The implementation of automatic transit data collection via Automatic Vehicle Location (AVL) and Automatic Passenger Counting (APC) systems provides an opportunity to create large, detailed datasets of transit operations. These datasets are valuable because they provide an opportunity to evaluate and optimize transit operations using methods that were previously infeasible and without the need for expensive manual data collection. This thesis develops a methodology to utilize data collected by typical AVL/APC system installations in order to (a) develop advanced performance measures to quantify schedule adherence and (b) automatically determine the causes of poor schedule adherence. The methodology addresses the difficulty that many small to medium sized transit agencies have in utilizing the data being collected by proposing a methodology that can be automated, thereby reducing resource and expertise requirements and allowing the data to be more effectively utilized. The ultimate output of the proposed methodology includes the following: 1. A ranked list of routes by direction (for a given time period) that identifies routes with the poorest schedule adherence performance. 2. Performance measures within any given route, direction, and time period that identify which timepoints are contributing most to poor schedule adherence. 3. Statistics indicating identified causes of poor schedule adherence at individual timepoints. 4. A visualization aid to be used in conjunction with the cause statistics generated in Step 3 in order to develop an effective strategy for improving schedule adherence issues. With this information, transit agencies will be able to act proactively to improve their transit system, rather than wait until they discover problems on their own or hear complaints from passengers and drivers. The methodology is tested and demonstrated through application to AVL/APC system data from Grand River Transit, a public transit agency serving Waterloo Region in Ontario, Canada.

Automatic Vehicle Location (AVL) and Automatic Passenger Counting (APC) systems can be powerful tools for transit agencies to archive large, detailed quantities of transit operations data. Managing data quality is an important first step for exploiting these rich datasets. This thesis presents an automated quality assurance (QA) methodology that identifies unreliable archived AVL/APC data. The approach is based on expected travel and passenger activity patterns derived from the data. It is assumed that standard passenger balancing and schedule matching algorithms are applied to the raw AVL/APC data along with any existing automatic validation programs. The proposed QA methodology is intended to provide transit agencies with a supplementary tool to manage data quality that complements, but does not replace, conventional processing routines (that can be vendor-specific and less transparent). The proposed QA methodology endeavours to flag invalid data as “suspect” and valid data as “non-suspect”. There are three stages: i) the first stage screens data that demonstrate a violation of physical constraints; ii) the second stage looks for data that represent outliers; and iii) the third stage evaluates whether the outlier data can be accounted for with valid or invalid pattern. Stop-level tests are mathematically defined for each stage; however data is filtered at the trip-level. Data that do not violate any physical constraints and do not represent any outliers are considered valid trip data. Outlier trips that may be accounted for with a valid outlier pattern are also considered valid. The remaining trip data is considered suspect. The methodology is applied to a sample set of AVL/APC data from Grand River Transit in the Region of Waterloo, Ontario, Canada. The sample data consist of 4-month’s data from September to December of 2008; it is comprised of 612,000 stop-level records representing 25,012 trips. The results show 14% of the trip-level data is flagged as suspect for the sample dataset. The output is further dissected by: reviewing which tests most contribute to the set of suspect trips; confirming the pattern assumptions for the valid outlier cases; and comparing the sample data by various traits before and after the QA methodology is applied. The latter task is meant to recognize characteristics that may contribute to higher or lower quality data. Analysis shows that the largest portion of suspect trips, for this sample set, suggests the need for improved passenger balancing algorithms or greater accuracy of the APC equipment. The assumptions for valid outlier case patterns were confirmed to be reasonable. It was found that poor schedule data contributes to poorer quality in AVL-APC data. An examination of data distribution by vehicle showed that usage and the portion of suspect data varied substantially between vehicles. This information can be useful in the development of maintenance plans and sampling plans (when combined with information of data distribution by route). A sensitivity analysis was conducted along with an impact analysis on downstream data uses. The model was found to be sensitive to three of the ten user-defined parameters. The impact of the QA procedure on network-level measures of performance (MOPs) was not found to be significant, however the impact was shown to be more substantial for route-specific MOPs.

The travel times of public transit systems that operate on mixed use right-of-ways are often dictated by the delays experienced at signalized intersections. When these delays become large and/or highly variable, transit quality degrades and agency operating costs increase. A number of transit priority measures can be applied, including transit signal priority or queue jump lanes. However, it is necessary that a process of prioritizing intersections for priority treatment be conducted so as to ensure the greatest return on investment is achieved. This thesis proposes and demonstrates a methodology to determine the distribution of stopped delays experienced by transit vehicles at signalized intersections using archived AVL (automated vehicle location) and APC (automated passenger counting) data. This methodology is calibrated and validated using queue length and bus unscheduled stopped delay data measured at a field site. Results show the proposed methodology is of sufficient accuracy to be used in practice for prioritizing signalized intersections for priority treatment. On the condition that a sample of the transit vehicle fleet is equipped with an AVL/APC system, the proposed methodology can be automatically implemented using the archived AVL/APC data and therefore avoid the need to conduct dedicated data collection surveys. The proposed methodology can provide estimates of (1) the maximum extent of the queue; and (2) measures of the distribution of stopped delays experienced by transit vehicles (e.g. mean, standard deviation, 90th percentile, etc.) caused by the downstream traffic signal. These measures can be produced separately for different analysis periods (e.g. different times of the day; days of the week; and time of the year) and can be compiled separately for different transit routes. These outputs can then be used to identify and prioritize signalized intersections as candidates for transit signal priority measures. The proposed method is suitable for application to most transit AVL/APC databases and is demonstrated using data from Grand River Transit, the public transit service provider in the Region of Waterloo, Ontario Canada.

<p>The Anaphase Promoting Complex/Cyclosome (APC/C) is a RING E3 ligase that plays essential roles both within and outside of the cell cycle. At the onset of anaphase, the APC/C targets cyclin B and securin for degradation, initiating chromosome separation and mitotic exit. Regulation of APC/C activity is critical for a functional cell cycle, and this is largely mediated by cytostatic factor (CSF) activity and the Spindle Assembly Checkpoint (SAC). </p> <p>Prior to fertilization, vertebrate eggs are arrested in metaphase of meiosis II by CSF activity, a key component of which is the APC/C inhibitor Emi2. Although the roles and regulation of Emi2 in maintaining CSF arrest have been extensively studied, its function during the oocyte maturation process, especially at the meiosis I to meiosis II (MI-MII) transition, was not well understood. Studies presented in this dissertation characterize an Emi2-mediated auto-inhibitory loop of the APC/C that provides the molecular basis of a critical biochemical event during the MI-MII transition--the partial degradation of cyclin B. In brief, phosphorylation of the Emi2 N-terminus by Cdc2/cyclin B targets it for proteasomal degradation in meiosis I (MI). During anaphase of MI, the APC/C triggers its own inactivation by degrading cyclin B, therefore stabilizing its inhibitor, Emi2. The timely inactivation of APC/C activity prevents the complete inactivation of Cdc2 kinase, which is crucial for prohibiting S phase onset and parthenogenetic activation of the oocytes.</p> <p>To better understand the regulation of the APC/C, a number of the studies presented here are aimed at identifying the mechanism for Emi2 inhibition of the APC/C. Many APC/C inhibitors have been reported to function as "pseudosubstrates", which inhibit the APC/C by preventing substrate binding. After carefully examining the ubiquitin reactions mediated by the APC/C in vitro, we have found that it is the last step in the ubiquitylation process, where ubiquitin is transferred from a charged E2 to the substrate, that is targeted by Emi2. In addition, biochemical studies have also revealed that Emi2 itself has RING-dependent ligase activity and this activity enables it to inhibit the APC/C in a sub-stoichiometrical manner. </p> <p>Although the ultimate goal for both CSF activity and the SAC signaling pathway is APC/C inhibition, a much more complicated regulatory network is known to control SAC. Previous researches in our lab have identified Xnf7 to be an APC/C inhibitor that is required for the SAC pathway in Xenopus egg extract. In an effort to characterize the human Xnf7 homolog, we have found that Trim39, a protein that has been implicated in apoptosis regulation, is required for the SAC pathway in RPE cells. Like Emi2, both Xnf7 and Trim39 are RING E3 ligases whose activity is essential for their function. Interestingly, the ligase activity of both proteins appears to be regulated by the checkpoint. While we continue to characterize the roles and regulation of both Trim39 and Xnf7 in the SAC, future investigations into the mechanisms that underlie APC/C inhibition by all the three E3 ligases--Emi2, Xnf7 and Trim39--would be of great interest.</p> / Dissertation

The purpose of thesis aims to investigate the mechanical behavior and properties of a centrally notched hybrid Al alloy/Carbon-Fiber/PEEK(APC-2) laminate at elevated temperature. The high performance hybrid composite laminates of 0.5mm Aluminum alloy sheets sandwiched by APC-2 cross-ply and guasi-isotropic laminates were fabricated. The prepregs of APC-2 were stacked into cross-ply [0/90]s and quasi-isotropic [0/45/90/-45] laminates spread uniformly with nanoparticles SiO2. The sheet surface was treated by chromic acid anodic method to achieve perfectly bonding with matrix PEEK. The modified diaphragm curing process was adopted to fabricate Al/APC-2 hybrid nanocomposite laminates. The panels were cut into the specimens and then drilled an diameter hole in the center with diameters of 1,2,4,6 mm. The MTS 810 material testing machine was used to conduct the tension and fatigue tests. In addition, the MTS 651 environmental chamber was installed to control and keep the specific testing temperatures, such as ,25¢XC(RT), 75¢XC, 100¢XC, 125¢XC and 150¢XC. At first, the nominal stress(£mnom) and stress-strain diagram were obtained due to static tension tests at elevated temperature. The constant stress amplitude tension-tension cyclic tests were carried out by using load-control mode at a sinusoidal loading with frequency of 5Hz and stress ratio R=0.1. The received fatigue data were plotted in normalized S-N curves at variously elevated temperature. For the tensile tests, at the same temperature the nominal stress of cross-ply specimens was higher than that of quasi-isotropic specimens. Comparing with the notched and unnotched of cross-ply specimens, the nominal stress of notched specimens was about 60% to 80% that of unnotched specimens. Besides, as for the notched and unnotched quasi-isotropic specimens, the nominal stress of notched specimens was about 75% to 85% that of unnotched specimens. Then, the fatigue life and stress-cycles (S-N) curves of notched specimens were obtained often tension-tension fatigue tests. In the case of the same loading, notched specimens possess worse fatigue behavior, but in the same normalized stress ratio, the S-N curves of the unnotched were below the notched ones. The fatigue resistance of notched samples decrease as the temperature rising.

The aims of this thesis are fabrication of Ti/APC-2 hybrid nanocomposite laminates and investigation of their mechanical properties at elevated temperature. The prepregs of APC-2 were stacked into cross-ply [0/90]s and quasi-isotropic [0/45/90/-45] laminates spread uniformly with nanoparticles SiO2. The sheet surface was treated by chromic acid anodic method to achieve perfectly bonding with matrix PEEK. The prepregs were sandwiched with the Ti alloy sheets. The modified diaphragm curing process was adopted to produce Ti/APC-2 hybrid nanocomposite laminates. The nanocomposite laminates were a five-layer composite with two 0.55 mm thick APC-2 layers sandwiched by three 0.5 mm thick Gr.1 titanium alloy sheets. The MTS 810 material testing machine was used to conduct the tension and fatigue tests. In addition, the MTS 651 environmental chamber was installed to control and keep the experimental temperature, such as 25¢XC, 75¢XC, 100¢XC, 125¢XC and 150¢XC. The mechanical proper&not;ties, such as ultimate tensile strength, longitudinal stiffness of cross-ply and quasi-isotropic nanocomposite laminates, were obtained from the static tensile test. The stress-strain diagrams were plotted in the corresponding temperature. The constant stress amplitude tension-tension cyclic tests were carried out by using load-control mode at a sinusoidal loading with frequency of 5Hz and stress ratio R=0.1. The received fatigue data were plotted in normalized S-N curves at variously elevated temperature. From the summarized results, some conclusions were made. First, the ultimate strength of Ti/APC-2 nanocomposits was better than Ti/APC-2 composites at room temperature; Second, Both two type nanocomposite laminates¡¦ ultimate strength and S-N curves go downwards as temperature rising, especially at 150¢XC; Third, The fatigue tensile strength of both hybrid composite laminates was the lowest at 150¢XC. Fourth, Ti/APC-2 quasi-isotropic nanocomposite laminates had better fatigue resistance than Ti/APC-2 cross-ply nanocomposite laminates. Finally,The longitudinal stiffness was in good agreement with prediction by using the modified ROM because of the changed curve fitting ranges.

ABSTRACT Chibby (or PIGEA-14) is a novel antagonist of the Beta-catenin pathway in nucleus. However, the tumor-suppressing function of Chibby and the importance of nuclear targeting to the cellular functions of Chibby have not been validated. By fusion of Chibby cDNA with green fluorescent protein (GFP) or Flag-tag, it was found that exogenous Chibby expression was detected in the nucleus as well as cytoplasm of transfected HeLa cells, but with a preferential nuclear localization (more than 50% cells with nuclear Chibby expression). Chibby overexpression significantly abrogated the cellular Beta¡Vcatenin activities and induced apoptosis in HeLa cells. Moreover, Chibby gene delivery attenuated the proliferation, migration, and anchorage-independent growth of HeLa cells, supporting the tumor suppressor function of Chibby. Mutation or deletion of the predicted nuclear localization sequence (NLS), at residues 123-126, significantly promoted the cytoplasmic localization of Chibby, indicating residues 123-126 is the NLS domain of Chibby. Interestingly, ecotopic expression of Chibby NLS mutants remained capable of inducing apoptosis and inhibiting Beta¡Vcatenin activities in HeLa cells. Besides, overexpression Chibby NLS mutants effectively attenuated the viability, motility and colonies formation of HeLa cells. Expression analysis revealed that Chibby NLS mutants retained Beta-catenin in the cytoplasm and prevented its nuclear entry, thereby inhibiting the Beta-catenin transcriptional activities. In summary, Chibby shuttles between nucleus and cytoplasm, and possesses the functions of tumor suppressor and Beta-catenin antagonist.

The thesis is to fabricate Al/APC-2 hybrid nanocomposite laminates and investigate their mechanical properties at elevated temperature. The prepregs of Carbon /PEEK were stacked into cross-ply [0/90]s and quasi-isotropic [0/45/90/-45] laminates spread uniformly with nanoparticles SiO2. The sheet surface was treated by chromic acid anodic method to achieve perfectly bonding with matrix PEEK. The prepregs were sandwiched with the Al alloy sheets. The modified diaphragm curing process was adopted to produce Al/APC-2 hybrid nanocomposite laminates. The hybrid nanocomposite laminates were a five-layer composite with two 0.55 mm thick Carbon/PEEK layers sandwiched by three 0.5 mm thick 2024-T3 Aluminum alloy sheets. The MTS 810 material testing machine was used to conduct the tension and fatigue tests. In addition, the MTS 651 environmental chamber was installed to control and keep the specific testing temperature, which was room temperature, 75¢XC, 100¢XC, 125¢XC and 150¢XC. The mechanical proper&not;ties, such as ultimate tensile strength and longitudinal stiffness of hybrid cross-ply and quasi-isotropic nanocomposite laminates, were obtained from the static tensile test, and the stress-strain diagrams were plotted in the corresponding temperature. The constant stress amplitude tension-tension cyclic tests were carried out by using load-control mode at a sinusoidal loading with frequency of 5Hz and stress ratio R=0.1. The received fatigue data were plotted in normalized S-N curves at variously elevated temperature. In order to observe the failure mechanism of samples, the scanning electron microscope was used. From the summarized results, some conclusions were made. First, the slope changed at strain=0.1% in the stress-strain diagram, and led to a noticeable error between the experimental data and ones calculated according to Rule of Mixtures. Second, the Al/APC-2 cross-ply nanocomposite laminates were less resistant to fatigue than quasi-isotropic. Third, the ultimate tensile strength of both hybrid composite laminates was the lowest at 150¢XC. Fourth, the Al/APC-2 quasi-isotropic nanocomposite laminates were more resistant to the temperature effect. Finally, The mechanical proper&not;ties were better for the surface treated by chromic acid anodic method than chemical etching.

Automatic Vehicle Location (AVL) and Automatic Passenger Counting (APC) systems can be powerful tools for transit agencies to archive large, detailed quantities of transit operations data. Managing data quality is an important first step for exploiting these rich datasets. This thesis presents an automated quality assurance (QA) methodology that identifies unreliable archived AVL/APC data. The approach is based on expected travel and passenger activity patterns derived from the data. It is assumed that standard passenger balancing and schedule matching algorithms are applied to the raw AVL/APC data along with any existing automatic validation programs. The proposed QA methodology is intended to provide transit agencies with a supplementary tool to manage data quality that complements, but does not replace, conventional processing routines (that can be vendor-specific and less transparent). The proposed QA methodology endeavours to flag invalid data as “suspect” and valid data as “non-suspect”. There are three stages: i) the first stage screens data that demonstrate a violation of physical constraints; ii) the second stage looks for data that represent outliers; and iii) the third stage evaluates whether the outlier data can be accounted for with valid or invalid pattern. Stop-level tests are mathematically defined for each stage; however data is filtered at the trip-level. Data that do not violate any physical constraints and do not represent any outliers are considered valid trip data. Outlier trips that may be accounted for with a valid outlier pattern are also considered valid. The remaining trip data is considered suspect. The methodology is applied to a sample set of AVL/APC data from Grand River Transit in the Region of Waterloo, Ontario, Canada. The sample data consist of 4-month’s data from September to December of 2008; it is comprised of 612,000 stop-level records representing 25,012 trips. The results show 14% of the trip-level data is flagged as suspect for the sample dataset. The output is further dissected by: reviewing which tests most contribute to the set of suspect trips; confirming the pattern assumptions for the valid outlier cases; and comparing the sample data by various traits before and after the QA methodology is applied. The latter task is meant to recognize characteristics that may contribute to higher or lower quality data. Analysis shows that the largest portion of suspect trips, for this sample set, suggests the need for improved passenger balancing algorithms or greater accuracy of the APC equipment. The assumptions for valid outlier case patterns were confirmed to be reasonable. It was found that poor schedule data contributes to poorer quality in AVL-APC data. An examination of data distribution by vehicle showed that usage and the portion of suspect data varied substantially between vehicles. This information can be useful in the development of maintenance plans and sampling plans (when combined with information of data distribution by route). A sensitivity analysis was conducted along with an impact analysis on downstream data uses. The model was found to be sensitive to three of the ten user-defined parameters. The impact of the QA procedure on network-level measures of performance (MOPs) was not found to be significant, however the impact was shown to be more substantial for route-specific MOPs.

The travel times of public transit systems that operate on mixed use right-of-ways are often dictated by the delays experienced at signalized intersections. When these delays become large and/or highly variable, transit quality degrades and agency operating costs increase. A number of transit priority measures can be applied, including transit signal priority or queue jump lanes. However, it is necessary that a process of prioritizing intersections for priority treatment be conducted so as to ensure the greatest return on investment is achieved. This thesis proposes and demonstrates a methodology to determine the distribution of stopped delays experienced by transit vehicles at signalized intersections using archived AVL (automated vehicle location) and APC (automated passenger counting) data. This methodology is calibrated and validated using queue length and bus unscheduled stopped delay data measured at a field site. Results show the proposed methodology is of sufficient accuracy to be used in practice for prioritizing signalized intersections for priority treatment. On the condition that a sample of the transit vehicle fleet is equipped with an AVL/APC system, the proposed methodology can be automatically implemented using the archived AVL/APC data and therefore avoid the need to conduct dedicated data collection surveys. The proposed methodology can provide estimates of (1) the maximum extent of the queue; and (2) measures of the distribution of stopped delays experienced by transit vehicles (e.g. mean, standard deviation, 90th percentile, etc.) caused by the downstream traffic signal. These measures can be produced separately for different analysis periods (e.g. different times of the day; days of the week; and time of the year) and can be compiled separately for different transit routes. These outputs can then be used to identify and prioritize signalized intersections as candidates for transit signal priority measures. The proposed method is suitable for application to most transit AVL/APC databases and is demonstrated using data from Grand River Transit, the public transit service provider in the Region of Waterloo, Ontario Canada.