The shear capacity of a post-tensioned, concrete I-girder may be influenced if the crushing capacity of the web is reduced by ducts for the tendons. An experimental investigation was conducted on compressively-loaded, high-strength concrete panels with embedded post-tensioning ducts to better understand the parameters influencing girder web crushing behavior. The panels were intended to represent portions of a girder web subjected to shear-induced, principal compressive stresses. Material properties and construction procedures utilized in the fabrication and erection of bridge members in the field were considered. The primary goal of this study was to assess the impacts of various parameters on web crushing capacity. The results were needed to determine which variables should be considered for shear testing of full-scale girders. The parameters considered in the panel test program were duct type, grouting, member thickness, and the inclusion of confining reinforcement near the ducts. Notable findings from this study indicate that 1) elements with plastic ducts exhibit lower capacities than those with steel ducts, 2) a significant size effect exists when determining crushing capacity, and 3) the presence of a small amount of reinforcement placed near a duct through a member’s thickness can greatly improve its capacity. Results indicated that American design codes may be severely unconservative in their handling of ducts when designing for shear. Recommendations to refine and expand the standard approach for reducing web crushing capacity were developed. Additionally, a new means of estimating web crushing capacity was introduced. / text

published_or_final_version / Chinese Medicine / Master / Master of Philosophy

Background and objectives: Endothelial dysfunction and cancer are two of the important aspects of obesity-related medical complications, the prevalence of which is reaching an epidemic level worldwide. The protein kinase LKB1 has been shown to play opposite roles in these two metabolic diseases by promoting cellular senescence and inhibiting cell proliferation through regulating a series of its downstream targets. However, the molecular mechanisms wherebyLKB1 itself is regulated by its upstream molecules remains poorly understood. The major objectives of this study are to identify novel upstream regulators of LKB1 and to investigate how these upstream regulators modulate the subcellular localization and physiological functions of LKB1 by post-translational modifications. Key findings: 1. Our proteomic analysis demonstrated that LKB1 was modified by both acetylation and phosphorylation. The acetylation sites of mouseLKB1 include Lys48, Lys64and Lys312. The phosphorylation sites of mouseLKB1 include: Ser31, Thr32,Tyr36, Ser69, Thr71, Ser334and Thr336. 2. In both human embryonic kidney 293 (HEK293)cells and primary porcine aortic endothelial cells (PAECs), the nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase SirT1 attenuated the acetylation levels of LKB1,which consequently resulted in enhancedLKB1ubiquitination, thereby leading to the proteasome-mediated degradation of LKB1. 3. In primary PAECs, overexpression of SirT1 protected cells from cell cycle arrest and cellular senescence, whereas overexpression of LKB1 exhibited the opposite effects.SirT1 antagonizedLKB1-induced G1 phase arrest and cellular senescence by promoting the deacetylation and protein degradation of LKB1. 4. The in vitro phosphorylation assay and mass spectrometry analysis demonstrated that LKB1 could be phosphorylated by the Akt kinase at Ser334which was critical for the interaction between LKB1 and 14-3-3. The enhanced association between LKB1 and 14-3-3 subsequently attenuated the interaction between LKB1 and Ste20 related adaptor α(STRADα), which further promoted the nuclear accumulation of LKB1. 5. The cell proliferation and cell cycle distribution analysis of the stably-transfected MDA-MB-231 breast cancer cells demonstrated that overexpression of the LKB1 mutant S334D, which mimicked Ser334 phosphorylation and localized exclusively in the nucleus, completely lost its anti-tumor activities. On the other hand, the S334A mutation enhanced the tumor suppressive functions of LKB1. 6. Nude mice inoculated with the LKB1 S334A stably-transfected MDA-MB-231 cells exhibited delayed tumor onset, decreased tumor growth rate and tumor weight. By contrast, inoculation of nude mice with the MDA-MB-231 cells overexpressing LKB1 S334D mutation showed the opposite effects on these parameters. Conclusions: These results collectively suggest that the deacetylase SirT1 and the protein kinase Aktare the two important upstream regulators of LKB1. SirT1 prevents LKB1-induced cellular senescence and protect endothelial ageing by promoting proteasome-mediated degradation of LKB1. Akt inhibits the tumor-suppressive activity of LKB1 by enhancing the phosphorylation-dependent nuclear translocation. Further investigations on the precise mechanisms whereby SirT1 and Akt regulate LKB1 functions may help to design novel therapeutic strategies for treating obesity-related diseases, such as diabetes, cardiovascular disease and cancer. / published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

This study describes case managers' perceptions of the association between methamphetamine and child neglect. The analysis indicates that out of 30 women, 100.0% agreed that the use of methamphetamine is associated with child neglect. Children are being neglected due to methamphetamine causing impairment in the parents' ability to appropriately care for their children. The study findings note a statistically significant relationship between the variables at the .05 level of probability.

The alteration mineralogy, major and trace element chemistry, and Sr-Nd-Pb-Hf isotopic compositions of post-shield lavas from Mauna Kea, Kohala, and Hualalai on the island of Hawaii in the Pacific Ocean are used to constrain the origin and distribution of heterogeneities in the Hawaiian mantle plume. Ocean island basalts contain a variety of secondary minerals that must be removed by acid-leaching to achieve high-precision Pb isotopic compositions, a powerful geochemical tracer of variation in plume source composition. Post-shield lavas range from transitional/alkalic basalt to trachyte and are enriched in incompatible trace elements (e.g. LaN/YbN=6.0-16.2) relative to shield stage tholeiites. Post-shield lavas are characterized by a limited range of Sr-Nd-Hf isotopic compositions(⁸⁷Sr/⁸⁶Sr=0.70343-0.70365; ¹⁴³Nd/¹⁴⁴Nd = 0.51292-0.51301;¹⁷⁶Hf/¹⁷⁷Hf= 0.28311-0.28314) and have Pb isotopic compositions(²⁰⁶Pb/²⁰⁴Pb = 17.89-18.44; ²⁰⁷Pb/²⁰⁴ 15.44-15.49;²⁰⁸Pb/²⁰⁴Pb= 37.68-38.01) that belong to their respective Kea or Loa side of the Pb-Pb boundary. Mauna Kea lavas show a systematic shift to less radiogenic Pb isotopic compositions from the shield to post-shield stage and trend to low ⁸⁷Sr/⁸⁶Sr towards compositions characteristic of rejuvenated stage lavas. Hualalai post shield lavas lie distinctly above the Hf-Nd Hawaiian array (ƐHf = +12 to +13; ƐNd = +5.5 to +6.5) and have some of the least radiogenic Pb isotopic compositions (e.g.²⁰⁶/²⁰⁴pb= 17.89-18.01) of recent Hawaiian volcanoes. In contrast, comparison of Kohala with the adjacent Mahukona shows that lavas from these volcanoes become more radiogenic in Pb during the late stages of volcanism. The Sr-Nd-Pb-Hf isotope systematics of the post shield lavas cannot be explained by mixing between the Kea and Koolau end-members or by assimilation of Pacific lithosphere and are consistent with the presence of ancient recycled lower oceanic crust and sediments in their source. More than one depleted component is sampled by the post-shield lavas and these components are long-lived features of the Hawaiian plume that are present in both the Kea and Loa source regions. The geochemistry of the post-shield lavas provide evidence for a bilaterally zoned plume, where the compositional boundary between the Kea and Loa sources is complex and vertical components of heterogeneity are also significant.

Signal Transduction is mediated by protein complexes whose spatial- and temporal-distribution, composition and function within cells are often regulated by different post-translational modifications (PTM). As PTMs add or subtract a specific mass difference to a protein, mass spectrometry becomes very amenable for modification analysis. These modifications have conventionally been monitored by fragmenting the modified protein or peptide by collision induced dissociation (CID) within the mass spectrometer, and then screening for the characteristic neutral fragment or fragment ion (marker ion), which is particular to the modification in question. Unfortunately, there are two major issues with respect to the traditional mass spectrometric analysis of PTMs: (1) as there are over 300 known types of modifications, the characteristic fragmentation of only a fraction of these modifications has been studied and (2) the traditional mass spectrometric approaches can only monitor these modifications sequentially, and thus comprehensive modification analysis would be unfeasible considering the breadth of PTMs. The following work aims to address these issues by (1) analyzing PTMs that have never been characterized mass spectrometrically and (2) developing a multiplexed technique for comprehensive PTM monitoring by simultaneously screening for all known characteristic fragments. With respect to the first issue, the characteristic fragmentation of lipid modifications and HNO-induced modifications was investigated. The most prevalent indicator(s) of the modification within the mass spectra are as follows: fragmentation of N-terminal myristoylated peptides produced marker ions at 240 and 268 Th, fragmentation of cysteine farnesylated peptides produced a marker ion at 205 Th and a neutral fragment of 204 Da, and fragmentation of cysteine palmitoylated peptides produced a neutral fragment of 272 Th. For HNO-induced modifications, fragmentation of the sulfinamide- and sulfinic acid-modified peptides produced a neutral fragment of 65 Da and 66 Da, respectively. With respect to the second issue, a multiplexed technique for monitoring modifications that fragment as neutral losses, termed Multiple Neutral Loss Monitoring (MNM), has been developed, successfully validated, and then shown to be the most sensitive approach for PTM analysis. MNM, combined with a second multiplexed approach, targeted Multiple Precursor Ion Monitoring, has been used to provide a comprehensive PTM analysis.

No description available.

This study focuses on investigating the effect of post-harvest handling conditions and storage time on the dehulling efficiency and cooking quality of two varieties of red lentils, as well as optimizing the dehulling conditions. The effects of storage time, storage moisture content and storage temperature, as well as the effect of different storage pre-treatments aiming to simulate post-harvest handling, were studied. Dehulling efficiency was mostly affected by the pre-milling moisture content, regardless of the storage conditions. Pre-treatments involving moisture content changes lowered the dehulling efficiency of both varieties of red lentils, whereas freezing and thawing cycles had less of a negative effect on the dehulling characteristics. Textural parameters were mostly affected by storage time; samples became harder after storage. The final recommendation arising from this study is to monitor the moisture content of lentils during storage as it has a detrimental effect on both the dehulling and cooking quality.

Four experiments were conducted to determine a management strategy for providing effective electrolyte concentrations in the drinking water of newly weaned piglets to encourage early fluid and feed intake [weaning age=19±1 d, n=360]. In Exp. 1, electrolytes (Vetoquinol, QC, Canada) were provided at the label dose of 60 ml/L of water for 0, 6, 12, 18 or 24 h on d1-d3. In Exp. 2, electrolytes were given ad lib at 100, 75, 50, 25 or 12.5 % of the label dose on d1-d3 (72 h). In Exp. 3, electrolytes, at the label dose, or water (control) were given ad lib on d1, d1 and d2, d1-d3, or d1 and d3. In Exp. 4, based on the results of the previous experiments, the most effective combinations of "hours/concentration/days"(12 h of 25 % or 50 % on d1 or alternate days) were tested. All piglets had water ad lib from d4-d14. In Exp. 1, higher feed disappearance was observed in the 0, 6 and 12 h/d than 18 h/d and 24 h/d electrolyte groups (P<0.05). In Exp. 2, by d14 piglets in the 12.5, 50, 75, and 100 % groups experienced lower weight gain and daily FI than those in the 25 % group (P<0.05). In Exp. 3, piglets that received electrolytes on d1 only had comparable FI to those in the water group (respectively; 64.55 g/pig/day vs. 75.59 g/pig/day; SEM=8.61). Overall, evidence indicated that weanlings tended to benefit from electrolyte administration at 25 % of the label dose and durational period of ≤ 12 h/d. However, in Exp. 4 testing neither 25 % or 50 % concentration for 12 h/d result in improved daily FI despite the increased FLI in groups given electrolytes on alternate days. The results suggest that high electrolyte intake occurred at the expense of feed intake.

The educational attainment gap between Canada’s Aboriginal and non-Aboriginal peoples both reflects and perpetuates a parallel disparity in socioeconomic conditions. Aboriginal peoples’ distrust of and disengagement from educational systems can be linked to the history of their relationship with the settler state. Therefore, decolonizing education may be one way to address the education gap. This qualitative study of ten Aboriginal graduates from one of Urban Circle’s post-secondary programs explored graduates’ perceptions of the integration of Aboriginal cultural context and content in their program and the effect of these experiences on program completion. Responses revealed five main themes: 1) the cultural context of Urban Circle restored Aboriginal identity; 2) supportive relationships were important to graduates’ success in the FSW/FASD program; 3) the Life Skills course facilitated personal growth, employment readiness and program success; 4) the cultural context of Urban Circle has influenced graduates’ professional work; and 5) Urban Circle had positive influences on graduates’ personal lives. The findings indicate that the cultural content and context at Urban Circle positively impacted student’s educational experience and contributed to their completion of their program.