Glucagon-like peptide-2 (GLP-2) is an intestinotrophic and intestinal anti-inflammatory hormone. Hence, I hypothesized that treatment with degradation-resistant hGly2GLP-2 increases, while blocking endogenous GLP-2 decreases colorectal cancer (CRC) in rodents. In mice, treatment with dextran sodium sulphate (DSS) and azoxymethane (AOM) induced colitis-associated CRC, which was further increased by treatment with hGly2GLP-2 and reduced by blocking endogenous GLP-2 with the antagonist hGLP-23-33. Moreover, while colonic damage score (CDS) was not altered by hGly2GLP-2 or hGLP-23-33 treatment, hGly2GLP-2 increased small intestinal growth and hGLP-23-33 reduced jejunal crypt cell proliferation. In rats fed with of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and high fat (HF) diet for aberrant crypt foci (ACF) induction, treatment with hGly2GLP-2 increased small intestinal growth and ACF occurrence. Moreover, in rats fed with PhIP-HF diet for tumour induction, early treatment with hGly2GLP-2 appears to increase the occurrence of intestinal tumours. Collectively, these findings indicate a pro-carcinogenic role for both exogenous and endogenous GLP-2.

Shiga-like toxin 1 (SLT-1) is produced by Escherichia coli strains like the pathogenic strain O157:H7. These bacterial strains are responsible for worldwide cases of food poisoning and water contamination, and the toxin is a major cause of hemorrhagic colitis and the hemolytic uremia syndrome. SLT-1 is defined as a type II ribosome-inactivating protein (RIP) and belongs to a family of plant and bacterial AB toxins. The A1 chain blocks protein synthesis in eukaryotic cells by depurinating a single adenine base in 28S rRNA. The mechanisms by which the A chain of SLT-1 interacts with the host components to route itself to the cytosol remains largely unknown. This thesis project identified a list of putative cellular proteins that interact with the SLT-1 A1 chain by the use of yeast-2-hybrid (Y2H) screens and HeLa lysate pull down/mass spectrometry analyses. Further assessment of the top 8 host interactors did not yield true interactions.

An earlier approach to restore homeostatic levels of ECM degrading matrix metalloproteases (MMPs) by the Sefton Lab utilized hydroxamate-based MMP inhibitory (MI) beads. While the MI beads delayed ECM degradation in the context of skin wound healing, they caused elevated cell infiltration in a subcutaneous implant model. The primary goal of this project was to further investigate this finding using an air pouch implant model in mice and a different control group – methacrylic acid-based (MAA) beads. Exudate analysis indicated that the MI beads, implanted subcutaneously with gelatin discs, elicited a similar biological response as the MAA beads. Exudates corresponding to both biomaterials had similar cell counts and chemokine levels, which were greater than those corresponding to the control used earlier, poly-methyl methacrylate-based (PMMA) beads. Further, both MI and MAA beads activated infiltrating macrophages in the classical manner, and influenced the activity of an MMP8 catalytic domain in a similar manner.

Glucagon-like peptide-2 (GLP-2) is an intestinotrophic and intestinal anti-inflammatory hormone. Hence, I hypothesized that treatment with degradation-resistant hGly2GLP-2 increases, while blocking endogenous GLP-2 decreases colorectal cancer (CRC) in rodents. In mice, treatment with dextran sodium sulphate (DSS) and azoxymethane (AOM) induced colitis-associated CRC, which was further increased by treatment with hGly2GLP-2 and reduced by blocking endogenous GLP-2 with the antagonist hGLP-23-33. Moreover, while colonic damage score (CDS) was not altered by hGly2GLP-2 or hGLP-23-33 treatment, hGly2GLP-2 increased small intestinal growth and hGLP-23-33 reduced jejunal crypt cell proliferation. In rats fed with of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and high fat (HF) diet for aberrant crypt foci (ACF) induction, treatment with hGly2GLP-2 increased small intestinal growth and ACF occurrence. Moreover, in rats fed with PhIP-HF diet for tumour induction, early treatment with hGly2GLP-2 appears to increase the occurrence of intestinal tumours. Collectively, these findings indicate a pro-carcinogenic role for both exogenous and endogenous GLP-2.

Shiga-like toxin 1 (SLT-1) is produced by Escherichia coli strains like the pathogenic strain O157:H7. These bacterial strains are responsible for worldwide cases of food poisoning and water contamination, and the toxin is a major cause of hemorrhagic colitis and the hemolytic uremia syndrome. SLT-1 is defined as a type II ribosome-inactivating protein (RIP) and belongs to a family of plant and bacterial AB toxins. The A1 chain blocks protein synthesis in eukaryotic cells by depurinating a single adenine base in 28S rRNA. The mechanisms by which the A chain of SLT-1 interacts with the host components to route itself to the cytosol remains largely unknown. This thesis project identified a list of putative cellular proteins that interact with the SLT-1 A1 chain by the use of yeast-2-hybrid (Y2H) screens and HeLa lysate pull down/mass spectrometry analyses. Further assessment of the top 8 host interactors did not yield true interactions.

Plk4 is the most divergent member of the family of polo like kinases (Plks). Plk4-/- embryos arrest at approximately day 7.5 p.c. but Plk4+/- mice are viable and fertile. However, 50% of Plk4+/- mice develop spontaneous tumours of the liver, lung and soft tissues by 2 years of age. Here I investigate the mechanisms that underlie Plk4-related tumourigenesis. Plk4+/- murine embryonic fibroblasts (MEFs) spontaneously become immortal in vitro with increasing passage number and are tumourigenic in vivo when injected into NOD SCID mice. Cytogenetic analysis showed that Plk4 deficient cells are chromosomally unstable with a large number of chromosomal aberrations and increased ploidy. These results demonstrate that early loss of a single Plk4 allele is sufficient to drive cell immortalization, chromosomal instability and tumourigenicity in vivo. In two independent expression array analyses, gene expression patterns that would decrease cell migration were overrepresented in Plk4+/- MEFs. A series of spreading and migration assays functionally validated these results, supporting the hypothesis that Plk4 regulates cell motility. Endogenous Plk4 localized to filopodia and lamellipodia in motile cells and to protrusions of spreading cells; the latter localization was transient and it disappeared by 4h after cell seeding, at which point Plk4 was located in the centrosomes, as typically observed in interphase cells. Transient transfection with Flag-Plk4 enhanced spreading and migration, as well as actin remodeling. Taken together, these data demonstrate temporal regulation of Plk4 in relation to the process of membrane remodeling, and a functional role for Plk4 in cell motility. Plk4 is haploinsufficient for tumour suppression in mice. Plk4 is located at human chromosome 4q28, a region often deleted in primary liver cancer specimens. Here I show that loss-of-heterozygosity (LOH) occurs at the Plk4 locus in ≈50% of human hepatocellular carcinomas (HCC) as well as in preneoplastic cirrhotic liver nodules. LOH at Plk4 is associated with reduced Plk4 expression in HCC tumours, but not with mutations in the remaining allele. These results implicate Plk4 as a potential haploinsufficient tumour suppressor in the genesis of human HCC. With continuing high rates of the predisposing conditions Hepatitis B and non-alcoholic steatohepatitis, and delayed diagnosis, HCC is a global health issue and carries a grave prognosis. A better understanding of genetic predisposition will help guide future screening programs.

Plk4 is the most divergent member of the family of polo like kinases (Plks). Plk4-/- embryos arrest at approximately day 7.5 p.c. but Plk4+/- mice are viable and fertile. However, 50% of Plk4+/- mice develop spontaneous tumours of the liver, lung and soft tissues by 2 years of age. Here I investigate the mechanisms that underlie Plk4-related tumourigenesis. Plk4+/- murine embryonic fibroblasts (MEFs) spontaneously become immortal in vitro with increasing passage number and are tumourigenic in vivo when injected into NOD SCID mice. Cytogenetic analysis showed that Plk4 deficient cells are chromosomally unstable with a large number of chromosomal aberrations and increased ploidy. These results demonstrate that early loss of a single Plk4 allele is sufficient to drive cell immortalization, chromosomal instability and tumourigenicity in vivo. In two independent expression array analyses, gene expression patterns that would decrease cell migration were overrepresented in Plk4+/- MEFs. A series of spreading and migration assays functionally validated these results, supporting the hypothesis that Plk4 regulates cell motility. Endogenous Plk4 localized to filopodia and lamellipodia in motile cells and to protrusions of spreading cells; the latter localization was transient and it disappeared by 4h after cell seeding, at which point Plk4 was located in the centrosomes, as typically observed in interphase cells. Transient transfection with Flag-Plk4 enhanced spreading and migration, as well as actin remodeling. Taken together, these data demonstrate temporal regulation of Plk4 in relation to the process of membrane remodeling, and a functional role for Plk4 in cell motility. Plk4 is haploinsufficient for tumour suppression in mice. Plk4 is located at human chromosome 4q28, a region often deleted in primary liver cancer specimens. Here I show that loss-of-heterozygosity (LOH) occurs at the Plk4 locus in ≈50% of human hepatocellular carcinomas (HCC) as well as in preneoplastic cirrhotic liver nodules. LOH at Plk4 is associated with reduced Plk4 expression in HCC tumours, but not with mutations in the remaining allele. These results implicate Plk4 as a potential haploinsufficient tumour suppressor in the genesis of human HCC. With continuing high rates of the predisposing conditions Hepatitis B and non-alcoholic steatohepatitis, and delayed diagnosis, HCC is a global health issue and carries a grave prognosis. A better understanding of genetic predisposition will help guide future screening programs.

The central theme of this thesis is to prove results about infinite mathematical objects by studying the behaviour of their finite substructures. In particular, we study B-matroids, which are an infinite generalization of matroids introduced by Higgs \cite{higgs}, and graph-like spaces, which are topological spaces resembling graphs, introduced by Thomassen and Vella \cite{thomassenvella}. Recall that the circuit matroid of a finite graph is a matroid defined on the edges of the graph, with a set of edges being independent if it contains no circuit. It turns out that graph-like continua and infinite graphs both have circuit B-matroids. The first main result of this thesis is a generalization of Whitney's Theorem that a graph has an abstract dual if and only if it is planar. We show that an infinite graph has an abstract dual (which is a graph-like continuum) if and only if it is planar, and also that a graph-like continuum has an abstract dual (which is an infinite graph) if and only if it is planar. This generalizes theorems of Thomassen (\cite{thomassendual}) and Bruhn and Diestel (\cite{bruhndiestel}). The difficult part of the proof is extending Tutte's characterization of graphic matroids (\cite{tutte2}) to finitary or co-finitary B-matroids. In order to prove this characterization, we introduce a technique for obtaining these B-matroids as the limit of a sequence of finite minors. In \cite{tutte}, Tutte proved important theorems about the peripheral (induced and non-separating) circuits of a $3$-connected graph. He showed that for any two edges of a $3$-connected graph there is a peripheral circuit containing one but not the other, and that the peripheral circuits of a $3$-connected graph generate its cycle space. These theorems were generalized to $3$-connected binary matroids by Bixby and Cunningham (\cite{bixbycunningham}). We generalize both of these theorems to $3$-connected binary co-finitary B-matroids. Richter, Rooney and Thomassen \cite{richterrooneythomassen} showed that a locally connected, compact metric space has an embedding in the sphere unless it contains a subspace homeomorphic to $K_5$ or $K_{3,3}$, or one of a small number of other obstructions. We are able to extend this result to an arbitrary surface $\Sigma$; a locally connected, compact metric space embeds in $\Sigma$ unless it contains a subspace homeomorphic to a finite graph which does not embed in $\Sigma$, or one of a small number of other obstructions.

<p>Biomass derived oil (BDO) reforming with CO2 was carried out at 800oC under atmospheric pressure in a tubular fixed bed vertical reactor packed with quartz particles. The feed gas was a mixture of CO2 and N2 at various compositions with a flow rate of 30 to 60 cm3/min. The BDO flow rate was 5 g/h. The product gas consisted mostly of H2, CO, CO2, CH4 and C2H4.</p><p>The maximum production of synthesis gas (~76 mol%) was observed at a total carrier gas flow rate of 60 cm3/min and a mole fraction of CO2 in carrier gas of 0.1. Maximum hydrogen (42 mol%) and H2 to CO molar ratio (1.44) were obtained while using only N2 as the carrier gas at a flow rate of 50 cm3/min. In the range of residence time considered, CO2 was not consumed in BDO gasification at 800oC but helped to increase gas production at the expense of the char.</p><p>Pyrolysis of lard was performed to produce a diesel-like liquid and a high heating value gaseous fuel. Lard was fed into the reactor at 5 g/h using N2 (10-70 cm3/min) as carrier gas. Two particle size ranges of quartz particles (0.7-1.4 and 1.7-2.4 mm) were used as reactor packing material. The liquid product essentially consisted of linear and cyclic alkanes and alkenes, aromatics, ketones, aldehydes and carboxylic acids. The maximum yield for diesel-like liquid product (37g/100g lard) was obtained at 600oC, residence time of 1.5 s and packing particle size of 1.7- 2.4 mm. The liquid product obtained at 600oC, carrier gas flow rate of 50 cm3/min and quartz packing particle size of 0.7-1.4 mm has a cetane index of 46, specific gravity of 0.86, a heating value of 40 MJ/kg and cloud and pour points of 10 and -18 respectively. The heating value of the product gas ranged between 68 and 165 MJ/m3. This study shows that there is a potential for producing diesel-like liquid from pyrolysis of lard. It also identifies the pyrolysis of animal fats as a source of high heating value gaseous fuel.</p><p>Steam reforming of lard was performed at 500, 550, 600 and 800oC and at steam to lard mass ratios of 0.5 to 2.0. The maximum diesel-like liquid yield from the steam reforming process (39 g/100g of lard) was obtained at a steam to lard ratio of 1.5 and a temperature of 600oC. Higher cetane index (52) and lower viscosity (4.0 mPa.s at 40oC) were obtained by addition of steam. The net energy recovered from pyrolysis and steam reforming processes were 21.7and 21.9 kJ/g of lard respectively. Thus, the processes are energy efficient.</p><p>In comparison, lard is a better feedstock for the production of hydrogen, char, high heating value gas and high H2/CO ratio than BDO. On the other hand, BDO is the preferred feedstock for the production of synthesis gas with H2/CO in the vicinity of 1.</p>

In high-speed digital circuits, in order to utilize the space of printed circuit boards(PCB) efficiently, the signal via is a heavily used interconnection structure to communicate different signal layers. However, because of vias are small and irregular structure in the PCB. When we try to simulate these problems with traditional FDTD method. We must using more fine grid to approximate the structure, so it will take a lot CPU memory and computing times. In this author, we try to combine FDTD and FVTD method. Take FVTD method in these partial small structure and magnify grid in a ratio. Finally, combine the larger FDTD grid to achieve reducing the numbers of grids that will save CPU memory and raise computing speed. In addition, we will present another solution that shifting via to replace using small size via based on a method that is using cascaded EBG structure achieve broadband effects to cost down.