unpolished multimode sensors. The sensitivity calculated was comparable with the sensitivity of the Kretschmann arrangement The transmissive aluminum-clad fiber sensor was shown to be effective in providing a response to the process of corrosion. Varying lengths of aluminum-clad fiber was spliced to acrylate multimode fiber and different wavelengths of sources were used to test the sensor in a bath of NaOH. The results were similar and reproducible. A tapered sensor configuration was attempted and proved to be very useful. / Master of Science