Ionized cluster beam deposition, and thin film analysis

In 1972 the ionized cluster beam (ICB) deposition technique was introduced as a new method for thin film deposition. At that time the use of clusters was postulated to be able to enhance film nucleation and adatom surface mobility, resulting in high quality films. Although a few researchers reported singly ionized clusters containing 10$\sp2$-10$\sp3$ atoms, others were unable to repeat their work. The consensus now is that film effects in the early investigations were due to self-ion bombardment rather than clusters. Subsequently in recent work (early 1992) synthesis of large clusters of zinc without the use of a carrier gas was demonstrated by Gspann and repeated in our laboratory. Clusters resulted from very significant changes in two source parameters. Crucible pressure was increased from the earlier 2 Torr to several thousand Torr and a converging-diverging nozzle 18 mm long and 0.4 mm in diameter at the throat was used in place of the 1 mm x 1 mm nozzle used in the early work. While this is practical for zinc and other high vapor pressure materials it remains impractical for many materials of industrial interest such as gold, silver, and aluminum. The work presented here describes results using gold and silver at pressures of around 1 and 50 Torr in order to study the effect of the pressure and nozzle shape. Significant numbers of large clusters were not detected. Deposited films were studied by atomic force microscopy (AFM) for roughness analysis, and X-ray diffraction.^ Nanometer size islands of zinc deposited on flat silicon substrates by ICB were also studied by atomic force microscopy and the number of atoms/cm$\sp2$ was calculated and compared to data from Rutherford backscattering spectrometry (RBS). To improve the agreement between data from AFM and RBS, convolution and deconvolution algorithms were implemented to study and simulate the interaction between tip and sample in atomic force microscopy. The deconvolution algorithm takes into account the physical volume occupied by the tip resulting in an image that is a more accurate representation of the surface.^ One method increasingly used to study the deposited films both during the growth process and following, is ellipsometry. Ellipsometry is a surface analytical technique used to determine the optical properties and thickness of thin films. In situ measurements can be made through the windows of a deposition chamber. A method for determining the optical properties of a film, that is sensitive only to the growing film and accommodates underlying interfacial layers, multiple unknown underlayers, and other unknown substrates was developed. This method is carried out by making an initial ellipsometry measurement well past the real interface and by defining a virtual interface in the vicinity of this measurement. ^

Continuous property measurement techniques and physics based mathematical model for frost growth control

The development of a new set of frost property measurement techniques to be used in the control of frost growth and defrosting processes in refrigeration systems was investigated. Holographic interferometry and infrared thermometry were used to measure the temperature of the frost-air interface, while a beam element load sensor was used to obtain the weight of a deposited frost layer. The proposed measurement techniques were tested for the cases of natural and forced convection, and the characteristic charts were obtained for a set of operational conditions. ^ An improvement of existing frost growth mathematical models was also investigated. The early stage of frost nucleation was commonly not considered in these models and instead an initial value of layer thickness and porosity was regularly assumed. A nucleation model to obtain the droplet diameter and surface porosity at the end of the early frosting period was developed. The drop-wise early condensation in a cold flat plate under natural convection to a hot (room temperature) and humid air was modeled. A nucleation rate was found, and the relation of heat to mass transfer (Lewis number) was obtained. It was found that the Lewis number was much smaller than unity, which is the standard value usually assumed for most frosting numerical models. The nucleation model was validated against available experimental data for the early nucleation and full growth stages of the frosting process. ^ The combination of frost top temperature and weight variation signals can now be used to control the defrosting timing and the developed early nucleation model can now be used to simulate the entire process of frost growth in any surface material. ^

Contribution of the vasculature to the Alzheimer's disease process

One of the pathological hallmarks of Alzheimer's disease (AD) brain is extracellular β-amyloid (Aβ) plaques containing 39-42 amino acid Aβ peptides. The deposition of Aβ around blood vessels, known as Cerebral amyloid angiopathy (CAA), is also a common feature in AD brain. Vascular density and cerebral blood flow are reduced in AD brains, and vascular risk factors such as hypertension and diabetes are also risk factors for AD. We have shown previously that Aβ peptides can potently inhibit angiogenesis both in-vitro and in-vivo, but the mechanism of action for this effect is not known. Therefore, my first hypothesis was that particular amino acid sequence(s) within the Aβ peptide are required for inhibition of angiogenesis. From this aim, I found a peptide sequence which was critical for anti-angiogenic activity (HHQKLVFF). This sequence contains a heparan sulfate proteoglycan growth factor binding domain implying that Aβ can interfere with growth factor signaling. Leading on from this, my second hypothesis was that Aβ can inhibit angiogenesis by binding to growth factor receptors. I found that Aβ can bind to Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2), and showed that this is one mechanism by which Aβ can inhibit angiogenesis. Since the vasculature is disrupted in AD brains, I investigated whether a strategy to increase brain vascularization would be beneficial against AD pathology. Therefore, my third hypothesis was that voluntary exercise (which is known to increase brain vascularization in rodents) can ameliorate Aβ pathology, increase brain vascularization, and improve behavioral deficits in a transgenic mouse model of AD. I found that exercise has no effect on Aβ pathology, brain vascularization or behavioral deficits. Therefore, in the transgenic mouse model that I used, exercise is an ineffective therapeutic strategy against AD pathology and symptoms.

Comprehensive process maps for synthesizing high density aluminum oxide-carbon nanotube coatings by plasma spraying for improved mechanical and wear properties

Plasma sprayed aluminum oxide ceramic coating is widely used due to its outstanding wear, corrosion, and thermal shock resistance. But porosity is the integral feature in the plasma sprayed coating which exponentially degrades its properties. In this study, process maps were developed to obtain Al2O3-CNT composite coatings with the highest density (i.e. lowest porosity) and improved mechanical and wear properties. Process map is defined as a set of relationships that correlates large number of plasma processing parameters to the coating properties. Carbon nanotubes (CNTs) were added as reinforcement to Al2O 3 coating to improve the fracture toughness and wear resistance. Two novel powder processing approaches viz spray drying and chemical vapor growth were adopted to disperse CNTs in Al2O3 powder. The degree of CNT dispersion via chemical vapor deposition (CVD) was superior to spray drying but CVD could not synthesize powder in large amount. Hence optimization of plasma processing parameters and process map development was limited to spray dried Al2O3 powder containing 0, 4 and 8 wt. % CNTs. An empirical model using Pareto diagram was developed to link plasma processing parameters with the porosity of coating. Splat morphology as a function of plasma processing parameter was also studied to understand its effect on mechanical properties. Addition of a mere 1.5 wt. % CNTs via CVD technique showed ∼27% and ∼24% increase in the elastic modulus and fracture toughness respectively. Improved toughness was attributed to combined effect of lower porosity and uniform dispersion of CNTs which promoted the toughening by CNT bridging, crack deflection and strong CNT/Al2O3 interface. Al2O 3-8 wt. % CNT coating synthesized using spray dried powder showed 73% improvement in the fracture toughness when porosity reduced from 4.7% to 3.0%. Wear resistance of all coatings at room and elevated temperatures (573 K, 873 K) showed improvement with CNT addition and decreased porosity. Such behavior was due to improved mechanical properties, protective film formation due to tribochemical reaction, and CNT bridging between the splats. Finally, process maps correlating porosity content, CNT content, mechanical properties, and wear properties were developed.

Professional Growth and Performance Appraisals of School Administrators: A Contemporary Model

A sound performance appraisal process for school administrators contains key components in accordance with legislation, board policy and contractual agreements. This paper examines the performance appraisal process for administrators in one Canadian school district that may serve as a guideline for individual educators who are committed with on-going professional development.

Reactive Oxygen Species via Redox Signaling to PI3K/AKT Pathway Contribute to the Malignant Growth of 4-Hydroxy Estradiol-Transformed Mammary Epithelial Cells

The purpose of this study was to investigate the effects of 17-β-estradiol (E2)-induced reactive oxygen species (ROS) on the induction of mammary tumorigenesis. We found that ROS-induced by repeated exposures to 4-hydroxy-estradiol (4-OH-E2), a predominant catechol metabolite of E2, caused transformation of normal human mammary epithelial MCF-10A cells with malignant growth in nude mice. This was evident from inhibition of estrogen-induced breast tumor formation in the xenograft model by both overexpression of catalase as well as by co-treatment with Ebselen. To understand how 4-OH-E2 induces this malignant phenotype through ROS, we investigated the effects of 4-OH-E2 on redox-sensitive signal transduction pathways. During the malignant transformation process we observed that 4-OH-E2 treatment increased AKT phosphorylation through PI3K activation. The PI3K-mediated phosphorylation of AKT in 4-OH-E2-treated cells was inhibited by ROS modifiers as well as by silencing of AKT expression. RNA interference of AKT markedly inhibited 4-OH-E2-induced in vitro tumor formation. The expression of cell cycle genes, cdc2, PRC1 and PCNA and one of transcription factors that control the expression of these genes – nuclear respiratory factor-1 (NRF-1) was significantly up-regulated during the 4-OH-E2-mediated malignant transformation process. The increased expression of these genes was inhibited by ROS modifiers as well as by silencing of AKT expression. These results indicate that 4-OH-E2-induced cell transformation may be mediated, in part, through redox-sensitive AKT signal transduction pathways by up-regulating the expression of cell cycle genes cdc2, PRC1 and PCNA, and the transcription factor – NRF-1. In summary, our study has demonstrated that: (i) 4-OH-E2 is one of the main estrogen metabolites that induce mammary tumorigenesis and (ii) ROS-mediated signaling leading to the activation of PI3K/AKT pathway plays an important role in the generation of 4-OH-E2-induced malignant phenotype of breast epithelial cells. In conclusion, ROS are important signaling molecules in the development of estrogen-induced malignant breast lesions.

Site specific growth of metal catalyzed silica nanowires for biological and chemical sensing

In this research the integration of nanostructures and micro-scale devices was investigated using silica nanowires to develop a simple yet robust nanomanufacturing technique for improving the detection parameters of chemical and biological sensors. This has been achieved with the use of a dielectric barrier layer, to restrict nanowire growth to site-specific locations which has removed the need for post growth processing, by making it possible to place nanostructures on pre-pattern substrates. Nanowires were synthesized using the Vapor-Liquid-Solid growth method. Process parameters (temperature and time) and manufacturing aspects (structural integrity and biocompatibility) were investigated. Silica nanowires were observed experimentally to determine how their physical and chemical properties could be tuned for integration into existing sensing structures. Growth kinetic experiments performed using gold and palladium catalysts at 1050°C for 60 minutes in an open-tube furnace yielded dense and consistent silica nanowire growth. This consistent growth led to the development of growth model fitting, through use of the Maximum Likelihood Estimation (MLE) and Bayesian hierarchical modeling. Transmission electron microscopy studies revealed the nanowires to be amorphous and X-ray diffraction confirmed the composition to be SiO2 . Silica nanowires were monitored in epithelial breast cancer media using Impedance spectroscopy, to test biocompatibility, due to potential in vivo use as a diagnostic aid. It was found that palladium catalyzed silica nanowires were toxic to breast cancer cells, however, nanowires were inert at 1μg/mL concentrations. Additionally a method for direct nanowire integration was developed that allowed for silica nanowires to be grown directly into interdigitated sensing structures. This technique eliminates the need for physical nanowire transfer thus preserving nanowire structure and performance integrity and further reduces fabrication cost. Successful nanowire integration was physically verified using Scanning electron microscopy and confirmed electrically using Electrochemical Impedance Spectroscopy of immobilized Prostate Specific Antigens (PSA). The experiments performed above serve as a guideline to addressing the metallurgic challenges in nanoscale integration of materials with varying composition and to understanding the effects of nanomaterials on biological structures that come in contact with the human body.

Site Specifc Growth of Metal Catalyzed Silica Nanowires for Biological and Chemical Sensing

In this research the integration of nanostructures and micro-scale devices was investigated using silica nanowires to develop a simple yet robust nanomanufacturing technique for improving the detection parameters of chemical and biological sensors. This has been achieved with the use of a dielectric barrier layer, to restrict nanowire growth to site-specific locations which has removed the need for post growth processing, by making it possible to place nanostructures on pre-pattern substrates. Nanowires were synthesized using the Vapor-Liquid-Solid growth method. Process parameters (temperature and time) and manufacturing aspects (structural integrity and biocompatibility) were investigated. Silica nanowires were observed experimentally to determine how their physical and chemical properties could be tuned for integration into existing sensing structures. Growth kinetic experiments performed using gold and palladium catalysts at 1050 ˚C for 60 minutes in an open-tube furnace yielded dense and consistent silica nanowire growth. This consistent growth led to the development of growth model fitting, through use of the Maximum Likelihood Estimation (MLE) and Bayesian hierarchical modeling. Transmission electron microscopy studies revealed the nanowires to be amorphous and X-ray diffraction confirmed the composition to be SiO2 . Silica nanowires were monitored in epithelial breast cancer media using Impedance spectroscopy, to test biocompatibility, due to potential in vivo use as a diagnostic aid. It was found that palladium catalyzed silica nanowires were toxic to breast cancer cells, however, nanowires were inert at 1µg/mL concentrations. Additionally a method for direct nanowire integration was developed that allowed for silica nanowires to be grown directly into interdigitated sensing structures. This technique eliminates the need for physical nanowire transfer thus preserving nanowire structure and performance integrity and further reduces fabrication cost. Successful nanowire integration was physically verified using Scanning electron microscopy and confirmed electrically using Electrochemical Impedance Spectroscopy of immobilized Prostate Specific Antigens (PSA). The experiments performed above serve as a guideline to addressing the metallurgic challenges in nanoscale integration of materials with varying composition and to understanding the effects of nanomaterials on biological structures that come in contact with the human body.