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      • Alkali-silica reaction in portland cement concrete: Testing methods and mitigation alternatives

        Touma, Wissam Elias The University of Texas at Austin 2000 해외박사(DDOD)

        RANK : 247343

        Identifying the susceptibility of an aggregate to the alkali-silica reaction (ASR) before using it in concrete is one of the most efficient practices for preventing damage and failure. Several tests have been developed for identifying aggregates subject to ASR, but each has its limitations. A three-year research study was initiated on January 1, 1998 at the University of Texas at Austin for investigating ASR in portland cement concrete. The scope of the study was essentially three fold: (1) investigate the predictive ability of ASTM C 1260 and C 1293, (2) develop more accurate and more efficient modifications of these procedures, and (3) investigate ASR mitigation alternatives. Aggregate samples from 14 sources from around the United States were acquired for the investigation. Aggregates were used in an extensive testing program, during which guidelines for predicting the potential alkali-silica reactivity of aggregates were developed and recommendations for minimizing concrete damage due to ASR were formulated. This dissertation includes an extensive review of the state-of-the-art of ASR, an illustration of the results generated, and a discussion of the conclusions obtained throughout this study.

      • From Ground Measurements to Global Models: Temporal and Spatial Characteristics of Drought and Extreme Precipitation Under Historical and Future Global Warming

        Touma, Danielle ProQuest Dissertations & Theses Stanford Universit 2018 해외박사(DDOD)

        RANK : 247343

        Drought and extreme precipitation events lead to devastating damages to human and natural systems. The characteristics of these extreme climate events, including the frequency, intensity, and spatial extent of extreme wet conditions or extreme dry conditions can shape the risk posed to a region by an event. There has been substantial evidence that global warming has altered and will continue to alter atmospheric, land, and ocean conditions, which in turn lead to changes in the characteristics of extreme climate events. Additional anthropogenic emissions are expected to modify the ocean, land, and atmosphere in the future, though the role that these changes will have on future extreme precipitation and drought events is still uncertain. In my dissertation, I employ a multitude of observed and modeled climate datasets available to quantify the characteristics of drought and extreme wet events under past and future anthropogenic warming. By systematically quantifying the intensity, frequency, duration and spatial extent of extreme climate events across datasets, I aim to provide a climatological assessment of extreme climate event characteristics, and identify spatial or temporal variations of these characteristics. The findings from this dissertation will allow further insight into the impact past and future global warming have on extreme climate events, and subsequently, the risks to human and natural systems. In my first chapter, I investigate the expected changes in the frequency, duration, and spatial extent of drought over the globe in the 21st century under increased anthropogenic warming. To capture drought index-based uncertainty, I calculate four different drought indices which use precipitation, runoff, and moisture deficit, and to capture model-based uncertainty, I use climate simulations from 15 global climate models (GCMs) in the CMIP5 database. By comparing drought characteristics in the historical (1961-2005) simulations to the RCP 8.5 scenario (2010-2099) simulations, I show increases in the frequency and spatial extent of drought over the 21st century. These increases over the tropics and subtropics, reaching 80 more percentage points in the spatial extent and 40 more drought events, are robust among climate models when using deficit-based drought indices, but less robust when using precipitation or runoff-based indices. Given that deficit-based indices directly account for variations in temperature, these indices capture the significant increases in temperature simulated under high levels of anthropogenic emissions throughout the 21st century. These findings suggest that there is an increasing risk in drought stresses in many regions given the current trajectory of greenhouse gas emissions and associated warming temperatures. In my second chapter, I develop a geostatistical method to assess the spatial extent, or length scales, of extreme precipitation in GCHN-D station data. A climatological assessment over the US from 1965-2014 reveals significant seasonal and regional variations in the length scales of extreme daily precipitation. The eastern half of the US has daily extreme precipitation length scales reaching 400km during the winter months, but the length scales are halved during the summer months. The Northwest region, on the other hand, has little seasonal variation, with short extreme precipitation length scales of approximately 150km year-round. Though the magnitude of extreme precipitation length scales can be sensitive to certain choices in my method, the seasonal and regional variations remain relatively intact and can plausibly be explained by well-known atmospheric phenomena. This chapter introduces a valuable framework that can be used to quantify changes in the spatial extents of extreme climate events in the US and globally, and examine the impacts of varying spatial extents of extreme precipitation events on human and natural systems.

      • Dissecting Transient Protein Interactions Implicated in Cardiovascular Disease: G Protein-Coupled Receptors and Cardiac Myosin-Binding Protein C

        Touma, Anja Marie ProQuest Dissertations & Theses University of Minn 2021 해외박사(DDOD)

        RANK : 247343

        Weak, transient protein-protein interactions in the cell are being increasingly appreciated, yet characterization of these interactions presents a unique challenge. We have used protein engineering techniques, including ER/K α-helical linkers and DNA nanotechnology, to characterize G protein-coupled receptor (GPCR) and cardiac myosin-binding protein C (cMyBP-C) interactions.The cellular environment can have a significant impact on GPCR signaling and functional selectivity. Our lab has found that GPCR interactions with non-cognate G-proteins can enhance, or ‘prime’, signaling through the canonical pathway. To investigate the impact of non-cognate interactions on signaling in two promiscuous Gi-coupled receptors, adenosine type 1 (A1R) and cannabinoid type 1 (CB1), we utilized a variation of the Systematic Protein Affinity Strength Modulation (SPASM) approach to observe the impact on downstream signaling in live cells. To the C-terminus of intact A1R or CB1, we tethered native G-peptides (s-pep, i-pep, and q-pep) derived from the Gα subunit of G-proteins. We found that i-pep and q-pep enhanced Gi signaling while suppressing Gq signaling. This study provides an initial model for the impact of G-peptide interactions in Gi-coupled receptors, and highlights the potential of G-peptide interactions to enhance receptor specificity.CMyBP-C is an important regulator of cardiac muscle contraction and is commonly implicated in hypertrophic cardiomyopathy (HCM). However, the mechanism of regulation by cMyBP-C remains unclear due to experimental challenges in dissecting these weak, transient interactions. In this study we utilized a nanosurf assay, containing a synthetic β-cardiac myosin thick filament, to systematically probe cMyBP-C interactions with actin and myosin. We recapitulated inhibition of β-cardiac myosin HMM nanotube motility by C0-C2 and C1-C2 N-terminal fragments. Equivalent inhibition of an β-cardiac myosin S1 construct suggests the actin-cMyBP-C interaction dominates this inhibitory mechanism. We found that a C0-C1f fragment lacking the majority of the M-domain did not inhibit β-cardiac myosin nanotube motility, confirming the importance of the M-domain in regulatory interactions. Release of inhibition by phosphomimetic fragments further highlights the importance of the phosphorylatable serines in the regulatory M-domain. These results shed light on the mechanism of cMyBP-C and highlight the utility of the nanosurf assay for precisely manipulating and defining transient protein interactions.

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