VictorJuiz/thesis huggingface dataset:
Structure determination of the apo-form of human inosine 5'-monophosphate dehydrogenase type II

Human inosine 5'-monophosphate dehydrogenase (IMPDH) controls a key metabolic step in the regulation of cell differentiation and growth. The catalytic reaction involves the NAD-dependent oxidation of inosine 5'-monophosphate (IMP) to xanthosine 5' -monophosphate (XMP), which is the rate-limiting step in the ' de novo' biosynthesis of guanine nucleotides. There are two identifiable isoforms of IMPDH, type I and type II. Type I is a tissue-specific, constitutively expressed protein while the type II isoform is significantly up-regulated in neoplastic and differentiating cells. As a consequence, IMPDH has been validated as a target in antitumor and immunosuppressive drug design. A method was developed to obtain milligram quantities of the human type II IMPDH isoform by amplification of the coding region cDNA by PCR, recombining the cDNA into a bacterial high-level expression plasmid, and large-scale protein purification to obtain between 25 and 30 mg of protein per liter of bacterial culture. Large, single crystals of the apo-form of the enzyme were reproducibly grown. They were suitable for X-ray diffraction analysis and diffraction data were collected to 3.2 Å resolution. The crystal structure was solved by molecular replacement using the hamster IMPDH II structure as a search model followed by model building and refinement. The residuals for the final model were Rcryst = 23.0% and Rfree = 28.9%. Analysis of the model demonstrated that the main fold of the enzyme was an Ã/ß barrel. It was also revealed that parts of the protein surrounding the active site were disordered. When comparing the human apo-form of IMPDH II to the human IMPDH II structure that was complexed with ligands, these regions become ordered upon ligand association. Sequence alignments indicated that these regions are conserved throughout evolution and that this type of ordering was most probably fundamental to the proper function of the enzyme. These structural data were consistent with published functional data that showed that IMPDH undergoes significant conformational changes on substrate association and that the apo-form of IMPDH has multiple structural conformations.
Risk perception and reasoning performance in high and low risk adolescents

The goal of this exploratory research was to examine whether high and low risk male adolescents differed on a group of measures associated with risk perception and risk behaviour. Based on previous research, it was expected that high risk adolescents would consistently report and display more risk related behaviours than low risk adolescents. Cognitive ability and thinking dispositions were examined as correlates of performance on these tasks. A sample of ninety male adolescents were subdivided into two groups--a high or low risk group based on the frequency of school suspensions. Tasks included: two self-report measures consisting of a risk perception questionnaire and a future life events inventory; two reasoning tasks consisting of a gambling task and a marble task; a cognitive ability measure; and a thinking dispositions questionnaire. The high risk students reported less fear of the dangers associated with high risk activities, displayed lower optimism, and these students were also the high risk choosers on the gambling task of cost-benefit reasoning. No differences were found on the marble reasoning task. Some evidence was found for a "syndrome of problem behaviour", as students who engaged in one high risk activity were more likely to engage in other high risk activities. High and low risk students did not differ in cognitive ability and some trends were found which suggest that thinking dispositions may explain differences between the two groups of students. The implications of these findings are discussed in terms of a somatic marker hypothesis (Bechara et al., 1994) and a generic dual process framework for reasoning (Stanovich & West, 2000).
Seismic upgrade and repair of square reinforced concrete columns with carbon FRP jackets

Insufficient transverse reinforcement renders reinforced concrete columns ineffective dissipaters of large seismic energy and the inadequate ductility typically leads to failure. This research evaluates the effectiveness of strengthening deficient and repairing damaged columns with carbon fibre reinforced polymer (CFRP) jackets under earthquake loading. Near full-scale columns consisted of 305 x 305-mm cross sections with concrete strengths ranging from 31.4-MPa to 43.0-MPa. Eight specimens were tested under lateral cyclic excursions while subjected to constant axial loads. Four additional specimens were tested under pure axial loads. Results indicate that decreased lateral expansion rates provided from CFRP confinement enhanced ductility, energy dissipation, shear and moment capacities of deficient specimens. Seismic behaviour was superior to similar columns designed according to various earthquake code provisions although higher axial load levels reduced improvements and responses were subordinate to comparable retrofitted circular specimens. Retrofit improvements observed following CFRP repair of degraded columns depended on the severity of damage sustained.
A random effect model with quality score for meta-analysis

Meta-analysis is a set of statistical maneuvers to quantitatively summarize multiple related studies. There are two major statistical approaches to meta-analysis. One is fixed effect models, which assume that all studies are governed by a common treatment effect, and take the studies be analyzed as the universe of interest; the other is random effect models, which allow different treatment effects for different studies, and treat these studies as representing a sample from a larger population of possible studies. Because the reliability of data used in the meta-analysis is different, in order to get more accurate results, quality scores can be introduced to model the data reliability. In this thesis, I study a random effect model incorporating quality score for meta-analysis in comparison with three other models. I apply likelihood methods and the bootstrap to estimate the study effect, and the bias and standard errors of the estimators. I apply the model to a real data set, and to simulated data sets. By analyzing systematic computational results, I find that the random effect model with quality score can offer better accuracy, precision and coverage of the estimate of study effect than the other three models.
The savage Indian and the foreign plague, mapping racial categories and legal geographies of race in British Columbia, 1871-1925

This dissertation explores how the myth of British Columbia as a white settler society was socially, legally, and spatially constituted from 1871-1925. Drawing from a wide range of archival sources, including government and missionary correspondence, police court records, trial transcripts, maps, and photographs, I examine how the exclusion of Aboriginal and Chinese peoples--two communities who were racially marked in distinct ways and subjected to unique forms of regulation--enabled state and religious administrators to assert a "pure" British identity in the province. Throughout the late nineteenth and early twentieth centuries, the desire for white supremacy in British Columbia was largely constituted geographically. Government officials, I contend, relied on a variety of segregationist strategies in their efforts to carve up the province into racially marked districts. This process commenced with the enactment of reserves and was followed by the initiatives of government and non-government administrators who in various ways supported the social and legal creation of racialized spaces. In much the same way that Indigenous peoples were managed through the reserve system, Chinese immigrants came to be governed through the formal and informal spatial confines of Chinatowns. Racism was not only about keeping whites up and the "lower orders" down. Instead, it was also about placing whites and communities of color in their "proper" 'spaces'. The making of distinct racial geographies was never a forgone conclusion, however. Racialized areas were not entirely closed off from white society, nor was segregation always a desired goal at all times and by all colonizers. To begin with, the boundaries that separated reserves, Chinatowns, and white cities were porous and permeable. Although government authorities and missionaries enacted a series of legal and quasi-legal policies through which to police racial borders, spatial governance was often frustrated. While Native and Chinese peoples sometimes overtly resisted spatial boundaries and at other times simply ignored them, the competing and contradictory colonial agendas of state, church, and capital meant that many whites also challenged the making of particular racialized geographies. The spatial organization of race proved to be a constant struggle for government and religious authorities in Canada's most westerly province.
Design For Variety to achieve responsive design customization based on the modeling of design flexibility

Design For Variety (DFV) is an engineering approach in general to accommodate rapid, unpredictable market changes in an engineered product by means of ' rapid' product customization. Treated as a systematic approach, it is developed in this thesis for achieving 'responsive' design customization by generating a family of designs scaled from a commonly shared design platform. In this methodology, model-based design platforms are formalized and formulated from a 'core' design to create a set of custom designs. Besides, this thesis also contributes on three aspects including (1) a formal approach for design flexibility modeling in the absence/presence of uncertainty, (2) a suite of DFV models and their computational approaches for obtaining various design platforms, and (3) a systematic approach for achieving responsive design customization. Finally, a simple yet illustrative design example is utilized to test the validity and utility of the methodology developed, along with the discussions of the design results.
Getting a handle on tangs, defining the Dakhleh Unit of the Aterian Technocomplex : a study in surface archaeology from Dakhleh Oasis, Western Desert, Egypt

The Aterian is a later Middle Stone Age (MSA) Technocomplex of northern Africa. Associated human skeletal remains are classified as anatomically modern and chronometric determinations indicate the Aterian may encompass 90,000 to 20,000 B.P. Many sites are found in surface context. Levallois technology is the predominant method for reduction of stone, and other methods are also known. The Aterian is problematic for models of the origin of behaviourally modern humans because of the late dates and the use of technology elsewhere associated with behavioural "archaism". In this work, I define the Dakhleh Unit (DU) of the Aterian, based on material from Dakhleh Oasis and I compare the DU to Aterian material recovered from other Western Desert locations. DU artefacts were recovered from fifty localities in the Dakhleh Oasis. These occur in association with different geomorphic features, and in several geographic clusters. Material was recovered from surface contexts but analysis of the degree of abrasion and typology suggests that most aggregates examined can be assigned predominantly to the DU. Analysis of artefact raw materials indicates that local materials were favoured, but that chert was transported some distance for reduction. The composition of different aggregates within the oasis leads me to conclude that aggregates can be classified as workshops, occupation locations or special-use areas. Workshops are found in different geographic regions than occupation localities. Technological analysis confirmed that a variety of different methods were used to produce blanks. Examination of retouched tools showed that some were modified only on the edges, while others were extensively modified. Many retouched tools were modified to aid in hafting, either through basal-thinning or tanging. Comparison with published accounts of older MSA material from the eastern Sahara shows that there are similarities in reduction strategies and raw material preferences, but that there are many more formed retouched tools in the DU, particularly tools modified for hafting. This is interpreted to indicate that there is continuity in northeast Africa, that there are indications of modernity in the Aterian, and that trait lists descriptive of the change to modernity in Europe are not useful in northern Africa.
Cloning and characterization of RTL-1, a novel CUB domain-encoding gene expressed in the developing and mature mouse nervous system

A novel CUB domain encoding gene, 'Rtl-1' (r_etinal t_olloid-l_ike-1), was identified using an 'in silico' screen to find genes of potential importance to retinal development. Rtl-1 has >40% amino acid identity with the CUB domains of tolloid and neuropilin proteins. Expression studies in mouse were initiated as a first step towards understanding the role of ' Rtl-1' in mammalian neural development. Adult expression of ' Rtl-1' is neuro-specific. In mature retina, 'Rtl-1' is expressed specifically in bipolar cells, the major interneurons of the retina. During development, 'Rtl-1' is expressed in developing neuroretina and other areas including spinal cord, cochlea, and vomeronasal organ. Two secreted isoforms (Rtl-1A and Rtl-1B) and a putative transmembrane isoform (Rtl-1C) are probable alternative splice products. A 'Rtl-1 ' homolog, 'Rtl-2', will be briefly discussed. Homologs were also identified in 'Caenorhabitis elegans' and ' Drosophila melanogaster'. Thus, Rtl-1 and Rtl-2 define a novel family of putative transmembrane proteins conserved between invertebrates and vertebrates.
Alzheimer amyloid-ß peptide aggregation, alternate products of fibril formation

In Alzheimer disease (AD), polymerization of the amyloid ß peptide (Aß) to form fibrillar deposits in the brain is associated with neurodegeneration. Because of this, researchers have worked to understand fibrillogenesis and the toxicity of fibrils. However, recent discoveries suggest intermediate structures in Aß fibril formation are also toxic. We sought to gain a better understanding of intermediate structures in the fibrillogenesis pathway, describe conditions where Aß forms biologically inert amorphous amyloid rather than neurotoxic fibrillar amyloid, and elucidate some of the extrinsic factors controlling conversion of Aß monomers to fibrils. At low micromolar concentrations, Aß40, the 40 residue form of Aß, assembled into two types of soluble oligomers depending upon pH. Dimer/tetramers with irregular secondary structure formed at neutral pH while spherical particles with a mass of 0.94 megadaltons and ß-sheet secondary structure formed at pH 3. Both structures were stable for at least 4 weeks; this stability will allow for further investigation using high-resolution techniques. In the laboratory, Aß often precipitates to form non-specific aggregates. We sought to characterize these aggregates for use as an 'in vitro ' model for amorphous amyloid. These aggregates were ß-structured at peptide concentrations >10 [mu]M and unfolded at lower concentrations. The structured aggregates were tightly packed containing peptides inaccessible to water. Peptides in the unstructured aggregates were loosely packed, mobile and accessible to water. Structured aggregates appeared protofibrillar and developed into mature fibrils after several weeks whereas the unstructured aggregates were invisible by EM and did not generate fibrils. These findings suggest the unstructured aggregates share many properties with the amorphous amyloid of AD and may aid in studying amorphous amyloid 'in vitro'. We used the organic osmolytes trimethylamine 'N'-oxide (TMAO) and glycerol as mimics of naturally occurring chaperone molecules to investigate their effects upon fibrillogenesis. TMAO and glycerol accelerated the Aß random coil to ß-sheet conformational change. This transition occurred with the immediate conversion of amorphous unstructured aggregates to uniform globular structures. TMAO and glycerol also mediated the transformation of protofibrils to mature fibrils. Thus, the effects of extrinsic factors such as chaperone molecules must be considered when studying Aß fibrillogenesis.
Mixed quantum-classical dynamics and statistical mechanics

Mixed quantum-classical equations of motion are derived for a quantum subsystem of light particles interacting with a classical bath of massive particles. The resulting Liouville equation serves as a starting point for both dynamical and statistical mechanical studies. To elucidate the nature of the dynamics, the differential equation is reformulated as an iterated integral which involves a concatenation of classical evolution segments for the bath phase space coordinates separated by operators that change the quantum state and bath momenta. A hybrid molecular dynamics-Monte Carlo algorithm is constructed to solve the integral equation. The non-equilibrium statistical mechanics of mixed quantum-classical systems in the linear response regime is developed in analogy to full quantum mechanics by appealing to the formal algebraic structure of both theories. The structure of the equilibrium density matrix in the canonical ensemble and the common forms for equilibrium time correlation functions are analyzed. Some numerical results are presented for a two-level quantum subsystem coupled to low dimensional classical baths.
Assessment of a screening test for MMP-8 activity in the diagnosis of periodontal diseases

Active neutrophil collagenase (MMP-8) is associated with progressive periodontitis and the measurement of this enzyme in gingival crevicular fluid (GCF) can facilitate diagnosis. Assays with sufficient sensitivity to detect collagenase in GCF currently use radiolabelled substrates and can take several days to complete. To provide a more rapid analysis of collagenase activity that is better adapted to clinical studies, I validated the use of a novel assay (biotinylated-collagen assay: SBA) based on chemiluminescent detection of biotinylated collagen digestion products. The assay can detect $<$56 pg collagen degraded/hour, which is comparable to the most sensitive radioactive assay. The total assay time is 22 hours and reproducibility on replicate measurements was high (r = 0.96). In direct comparisons of MMP-8 activity in GCF and peripheral blood neutrophils (PMNs) (n = 76) determined by the SBA and radioactive assays, a high correlation (r = 0.97) was obtained. To optimize the GCF collection protocol, the stability of MMP-8 activity in GCF samples was examined. Cross-sectional and longitudinal analyses of frozen GCF showed that MMP-8 activity increased with increasing severity of periodontitis and decreased following treatment. To examine the relationship between activation and binding to native or denatured collagen, MMP-8 from PMN (N = 52) and from GCF samples (N = 7) was incubated on plastic substrates coated with either type I collagen (fibrils or monomers) or gelatin. The results indicate that active MMP-8 can bind to fibrillar collagen, is localized in diseased tissue and can be detected in GCF by a novel assay that is specific, simple, rapid and reproducible and which can facilitate periodontal diagnosis. (Abstract shortened by UMI.)
Adaptive Service Provisioning in Partitionable Wireless Mobile ad-hoc Networks

In wireless ad-hoc networks spontaneously formed by mobile nodes, diverse node movements cause the network to partition into completely disconnected subnetworks. The network partitioning poses significant challenges to the provisioning of centralized service in the ad-hoc network, since as the result of partitioning, many mobile nodes become disconnected from the central server. In this thesis, we propose a collection of novel run-time algorithms that adaptively maintain the availability of the centralized service to all mobile nodes while minimizing the service cost incurred. We exploit the mobility pattern exhibited by mobile hosts. In particular, the central server predicts network partitioning using techniques to recognize the mobility pattern and replicate service in advance. The regular mobile nodes judiciously select service based on mobility similarity to adapt to the dynamic network partitionings. Our simulation results show the algorithms proposed can efficiently provide network-wide service accessibility in the frequently partitionable ad-hoc networks.
Lightpath routing and resource reservation, an integrated solution for IP over DWDM networks

With the rapid development in optical devices, more sophisticated and intelligent optical nodes are built to offer more flexibility to Dense Wavelength Division Multiplexing (DWDM) networks. To transport data packets over DWDM networks more efficiently, the design of the overall system requires a de-layering process. This is done by removing intermediate layers (i.e. ATM, SONET), and made the IP layer as the new convergence layer for data packet transmission over DWDM networks. The new protocol stack is realized with the integration of the IP and MPLS control planes with optical network extensions. This thesis focuses on the issues of lightpath routing and resource reservation in DWDM networks. The combination of these two components forms a dynamic lightpath provisioning framework for data packet transmission. In this dissertation, we first study multiple constraint-based routing algorithms. Next, we introduce a traffic aggregation framework at edge optical nodes with extra enhancement to the MPLS framework. Finally, we investigate the effect of our proposed framework by varying multiple parameters. These parameters are number of lambdas per fiber, link state updating policy, network topology design, request rate and offered load distribution.
Vietnamese tone, tone is not pitch

This thesis is an in-depth study of the phonology and phonetics of tones in Northern Vietnamese dialects. It examines tone within the framework of markedness theory, the phonetic realizations of tones, the relationship between the phonetics and phonology of tones, and the implications of the proposed analysis for other dialects of Vietnamese. First, I propose a phonological model in which tones are structurally organized. In this model, tones are grouped together as constituents according to their markedness relationship. Evidence for the structural organization of tones comes from neutralization in dialects and reduplication, and also from tonal frequency in the language, poetry, borrowings and clitics. This evidence points to tones having two major constituents, contour and register, each of which can pattern independently. Second, I show that the proposed features are grounded phonetically. I argue that instead of pitch height being contrastive as is generally assumed, it is phonation types of creakiness and breathiness which are distinctive as the register feature in North Vietnamese, and the differences in pitch heights are predictable. In the Vietnamese literature, it is claimed that there is a mismatch between the phonetics and phonology of two tones, ' hoi' and 'nga' in reduplication. Flip-flop rules were suggested to account for the mismatch. I show that using phonation types as distinctive feature not only can explain various tonal patterns in the language, it also makes this mismatch an illusory one, which, in turns, makes ad hoc flip-flop rules in previous models unnecessary. In addition, I argue that the domain of Vietnamese tone is not the syllable or mora, but the rhyme, and that the crucial portion for distinguishing the tones is the middle point in 'hoi' and 'nga', and the endpoint in other tones. Finally, I show that the model correctly predicts certain types of neutralization in other Vietnamese dialects, in language acquisition, and in other tone languages.