VictorJuiz/thesis huggingface dataset:
Probing the structural basis of antigen-antibody interactions, structure of MRK-16 Fab-peptide complex

X-ray crystallographic techniques have played a very important role in the understanding of the structural basis of antibody specificity. From the wealth of information that can be gained from the database of solved structures, it is clear that the atomic recognition of antigens by antibodies is a complex process. The main focus of this thesis has been to understand in detail the structural basis of antigen-antibody interactions using P-glycoprotein (Pgp), and mAb MRK-16 as a model system. Pgp was chosen because of its role in causing resistance to cancer chemotherapy and MRK-16 due to its role in the reversal of multidrug resistance. The structure of the antibody binding fragment (Fab) from monoclonal antibody MRK-16 in complex with its peptide epitope has been determined using the technique of X-ray diffraction to a resolution of 2.8 A. The crystallographic analysis of the complex brings out salient and unique features of its structure. The Fab crystallized so that, of the two molecules present in the crystallographic asymmetric unit, only one is liganded to the peptide epitope. The peptide-Fab interactions are stabilized by H-bonds, van der Waals interactions and salt-bridges. One of the loops forming the antigen binding sites revealed an unusual conformation. This prompted analysis of the loop conformations of all the three dimensional structures available in search of the existence of a similar loop to MRK-16. Analysis carried out on the various conformations of the antigen binding loops brought out the occurrence of a new form. In addition, this study has led to the finding of a new flexible region in the constant region of the Fab, that may provide yet another level of conformational flexibility to the antibody molecule. The results presented here pave the way for the use of MRK-16 as an aid to the structural study of P-glycoprotein, to improve our knowledge of antibody-antigen recognition, and as a starting point for the design of potential therapeutics.
Molecular and cellular selection of the immunoglobulin heavy chain repertoire during B cell development

The diversity of immunoglobulins (Ig's) produced by B lymphocytes is a key component of adaptive immunity. Ig diversity is largely generated by a somatic gene rearrangement process known as V(D)J recombination. Although V(D)J recombination is potentially capable of producing a vast array of distinct Ig molecules, only a small fraction of this potential is expressed in the actual Ig repertoire of an organism. In Chapter 2, I describe an assay which allows quantitative analysis of gene segment usage in the Ig heavy chain (HC) repertoire. It was found that the initially generated HC repertoire is not random, but is characterized by the predominant usage of a V$\rm\sb{H}$ segment called V$\rm\sb{H}$81x. I further demonstrate that usage of this gene segment declines at several key points during B cell development. Chapters 3 and 4 describe experiments which characterize the selection events leading to the decline in V$\rm\sb{H}$81x usage. It was found that the initial decline in V$\rm\sb{H}$81x usage can occur in the absence of HC cell surface expression, suggesting that molecular selection at the level of V(D)J recombination is involved. Experiments using an in vitro model of B cell differentiation provided further evidence for molecular selection and indicated that adult, but not fetal, B cell progenitors are also negatively selected based on expression of V$\rm\sb{H}$81x-encoded HCs. I suggest that this latter result may be indicative of a general difference in HC repertoire selection by fetal and adult precursors. In the latter part of Chapter 3, I examine the relationship between HC cell surface expression and the ability of B cell precursors to proliferate and differentiate in response to the growth factor interleukin 7 (IL7). It was found that, while surface expression of HC is not required to initiate IL7-responsiveness, it does appear to influence the threshold levels of IL7 required to trigger proliferation of B cell precursors. In summary, this thesis examines the mechanisms which influence Ig HC repertoire development, and provides new insight into the importance of molecular repertoire selection mechanisms, differences between fetal and adult repertoire selection and the role of HC in regulating growth factor responsiveness.
Performance requirements for information systems

An important challenge during information system development is to deal with performance requirements, such as "achieve good response time for authorising credit card sales." Performance requirements are an important class of non-functional requirements (quality requirements, or NFRs). Effective systems should attain NFRs (such as performance and accuracy) and functional requirements (e.g., "credit card systems should authorise sales"). However, NFRs are generally difficult to handle, as they can conflict with each other, and have a global impact on a system. These difficulties apply to performance requirements, which interact with implementation alternatives which have varying characteristics and tradeoffs. The objective of this thesis is to provide a systematic treatment of performance requirements for information systems. Accordingly, a "Performance Requirements Framework" (PeRF) is presented to help developers "build performance into" customised solutions, by considering the particular characteristics of a system being developed, and drawing on catalogues of performance and development knowledge. To provide a systematic process for treating performance requirements, PeRF incorporates an existing framework for NFRs, the "NFR Framework," which offers a goal-oriented, qualitative approach to representing and refining NFRs, selecting among target alternatives, justifying decisions, and evaluating their impact on meeting NFRs. PeRF offers catalogues of knowledge of information systems, their design, implementation and performance. Catalogues organise experience in translating conceptual specifications expressed in semantic data models into relational database implementations. Catalogues also incorporate existing principles for designing performance into systems. Catalogues are organised along several axes. One axis arranges specification-language features in a layering mechanism, which further structures the process of addressing performance requirements. Catalogues are available in the "Performance Requirements Assistant", a partial developer's tool, adapted from the existing "NFR Assistant." Some evidence for the framework is provided by empirical studies of information systems. The studies address a variety of performance requirements, domains (credit cards and tax appeals), system characteristics and specification-language features. Tradeoffs are handled by considering organisational workloads and priorities. Some of these and other studies of NFRs were reviewed by people familiar with the domains studied. They offered some preliminary support for the usefulness of certain aspects of the framework, while raising some important open issues.
An analysis of growth and differentiation of human neuroblastoma, identification of HMG-CoA reductase and a novel zinc finger gene as potential mediators

Several biological and clinical features of neuroblastoma suggest that this neural crest derived tumor retains the potential for further differentiation. Delineating these events may provide insights for eventual clinical management of this chemorefractory disease. The NUB-7 human neuroblastoma derived cell line, established in our laboratory, uniquely displayed features of both primitive neuronal and Schwannian cells and was further inducible along both cell lineages with dibutyryl cyclic AMP and retinoic acid respectively. This differentiation potential mimics the in vivo differentiation patterns of neuroblastoma. Using the novel molecular technique of differential display, we identified 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and a novel zinc finger gene as potential differentiation responsive genes in NUB-7. HMG-CoA reductase functions as the rate limiting enzyme of the mevalonate pathway involved in de novo cholesterol synthesis and cell cycle progression. Its expression and modulation during neuroblastoma induced differentiation implicated HMG-CoA reductase as a key regulator of neuroblastoma growth and a mediator of the biological effects of retinoic acid. Lovastatin, a non-reversible competitive inhibitor of HMG-CoA reductase induced marked cytotoxicity in neuroblastoma cell lines expressing P-glycoprotein, a well recognized drug efflux pump involved in chemoresistance. Moreover, this cytotoxicity was enhanced by the addition of dibutyryl cyclic AMP but not retinoic acid. These observations support the possible clinical utility of HMG-CoA reductase inhibitors in combination with differentiating agents in the treatment of neuroblastoma. A second novel clone, designated zf5-3, was localized to chromosome 19 and possessed 4 zinc finger DNA binding motifs characteristic of a wide variety of transcriptional regulators. The expression of zf5-3 was restricted to fetal neuronal, hepatic and renal tissues and their tumor derived cell lines. The expression of zf5-3 was downregulated during nervous tissue maturation as well as induced neuronal maturation of various neuroblastoma cell lines. These observations implicate zf5-3 as a potential mediator of differentiation in fetal neuronal tissues and their derived tumors including neuroblastoma through the maintenance of the undifferentiated state.
The response of lake thermal stratification to climatic conditions and effects on fish growth

Climate change is expected to alter aspects of lake thermal stratification such as onset of stratification, epilimnion and hypolimnion temperatures and thermocline depth. Climate change effects on fish will likely be mediated through alterations to their thermal habitat. The long-term water temperature and meteorology data sets for South Bay of Lake Huron, Ontario, (1955-92) and for Lake Opeongo, Ontario, (1958-96) offer an empirical record of the historical covariations between climatic conditions, lake stratification patterns and fish growth. Generally, in warmer years the thermal structures of these lakes are characterized by an earlier onset of stratification, a warmer spilimnion, a shallower thermocline and a larger temperature difference between upper and bottom layers. These stratification patterns are associated with increased growth in smallmouth bass Micropterus dolomieui (warm water species), and in rainbow smelt Osmerdus mordax and yellow perch Perca flavescens (cool water species) and with reduced growth in lake trout Salvelinus namaycush (cold water species). The historical covariations between climatic conditions and stratification patterns between stratification patterns and fish growth suggest that climatic conditions filter to fish thorough the aspect of their thermal environment that is related to their behaviour or life history. The historical covariations provide patterns of association from which the response of thermal stratification and fish growth to climate change are forecast.
An investigation of the course design process used by university faculty

How do university teachers develop their courses? Do they develop them according to recommendations in the literature? This study compares what university teachers said they did to develop a course with a systematic instructional design/development process. Interviews were held with university faculty members to ascertain their course development processes. Comparison of their responses with recommendations by instructional developers using a systematic approach to course development showed differences in the way they talk about course development. Several factors prevent, to varying degrees, humanities professors from developing their courses according to the recommended processes: time to prepare, prior knowledge of student group, their desire to be flexible, and their desire to encourage students to be self-directed. A major constraint is the basic difference in approach to course development. University humanities faculty members operate under belief systems based on paradigms in some ways divergent from that of the paradigm under which the instructional developer operates. It may be for that reason, and the type of knowledge in use, that humanities professors are reluctant to utilize the systematic approach to developing their courses.
University autonomy in China

University autonomy has been introduced in Chinese higher education since the beginning of the 1980s. However, what it really means in the Chinese context is still a question. My study aims at defining the concept of university autonomy and exploring Chinese university members' insights into its meaning in the Chinese context. I use the case study method and have investigated Sichuan Union University, Chongqing Teachers' College, and Chongqing Industry Management Institute in China. Data have been collected exclusively on campus, mainly through interviews with administrators, Party workers, teachers, and students (36 persons altogether) in these institutions. The analysis seeks to draw out common points of the understanding of university autonomy among the interviewees within each institution. Some comparisons among the three institutions have also emerged. I have adopted some other methods such as document review, informal interview, discussion meeting, and campus observation, in order to achieve the validity and reliability of the study. The findings show that university autonomy in China is defined not only as a form of power or control, but also as an art of using this power for universities to continue their historical mission of serving society within the framework of government policies. University autonomy in China is found different from this concept in the West. However, it is based not only on the Chinese intellectual tradition, but also on aspects of the Chinese experience of learning from the West. In conclusion, university autonomy in China can be best understood in relation to Chinese culture. Its meaning is determined by several factors, including the political influences on the goals of higher education throughout China's history, the intellectual tradition in the pre-modern period, the development patterns of Chinese higher education in the modern period, the economic and political change in the reform period, and above all, university members' current experience in creating conditions for greater freedom of action on their own part. From their experience is seen the historical continuity of a Chinese way of thinking--knowing through doing concrete things, through collective engagement in action, and through analysis of the outcomes of action.
Robotic manipulator control, fundamentals of task space design

The task space-based approach to the design of robot control as an alternative to the joint space-based approach is an important area of robotics research and development. However, its theoretical foundation is less well established. This thesis addresses the fundamental issues related to the task space-based approach and contributes to the development of its theoretical foundation. The focus is on two important task space-based control problems: simultaneous position and force control (P/F control) of non-redundant robots redundant robots respectively. The common feature of the corresponding task space controllers is that each consists of two subcontrollers. The design of these controllers requites decomposing the task space and/or joint space into two subspaces. The central issues in the design of the task space controllers studied here are: (i) the decomposition and (ii) the interaction between the subcontrollers. Three principles are proposed as the guides for design of the task space controllers: (1) The Principle of Invariance for the decomposition of task space; (2) The Principle of Minimum Interaction for the design of P/F control; (3) The Principle of Non-Interaction for the design of task space control of redundant robots. Two design frameworks are developed based on these principles. The first uses the principle of invariance and the principle of minimum interaction. It consists of a generic design methodology for P/F control design and a platform for the analysis and evaluation of existing and future P/F control schemes. The second framework proposes a generic design methodology for the design of task space control of redundant robots based on the principle of non-interaction. Together with the established task space approaches to position control of non-redundant robots, the methodology proposed in this thesis yields a complete framework for task space-based control design. The conclusions of this thesis are not primarily the results of empirical studies; they are theoretical in nature and supported by logical reasoning.
Ideology in the fantastic narrative of Charles Nodier

This study undertakes a socio-political reading of a selection of Charles Nodier's fantastic tales. Nodier was significantly influential in the literary circles of late 1820's and early 1830's France as host of the salon at the Arsenal library, to which he was named librarian in 1824. He also participated frequently in the intellectual and literary life of France by writing many essays on history, politics and literature, and by contributing regularly to several journals; and this, during a period of great social, political and ideological change. Nodier's career as journalist and essayist spanned a period from the last years of the Napoleonic Empire to the middle years of the July Monarchy. The choice of fantastic short-stories as the principal corpus for a socio-political reading of Nodier may seem problematical, since the genre itself is not usually regarded as being particularly ideological. Nevertheless, Nodier's tales themselves contain many references to 'real-world' social and political issues. Therefore, one of the principal goals of the present study is to describe precisely the role of ideology, as part of the socio-political commentary, in Nodier's tales. Starting with an overview of socio-political and ideological readings of the genre, and finding that none entirely do justice to Nodier's fantastic narrative, I attempt to devise an approach to ideology in fantastic literature that is tailored to Nodier's works, with close readings of three of Nodier's best known and thematically richest tales: Trilby, ou le lutin d'Argail (1822), La Fee aux Miettes (1832) and Ines de Las Sierras (1837). In addition, Nodier's essay, Du Fantastique en litterature (1830), and two shorter tales, the Histoire d'Helene Gillet (1832) and Jean-Francois les Bas-bleus (1832), provide insight into his theory of the genre, and his division of it into three 'types'. There is in fact an ideological evolution in Nodier's tale-writing that corresponds to these three 'types'. With the aid of recent discussions on ideology, it becomes possible to speculate on the significance of this evolution.
Combinatorial and algebraic aspects of polynomials over finite fields

This thesis investigates several algebraic algorithms that deal with univariate polynomials over finite fields. Our main focus is the factorization problem, but we also consider polynomial irreducibility tests, and constructions of both irreducible polynomials and finite fields. A methodology based on generating functions and their asymptotic analysis allows us to study the behavior of the algorithms in question. This analysis reveals parameters of intrinsic interest for understanding the behavior of the algorithms. Moreover, they provide insight into the structure of polynomials over finite fields in a broader sense. First, we summarize and extend known results on counting random polynomials. We investigate properties such as the average number of irreducible factors whose degrees lie in an interval, the average number of polynomials with no factors or with all factors having degrees in an interval, among others. We briefly state problems where these results give useful information. We also survey the known algorithms for factoring polynomials. Second, we give the first average-case analysis of a complete polynomial factorization algorithm. We fully analyze the classical method for factoring polynomials over finite fields consisting of three stages: squarefree factorization, distinct-degree factorization, and equal-degree factorization, including some variants for each stage. Given a partition of the possible degrees of the irreducible factors of a polynomial, we study how they split into subintervals. This naturally relates with recent factorization algorithms. It turns out that more computational work is needed when a subinterval contains the degrees of more than one irreducible factor. We study several properties of such intervals. Finally, the methodology is applied to other problems involving polynomials over finite fields. We give two variations of existing algorithms for testing the irreducibility of polynomials. In addition, we provide a construction of very sparse irreducible polynomials. We conclude by improving lower bounds for the Euler function for polynomials and for the density of normal elements.
Blind identification of nonlinear systems based on higher order cyclic spectra

In this thesis, the blind identifiability of linear subsystems of discrete-time nonlinear models consisting of two finite-memory Linear Time Invariant (LTI) filters separated by a finite-order Zero-Memory Nonlinearity (ZMNL) of the polynomial type (the LTI-ZMNL-LTI model) is established assuming circular Gaussian and Quadrature Amplitude Modulated (QAM) Non-Gaussian input sequences exhibiting circular-like properties. A range of identification algorithms are proposed. Identification of some general Volterra models is also considered. It is shown that with circular stationary Gaussian inputs the impulse responses of the two LTI filters of an $N\sp{th}$ order LTI-ZMNL-LTI can be recovered from only a 2-D slice of the $N+1\sp{th}$ order polyspectrum of the output. Some simple cepstral domain identification algorithms are proposed. The identifiability of some nonlinear models with stationary Non-Gaussian QAM inputs is also considered. The blind identifiability of LTI-ZMNL-LTI models using QAM-type cyclostationary inputs is established. Two sets of identification algorithms result, one based on the cross-polyspectra of the Translation Series representors of the output, and the other based on the cyclic polyspectra. The algorithms proposed in this thesis for nonlinear system identification are blind, and are a new application of the theory of cyclostationarity. The algorithms are analytically simple, suppress several types of noise and interference, do not require the estimation of the ZMNL coefficients, allow the LTI filters to have a Non-Minimum Phase (NMP) response, and are shown by Monte-Carlo simulations to perform effectively.