An increasing number of proteins with unknown function have their three-dimensional structure solved at high resolution. This situation, largely due to structural genomics initiatives, has been stimulating the development of automated structure-based function prediction methods. Knowledge of residues important for function – and more particularly – for binding can help automated prediction of function in different ways. The properties of a binding site such as its shape or amino acid composition can provide clues on the ligand that may bind to it. Also, having information on functionally important regions in similar proteins can refine the process of annotation transfer between homologues. Experimental results indicate that functional residues often have an unfavourable contribution to the stability of the folded state of a protein. This observation is the underlying principle of several computational methods for predicting the location of functional sites in protein structures. These methods search protein structures for destabilising residues, with the assumption that these are likely to be important for function. We have developed a method to detect clusters of destabilising residues which are in close spatial proximity within a protein structure. Individual residue contributions to protein stability are evaluated using detailed atomic models and an energy function based on fundamental physico-chemical principles. Our overall aim in this work was to evaluate the overlap between these clusters of destabilising residues and known binding sites in proteins. Unfortunately, reliable benchmark datasets of known binding sites in proteins are sorely lacking. Therefore, we have undertaken a comprehensive approach to define binding sites unambiguously from structural data. We have rigorously identified seven issues which should be considered when constructing datasets of binding sites to validate prediction methods, and we present the construction of two new datasets in which these problems are handled. In this regard, our work constitute a major improvement over previous studies in the field. Our first dataset consists of 70 proteins with binding sites for diverse types of ligands (e.g. nucleic acids, metal ions) and was constructed using all available data, including literature curation. The second dataset contains 192 proteins with binding sites for small ligands and polysaccharides, does not require literature curation, and can therefore be automatically updated. We have used our dataset of 70 proteins to evaluate the overlap between destabilising regions and binding sites (the second dataset of 192 proteins was not used for that evaluation as it constitutes a later improvement). The overlap is on average limited but significantly larger than random. The extent of the overlap varies with the type of bound ligand. Significant overlap is obtained for most polysaccharide- and small ligand-binding sites, whereas no overlap is observed for nucleic acid-binding sites. These differences are rationalised in terms of the geometry and energetics of the binding sites. Although destabilising regions, as detected in this work, can in general not be used to predict all types of binding sites in protein structures, they can provide useful information, particularly on the location of binding sites for polysaccharides and small ligands. In addition, our datasets of binding sites in proteins should help other researchers to derive and validate new function prediction methods. We also hope that the criteria which we use to define binding sites may be useful in setting future standards in other analyses.

Deformational properties of soil, in terms of modulus and damping, exert a great influence on seismic response of soil sites. However, these properties for sands containing some portion of fines particles have not been systematically addressed. In addition, simultaneous modelling of the modulus and damping behaviour of soils during cyclic loading is desirable. This study presents an experimental and computational investigation into the deformational properties of sands containing fines content in the context of site response analysis. The experimental investigation is carried on sandy soils sourced from Christchurch, New Zealand using a dynamic triaxial apparatus while the computational aspect is based on the framework of total-stress one-dimensional (1D) cyclic behaviour of soil. The experimental investigation focused on a systematic study on the deformational behaviour of sand with different amounts of fines content (particle diameter ≤ 75µm) under drained conditions. The silty sands were prepared by mixing clean sand with three different percentages of fines content. A series of bender element tests at small-strain range and stress-controlled dynamic triaxial tests at medium to high-strain ranges were conducted on samples of clean sand and silty sand. This allowed measurements of linear and nonlinear deformational properties of the same specimen for a wide strain range. The testing program was designed to quantify the effects of void ratio and fines content on the low-strain stiffness of the silty sand as well as on the nonlinear stress-strain relationship and corresponding shear modulus and damping properties as a function of cyclic shear strains. Shear wave velocity, Vs, and maximum shear modulus, Gmax, of silty sand was shown to be significantly smaller than the respective values for clean sands measured at the same void ratio, e, or same relative density, Dr. However, the test results showed that the difference in the level of nonlinearity between clean sand and silty sands was small. For loose samples prepared at an identical relative density, the behaviour of clean sand was slightly less nonlinear as compared to sandy soils with higher fines content. This difference in the nonlinear behaviour of clean sand and sandy soils was negligible for dense soils. Furthermore, no systematic influence of fines content on the material damping curve was observed for sands with fines content FC = 0 to 30%. In order to normalize the effects of fines on moduli of sands, equivalent granular void ratio, e*, was employed. This was done through quantifying the participation of fines content in the force transfer chain of the sand matrix. As such, a unified framework for modelling of the variability of shear wave velocity, Vs, (or shear modulus, Gmax) with void ratio was achieved for clean sands and sands with fines, irrespective of their fines content. Furthermore, modelling of the cyclic stress-strain behaviour based on this experimental program was investigated. The modelling effort focused on developing a simple constitutive model which simultaneously models the soil modulus and damping relationships with shear strains observed in laboratory tests. The backbone curve of the cyclic model was adopted based on a modified version of Kondner and Zelasko (MKZ) hyperbolic function, with a curvature coefficient, a. In order to simulate the hysteretic cycles, the conventional Masing rules (Pyke 1979) were revised. The parameter n, in the Masing’s criteria was assumed to be a function of material damping, h, measured in the laboratory. As such the modulus and damping produced by the numerical model could match the stress-strain behaviour observed in the laboratory over the course of this study. It was shown that the Masing parameter n, is strain-dependent and generally takes values of n ≤ 2. The model was then verified through element test simulations under different cyclic loadings. It was shown that the model could accurately simulate the modulus and the damping simultaneously. The model was then incorporated within the OpenSees computational platform and was used to scrutinize the effects of damping on one-dimensional seismic site response analysis. For this purpose, several strong motion stations which recorded the Canterbury earthquake sequence were selected. The soil profiles were modelled as semi-infinite horizontally layered deposits overlying a uniform half-space subjected to vertically propagating shear waves. The advantages and limitations of the nonlinear model in terms of simulating soil nonlinearity and associated material damping were further scrutinized. It was shown that generally, the conventional Masing criteria unconservatively may underestimate some response parameters such as spectral accelerations. This was shown to be due to larger hysteretic damping modelled by using conventional Masing criteria. In addition, maximum shear strains within the soil profiles were also computed smaller in comparison to the values calculated by the proposed model. Further analyses were performed to study the simulation of backbone curve beyond the strain ranges addressed in the experimental phase of this study. A key issue that was identified was that relying only on the modulus reduction curves to simulate the stress-strain behaviour of soil may not capture the actual soil strength at larger strains. Hence, strength properties of the soil layer should also be incorporated to accurately simulate the backbone curve.

Analysis of lithics, particularly flake debitage, from a small Preclassic Maya community provides data bearing upon the manufacture and distribution of stone tools in the northern Belizean region during the Middle and Late Preclassic eras. These data suggest a complex relationship among contemporaneous communities with regard to raw material and tool acquisition and manufacture. There is no evidence of monopoly of raw material resources by any one group; rather, a mixed pattern is seen involving distribution both of partly processed raw material and of certain finished formal tool types. These formal types, as well as befaces in general, are seen to be increasingly important through time, possibly related to changing agricultural practices. While no conclusions can be drawn on the basis of presently available lithic data as to the nature of the Preclassic regional lithic distribution system, ethnographic and archaeological analogies are used to suggest some possible economic scenarios.

Traditionally, the analysis of ceramics has played a major role in archaeological research the world over, and this is particularly true in the Maya area where until recently ceramic studies have been used for the sole purpose of chronological ordering. This dissertation discusses the historic development of ceramic research in Maya archaeology, as well as documenting the present role of ceramic analyses, as preface to the analysis of the ceramics from Cuello, a small site in northern Belize. Excavations at the site indicate that the area under study, Platform 34, was occupied from the Early Formative at about 2,000 b.c. until the Late Formative at about a.d. 250, when Platform 34 was apparently largely abandoned, although other areas of the site continue to be occupied. The analysis of the ceramics from Cuello proceeds utilizing the traditional type: variety classification system to order the ceramics chronologically. The Cuello typology, in accordance with the major period of occupation of Platform 34, spans a period of time beginning in the Early Formative with the Swasey Complex, and ending in the Late Formative with the Cocos Complex. While some typological comparisons of ceramics among sites in the Maya Lowlands are made to place Cuello securely within a chronological framework, the main thrust of the analysis is to understand intra-site ceramic variability. Unlike earlier maya ceramic analyses, the present one continues with a vessel form classification, since forms are considered sensitive indicators of functional variability within the site. It is shown, through this analysis, that ceramic analyses are useful for more than chronological ordering,and when ceramic variability is examined within the archaeological contexts in which the ceramics are found, has the potential of informing on functional and social patterns on an intra-site level.

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No description available.

In winter-cities such as Saskatoon there exists a significant potential to improve cold-weather walking conditions for most pedestrians. To realize the walkability potential of a winter-city downtown, by necessity automobile traffic must be reduced. However, when surface parking lots are permitted to operate in abundance, isolated and uncoordinated, and detached from overall planning and transportation policy, automobile traffic reduction downtown cannot be efficiently achieved. In many winter-cities, Saskatoon included, downtown parking lots in fact are oversupplied. Vital space for housing, employment and public space is thereby reduced and pedestrian winter exposure to wind chill and sidewalk ice is increased by breaks in the urban fabric. Systematic conversion of surface parking lots into mixed use would not only enhance incentives to walk, but simultaneously would reduce the incentive to drive. The question thus arises whether and how can we screen a large number of surface parking lots for a limited number of candidate-sites that could be earmarked for infill redevelopment. A screening methodology that prioritizes potential parking lot sites ought to account for a wide range of criteria that address urban design, development-potential, proximity, and microclimate. In a case study of parking lots in downtown Saskatoon, a screening methodology has yielded one priority site out of an inventory of twenty-four sites. Integrated within public transit policy the proposed methodology has generic applicability to downtown areas elsewhere, and can advance the goal of safety and higher residential density downtown.

NtdB is an enzyme encoded within the ntd operon in Bacillus subtilis. This operon is reported to contain a complete set of genes necessary for the biosynthesis of 3,3'-neotrehalosadiamine (NTD), a compound composed of two kanosamine subunits linked together by a 1,1'-(α,β)-linkage. Both NTD and kanosamine have reported antibiotic properties. The function of NtdB has been a matter of speculation, but has never been investigated in vitro. Using a phosphate assay and an array of substrates, NtdB was determined to be a phosphatase, specific to kanosamine-6-phosphate (K6P) (kcat = 32 ± 1 s-1, Km = 93 ± 7 µM). Site-directed mutagenesis of amino acid residues in the core and the cap domains of the enzyme identified residues important for the catalytic reaction and substrate specificity. These mutations confirmed the presence of four motifs, characteristic of members of the haloacid dehalogenase (HAD) superfamily, and allowed identification of the substrate binding site of the enzyme. KabB, a homologue of NtdB from Bacillus cereus, showed notably lower activity with K6P than NtdB. This research defines the role of NtdB as a specific K6P phosphatase and challenges the previously reported NTD biosynthesis pathway by demonstrating a novel pathway for the production of the antibiotic kanosamine.

In recent years, a number of advanced Information and Communication Technology (ICT) solutions have been developed to assist in the management of business processes and working environments. Radio Frequency Identification (RFID) tagging technology and mobile computing are two such technologies which have been adopted for use in hybrid systems because they can monitor and manage industrial health, safety and welfare activities.

This thesis looks at the ways in which performance can integrate participants and local context into the development of new devised work. This practice-led research is based on a methodology that grew out of three performance case studies completed in diverse international settings with a varied range of participants. The case studies are: Napoli Scorticata completed in 2007 in Naples, Italy; Youth Visions, completed in 2008 in Northeastern Ghana, West Africa; Triangulated City, completed in 2009 in Beirut, Lebanon. Within these diverse contexts the research questions the role of authorship when working in socially engaged practice, focusing on how practitioners can shift the focus from the artist to the body politic. Merging social engagement with a site-responsive approach, the research proposes that the artistic medium is the social system and as such argues that the modes of employment require a focus of appreciation on the generative process, context and product combined. The research is presented in two parts. Part I is an interactive DVD with images of the development process and final presentations as well as a video of each performance work. Part II is a written thesis that explores the modes of engagement, outlines the methods of development and structures a general working methodology that can be referenced by other performance practitioners. The thesis proposes Applied Live Art as a term to describe practices that include a hybrid of time-based media options, which include a social component as their primary focus. The research outcomes conclude with an analysis of place making and its importance when working with both site and society.