No / This paper studies the selective maintenance problem for multi-state series systems working in variable loading conditions in the next mission. In the mission, a component's degradation depends on its current state and the load applied on it. A load-dependent degradation model is proposed for multi-state components operating in variable loading conditions. This model is inspired by the load-sharing model where many components share a common workload and the failure rate of a component depends on the state of other components. A Monte-Carlo simulation method is presented to simulate the multi-state component's degradation and to evaluate the system reliability. The final objective is to determine the best selective maintenance strategy to maximize the expected system reliability in the next mission within available resources. An illustrative example, reliability estimation results, and analysis of optimal selective maintenance scenarios for different levels of budget limitation are provided.

No / This paper studies the selective maintenance problem for multi-state systems with structural dependence. Each component can be in one of multiple working levels and several maintenance actions are possible to a component in a maintenance break. The components structurally form multiple hierarchical levels and dependence groups. A directed graph is used to represent the precedence relations of components in the system. A selective maintenance optimization model is developed to maximize the system reliability in the next mission under time and cost constraints. A backward search algorithm is used to determine the assembly sequence for a selective maintenance scenario. The maintenance model helps maintenance managers in determining the best combination of maintenance activities to maximize the probability of successfully completing the next mission. Examples showing the use of the proposed method are presented.

Yes / This paper presents a study on selective maintenance for multi-state series-parallel systems with economically dependent components. In the selective maintenance problem, the maintenance manager has to decide which components should receive maintenance activities within a finite break between missions. All the system reliabilities in the next operating mission, the available budget and the maintenance time for each component from its current state to a higher state are taken into account in the optimization models. In addition, the components in series-parallel systems are considered to be economically dependent. Time and cost savings will be achieved when several components are simultaneously repaired in a selective maintenance strategy. As the number of repaired components increases, the saved time and cost will also increase due to the share of setting up between components and another additional reduction amount resulting from the repair of multiple identical components. Different optimization models are derived to find the best maintenance strategy for multi-state series-parallel systems. A genetic algorithm is used to solve the optimization models. The decision makers may select different components to be repaired to different working states based on the maintenance objective, resource availabilities and how dependent the repair time and cost of each component are. © 2013 Elsevier Ltd. All rights reserved. / Natural Sciences and Engineering Research Council of Canada (NSERC) and Vietnam International Education Development (VIED)

Yes / In this paper, we will consider the selective maintenance problem for multistate series systems with stochastic dependent components. In multistate systems, the health state of a component may vary from perfect functioning to complete failure. The stochastic dependence (S-dependence) between components is discussed and categorized into two types in multistate context. First, the failure of a component can immediately cause complete failures of some other components in the system. Second, as components deteriorate, the reduced working performance rate of a multistate component affects the state as well as the degradation rate of its subsequent components in series structure. The system reliability is evaluated using an approach based on stochastic process. A cost-based selective maintenance model is developed for the multistate system with S-dependent components to maximize the total system profit, which includes the production gain and loss in the next mission as well as possible maintenance costs for the system. Analyses of systems with independent and dependent components are provided. It is observed that ignoring S-dependence in the system may lead to alternative maintenance decision making and an optimistic estimation of the system performance.

Yes / Harnessing the differences between cancer and non-cancer tissues presents new opportunities for selective targeting by anti-cancer drugs. CD13, a heavily glycosylated protein, is one example with significant unmetclinical potential in cancer drug discovery. Despite its high expression and activity in cancers, CD13 is also expressed in many normal tissues. Here, we report differential tissue glycosylation of CD13 across tissues and demonstrate for the first time that the nature and pattern of glycosylation of CD13 in preclinical cancer tissues are distinct compared to normal tissues. We identify cancer-specific O-glycosylation of CD13, which selectively blocks its detection in cancer models but not in normal tissues. In addition, the metabolism activity of cancer-expressed CD13 was observed to be critically dependent on its unique glycosylation. Thus, our data demonstrate the existence of discrete cancer-specific CD13 glycoforms and propose cancer-specific CD13 glycoforms as a clinically useful target for effective cancer-targeted therapy.

My graduate work focused on the syntheses and pharmacology of species-selective aryl methylcarbamate acetylcholinesterase inhibitors to combat the malaria-transmitting mosquito, Anopheles gambiae. We identified six novel carbamates that demonstrated levels of target selectivity exceeding our project milestone of 100-fold. Among the C2-substituted phenylcarbamates examined (class II), 2'-(2- ethylbutoxy)phenyl N-methylcarbamate (9bd*) was extraordinarily selective (570-fold ± 72). The high level of selectivity observed for many of the class II carbamates was attributed to a helical displacement within the active site of An. gambiae acetylcholinesterase, able to accommodate carbamates with larger C2-substituted secondary β-branching side chains. Conversely, this type of side chain forms unfavorable interactions within the active site of human acetylcholinesterase. The C3-substituted carbamates (class I), such as terbam (9c), were less selective than many of the class II carbamates; however, class I carbamates related to terbam (9c) were highly toxic to An. gambiae. In particular, the contact toxicity measured for 9c (LC₅₀ = 0.037 mg/mL) was equal to the commonly used agricultural insecticide, propoxur (9a, LC₅₀ = 0.037 mg/mL). In total, seventy aryl carbamates were screened for their inhibition potency and contact toxicity towards An. gambiae. The common final step in all of these syntheses was the carbamoylation of a phenol, which normally proceeded in a 70 to 90% yield. Thirty seven novel carbamates are reported out of the seventy two prepared. Although sixteen of the phenols were commercially available, the others were prepared with known and adapted synthetic methodologies. The emerging structure-activity relationships led us to focus on the synthesis of 3-tert-alkylphenols (Class I) and 2-alkoxy or 2-alkylthio-substituted phenols (Class II). Three methods particularly stand out: First, we applied the methods of Tanaka to prepare 3-tert-alkylphenols wherein a methyl group was replaced by a trifluoromethyl group. Second, we adapted the methods of Tanaka to prepare 3-tert-alkylphenols that lack fluorine substitution. This method is competitive with the little known method of Reetz to convert aryl ketones to the corresponding 1,1-dimethylalkyl group and allows one to access electron rich tert-alkyl-substituted aromatics that are not accessible by the Friedel-Crafts alkylation (Friedel-Crafts restricted). Third, we found a convenient and high-yielding method for selective S-alkylation of 2-mercaptophenol. In addition to the synthesis of carbamates, the preparation of one hundred three intermediates, phenols, and electron rich tert-alkyl arenes are reported. / Ph. D.

The focus of this thesis is the critical review of Additive Printing (AP) or 3D-printing, and optimization strategies for the introduction of new materials. During the course of tenure, four classes of solids were investigated to determine the hurdles presented from each system. Specifically, the investigation developed techniques for optimization of ink production, green-film deposition, and laser sintering parameters surrounding the Optomec AJP system (AJP). In the assessment, statistical experimental design, analysis and material characterization techniques have been utilized. Final recommendations disseminate current best practices for new ink and material development, along with factor analysis of input variables for phase and material properties, along with insights for future research of these systems. The first chapter provides a general introduction to the field of AP. The second chapter focuses specifically on Optomec aerosol-jet process (AJP) techniques, and expands the discussion to process parameters, information concerning the fabrication/characterization procedure followed for each system, and includes: a detailed description of the materials investigated. This is important because printing parameters, optimization, and approach may be divergent for optimization within each strain; and is meant as an aid to resolve some technical issues for future investigators. The third chapter is fully dedicated to the results concerning the fabrication and the characterization of amorphous boron powder to film. Chapter four discusses future research options, ideas and directions. Appendices are provided for any which wish to investigate the orthogonal arrays used, or the combinatorial effects resulting in the attributes of the material system final products. / Master of Science

Great improvements are continuously being made in the solid free form fabrication (SFF) industry in terms of processes and materials. Fully functional parts are being created directly with little, if any, finishing. Parts are being directly fabricated with engineering materials such as ceramics and metals. This thesis aims to facilitate a substantial advance in rapid prototyping capabilities, namely that of fabricating parts with continuously heterogeneous material compositions. Because SFF is an additive building process, building parts layer-by-layer or even point-by-point, adjusting material composition throughout the entire part, in all three dimensions, is feasible. The use of fine powders as its build material provides the potential for the Selective Laser Sintering (SLS), ThreeDimensional Printing (3DP), and Freeform Powder Molding (FPM) processes to be altered to create continuously heterogeneous material composition. The current roller distribution system needs to be replaced with a new means of delivering the powder that facilitates selective heterogeneous material compositions. This thesis explores a dense phase pneumatic conveying system that has the potential to deliver the powder in a controlled manner and allow for adjustment of material composition throughout the layer. / Master of Science

Scanning Electrochemical Microscopy (SECM) is most commonly used to spatially resolve reaction rates, image surface topography and surface reactivity. In this research, SECM is applied to various chemical systems in order to resolve local reaction chemistry and to produce patterns with dimensions of tens of microns in n-alkanethiol passivated gold substrates. Upon completing construction of the instrumentation, SECM was applied to capillary electrophoresis to accurately and reproducibly place the electrode directly above a very small capillary opening. Feedback SECM was then used to image and pattern surfaces, effectively distinguishing between insulating and conductive domains. Finally, the size of desorbed features patterned on a passivated gold substrate were studied as a function of both applied potential and ionic strength. Electrochemical detection in capillary electrophoresis requires decoupling the voltage applied to the working electrode from the separation voltage applied across the capillary. End-capillary electrochemical detection achieves this by placing the electrode just outside the ground end of the separation capillary. Obtaining adequate signal-to-noise in this arrangement requires using small inner diameter capillaries. Decreasing the inner diameter of the separation capillary, however, increases the difficulty of aligning the microelectrode with the open end of the capillary. Using SECM, the position of the capillary opening is determined while electroactive material is continuously emerging from the end of the capillary. The SECM instrument is then used to place the electrode at the position of maximum current for subsequent separations. Subsequent measurements found that the best signal-to-noise is obtained when the detection electrode is placed directly opposite the capillary opening and just outside of the capillary opening. When the electrode is further above the opening (but still opposite the capillary opening), the signal-to-noise does not dramatically decrease until the electrode is more than 30 μm above the 10 μm inner-diameter capillary. Limits of detection for 2,3-dihydroxybenzoic acid were found to be 8.2 fmol when aligned manually, and 3.8 fmol when the SECM is used to automatically align the microelectrode. SECM was then used to image a series of multi-disk electrode arrays in order to demonstrate the ability of the instrument to discriminate between conductive and insulating domains. Upon demonstrating the capacity of the SECM to image very small domains of conductor on an insulating substrate, n-alkanethiol passivated gold surfaces were patterned using site-selective desorption. A number patterns, potentially useful for enzyme deposition, were subsequently produced in the passivated gold substrate. The feature size of the desorbed domains was monitored as a function of applied potential and the ionic strength of the solution used for desorption. Results showed that applying a more negative potential or increasing the ionic strength of the solution increased the magnitude of the electric field at the surface of the passivated gold substrate and resulted in a more complete, larger desorption. Both ionic strength and applied desorption potential prove to be parameters useful for controlling the size of patterned features in site selective desorption. / Master of Science

Wavelet Modulation (WM)---also referred to as fractal modulation---simultaneously sends data at multiple rates through an unknown channel. This novel multirate diversity strategy offers improved message recovery over conventional modulation techniques: if the message is not received at one rate due to the channel disturbances, it can be received at another rate where the channel is clear. Previous research has demonstrated the performance of wavelet modulation in Gaussian channels. This paper extends the investigation to the performance of wavelet modulation in time varying channels. We show that bit error rate (BER) wavelet demodulation performance in the additive, white, Gaussian noise (AWGN) channel is comparable to theoretical binary phase shift keying. Our results depict the improvement in performance that can be realized for time varying channels by utilizing the various rates of wavelet modulation; BER versus SNR curves for each fading channel show how the message at one rate can be more accurately recovered than at another rate. Furthermore, we also present results indicating the dramatic improvement in wavelet demodulation performance when multiple rates are available and utilized for demodulation. This improvement in performance is highly visible in BER performance for the AWGN and flat fading channels. Finally, a comparison of binary phase shift keying (BPSK) and WM in a frequency selective channel is performed. The BER improvement of WM is shown when demodulation is done at rates which are least corrupted by ISI. We illustrate our new algorithm that: identifies the channel characteristics; determines which rates are maximally corrupted by ISI; and, utilizes only those uncorrupted copies in demodulation. / Master of Science