VictorJuiz/thesis huggingface dataset:
Optimizing the cache performance of non-numeric applications

The latency of accessing instructions and data from the memory subsystem is an increasingly crucial performance bottleneck in modern computer systems. While cache hierarchies are an important first step, they alone cannot solve the problem. Further, though a variety of latency-hiding techniques have been proposed, their success has been largely limited to regular, numeric applications. Few promising latency-hiding techniques that can handle irregular, non-numeric codes have been proposed, in spite of the popularity of such codes in computer applications. This dissertation investigates hardware and software techniques for coping with the 'instruction-access latency' and 'data-access latency' in 'non-numeric' applications. To deal with instruction-access latency, we propose 'cooperative instruction prefetching ', a novel technique which significantly outperforms state-of-the-art instruction prefetching schemes by being able to prefetch more aggressively and much further ahead of time while at the same time substantially reducing the amount of useless prefetches. To cope with data-access latency, we investigate three complementary techniques. First, we study how to use 'compiler-inserted data prefetching ' to tolerate the latency of accessing pointer-based data structures. To schedule prefetches early enough, we design three prefetching schemes to overcome the pointer-chasing problem associated with these data structures, and we automate them in an optimizing research compiler. Second, we study how to safely perform an important class of locality optimizations, namely ' dynamic data layout optimizations', in non-numeric codes. Specifically, we propose the use of an architectural mechanism called 'memory forwarding ' which can guarantee the safety of data relocation, thereby enabling many aggressive data layout optimizations (which also facilitate prefetching) that cannot be safely performed using current hardware or compiler technology. Finally, in an effort to minimize the overheads of latency tolerance techniques, we propose new cache miss prediction techniques based on 'correlation profiling'. By correlating cache miss behaviors with dynamic execution contexts, these techniques can accurately isolate dynamic miss instances and so pay the latency tolerance overhead only when there would have been cache misses. Detailed design considerations and experimental evaluations are provided for our proposed techniques, confirming them as viable solutions for coping with memory latency in non-numeric applications.
Characterization of the activation and inactivation of invertebrate Gq in the squid retina

iG$\rm\sb{q}$ has been identified as an important mediator of signal transduction in the invertebrate visual system but remains largely uncharacterized. The aim of my research is to understand the regulation of activation and inactivation of iG$\rm\sb{q}$ in this system. iG$\rm\sb{q}$ was extracted from squid photoreceptors in both a membrane bound and soluble form which display very different binding characteristics and GTPase activity. Membrane bound iG$\rm\sb{q}$ exhibited rapid, light dependent guanine nucleotide binding with strikingly different affinities for GTP versus GDP, and slow GTPase activity. In contrast, soluble iG$\rm\sb{q}$ exhibited slow, light independent binding with equal affinity for GTP and GDP and relatively rapid GTPase activity. Semi-purification of soluble iG$\rm\sb{q}$ resulted in the loss of GTPase activity which was partially restored by addition of PLC 140. These findings provide valuable information about the activation and inactivation of iG$\rm\sb{q}$ in this system and suggest a possible function for solubilization of iG$\rm\sb{q}.$
Interaction of chloride/bicarbonate anion exchangers with carbonic anhydrase II

An interaction between human erythrocyte carbonic anhydrase II (CAII) and Band 3 has been identified and characterized. Immunofluorescence demonstrated that tomato lectin-mediated clustering of Band 3 in ghost membranes caused a similar clustering of CAII, indicating an 'in situ' association. Similarly, Band 3 and CAII could be cosolubilized and coimmunoprecipitated. This association was found to be mediated through the carboxyl-terminal region (Ct) of Band 3. A sensitive microtitre plate assay using a GST-fusion protein of the 33 residue Ct was developed. This assay was used to show that the interaction between the Ct and CAII was slow, but this rate could be enhanced by low ionic strength and acidic pH. The binding site on the Ct of Band 3 was further examined using truncation and point mutations of this sequence. Removal of the terminal 21 residues of Band 3 did not affect the interaction with CAII. However, further truncation of four residues (887-890) resulted in a loss of binding to CAII. Acidic residues in this region were required since mutation of the endogenous sequence (D887ADD) to DAAA, AAAA, or NANN caused a loss of the interaction. The Ct of AE2, a ubiquitous isoform of Band 3, was also able to bind specifically to CAII. The complementary binding site for the Ct of Band 3 on the surface of CAII was probed by a similar strategy. Since CAI, an isoform with 60% sequence identity, is unable to bind Band 3, sequence differences between the two proteins were examined. CAII was found to possess a histidine-rich cluster near the amino terminus of the protein, not found in CAI. When this region was truncated, or mutated to the homologous residues in CAI, the interaction between Band 3 and CAII was lost. These results provide a structural basis for the Jacobs-Stewart cycle, which describes the equilibrium of CO2 and bicarbonate across the red cell membrane. A complex between anion exchangers and CAII may form a capno-metabolon, and increase the efficiency Of CO2 movement.
The interface of tort and contract in the Canadian construction case

This thesis considers jurisprudence testing the boundaries of tort and contract law. Of particular interest are those cases arising from and impacting on construction disputes. Important recent developments in fundamental legal doctrine are analysed as well as the construction contracts and insurance policies forming part of the factual matrix to the construction case. The writer's conclusion is the courts should be especially deferential to private ordering in these cases. The direct and indirect contractual arrangements between the litigants help define or limit tort duties between them.
Strategies for isolation and expression of ribozymes for use in HIV gene therapy

Ribozymes are small, catalytic RNA molecules which possess endoribonuclease activities. They can be expressed as part of tRNA genes because of the strong tRNA promoter and the stable tRNA structure. Thus, a ribozyme which is inserted into a tRNA molecule will be produced in large quantities and will be protected from RNase degradation in cells. tRNA3Lys was used for constructing HIV-1 RNA-specific tRNA-ribozymes. This tRNA is the primer used by HIV-1 for reverse transcription, and is co-packaged within the virus particles. By using the recombinant tRNA3Lys the virus may be tricked into packaging the tRNA-ribozymes. Being in such close proximity, the ribozymes have the potential to bind and cleave HIV-1 RNA within the virus particles. A hammerhead ribozyme targeted against the HIV-1 'env'-coding region was expressed as part of the anticodon loop of human tRNA3 Lys without sacrificing tRNA stability or ribozyme catalytic activity. These tRNA-ribozymes were isolated from a library which was designed to contain linkers (sequences connecting the ribozyme to the anticodon loop) of random sequence and variable length. The linkers on either side of the ribozyme ranged in length from 0 to 20 nucleotides. Active tRNA-ribozymes were selected ' in vitro' by placing the ribozyme and its target 'in cis' so that 'cis' cleavage can occur. The tRNA-ribozymes that possessed ideal combinations of linkers were expected to recognize the 'cis' target site more freely and undergo cleavage. The cleavage products containing active tRNA-ribozymes were separated from uncleaved target RNA due to size difference and used for reverse transcription followed by PCR. 'In vitro' selected tRNA-ribozymes were cloned in the pGEM4Z plasmid and characterized. tRNAAC-Rz (0/0), tRNAAC-Rz (2/0), tRNAAC-Rz (4/0), tRNAAC-Rz (8/0) and tRNAAC-Rz (10/0) were selected from this library. These tRNA-ribozymes were stable, possessed cleavage efficiencies lower or similar to the linear hammerhead ribozyme, and could be transcribed by a cell extract containing RNA polymerase III. Retroviral vectors expressing tRNA-ribozymes were tested in a human CD4+ T cell line and were shown to inhibit HIV-1 replication. These tRNA3Lys-based hammerhead ribozymes should therefore prove to be valuable for both basic and applied research.
Three types of nerve terminals based on vesicle morphology in the blue crab stomach pyloric muscles

Movements of the gastric mill and pylorus in the stomach of the blue crab 'Callinectes sapidus' are brought about by a series of striated muscles which receive exclusively excitatory input from neurons in the stomatogastric ganglion. Electron microscopic examination of the pyloric muscles of the p11, p12, p13 and p14 motor unit revealed the presence of two other putative types of innervation, namely inhibitory and neuromodulatory, based on vesicle morphology. The first type, excitatory, was readily identified by the spherical shape of its small, clear synaptic vesicles. The second type, inhibitory, was identified by the presence of elliptically shaped clear synaptic vesicles. Both of these terminal types were observed in all four muscles examined. The third type, neuromodulatory, seen in only the p14 muscle was characterized by the presence of primarily large dense core vesicles containing eccentrically located cores. All three nerve terminal types formed synaptic contacts, with dense bars, with the pyloric muscle membrane. Altogether, the existence of excitatory, inhibitory and neuromodulatory innervation of the pyloric muscles implies a level of modulatorion at the periphery that is as complex as that found in the stomatogastric ganglion itself.
Magnetic resonance thermometry for image-guided thermal therapy

The integration of medical-image guidance in medicine can enable the adaption of novel minimally-invasive surgeries and therapies. Thermal-coagulation therapy is a procedure that will benefit from image guidance and have clinical significance as an alternative to conventional treatments such as resective surgery or radiation therapy. The goal of this thermal therapy is to elevate diseased tissue temperature to induce necrosis while ensuring that the thermal treatment to surrounding healthy tissue is below toxic levels. The spatial-temporal delivery of heat energy requires control which is ideally provided through mapping of the three dimensional distribution of temperature in tissue. This thesis explores the use of real-time magnetic resonance imaging (MRI) for monitoring and guiding thermal-coagulation therapy. Specifically, a method of spatially-resolving the temperature distribution is described that incorporates the temperature-sensitivity of the proton-resonance frequency (PRF). This thermal-imaging method is implemented by measuring temperature-dependent phase shifts from a gradient-echo pulse sequence. Thermal calibration results are presented which show the temperature dependent PRF-shift to be independent of 'ex vivo' tissue type, within an experimental precision of 4%. The PRF-shift method of MR thermometry is shown to be capable of quantitatively accurate temperature measurements. However, it is identified that attention is required to several considerations, such as temperature-induced changes in the volume-magnetic susceptibility and electrical conductivity of tissue. The ability for real-time prediction of the spatial extent of thermal-coagulation necrosis is demonstrated with results obtained in an 'in vivo' canine prostate model. In this experiment, laser heating of the prostate gland was performed simultaneously with MR-thermal mapping. Using histological sections of the prostate gland to indicate the boundary of necrosis, a discriminant analysis revealed the onset of thermal-coagulative necrosis to be characterized by a critical temperature of approximately 51°C, or equivalently with an Arrhenius 't'43 period of approximately 200 minutes. It is concluded that real-time quantitative MR-thermal mapping is a visualization tool that can be used effectively for delivery and control of thermal-coagulation therapy.
Supporting design for remanufacture through a waste-stream analysis of automotive engine remanufacturers

An analysis of waste streams of original equipment and independent remanufacturers is undertaken in order to reveal barriers to remanufacture. Discarded parts are categorized by failure mode and by scrap mode. A statistical analysis supports that the sample counted is large enough to represent the population of discarded engine parts. Worn parts that cannot be further refurbished are found to constitute the greatest proportion of parts entering the waste stream, on both a part-count and mass basis. Four sets of design-for-remanufacture guidelines are developed from the results of the waste-stream analysis, and from modifying other design methods (Failure Mode and Effects Analysis and Quality Function Deployment) to focus on remanufacture. A method of integrating different life-cycle design concerns is suggested.
Specification and design of a high speed simulation and control system

The specifications for a fast real-time control system to replace the current UHP40 system were determined. The major components involve a fast PCI based TMS320C6701 DSP card, fast analog-to-digital conversion capabilities, and programmable logic on the hardware side and a fast monitor program running on a Windows NT machine and associated kernel routines on the DSP. Two designs were examined and components were selected to implement to meet the specifications. Various tests were performed to characterize the system's speed and communications characteristics. A system that met most of the requirements was delivered.
Exploration, knowledge, and empire in Africa, the Emin Pasha Relief Expedition, 1886-1890

The Emin Pasha Relief Expedition travelled from the mouth of the Congo River to Zanzibar between 1886 and 1890. The Expedition's ostensible purpose was to bring relief supplies to Emin Pasha, the governor of Equatoria, in the Egyptian Sudan. However, the Expedition was also linked to the formation of the Imperial British East Africa Company and to Leopold II of Belgium's nascent Congo Free State. The Expedition's aftermath included months of public debate in Britain and elsewhere about its purpose and conduct, as well as broader discussion of the nature of European travel in Africa. Within Africa, the Expedition attempted to create a new route between the upper Congo River and Lake Albert. In this effort it built on and competed with the east-coast based traders active in the region, thus becoming part of a broader process of violent transformation on the expanding frontier of long-distance trade. To date, scholarly and popular writing about the Expedition have focused on its place in European imperial politics and on its European participants. This thesis employs newly available primary sources to examine previously neglected aspects of the Expedition and of late nineteenth century travel in East-Central Africa. Drawing on recent work in the sociology of science and technology, it examines the ways in which European travellers made use of African expertise and resources for travel. It traces the dynamic links the Expedition created between persons, institutions, objects, texts, and the physical environment in East-Central Africa and elsewhere. It provides an opportunity to study the construction of agency and identity, as well as the ways in which power was constituted and deployed in specific interactions between Africans and Europeans. These interactions were part of a mutual, but contested construction of Africa and Africans on which subsequent European imperial activities in the region were based. Further, because this Expedition was so well-documented, it allows an intensive study of the strategies of the its Zanzibari porters. Accounts of the Expedition also provide a unique opportunity to study the dynamics of unequal access to food within large European-led caravans, using the concept of entitlement.
Gentlemen bankers, politicians and bureaucrats, the history of the Canadian Bankers Association, 1891-1924

This is a history of the Canadian Bankers Association, a Canadian trade association unlike any other. Its origins are linked to deficiencies in Canada's Bank Act, 1871 and policies distancing the federal government from demands for assistance from weak banks and their victims--depositors, note holders and investors. Bank failures in the 1870s and 1880s added weight to calls for safer banks and more government regulation, pressure many bankers feared would cause reforms undermining the flexibility the Bank Act allowed them to exercise in their day to day business. A small number of prominent bankers avoided this danger by proposing a fund all banks would to contribute for the protection of note holders. They also suggested a bankers' association to guard the interests of the fund's contributors and ultimately the public. When bankers launched their organization, it had specific, yet unwritten, obligations to the federal government. It was supposed to make banking safer and, under pressure from the finance department, limit competition for deposits, a business the government was involved in through its Post Office and Dominion Savings Banks. This thesis will trace the role of the CBA between 1891 and 1924 and show it was anything but a "cozy cartel," as some scholars have alleged. Competition and rivalry divided Canadian bankers and produced a feckless trade association that could do little to meet calls from governments and those that elected them for safer banks. For Canadian bankers and their association, failure soured relations with politicians and sowed the seeds of public cynicism, leaving a legacy that has shaped the way Canadian governments make bank policy.
Role of nitric oxide in the treatment of type 2 diabetes with American ginseng (Panax quinquefolius. L.)

To investigate the role of nitric oxide (NO) in the treatment of diabetes with American ginseng extract (AG), a double-blind, placebo-controlled study was conducted in 24 type 2 diabetic subjects. They were randomized to take either AG 2.25g/day or placebo for 8 weeks, then crossover with at least 4 weeks washout. Blood pressure was determined and fasting blood was taken to assess NO, glycemic parameters and lipid peroxidation. During AG treatment, NO increased significantly compared to placebo (P = 0.031). The change was negatively correlated to HbA1c (R = -0.42, P = 0.043), which decreased (P = 0.026) following AG. Fasting blood glucose, lipid peroxidation and blood pressure were improved with AG (P < 0.05 respectively). It is concluded that in type 2 diabetes, AG reduced cardiovascular risk factors such as hypertension and improved glycemic control which was associated with NO enhancement.
A biophysical study of human type II inosine 5'-monophosphate dehydrogenase, identification of a reversible self-associating system and an active monomeric species

Understanding how the structure of a protein affects its self-association characteristics and, perhaps more importantly, its interactions with other ligands are critically important for identifying its function in the body. We have undertaken a comprehensive investigation of human type II inosine 5'-monophosphate dehydrogenase (IMPDH-II), an enzyme involved in purine biosynthesis for replicating cells, by circular dichroism, spectroscopy, mass spectrometry, non-denaturing PAGE, and 'in situ ' high resolution atomic force microscopy. While the structure of the tetrameric form of IMPDH-II has been reported, our studies have provided the first evidence that the enzyme exists in a reversible self-associating equilibrium state comprising monomeric, dimeric and tetrameric species, and that the monomeric form is functionally active. These studies establish a biophysical approach for investigating the structure-function-association characteristics of biomolecular complexes.
Investigation of the interindividual variability in hepatic cytochrome P450 CYP3A4, association with CYP3A4*1B

In this study, we determined the association of 'CYP3A4*1B' ('CYP3A4-V') to the large interindividual variability in hepatic CYP3A4. We observed a non-normal distribution in the amount of immunoreactive CYP3A4 present in 48 human liver samples. Probit and NTV analyses revealed that 38% of these samples had CYP3A4 protein levels below an apparent antimode of 21 pmol CYP3A4/mg microsomal protein. Interestingly, probit and NTV plots of testosterone 6ß-hydroxylation activity, a marker for CYP3A4 activity, of two liver banks also revealed approximately 40% of the population below an analogous antimode. This data suggests that approximately 40% of the Caucasian population forms a distinct subpopulation with low CYP3A4 activity. To determine whether 'CYP3A4*1B' associates with this low activity, we characterized our liver banks via a novel 'CYP3A4*1B' genotype assay. We found a 'CYP3A4*1B' allele frequency of 6% in the Caucasian population. Furthermore, we report no association between 'CYP3A4*1B ' and testosterone 6ß-hydroxylation. This study suggests ' CYP3A4*1B' allele has no association with CYP3A4 activity.
Regulation of the mating pheromone and invasive growth responses in yeast by two MAP kinase substrates

In S. cerevisiae, components of a MAP kinase pathway form part of the response to different upstream signals resulting in separate developmental outcomes, mating and filamentous growth. Two proteins, Rst1 and Rst2 (a.k.a. Dig1 and Dig2), were found to physically associate with a mating MAP kinase Fus3 and a mating and filamentous growth specific transcription factor, Ste 12. Although rst1 and rst2 single mutants had no obvious phenotype, rst1 rst2 double mutants had constitutively active mating specific gene expression and filamentous growth. Rst1 and Rst2 were prominent substrates in Fus3 immune complex kinase reactions from pheromone treated cells. Association of Fus3 with Ste12 required Rst1 and Rst2, and activation of Fus3 by pheromone caused release of Ste12 from Fus3 complex. Consistent with a role in Ste12 regulation, Rst1 and Rst2 were localized to the nucleus. Therefore, Rst1 and Rst2 may repress mating and filamentous growth by directly inhibiting Ste12.
Widowhood: The relationship between social support, health and loneliness

A descriptive correlational study utilizing a convenience sample of 30 elderly widows examined the relationships between the perceived provisions of social support and the dimensions of health, the perceived provisions of social support and loneliness, and loneliness and the dimensions of health. Data were collected during one interview using a Demographic Data Sheet; the Social Provisions Scale, the Health Status Profile-SF-36; and the UCLA Loneliness Scale. Data analysis revealed several positive and strong relationships between the perceived provisions of social support and the dimensions of health. A negative but moderate relationship was found between the provision of attachment in social support and loneliness. Several negative but strong relationships were found between loneliness and the dimensions of health. The results of this study support the literature that links social support to health, and perception of good health to less loneliness. The findings did not support the literature that suggests that the loss of an attachment figure (spouse) leads to the experience of loneliness.