Rheumatoid arthritis (RA) is an autoimmune disease affecting approximately 1% of the population in the western world. It is characterised by a tissue specific attack of cartilage in peripheral joints. Collagen induced arthritis (CIA) is one of the most commonly used animal models for (RA), with similar symptoms and histopathology. CIA is induced by immunisation of mice with type II collagen (CII), and the immunodominant part was previously found to be located between residues 256-270. This thesis describes the interaction between the MHC molecule, glycopeptide antigens from CII and the T cells that is essential in development of CIA. The glycopeptide properties for binding to the mouse MHC molecule Aq have been studied, as well as interaction points in the glycopeptide that are critical for stimulation of a T-cell response. The thesis is based on five studies. In the first paper the minimal glycopeptide core, that is required for binding to the Aq molecule while still giving a full T cell response was determined. The second paper studied the roles of amino acid side-chains and a backbone amide bond as T-cell contact points. In the third paper the hydrogen bond donor-acceptor characteristics of the 4-OH galactose hydroxyl group of the glycopeptide was studied in detail. In the fourth paper we established a structure activity relationship (QSAR model) for (glyco)peptide binding to the Aq molecule. Finally, the stereochemical requirements for glycopeptide binding to the Aq molecule and for T-cell recognition was studied in the fifth paper. The study was performed using collagen glycopeptide analogues, which were synthesised on solid phase. Amide bond and hydroxyl group isosteres were introduced for study of hydrogen bond donor-acceptor characteristics. Statistical methods were used to design a representative peptide test set and in establishing a QSAR model. The results give a deeper understanding of the interactions involved in the ternary MHC-glycopeptide-T cell complex. This information contributes to research directed towards finding new treatments for RA.

In our society in the 21st century one of the greatest challenges is to provide raw materials to the industry in a sustainable way. This requires increased use of renewable raw materials such as wood. Wood is widely used in pulp, paper and textile industries and ongoing research efforts aim to extend the use of wood in e.g. liquid biofuels and green chemicals. At Umeå Plant Science Center (UPSC) poplar trees are used as model systems to study wood formation. The objective is to understand the function of the genes underlying the wood forming process. This knowledge could result in improved chemical and physical wood properties suitable for different industrial processes. This will in turn meet the demands for a sustainable development. This thesis presents tools and strategies to unravel information regarding genetic perturbations in poplar trees by the use of nuclear magnetic resonance (NMR) spectroscopy and multivariate analysis (MVA). Furthermore, gas chromatography/mass spectrometry (GC/MS) is briefly discussed in this context. Multivariate methods to find patterns and trends in NMR data have been used for more than 30 years. In the beginning MVA was applied in pattern recognition studies in order to characterize chemical structures with different ligands and in different solvents. Today, the multivariate methods have developed and the research have changed focus towards the study of biofluids from plant extracts, urine, blood plasma, saliva etc. NMR spectra of biofluids can contain thousands of resonances, originating from hundreds of different compounds. This type of complex data can be hard to summarize and interpret without appropriate tools and require sophisticated strategies for data evaluation. Related fields of research are rapidly growing and are here referred to as metabolomics. Five different research projects are presented which includes analysis of poplar samples where macromolecules such as pectin and also small molecules such as metabolites were analysed by high resolution magic angle spinning (HR/MAS) NMR spectroscopy, 1H-13C HSQC NMR and GC/MS. The discussion topics include modelling of metabolomic time dependencies in combination with genetic variation, validation of orthogonal projections to latent structures (OPLS) models, selection of putative biomarkers related to genetic modification from OPLS-discriminant analysis (DA) models, measuring one of the main components found in the primary cell-walls of poplar i.e. pectin, the use of Fourier transformed two-dimensional (2D) NMR data in OPLS modelling and model complexity in a PLS model.

In the last decade there has been increasing research interest in the value of bio-sourced materials from lignocellulosic biomass. The dissolution of cellulose by ionic liquids (ILs) has led to investigations including the dissolution of cellulose, lignin, and complete biomass samples and the in situ processing of cellulose. Rapid quantitative measurement of cellulose dissolution in ILs is difficult. In this work, Fourier transform infrared spectroscopy (FTIR) spectra of cellulose dissolved in 1-ethyl-3-methylimidazolium acetate ([emim][OAc]) were subjected to partial least squares (PLS) regression to model dissolved cellulose content. PLS regression was used due to the ease in developing predictive models with this technique in addition to linear regression being ineffectual for modeling when applied to potentially thousands of variables. Applying a normalization data treatment, before regression, generated a model that estimated cellulose content within 0.533 wt%. The methods described provided the basis for a rapid methodology to determine dissolved cellulose content. Development of rapid and facile screening techniques to determine the effectiveness of various ILs as solvents for cellulose or lignin will aid in the development of lignocellulosic based bioproducts. In this work, optical microscopy with and without the use of cross-polarized lenses, was used to monitor cellulose and lignin dissolution in two imidazolium-based and two phosphonium-based ILs as well as n,n-dimethylacetamide/lithium chloride (DMAc/LiCl), demonstrating that this technique could be applied more broadly than solely for ILs. The described optical microscopy methodology was more rapid and sensitive than more traditional techniques, such as visual inspection. The viscosity of [emim][OAc] (162 cP) is 100 times that of water at 20°C and could inhibit its use as a solvent for cellulose. There is a need for simple, low-cost and environmentally benign methods to reduce the viscosity of ILs to aid in cellulose dissolution. In this work, 4 wt% cellulose dissolved in [emim][OAc] was subjected to 50 psi CO2 and 20 psi N2, as a control environment, at both 50°C and 75°C. After 24 hours a nearly 2-fold increase in dissolved cellulose over the N2 control was demonstrated through the application of a 50 psi CO2 environment for cellulose dissolution in [emim][OAc] at 50°C. / Thesis (Master, Chemical Engineering) -- Queen's University, 2011-05-25 22:58:17.744

Quantitative structure-activity relationships (OSAR) constitute empirical analogy models connecting chemical structure and biological activity. The analogy approach to QSAR assume that the factors important in the biological system also are contained in chemical model systems. The development of a QSAR can be divided into subproblems: 1. to quantify chemical structure in terms of latent variables expressing analogy, 2. to design test series of compounds, 3. to measure biological activity and 4. to construct a mathematical model connecting chemical structure and biological activity. In this thesis it is proposed that many possibly relevant descriptors should be considered simultaneously in order to efficiently capture the unknown factors inherent in the descriptors. The importance of multivariately and multipositionally varied test series is discussed. Multivariate projection methods such as PCA and PLS are shown to be appropriate far QSAR and to closely correspond to the analogy assumption. The multivariate analogy approach is applied to a beta- adrenergic agents, b haloalkanes, c halogenated ethyl methyl ethers and d four different families of peptides. / <p>Diss. (sammanfattning) Umeå : Umeå universitet, 1986, härtill 8 uppsatser</p> / digitalisering@umu

The main purpose of the present studies has been to develop the Defense Mechanism Test (DM1) for clinical assessment of severe psychopathology with the focus on the concept of Borderline Personality Organization (BPO) according to Kemberg. By relating the DMT and the Structural Interview to each other, the concurrent validity of the concept of Personality Organization (PO) for psychiatric inpatients has been investigated. Two different assessment approaches have been used for this purpose. One has been to take a theoretical perspective as the starting-point for the classification of PO by means of the DMT. The other has been a purely empirical approach designed to discern natural and discriminating patterns of DMT distortions for different diagnostic groups. A dialogue is also in progress between DMT and current research on the Rorschach test in order to increase understanding of borderline phenomena and pathology. The overall results support Kemberg's idea that borderline patients are characterized by specific intrapsychic constellations different from those of both psychotic and neurotic patients. Both the DMT and the Structural Interview provide reliable and consistent judgements of PO. Patients with the syndrome diagnosis Borderline Personality Disorder exhibit different perceptual distortions from patients suffering from other personality disorders. The classic borderline theory is a one-dimensional developmental model, where BPO constitutes a stable intermediate form between neurosis and psychosis. The present results suggest that a two-dimensional model might be more powerful. Hence, the level of self- and object representations and reality orientation might be considered both from a developmental gad an affective perspective across varying forms of pathology. Kemberg suggests that borderline and psychotic patients share a common defensive constellation, centered around splitting, organizing self- and object representations. This view did not find support. The defensive pattem of the BPO patients is significantly different from the PPO defensive pattern. The BPO patients form their self- and object images affectively and thus the self- and object representations would seem to influence the defensive organization and not the other way around. The results have implications for the procedure and the interpretation of the DMT e.g. one and the same DMT picture can discern different kinds of personality; reactions other than the operationalized defense categories in the DMT manual can be valid predictors of PO; some of the DMT defenses described in the manual have to be reconceptualized such as isolation, repression and to some degree denial. Multivariate models are powerful tools for the integration of reactions to DMT into diagnostic patterns. / <p>Diss. (sammanfattning) Umeå : Umeå universitet, 1992, härtill 4 uppsatser.</p> / digitalisering@umu

Submitted by Alexandre Quevedo Rocha (alexandreque@hotmail.com) on 2016-12-12T16:57:12Z No. of bitstreams: 1 Dissertação _ Alexandre Quevedo _ Versão Final.pdf: 1223961 bytes, checksum: 4dce0bbe8d0aa8f084c221af0e924df5 (MD5) / Rejected by Fabiana da Silva Segura (fabiana.segura@fgv.br), reason: Prezado Alexandre Peço que faça as seguintes alterações Título - Letra maiúscula, corrigir (Capa e Contra Capa) Excluir os números nas páginas até o sumário, elas contam no sumário, não aparecem nesses primeiras páginas Corrigir a linha: Estratégia e Mercado - Deve conter o resumo e palavras chaves e inglês (Abstract e Keywords) Após as alterações peço submeter o trabalho novamente on 2016-12-12T18:27:08Z (GMT) / Submitted by Alexandre Quevedo Rocha (alexandreque@hotmail.com) on 2016-12-12T18:49:27Z No. of bitstreams: 1 Dissertação _ Alexandre Quevedo _ Versão Final.pdf: 1220579 bytes, checksum: 8be268dc50fac59de1eca105c1f29e7d (MD5) / Rejected by Fabiana da Silva Segura (fabiana.segura@fgv.br), reason: Prezado, Alexandre Seu nome saiu do final da capa, e tem que estar no inicio da contra capa, peço corrigir e postar novamente, te mandei o print da tela on 2016-12-12T18:52:04Z (GMT) / Submitted by Alexandre Quevedo Rocha (alexandreque@hotmail.com) on 2016-12-12T18:58:41Z No. of bitstreams: 1 Dissertação _ Alexandre Quevedo _ Versão Final.pdf: 1219692 bytes, checksum: f616cc8455f1014aaf284257e1fcdf8e (MD5) / Rejected by Fabiana da Silva Segura (fabiana.segura@fgv.br), reason: Alexandre, Agora não tem a contra capa, É capa, contra capa, ficha catalográfica, folha de assinaturas...agradecimentos, resumo, abstract Fabiana on 2016-12-12T19:58:23Z (GMT) / Submitted by Alexandre Quevedo Rocha (alexandreque@hotmail.com) on 2016-12-12T20:22:34Z No. of bitstreams: 1 Dissertação _ Alexandre Quevedo _ Versão Final.pdf: 1222500 bytes, checksum: b6c29f82e1a93c6768342401d85c83ae (MD5) / Approved for entry into archive by Fabiana da Silva Segura (fabiana.segura@fgv.br) on 2016-12-12T21:39:34Z (GMT) No. of bitstreams: 1 Dissertação _ Alexandre Quevedo _ Versão Final.pdf: 1222500 bytes, checksum: b6c29f82e1a93c6768342401d85c83ae (MD5) / Made available in DSpace on 2016-12-13T11:10:28Z (GMT). No. of bitstreams: 1 Dissertação _ Alexandre Quevedo _ Versão Final.pdf: 1222500 bytes, checksum: b6c29f82e1a93c6768342401d85c83ae (MD5) Previous issue date: 2016-11-30 / This study investigates some antecedents that impact individuals to have a positive attitude towards insurance, as well as one of its consequences, based on the critique of the normative theories about decision making under risk (Kahneman & Tversky, 1979; 1984; Thaler, 1980; Grapentine & Weaver, 2009). By a model of structural equations estimated by partial least squares, constructed from an empirical study with a sample of 215 participants, it was possible to verify that a positive attitude with respect to insurance can be given by means of different heuristic processes and by cognitive biases, such as: (i) the confidence (in honesty) of the insurance industry; (ii) the perception of risk for the good; and (iii) personal concern for finances; and this attitude toward insurance helps to explain willingness to pay for insurance, but that explanation becomes more relevant in cases where individuals own a car or house. This work also generates insights for the insurance industry and new studies on this topic. / Este estudo investiga alguns antecedentes que impactam indivíduos a terem uma atitude positiva em relação a seguro, assim como uma de suas consequências, com base na crítica às teorias normativas sobre a tomada de decisão sob risco (Kahneman & Tversky, 1979;1984; Thaler, 1980; Grapentine & Weaver, 2009). Por meio de um modelo de equações estruturais estimado por mínimos quadrados parciais, construído a partir de um estudo empírico com uma amostra de 215 participantes, foi possível verificar que uma atitude positiva em relação a seguro pode ser dada por meio de diferentes processos heurísticos e por vieses cognitivos, como: (i) a confiança (na honestidade) da indústria de seguro; (ii) a percepção de risco em relação ao bem; e (iii) a preocupação pessoal com as finanças; e essa atitude em relação a seguro ajuda a explicar a disposição em se pagar por um seguro, porém essa explicação se torna mais relevante nos casos em que indivíduos possuem carro ou casa. Este trabalho também gera insights para a indústria de seguro e novos estudos sobre este tema.

Fundação de Amparo a Pesquisa do Estado de Minas Gerais / In this work, the technique of infrared spectroscopy coupled with Eastern methods of Multivariate Calibration Partial Least Squares (PLS) and Partial Least Squares Interval (iPLS) was applied in order to develop methodology capable of quantifying adulterations oil and alcohols in biodiesels Soy and residual oil and its blends with diesel , and to quantify adulterations residual oil lubricant automotive (RAL) in commercial samples of S-10 diesel at filling stations distributed in Brazil by Petrobras S.A. Most multivariate calibration models with variable selection generated by iPLS presented information gain, decrease in the number of latent variables and lower error values when compared to global PLS models. All models constructed showed values of acceptable errors with Medium Error below 4.5%, while the maximum accepted value, determined by current standards is 10%. Thus, the proposed methodologies can be applied in quality control of these biodiesels and their blends with diesel as it were analytically validated by calculating Figures of Merit. / Neste trabalho, a técnica de Espectroscopia no Infravermelho Médio aliada aos métodos de Calibração Multivariada por Quadrados Mínimos Parciais (PLS) e Quadrados Mínimos Parciais por Intervalos (iPLS) foi aplicada, visando desenvolver metodologia capaz de quantificar adulterações por óleo e alcoóis em Biodieseis de Soja e óleo residual e suas misturas com diesel, assim como quantificar adulterações por óleo lubrificante automotivo residual (OLAR) em amostras comerciais de diesel S-10 distribuído em postos de abastecimento no Brasil por Petrobrás S.A. A maioria dos modelos de calibração multivariada com seleção de variáveis por iPLS gerados apresentou ganho de informação, diminuição no número de variáveis latentes e menores valores de erros quando comparados aos modelos PLS globais. Todos os modelos construídos apresentaram valores de erros aceitáveis, com Erro Médio inferiores a 4,5%, sendo que o valor aceito máximo, estabelecido por normas vigentes é de 10,0%. Desta forma, as metodologias propostas podem ser aplicadas no controle de qualidade destes biocombustíveis e suas misturas com diesel, uma vez que foram analiticamente validadas através do cálculo de Figuras de Mérito. / Mestre em Química

Made available in DSpace on 2015-05-14T13:21:38Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 6875549 bytes, checksum: 3697064e0b5c3d3ac90181f954575bc7 (MD5) Previous issue date: 2013-06-21 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Tea has an economic and cultural importance, not only for producers and consumers, but also for a scientific interest. The organoleptic quality of the Camellia sinensis infusion depends on the nature and amount of several secondary metabolites (such as polyphenols, caffeine, amino acids, etc.), which can be directly related to the geographical origin of the tea plants. These components are the basis of the economic value of teas and its beneficial effects on human health. Therefore, there is a growing consumer s interest in high quality teas with a distinct geographical identity. In last decades, the analytical methods employing modern instrumental techniques have become more sensitive, reliable and fast. However, these techniques have advantages and limitations for the application in the analyses of the tea quality and their geographic origins. Thus, a combination of different techniques could be more useful than relying on a single method. Following these principles, we propose three new strategies for simultaneous classification of teas according to both the type (green and black) and geographic origin (Argentina, Brazil and Sri Lanka). The proposed methodologies employ the use of (1) digital images, (2) NIR spectroscopy, and (3) chemical composition (moisture, ash, caffeine, total polyphenols, fluoride and fifteen metals (Na, Mg, Al, P, K, Ca, Cr, Mn, Fe, Co, Ni, Cu, Zn, Cd and Pb) in both tea leaves and infusions). A correct classification of all tea samples (100% of correct classification) was always obtained using the Linear Discriminant Analysis associated with the variable selection technique taken by the Successive Projections Algorithm. Soft Independent Modeling of Class Analogy (SIMCA) and Partial Least Squares Discriminant Analysis (PLS-DA) were also used. The proposed strategies might be useful for the development of legislation for the quality control of teas in Brazil, which is still lacking / O chá tem uma importância econômica e cultural, não só para produtores e consumidores, mas também por um interesse científico. A qualidade organoléptica da infusão da Camellia sinensis depende da natureza e da quantidade de vários metabólitos secundários (tais como polifenóis, cafeína, aminoácidos, etc.), os quais podem ser relacionados diretamente com a origem geográfica das plantas. Estes componentes são a base do valor econômico do chá e de seus efeitos benéficos sobre a saúde humana. Por isso, há um crescente interesse dos consumidores por chás de alta qualidade com uma clara identidade geográfica. Durante as últimas décadas, as metodologias analíticas que empregam técnicas instrumentais modernas tornaram-se mais sensíveis, confiáveis e rápidas. Entretanto, tais técnicas têm vantagens e limitações para a aplicação da análise da qualidade do chá e de suas origens geográficas. Assim, uma combinação de diferentes técnicas analíticas pode ser mais útil do que depender de um único método. Seguindo estes preceitos, nós propusemos três novas estratégias para a classificação simultânea de chás de acordo com o tipo (verde e preto) e a origem geográfica (Argentina, Brasil e Sri Lanka). As metodologias propostas empregam o uso de (1) imagens digitais, (2) espectroscopia NIR e (3) composição química (umidade, cinza total, cafeína, polifenóis totais, fluoreto e quinze metais (Na, Mg, Al, P, K, Ca, Cr, Mn, Fe, Co, Ni, Cu, Zn, Cd e Pb) nas folhas e infusões dos chás). Uma classificação correta de todas as amostras de chás (100% de acerto) foi sempre obtida utilizando Análise Discriminante Linear associada à técnica de seleção de variáveis feita pelo Algoritmo das Projeções Sucessivas (SPA-LDA). Modelagem Independente e Flexível por Analogia de Classe (SIMCA) e Análise Discriminante por Mínimos Quadrados Parciais (PLS-DA) também foram utilizadas. Tais estratégias podem ser úteis para a elaboração de normas para o controle de qualidade de chás no Brasil, que ainda é inexistente

Trots att det inom forskningsvärlden propageras för formativ bedömning, kan man i dagsläget notera en mycket stor variation gällande införlivandet av, samt effekter av, formativ bedömning i skolor. Metoder för att kartlägga formativ bedömningspraxis fordras för att kunna särskilja på ”god” respektive ”mindre god” formativ bedömningspraxis. Syftet med föreliggande uppsats var att, med hjälp av en elevenkät och multivariata projektionsmetoder såsom PCA och PLS-DA, kartlägga, och särskilja, formativ bedömningspraxis hos sex olika gymnasieklasser som genomfört kursen kemi 2. Ett sekundärt syfte var även att, med samma verktyg, försöka karakterisera och särskilja frekvenser av olika genomförda undervisningsmoment inom samma kurs och klasser. Studien visade, på ett grafiskt och illustrativt sätt, en stor variation av upplevelser av formativ bedömning inom de tillfrågade klasserna. Vidare visade sig PCA vara ett utmärkt verktyg för att identifiera elevsvar som låg utanför den ”normala” variationen. Genom en PLS-DA-analys påvisades en skillnad i frekvenser av genomförda undervisningsmoment mellan två kommunala och en privat skola – även om dessa resultat bör tolkas med en viss försiktighet.

One of the challenges in the structural biological community is processing the wealth of protein data being produced today; therefore, the use of computational tools has been incorporated to speed up and help understand the structures of proteins, hence the functions of proteins. In this thesis, protein structure investigations were made through the use of Multivariate Analysis (MVA), and Fourier Transformed Infrared (FTIR), a form of vibrational spectroscopy. FTIR has been shown to identify the chemical bonds in a protein in solution and it is rapid and easy to use; the spectra produced from FTIR are then analysed qualitatively and quantitatively by using MVA methods, and this produces non-redundant but important information from the FTIR spectra. High resolution techniques such as X-ray crystallography and NMR are not always applicable and Fourier Transform Infrared (FTIR) spectroscopy, a widely applicable analytical technique, has great potential to assist structure analysis for a wide range of proteins. FTIR spectral shape and band positions in the Amide I (which contains the most intense absorption region), Amide II, and Amide III regions, can be analysed computationally, using multivariate regression, to extract structural information. In this thesis Partial least squares (PLS), a form of MVA, was used to correlate a matrix of FTIR spectra and their known secondary structure motifs, in order to determine their structures (in terms of "helix", "sheet", “310-helix”, “turns” and "other" contents) for a selection of 84 non-redundant proteins. Analysis of the spectral wavelength range between 1480 and 1900 cm-1 (Amide I and Amide II regions) results in high accuracies of prediction, as high as R2 = 0.96 for α-helix, 0.95 for β-sheet, 0.92 for 310-helix, 0.94 for turns and 0.90 for other; their Root Mean Square Error for Calibration (RMSEC) values are between 0.01 to 0.05, and their Root Mean Square Error for Prediction (RMSEP) values are between 0.02 to 0.12. The Amide II region also gave results comparable to that of Amide I, especially for predictions of helix content. We also used Principal Component Analysis (PCA) to classify FTIR protein spectra into their natural groupings as proteins of mainly α-helical structure, or protein of mainly β-sheet structure or proteins of some mixed variations of α-helix and β-sheet. We have also been able to differentiate between parallel and anti-parallel β-sheet. The developed methods were applied to characterize the secondary structure conformational changes of an unfolding protein as a function of pH and also to determine the limit of Quantitation (LoQ).Our structural analyses compare highly favourably to those in the literature using machine learning techniques. Our work proves that FTIR spectra in combination with multivariate regression analysis like PCA and PLS, can accurately identify and quantify protein secondary structure. The developed models in this research are especially important in the pharmaceutical industry where the therapeutic effect of drugs strongly depends on the stability of the physical or chemical structure of their proteins targets; therefore, understanding the structure of proteins is very important in the biopharmaceutical world for drugs production and formulation. There is a new class of drugs that are proteins themselves used to treat infectious and autoimmune diseases. The use of spectroscopy and multivariate regression analysis in the medical industry to identify biomarkers in diseases has also brought new challenges to the bioinformatics field. These methods may be applicable in food science and academia in general, for the investigation and elucidation of protein structure.