Search

Heterogeneous platforms play an increasingly important role in modern computer systems. They combine high performance with low power consumption. From mobiles to supercomputers, we see an increasing number of computer systems that are heterogeneous. The most well-known heterogeneous system, CPU+GPU platforms have been widely used in recent years. As they become more mainstream, serving multiple tasks from multiple users is an emerging challenge. A good scheduler can greatly improve performance. However, indiscriminately allocating tasks based on availability leads to poor performance. As modern GPUs have a large number of hardware resources, most tasks cannot efficiently utilize all of them. Concurrent task execution on GPU is a promising solution, however, indiscriminately running tasks in parallel causes a slowdown. This thesis focuses on scheduling OpenCL kernels. A runtime framework is developed to determine where to schedule OpenCL kernels. It predicts the best-fit device by using a machine learning-based classifier, then schedules the kernels accordingly to either CPU or GPU. To improve GPU utilization, a kernel merging approach is proposed. Kernels are merged if their predicted co-execution can provide better performance than sequential execution. A machine learning based classifier is developed to find the best kernel pairs for co-execution on GPU. Finally, a runtime framework is developed to schedule kernels separately on either CPU or GPU, and run kernels in pairs if their co-execution can improve performance. The approaches developed in this thesis significantly improve system performance and outperform all existing techniques.

Adult skeletal muscle is highly plastic and responds readily to environmental stimuli. One of the most commonly utilized methods to study skeletal muscle adaptations is immunofluorescence microscopy. By analyzing images of adult muscle cells, also known as myofibers, one can quantify changes in skeletal muscle structure and function (e.g. hypertrophy and fiber type). Skeletal muscle samples are typically cut in transverse or cross sections, and antibodies against sarcolemmal or basal lamina proteins are used to label the myofiber boundaries. The quantification of hundreds to thousands of myofibers per sample is accomplished either manually or semi-automatically using generalized pathology software, and such approaches become exceedingly tedious. In the first study, I developed MyoVision, a robust, fully automated software that is dedicated to skeletal muscle immunohistological image analysis. The software has been made freely available to muscle biologists to alleviate the burden of routine image analyses. To date, more than 60 technicians, students, postdoctoral fellows, faculty members, and others have requested this software. Using MyoVision, I was able to accurately quantify the effects of β-catenin knockout on myofiber hypertrophy. In the second study, I tested the hypothesis that myofiber hypertrophy requires β-catenin to activate c-myc transcription and promote ribosome biogenesis. Recent evidence in both mice and human suggests a close association between ribosome biogenesis and skeletal muscle hypertrophy. Using an inducible mouse model of skeletal myofiber-specific genetic knockout, I obtained evidence that β-catenin is important for myofiber hypertrophy, although its role in ribosome biogenesis appears to be dispensable for mechanical overload induced muscle growth. Instead, β-catenin may be necessary for promoting the translation of growth related genes through activation of ribosomal protein S6. Unexpectedly, we detected a novel, enhancing effect of myofiber β-catenin knockout on the resident muscle stem cells, or satellite cells. In the absence of myofiber β-catenin, satellite cells activate and proliferate earlier in response to mechanical overload. Consistent with the role of satellite cells in muscle repair, the enhanced recruitment of satellite cells led to a significantly improved regeneration response after chemical injury. The novelty of these findings resides in the fact that the genetic perturbation was extrinsic to the satellite cells, and this is even more surprising because the current literature focuses heavily on intrinsic mechanisms within satellite cells. As such, this model of myofiber β-catenin knockout may significantly contribute to better understanding of the mechanisms of satellite cell priming, with implications for regenerative medicine.

Numerous studies have established the relationships between working memory (WM), rapid automatized naming speed, reading comprehension, calculation, and word problem solving (WPS). However, there is limited research on the differential effects of the WM components (central executive, phonological loop, visual-spatial sketchpad) on WPS, and how speed, reading, calculation, and knowledge of word problem components mediate that relationship. The sample consisted of 413 between ages 6-10 (M = 8.38, SD = .51). The results yielded three important findings: 1) without any mediators, the phonological loop was the best predictor of WPS; 2) when other variables were entered into the model, reading and calculation were the strongest direct predictors of WPS; 3) results of the mediation model showed that speed mediated the relationship between the central executive component of WM and WPS, while reading mediated the relationship between the central executive and phonological loop and WPS. The educational implications of these findings are discussed.

Cells can be cultured in different formats, such as in three-dimensional (3D) tissue constructs, in free suspension, in microcarriers, or in attached monolayer. Microscale and microfluidic cell culture devices are potentially useful in future pharmaceutical development and biomedical applications. However, culturing cells at microscale or in a microfluidic device imposes unique challenges and deserves further investigations. For high-throughput cytotoxicity studies of anticancer drugs, increasing evidence indicates that 3D cell cultures create superior in vitro models to conventional monolayer cultures in multi-well plates. Due to high cell density in 3D culture, mass transport is critical. Perfusion culture via microfluidic operation provides continuous nutrient inflow and waste removal, significantly improving mass transport. To make it even more advantageous, 3D perfusion microbioreactors may help create an in-vivo like hydrodynamic microenvironment. In this study, a perfusion microbioreactor array was designed and fabricated for 3D culture of human colon cancer cells in modular fibrous matrix. Proliferation was monitored non-invasively with auto-fluorescence from green fluorescent protein expressed by engineered cells. Dose dependent response of the 3D cell proliferation to 5-fluorouracil was observed. The modular design allowed direct post-culture access to intact tissue constructs for various analyses. The perfusion microbioreactor array is a platform technology, which has a potential to be used as an in-vitro cancer model and in high throughput drug screening device.One of the challenges for microfluidic cell culture in an array was parallel flow control. Flow control in multiple hydrophobic microchannels with a common inlet was thus investigated. Based on a series of designs of perfusion microbioreactor arrays, theoretical analysis and experimental validation were developed. It was found that capillary pressure played a key role in parallel flow control in the startup phase. The theory and the experiments had an excellent match. A novel method of achieving parallel flow control at significantly reduced flowrates was developed by using fibrous matrices in the microchannels. This study provided a rational approach to achieving parallel flow control by design, material selection and operations. Another high-throughput cell culture platform developed in this study was a 24-well microbioreactor array for suspension culture. A central static mixer was fabricated to effectively break poor mixing patterns in multi-well-plate-based cell cultures, minimizing cell aggregate formation. Furthermore, evaporation was reduced with non-polar gas permeable membranes for both the bottom and the lid. Therefore, cell culture data quality was improved with the microbioreactor array. In addition, its mixing time and maximum oxygen transfer rate were characterized with optical methods. With design of experiment using the microbioreactor array, active factors for serum-free media were identified for Chinese hamster ovary cells producing monoclonal antibody (MAb). Microcarriers are useful in culturing anchorage-dependent cells in conventional stirred tank bioreactors. However, microcarrier cell cultures are very sensitive to shear stress and microcarrier collision in a stirred tank. Furthermore, high cost of commercial microcarriers also limits large scale use of this technology. In the perfusion microbioreactor array project, dynamic cell seeding onto small fibrous matrices was studied. Due to the similarity in operation, macroporous fibrous microcarriers were thus developed. In a comparative study, the fibrous microcarriers had comparable performances with several commercial microcarriers on cell attachment, cell growth and MAb production. Excellent protection of cells against high shear stress was achieved. In addition, the fibrous microcarriers provide over 1000-fold cost savings. These could be especially meaningful for large-scale microcarrier cell cultures, such as in viral vaccine production.

Separation of aromatic/aliphatic hydrocarbon mixtures by pervaporation has been of increasing interest in recent decades. Dozens of polymer materials have been reported for separations of benzene/cyclohexane and toluene/iso-ocatne mixtures. However, fundamental understanding of material structure and transport relations is not adequate to generalize guidelines for materials screening. The goals of this study are to tailor the structure of the polyimide materials, correlate the structure and transport relations, and establish guidelines for future materials. The 3, 5-Diaminobenzoic acid (DABA) containing polyimides were synthesized by both chemical and thermal solution imidization. The synthesized polyimides were formed into dense films by solution casting. The physical properties of the polyimides synthesized with monomers: 2, 2-bis (3, 4-dicarboxyphenyl) hexafluoropropane dianhydride (6FDA), 4, 6-trimethyl-1, 3-phenylendiamine (DAM) and DABA, were characterized by DSC, WAXD, GPC and density. The chemical structures were assessed by FTIR and NMR. The pervaporation and sorption of the synthesized polyimide membranes were tested in toluene/iso-octane mixtures at 100°C. The structure- transport property relations were established for the 6FDA-DAM/DABA membranes. The 6FDA-DAM/DABA polyimides were crosslinked by ethylene glycol. The pervaporation and sorption of the crosslinked membranes were tested in toluene/iso-octane mixtures at 100°C. Thermal imidization was found to give a higher imidization degree than chemical imidization. As a result, the polyimides made by chemical imidization contain a higher percentage of carboxylic acid groups than those made by thermal imidization. Chemical imidization gives higher film density, glass transition temperature and lower flux and higher selectivity for the toluene/iso-octane pervaporation than the thermally imidized membranes because of the higher carboxylic acid concentration. The chemically imidized membranes are slightly brittle after the crosslinking. Only the thermal imidization membranes have good flexibility and its pervaporation selectivity improves significantly after the crosslinking. Solubility selectivity and diffusivity selectivity of the 6FDA-DAM/DABA membranes were correlated with solubility parameters and fractional free volume, respectively. The structure-mass transport relations show that for the 6FDA-DAM/DABA membranes, both solubility selectivity and diffusivity selectivity contribute to the pervaporation selectivity. For the chemically imidized membranes, increased DABA concentration has a positive effect on solubility selectivity and diffusivity selectivity. For the thermally imidized membranes, increased DABA concentration has a significant effect on diffusivity selectivity only.

Photosynthetic water oxidation to form dioxygen occurs using a manganese cluster in the oxygen evolving complex (OEC). The higher oxidation states (S3 and S4) of the Mn cluster are still unclear. To examine the viability of a MnIV/V2=O complex as a model for the S4 state, [MnIII/IV2(2-OHsalpn) 2]+ (2-OHsalpn = N,N'-bis(salicylimino)-1,3-diaminopropan-2-ol) was oxidized at -78°C by meta-chloroperoxobenzoic acid (m-CPBA) to form [MnV/IV2=O(2-OHsalpn) 2]+. MnV=O reactivity was probed using a cyclohexene assay. Cyclohexene oxide was detected by GC-mass spectroscopy from the reaction of [MnIII/IV 2(2-OHsalpn)2]+ with m-CPBA in the presence of cyclohexene. The reaction proceeded for 20 turnovers. CO2(g) was observed from the same reaction in the absence of cyclohexene. The kinetics of the reaction in the absence of cyclohexene was followed by stopped-flow UV-Visible, freeze-quench EPR and XANES spectroscopies. Rapid formation (30 ms after the reaction was initiated) of a radical species and a MnIV/IV2 complex were detected. The generated MnV=O reacts with the product (m-chlorobenzoate) to form a radical then liberates CO2(g). Parallel mode EPR spectra also detected a multiline signal, which is identified as a MnIV 4 tetramer. The spectral features are very similar to the S1 state; however, the smaller spectral width indicates that the MnIV 4 model has a higher oxidation states than found in S 1. The proposed reaction mechanism suggests initial oxidation of Mn IV/IV2 to MnIV/V2=O, which can oxidize benzoate forming an organic radical species and a MnIV/IV 2 complex. Alternatively the MnIV/V2=O can rapidly comproportionate with a MnIII/IV2 species forming the MnIV4 tetramer. Despite previous literature reports that treat the manganyl group solely as a two-electron, oxo transfer moiety, this work demonstrates for the first time that the manganyl group can competitively undergo single electron reduction reactions.

This study represents a theoretical synthesis of the history of exact science. The persistent epistemological regularities identified in the study includes: (1) The Principle of Axiomaticism, or the Heraclitean-Confucian Principle. Every branch of physics and mathematics culminated in an axiomatized format. In fact, axiomatization and scientific underst and ing are equivalent. The historical roots of axiomaticism are traced; its congeniality with Aristotle's "teleological economy" is pointed out; so is its identity with Ernst Mach's "economy of mental effort." (2) The Principle of the Expansive Pools of Measurables. Knowledge in physics has been accumulated by way of empirical and intellectual manipulations of a number of physical measurables. The progress of physics corresponds to the "expansions" of "a pool of measurables," in one, or two, or all three possible manners. (3) The Principle of "Saving the Appearances." This ancient idea is now formulated as a principle in contrast to another ancient idea of "thinking up the true causes." In generalizing Pierre Duhem's work, this study shows that competition between these two attitudes has been persistent. (4) The Prinicple of Quasi-Deterministic Accumulation of Physical Science. Physical sciences are characterized by rigid internal logic. Did the historical building-up of physical sciences follow accidental courses? The answer is no, although neither was it historically deterministic. Since the accumulations of related positive results of sciences are sequential and orderly, they are described as quasi-deterministic. The study has been conducted with the observation that the whole history of physics serves well to illustrate all these historical regularities. The success of this viewpoint is evinced in a profound presentation of the Copernican Revolution, the Newtonian Synthesis, and the Chemical Revolution. As an epistemological exposition of the history of science, this study uses its own definition of science. In the beginning chapter, a thorough and exact definition of science is proposed, on the one h and , as an antidote to the movement that declares that "science is not all that scientific" and , on the other h and , as a successor to a number of definitions formulated by authors since antiquity. The study, however, concedes incompleteness in collecting and analyzing past definition of science.