COMPUTATIONAL ANALYSES OF THE UPTAKE AND DISTRIBUTION OF CARBON MONOXIDE (CO) IN HUMAN SUBJECTS

Carbon monoxide (CO) is an odorless, colorless, tasteless gas that binds to hemoglobin with high affinity. This property underlies the use of low doses of CO to determine hemoglobin mass (MHb) in the fields of clinical and sports medicine. However, hemoglobin bound to CO is unable to transport oxygen and exposure to high CO concentrations is a significant environmental and occupational health concern. These contrasting aspects of CO—clinically useful in low doses but potentially lethal in higher doses—mandates a need for a quantitative understanding of the temporal profiles of the uptake and distribution of CO in the human body. In this dissertation I have (i) used a mathematical model to analyze CO-rebreathing techniques used to estimate total hemoglobin mass and proposed a CO-rebreathing procedure to estimate hemoglobin mass with low errors, (ii) enhanced and validated a multicompartment model to estimate O2, CO and CO2 tensions, bicarbonate levels, pH levels, blood carboxyhemoglobin (HbCO) levels, and carboxymyoglobin (MbCO) levels in all the vascular (arterial, mixed venous and vascular subcompartments of the tissues) and tissue (brain, heart and skeletal muscle) compartments of the model in normoxia, hypoxia, CO hypoxia, hyperoxia, isocapnic hyperoxia and hyperbaric oxygen, and (iii) used this developed mathematical model to propose a treatment to improve O2 delivery and CO removal by comparing O2 and CO levels during different treatment protocols administered for otherwise-healthy CO-poisoned subjects

Cloning and Expression of Cytochrome P450\u3csub\u3ecam\u3c/sub\u3e

Polyaromatic hydrocarbons (PAHs) are ubiquitously present in the environment and have deleterious affects on humans. Cytochrome P450 enzymes have been found to be useful in the biodegradation of the PAHs through an initial hydroxylation step. This makes them more water-soluble and accessible to the action of other oxidases. Cytochrome P450cam is a model P450 enzyme that has been mutated for enabling PAH and alkane hydroxylation. P450s therefore have potential for use in commercial process for production of primary alcohols. Rhodococcus organisms have a special mechanism for transporting the hydrophobic hydrocarbons into their cells. Cloning of the P450cam gene into Rhodococcus can potentially provide a hydroxylation system with high conversion rates. To enable this, cytochrome P450cam gene (CYP101) was cloned into a Rhodococcus-Escherichia coli shuttle vector. This would provide tools to modify the gene and target specific PAHs. This study is aimed at developing a Rhodococcus-based biocatalyst using cytochrome P450 enzymes. The cytochrome P450cam gene was synthesized using PCR (polymerase chain reaction); the product was cloned into pKSD6-1 (a Rhodococcus-Escherichia coli shuttle vector) and transformed into Escherichia coli. The recombinant protein in Escherichia coli was produced by induction and the protein extract was analyzed using spectrophotometric analysis, camphor binding and carbon monoxide binding assays. The results showed a Soret band at 414nm but no carbon monoxide or substrate binding was observed. The control culture grown under similar conditions with only the pKSD6-1 gene did not show any absorption band at 414nm. These results together indicate that the gene has been cloned into the recombinant plasmid, but the enzyme being produced might be in an inactive form

Modeling of vias and via arrays in high speed printed circuit boards

This thesis presents modeling approaches for fast calculation of signals in dense via arrays in high speed printed circuit boards (PCBs) and model to hardware correlation study of solid and perforated disk resonators. A 2D finite difference (FD) method to extract the via capacitance which includes the via pad capacitance obtained by solving the laplace equation in the via domain in multi-layer geometries is presented and validated with analytical formulation for via capacitance. Next, closed-form expression for the impedance of an infinitely large parallel plane pair is derived and validated by comparing with cavity model for several numerical examples. The infinitely large parallel plane pair model is applicable to practical printed circuit board (PCB) design problems where there are multiple shorting vias around the signal vias of interest. With the presence of multiple shorting vias, reflections from the plane pair edges can be neglected since the shorting vias prevent the electromagnetic energy from leaking away from the local cavity around the signal vias. Next, improved multiple scattering method for fast calculation of signals in via arrays in plane pair is derived using analytical expressions. Parallel plate modes expressed as cylindrical waves are excited by the magnetic frill currents in via holes (antipads). Multiple scattering of these modes among vias as well as from the edge boundaries of the plate pair are rigorously considered with the addition theorem of the cylindrical waves. In the final part of this thesis, different approaches mentioned here are applied to study solid and perforated disk resonator behaviors and to correlate the simulated and measured results --Abstract, page iii

Modeling and estimation of crosstalk across a channel with multiple, non-parallel coupling and crossings of multiple aggressors in practical PCBS

In Section 1, the focus is on alleviating the modeling challenges by breaking the overall geometry into small, unique sections and using either a Full-Wave or fast equivalent per-unit-length (Eq. PUL) resistance, inductance, conductance, capacitance (RLGC) method or a partial element equivalent circuit (PEEC) for the broadside coupled traces that cross at an angle. The simulation challenge is resolved by seamlessly integrating the models into a statistical simulation tool that is able to quantify the eye opening at BERs that would help electrical designers in locating crosstalk sensitive regions in the high speed backplane channel designs. Section 2 investigates the FEXT crosstalk impact on eye opening at a specified bit error rate (BER) at different signal speeds for broadside and edge side differential coupled traces in inhomogeneous media and compared the results against homogeneous media models. A set of design guidelines regarding the material, coupled length and stackup parameter selection is formulated for designers based on the signaling speeds. The major objective of the study in Section 3 is to determine quantitatively the effect of crosstalk due to periodic broadside coupled routing. Another objective is to help designers figure out the “dos” and “don’ts” of broadside coupled routing for higher signaling rates. A new methodology is proposed in Section 4 to generate BER contours that capture the Tx driver jitter and ISI through the channel accurately using unique waveforms created from truth table bit combinations. It utilizes 2N short N bit patterns as waveforms and jitter correlation from current bit pattern into adjacent bit patterns to get equivalent transient simulation of a very large bit pattern. --Abstract, page iii

Manufacturing, Evaluation and Field Implementation of Recycled GFRP-Composite Railroad Ties

Wood railroad crossties resistance to current higher axle loads, speeds and frequency, along with the durability under harsh environments has proven to be inadequate. Additionally, defects such as decay, holes, splits, checks etc may further impair the strength and durability characteristics of the wood crossties. In this project, recycled polymer and discarded wood were used to increase the performance characteristics of the RR tie including resistance to higher axle loads, minimization of defects, and better performance under harsh environmental conditions. The objective of this study is to enhance and assess the strength characteristics of the timber crossties by using the glass fiber reinforced polymer (GFRP) composite shell. This research involved two different techniques for manufacturing the recycled composite ties, followed by laboratory testing of wood ties and GFRP recycled composite shell with wood core ties (thermoplastic) in WVU-CFC. The previous research program at WVU-CFC consisted of strengthening and evaluating the wood crossties by wrapping only the 12 inches wide steel plate embedment location using glass fiber fabrics saturated with resorcinol formaldehyde resin (thermoset).;In this research, over 200 recycled composite components were manufactured in the CFC laboratory that were used to mold 24 full-scale recycled composite ties with wood as a core material and GFRP composite as a shell material. The GFRP composite shell was manufactured using glass fabric reinforcement and Acrylonitrile Butadiene Styrene (ABS) resin. Two different fiber configurations were used in the manufacturing process-I (composite ties manufactured using twelve composite parts). Recycled composite ties produced under manufacturing process-I were tested under three point bending to evaluate the flexural rigidity. Test results of recycled composite ties from manufacturing process-I having fabric configuration-I were compared with those having fabric configuration-II. Further, recycled composite tie from manufacturing process-II (composite ties manufactured using two composite parts) along with wood crossties were tested under three point bending to evaluate the flexural rigidity, modulus of rupture, and static bending strength. Recycled composite ties showed higher static bending strength by approximately sixty percent than wood ties. Recycled composite ties also showed higher spike insertion and pullout strengths than the wood ties.;In order to study the dynamic response, a full-scale recycled composite tie produced through manufacturing process-II was embedded in gravel ballast and tested under flexural fatigue. The measured maximum deflection and applied bending moment values were compared with the theoretical values based on the classical beams on elastic foundation theory. The theoretical values were found to correlate well with the experimental values (within 10%). The research also included field testing of seven recycled composite ties on the South Branch Valley Railroad (SBVR) in Moorefield, WV. After three months of service, three ties with low fiber/fabric content showed localized horizontal cracking or some transverse cracks and the remaining four ties showed good field performance. Additional ties manufactured under this project are planned to be field-tested at TTCI, Pueblo, Colorado, test facilities. Conclusions and recommendations from this research work are summarized at the end of this report