Rozprawy doktorskie: „Antigen specificity”

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Košmrlj, Andrej 1981. "Statistical physics of T cell receptor development and antigen specificity". Thesis, Massachusetts Institute of Technology, 2011. http://hdl.handle.net/1721.1/68875.

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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Physics, 2011.
Cataloged from PDF version of thesis.
Includes bibliographical references (p. 147-158).
Higher organisms, such as humans, have an adaptive immune system that usually enables them to successfully combat diverse (and evolving) microbial pathogens. The adaptive immune system is not preprogrammed to respond to prescribed pathogens, yet it mounts pathogen-specific responses against diverse microbes, and establishes memory of past infections (the basis of vaccination). Although major advances have been made in understanding pertinent molecular and cellular phenomena, the mechanistic principles that govern many aspects of an immune response are not known. In this thesis, I illustrate how complementary approaches from the physical and life sciences can help confront this challenge. Specifically, I describe work that brings together statistical mechanics and cell biology to shed light on how key regulators of the adaptive immune system, T cells, are selected to enable pathogen-specific responses. A model of T cell development is introduced and analyzed (computationally and analytically) by employing methods from statistical physics, such as extreme value distributions and Hamiltonian minimization. Results show that selected T cell receptors are enriched in weakly interacting amino acids. Such T cell receptors recognize (i.e. bind sufficiently strongly to) pathogens through several contacts of moderate strength, each of which makes a significant contribution to overall binding. Disrupting any contact by mutating the pathogen is statistically likely to abrogate T cell recognition of the mutated pathogen. We propose that this is the mechanism for the specificity of T cells for unknown pathogens. The T cell development model is also used to discuss one way in which host genetics can influence the selection of T cells and concomitantly the control of HIV infection. A model of the T cell selection process as diffusion in a random field of immobile traps that intermittently turn "on" and "off" is developed to estimate the escape probability of dangerous T cells that could cause autoimmune disease. Finally, and importantly, throughout this thesis, I describe, how the theoretical studies are closely synergistic/complementary with biological experiments and human clinical data.
by Andrej Košmrlj.
Ph.D.

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Sandberg, Johan. "CD8⁺ T cell specificity in thymic selection and in the recognitionof antigen /". Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3686-2/.

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Forsström, Björn. "Characterization of antibody specificity using peptide array technologies". Doctoral thesis, KTH, Proteomik och nanobioteknologi, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-155723.

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Antibodies play an important role in the natural immune response to invading pathogens. The strong and specific binding to their antigens also make them indispensable tools for research, diagnostics and therapy. This thesis describes the development of methods for characterization of an- tibody specificity and the use of these methods to investigate the polyclonal antibody response after immunization. Paper I describes the development of an epitope-specific serum fractionation technique based on epitope map- ping using overlapping peptides followed by chromatographic separation of polyclonal serum. This technique together with another epitope mapping technique based on bacterial display of protein fragments were then used to generate antibody sandwich pairs (Paper I), investigate epitope variations of repeated immunizations (Paper II) and to determine the ratio of antibodies targeting linear and conformational epitopes of polyclonal antibodies (Paper III). Paper IV describes the optimization of in situ-synthesized high-density peptide arrays for epitope mapping and how different peptide lengths influ- ence epitope detection and resolution. In Paper V we show the development of planar peptide arrays covering the entire human proteome and how these arrays can be used for epitope mapping and off-target binding analysis. In Paper VI we show how polyclonal antibodies targeting linear epitopes can be used for peptide enrichment in a rapid, absolute protein quantification protocol based on mass spectrometry. Altogether these investigations demonstrate the usefulness of peptide arrays for fast and straightforward characterization of antibody specificity. The work also contributes to a deeper understanding of the polyclonal anti- body response obtained after immunization with recombinant protein frag- ments.

QC 20141111

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Moots, Robert J. "The fine specificity of HLA class I-restricted antigen recognition by cytotoxic T lymphocytes". Thesis, Open University, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.315327.

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Peche, Leticia Yamila. "Evidence of functional specificity within the MAGE-I family of tumor expressed proteins". Doctoral thesis, SISSA, 2008. http://hdl.handle.net/20.500.11767/4674.

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The Melanoma Antigen Genes (MAGE) belong to a large family of highly conserved genes, sharing an elevated degree of sequence homology. The characteristic feature of MAGE proteins is a C-terminal domain present in all the members of the family, termed the MAGE homology domain (MHD). Based on their expression pattern MAGE genes are classified in MAGE-I and MAGE-II genes. MAGE-I genes expression is restricted to tumor and male germ cells, and for this reason they form part of a growing group of genes named Cancer Testis Antigens (CTA). Expression of MAGE-I genes seems to be an early event during gametogenesis and tumorigenesis, and correlates with genomewide hypomethylation, an important event frequently observed in carcinogenesis. Since their discovery in 1991, MAGE-I genes were mostly studied for their potential use in immunotherapy against cancer or as prognostic markers in tumors. The biological roles that these proteins play in tumor development and progression were poorly investigated. Moreover, due to their sequence homology, MAGE-I proteins are still considered functionally redundant proteins. In the present work, we functionally characterized different MAGE-I genes, in particular MageA2 and MageB2 genes, demonstrating their functional specificity. We show that MageA2 protein confers wild-type p53 tumor suppressor-sensitive resistance to chemotherapeutic drugs, such as etoposide, by recruitment of HDAC3 to p53/MageA2 complex, thus repressing p53 transactivation function. The mechanism responsible for the repressive effect of MageA2, relies on an impaired acetylation of both p53 and histones surrounding p53 binding sites by MageA2/HDAC3 complexes. The correlation between MAGE-A expression and resistance to apoptosis has been analyzed in short-term melanoma cell lines, where combined treatment with etoposide and trichostatin A (an inhibitor of histone deacetylases) restores the p53 response and reverts chemoresistance in cells expressing high levels of MAGE-A. We also present evidence that MageA2 is able to repress PML3-induced p53 activity in a specific manner, by affecting PML3 mediated p53 acetylation at the PML3 nuclear bodies (PML3-NBs). The relevance of MageA2 expression on PML3 activity has been analyzed in a normal cellular context, in which PML3 induces premature senescence, an important barrier against cell transformation. In this regard, we demonstrate that MageA2 impairs the senescence response associated to PML3 expression in normal human fibroblast. A possible mechanism for the inhibitory effect of MageA2 on PML3 is that MageA2 could interfere with PML3 sumoylation. The specificity of MageA2 functions is demonstrated by the fact that, despite high level of homology, MageA4 is not recruited to the NBs, it does not affect p53 activity nor is able to interfere with PML3 induced senescence. Finally, we have preliminarily characterized the MageB2 protein, showing that it specifically localizes to the nucleolus where it is able to interact with many nucleolar proteins. Nucleolar stress induces MageB2 relocalization to the nucleoplasm, a characteristic behavior of nucleolar proteins that regulate processes such as rRNA metabolism or RNA processing. Moreover, since we observed that MageB2 induces pRb relocalization to the nucleoli and increases E2F1 transactivation function, including E2F1-induced rRNA transcription, we hypothesize that it could play a positive role in the regulation of cell proliferation. Altogether the work presented here consistently supports the notion that, despite the high level of sequence homology, there is a clear degree of functional specificity within members of the MAGE-I family. Hence, we can hypothesize that different MAGE-I proteins, for instance MageA2 and MageB2, could act within different pathways in the regulation of complex processes such as apoptosis, proliferation, and senescence. By targeting different signal transduction pathways their final outcome could be related to the establishment and progression of the tumors where they are expressed. In this Thesis, we give a comprehensive view on the functional differences among MAGE-I members, focusing on Mage-A and Mage-B members. Implementation of our investigation could be the first step leading to understanding of how expression of specific MAGE-I members could impact cancer cell behaviour thus prompting the use of MAGE-I genes as novel cancer specific targets for the development of new drug-based therapies.

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RIGAMONTI, VALERIA. "Development of a quantitative chemiluminescent immunoassay for the hepatitis B. antigen detection". Doctoral thesis, Università degli Studi di Milano-Bicocca, 2011. http://hdl.handle.net/10281/19390.

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The surface antigen of the hepatitis B (HBsAg) is the first detectable serological marker in infected patients. It enables to detect the infection in the first stages of the disease allowing a timely therapeutic intervention with a higher chance of success. A quantitative immunoassay will allow the customers to carry out the quantitative determination of the HBsAg at the start of treatment and during the follow up. Mutations that occur in a conformational surface region, called “a” loop, of HBsAg can cause an epitope loss impairing the antibody interaction deriving from host immune response as well as from vaccination and present in commercial immunoassays. DiaSorin new quantitative immunoassay has high sensibility and specificity and the ability to detect HBsAg mutants.

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Roter, Evan. "Beta2-glycoprotein I-specific T cells: antigen specificity and role in the induction of anti-phospholipid syndrome". Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=86847.

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Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by the presence of autoantibodies to phospholipid (PL)-binding proteins, such as β2-glycoprotein I (β2GPI), and clinical manifestations including thrombosis and/or recurrent pregnancy loss. APS patients have β2GPI-reactive T cells, but their origin is unclear. We hypothesized that mice immunized with human (foreign) β2GPI would produce T cells reactive with murine β2GPI. We further proposed that β2GPI oxidation, reduction, or binding to PL would alter T cell recognition of β2GPI. Splenic T cells from C57BL/6 mice immunized repeatedly with human β2GPI and lipopolysaccharide were found to produce IFN-γ in response to native human β2GPI, alone or bound to anionic PL; reduced β2GPI; and to a lesser extent oxidized β2GPI. However, the T cells did not respond to any form of murine β2GPI. β2GPI-reactive T cell hybridomas showed similar results. Antibodies to murine β2GPI were produced by immunization with human or murine β2GPI with complete Freund's adjuvant, but no β2GPI-reactive T cell response was observed. Our data indicate that a break in B cell tolerance to autologous β2GPI can occur in the absence of a detectable in vitro T cell response to this protein.
Le syndrome antiphospholipide (SAPL) est une maladie autoimmune caractérisée par la présence d'auto-anticorps antiphospholipides (aPL) dirigés contre des protéines liant les phospholipides anioniques dont la β2-glycoproteine I (β2GPI), ainsi que par des manifestations cliniques incluant la thrombose et la perte foetale récurrente. Les patients souffrant du SAPL possèdent des lymphocytes T sensibles au β2GPI mais leurs origines restent inconnues. Nous posons donc l'hypothèse que des souris immunisées avec β2GPI humain produiraient des lymphocytes T sensibles au β2GPI endogène. De surcroit, nous proposons que l'oxydation, la réduction, ou la liaison du β2GPI aux phospholipides affecterait l'identification du β2GPI par les lymphocytes T. Après de nombreuses immunisations avec du β2GPI humain, des lymphocytes T de rate provenant de souris C57BL/6 produisent de l'interferon-γ (IFN-γ) en présence soit de β2GPI humain - isolé ou lié à un phospholipide anionique; de β2GPI humain réduit; ainsi, mais à un degré moindre, de β2GPI humain oxydé. Toutefois, les lymphocytes T n'ont produit pas de réponses à aucune forme de β2GPI murin qui soient. Des résultats similaires avec hybridomes de lymphocytes T sensibles au β2GPI furent aussi obtenus. D'autre part des anticorps contre le β2GPI murin furent obtenus à la suite d'immunisations, utilisant du β2GPI humain ou murin conjointement avec de l'adjuvant de Freund, mais aucune réponse de lymphocytes T sensibles au β2GPI furent observée. Nos résultats indiquent que la tolérance des lymphocytes B au β2GPI autologue peut être brisée en absence d'une réponse détectable in vitro de lymphocytes T au β2GPI.

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8

Johansson, Daniel X. "Expression and interaction studies of recombinant human monoclonal antibodies /". Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-137-1/.

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Babakhani, Farah Kondori 1960. "IN VITRO PRODUCTION AND SPECIFICITY OF ANTI-DNA AUTO ANTIBODIES BY NEW ZEALAND BLACK/NEW ZEALAND WHITE F1 MICE". Thesis, The University of Arizona, 1986. http://hdl.handle.net/10150/276471.

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Lagardien, Zaida. "The characterisation of the peanut agglutinin an evolved plant lectin, with improved specificity to the Thompson Freidenriech antigen". Master's thesis, University of Cape Town, 2013. http://hdl.handle.net/11427/3136.

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Includes abstract.
Includes bibliographical references.
Peanut agglutinin (PNA), a carbohydrate binding protein, is able to recognise and bind a number of distinct carbohydrate structures that have been implicated in a number of disease pathologies in humans. In vitro studies of PNA have previously been shown to have some specificity for the Thomson Freidenriech antigen (T-antigen), found on malignant human cells, and this specificity has made PNA an important target for protein engineering experiments aimed at improving its specificity and affinity. A number of tumour cells are characterised by altered states and patterns of glycosylation on cell surfaces and suitably engineered lectins may be able to recognise tumour specific carbohydrate structures. This study was aimed at carrying out the biophysical characterisation of a set of PNA mutants which showed apparent improvement in specificity for the T-Antigen. Previous studies have aimed to engineer this lectin in order to direct its recognition properties towards the T-antigen and away from lactose, the preliminary binding affinities of these mutants being determined using Surface Plasmon Resonance (SPR). Here a set of PNA mutants were characterised, proteins expressed and purified to determine binding activities to the T-antigen, N-Acetyl-Dlactosamine (LacNAc) and lactose through the use of Protein Micro Array technology as well as Enzyme linked immunosorbant assays (ELISA).

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Törnblom, Magnus. "The diagnostic performance of prostate-specific antigen (PSA) in early detection of prostate cancer : considerations of sensitivity, specificity, lead-time and survival /". Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-660-X/.

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Lucca, Liliana. "Study of autoreative T cells exhibiting bi-specificity for a myelin and a neuronal antigen in a mouse model of multiple sclerosis". Toulouse 3, 2014. http://www.theses.fr/2014TOU30157.

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La sclérose en plaques (SEP) est une maladie neurologique causée par une inflammation du système nerveux central. Elle représente la cause non traumatique de handicap moteur chez les jeunes adultes et touche plus de 2. 5 millions de personnes dans le monde. Dans la SEP, le système immunitaire se trompe de cible et s'attaque à certains composants de la gaine qui isole les fibres nerveuses. Mon équipe d'accueil étudie les causes et conséquences de cette attaque mal dirigée. Spécifiquement, ils ont découvert que dans un modèle animal classique de SEP certaines cellules immunes reconnaissent simultanément deux composants de la fibre nerveuse en tant que cibles. Mon travail de recherche a consisté à caractériser ces cellules, leur origine, et à démontrer que cette double reconnaissance les rend plus pathogéniques. Mon travail sur ce nouveau mécanisme de l'auto-immunité va contribuer à clarifier la pathogenèse de la sclérose en plaques
Multiple sclerosis (MS) is a neurological disease caused by inflammation of the central nervous system. It represents the major non-traumatic cause of disability in young adults and affects 2. 5 million people worldwide. It is believed that in MS the immune system attacks molecular components of the myelin sheath that insulates nerve fibres. My host team research is dedicated to understanding the causes and consequences of this self-destructive behaviour of the immune system. In particular, they have discovered that in a classical animal model of MS certain immune cells recognize two molecular components of the neural fibre at the same time. My research work has consisted in characterizing these cells, understanding how they are generated and demonstrating that double-recognition enables them with a greater pathogenic potential. My work on this novel mechanism of autoimmunity contributes to shed light on the pathogenic processes underlying multiple sclerosis

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Laugel, Bruno. "Study of the interplay between antigen T-cell receptor and co-receptor in balancing the specificity and degeneracy of cytotoxic T-cell response". Thesis, University of Oxford, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.437180.

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Zeliszewski, Dominique. "Etude du polymorphisme et du role des molecules hla de classe 2 a l'aide de clones de lymphocytes t restreints et specifiques d'antigenes viraux". Paris 7, 1987. http://www.theses.fr/1987PA077248.

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Trad, Ahmad [Verfasser]. "Significance of the third hypervariable region of the antibody heavy (H) chain for antigen-specificity and expression of idiotypes during the thymus-dependent immune response / Ahmad Trad". Kiel : Universitätsbibliothek Kiel, 2010. http://d-nb.info/1019902469/34.

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Lafon, Monique. "La nucleocapside du virus rabique : une nouvelle cible pour la reponse immunitaire et pour la therapie". Paris 7, 1987. http://www.theses.fr/1987PA077219.

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Vazquez, Aimé. "Activation des lymphocytes B humains : interactions entre signaux spécifiques et non spécifiques". Paris 6, 1986. http://www.theses.fr/1986PA066436.

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Alheim, Mats. "Inhibitory receptors of natural killer cells : specificity and regulation /". Stockholm, 1998. http://diss.kib.ki.se/search/diss.se.cfm?19981009alhe.

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Mhanna, Vanessa. "The imprint of autoimmunity in the T-cell receptor repertoire". Electronic Thesis or Diss., Sorbonne université, 2021. http://www.theses.fr/2021SORUS336.

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L’activation des lymphocytes T repose sur leur récepteur de surface TCR, généré durant leur développement thymique par un processus de réarrangements somatiques aléatoires. Ce processus constitue la première étape de l’établissement du « répertoire TCR », définissant l’ensemble des TCR exprimés par les cellules T d’un organisme. Compte tenu de la dépendance des lymphocytes T pour leurs TCR, l’étude du répertoire permettrait de découvrir des TCR potentiellement impliqués dans la pathogenèse auto-immune. Dans ce but, j’ai étudié la contribution du répertoire TCR dans le développement du diabète chez les souris diabétiques non obèses (NOD) à jeune âge dans deux sous-populations de lymphocytes T régulateurs (Treg): les Tregs naïfs (nTregs) et les Tregs activés/mémoire (amTregs). Les résultats ont révélé une altération de la diversité du répertoire TCR périphérique des amTregs chez la NOD par rapport aux souris C57BL/6. Cette altération a été corrigée après l’administration d’interleukine-2 (IL-2), une cytokine indispensable à la survie et à l’expansion des Treg, et qui protège la NOD du diabète. Néanmoins, l’élimination des cellules T auto-réactives par sélection thymique a été décrite comme étant défective dans ce modèle murin. Ainsi, j’ai analysé le répertoire TCR des thymocytes, et identifié des séquences signatures spécifiques à NOD. Ces séquences ont été retrouvé dans les ganglions pancréatiques à une fréquence plus élevée que dans la rate de ces souris. De plus, les modèles d’apprentissage automatique ont révélé́ la présence de motifs d’acides aminés partagés par les séquences des signatures. Ces résultats suggèrent leur implication potentielle dans la maladie. Dans l’ensemble, mon projet met en évidence le potentiel du répertoire du TCR en tant que biomarqueur prédictif de la maladie dans la périphérie, ainsi que dans le thymus, le siège du développement des lymphocytes T et de la génération des TCR
The primary mediators of the immune system peripheral tolerance are the regulatory T-cells (Tregs), that act as suppressors of pro-inflammatory effector T-cells (Teffs). Any failure to accomplish this role can lead to autoimmunity. T lymphocytes’ activation relies on their surface receptors TCRs composed of an alpha (TRA) and a beta (TRB) chain, that bind antigenic peptides embedded in the major histocompatibility complex (MHC) molecules. The TCR is generated during T-cell development in the thymus by a random somatic rearrangement process, and which constitutes the first step in the shaping of the “TCR repertoire”, defining the TCRs expressed by all T-cells in the body. Given the tight reliance of T lymphocytes on their TCRs, the study of their repertoires would help discover TCRs that are involved in autoimmune pathogenesis. By investigating the TCR repertoire of two sub-populations of Tregs; naive (nTregs) and activated/memory (amTregs) Tregs in diabetes-prone non-obese diabetic (NOD) mice, I revealed the presence of an alteration in the NOD peripheral amTregs repertoire diversity compared to healthy C57BL/6 mice. This alteration was normalized following interleukin-2 (IL-2) administration, a crucial cytokine for Treg survival and expansion, and which protects mice from diabetes. Nevertheless, the hypothesis of a potential enrichment of diabetogenic Teffs in NOD mice is not excluded. Thus, I analysed the TCR repertoires of developing thymocytes during their thymic selection process, and identified NOD-specific signature sequences. The tracking of these sequences in NOD pancreatic islets revealed their higher proportions than in the spleen, and their enrichment in shared amino acid motifs, which together suggest their potential implication in the disease. Overall, my project highlights the power of the TCR repertoire as a predictive biomarker of disease in the periphery, as well as in the thymus, the home for T-cell development and TCR generation

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Waldenström, Margareta. "Mapping of the specificity in MHC class I recognition by natural killer cells /". Stockholm : Karolinska Univ. Press, 2000. http://diss.kib.ki.se/2000/91-89428-03-x/.

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Tusell, Sonia M. "Coronavirus receptors and host range /". Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2007.

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Thesis (Ph.D. in Molecular Biology) -- University of Colorado Denver, 2007.
Typescript. Includes bibliographical references (leaves 198-221). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;

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Figueroa, Z. E. F. "Specificity and protective effect of polyclonal antibodies to antigens of Plasmodium berghei and Plamodium chabaudi". Thesis, Open University, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.304217.

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Anton, Cristina. "Predição de malignidade de tumores ovarianos utilizando marcadores tumorais, índice de risco e ROMA". Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/5/5139/tde-07122011-121820/.

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INTRODUÇÃO: O câncer de ovário é o mais letal de todos os cânceres ginecológicos e requer ser tratado por ginecologistas especializados em centros terciários para se obter melhor prognóstico. Este trabalho tem como objetivo analisar e comparar quatro estratégias diferentes para predizer a benignidade ou malignidade de tumores pélvicos supostamente de origem ovariana utilizando para este fim, marcadores tumorais CA 125 e HE4, índice de risco de malignidade (IRM) e algoritmo ROMA. MÉTODOS: Neste estudo prospectivo foram avaliadas 128 pacientes com diagnóstico de tumores pélvicos supostamente de origem ovariana atendidas na Divisão de Clínica Ginecológica do Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo e Instituto do Câncer do Estado de São Paulo entre julho de 2008 e janeiro 2011. Foram calculadas a sensibilidade e a especificidade e construídas curvas ROC para comparar os quatro parâmetros (CA 125, HE4, ROMA e IRM) na eficácia de diferenciar tumores ovarianos. RESULTADOS: A sensibilidade obtida para CA 125, HE4, ROMA e IRM foi de, respectivamente, 70,4%, 79,7%, 74,1% e 63,0%. A especificidade para CA 125, HE4, ROMA e IRM foi de, respectivamente, 74,2%, 66,7%, 75,8% e 92,4%. Não houve diferença na comparação das áreas abaixo da curva ROC entre os quatro parâmetros. CONCLUSÕES: Nenhum dos quatro métodos estudados é o ideal na diferenciação de tumores ovarianos. Entre os quatro parâmetros analisados o HE4 foi o parâmetro com melhor sensibilidade na diferenciação de tumores ovarianos. A acurácia dos quatro métodos é equivalente e podem ser utilizados indistintamente para referenciar pacientes para serviços especializados no tratamento de câncer de ovário
BACKGROUND: Ovarian cancer is the most lethal of all gynecological cancers and requires to be treated by gynecologic oncologists in tertiary centers accustomed to treating this disease to achieve the best prognosis. This study aims to compare four different strategies to predict the benignity or malignancy of pelvic tumors presumably of ovarian origin using, for this purpose, tumor markers CA 125 and HE4, risk malignancy index (RMI) and algorithm ROMA. METHODS: This prospective study evaluated 128 patients supposedly with ovarian tumors treated at the Divisão de Clínica Ginecológica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo and at Instituto do Câncer do Estado de São Paulo between July 2008 and January 2011. We calculated sensitivity, specificity and ROC curves to compare the four parameters (CA 125, HE4, ROMA and RMI) ability to differentiate the ovarian tumors. RESULTS: The sensitivity obtained for CA 125, HE4, ROMA and RMI was, respectively, 70.4%, 79.7%, 74.1% and 63.0%. The specificity obtained for CA 125, HE4, ROMA and RMI was, respectively, 74.2%, 66.7%, 75.8% and 92.4%. There was no difference the areas under the ROC curve among the four parameters. CONCLUSIONS: None of the four studied methods is best in the differentiation of ovarian tumors. Among the four parameters analyzed, HE4 was the parameter with highest sensitivity in the differentiation of ovarian tumors. The accuracy of the four methods is equivalent and can be used interchangeably to refer patients for specialized services in the treatment of ovarian cancer

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Halary, Franck. "Etude des lymphocytes t gamma/delta humains : aspect du controle des fonctions biologiques et de la specificite antigenique (doctorat : immunologie)". Nantes, 1999. http://www.theses.fr/1999NANT10VS.

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Michaëlsson, Jakob. "Decoding NK cell receptor specificity : functional and structural studies of MHC class 1 subcomponents /". Stockholm : [Karolinska institutets bibl.], 2002. http://diss.kib.ki.se/2002/91-7349-286-8.

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Fernandez, Ramirez Juliana Esmeralda. "Evaluation of specificity of a walnut antiserum and detection of English walnut (Juglans regia) in food with ELISA and Real-Time PCR". Thesis, Uppsala University, Department of Medical Biochemistry and Microbiology, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-106350.

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Nuts of all kinds are common ingredients in food. For nut allergy sufferers the frequent use of nuts cause problems and "hidden" nuts in food products may elicit allergic reaction when such foods are consumed. Methods for detecting and quantifying walnut (and other nuts) with high sensitivity and specificity are therefore very important.

The objective of this project was to verify the specificity of a rabbit antiserum against walnut with immunodiffusion and to determine the size of the dominant walnut antigens with Western blotting. In addition, a commercial sandwich ELISA for walnut quantification was validated and compared with a qualitative real-time PCR.

The rabbit antiserum proved to be less specific but after absorption with cross-reacting nuts and seeds it showed high specificity. The ELISA kit reacted, except for walnut, with pecan and slightly with other nuts and seeds tested. The PCR showed an absolute specificity to walnut. As low levels as 2.5mg walnut/kg can be quantified with the ELISA. This is 8 to 100 fold less than with the PCR method. It is therefore concluded that the ELISA kit is more sensitive than the PCR method but the PCR method is more specific than the ELISA kit.

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BLOT, MARIE-FREDERIQUE. "Specificite des antigenes proteiques membranaires de mycoplasma gallisepticum et mise au point de deux techniques serologiques de diagnostic". Rennes 1, 1989. http://www.theses.fr/1989REN10066.

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Etude des antigenes proteiques membranaires de mycoplasma gallisepticum par electrophorese et immunoblotting. Identification du polypeptide le plus immunogene. Mise au point de deux reactifs serologiques utilisables, l'un en agglutination rapide sur lame, l'autre en technique elisa

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Cherif, Alhaji. "Mathematical evolutionary epidemiology : limited epitopes, evolution of strain structures and age-specificity". Thesis, University of Oxford, 2015. http://ora.ox.ac.uk/objects/uuid:28dec0f4-e6da-466a-905c-d875f132415e.

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We investigate the biological constraints determined by the complex relationships between ecological and immunological processes of host-pathogen interactions, with emphasis on influenza viruses in human, which are responsible for a number of pandemics in the last 150 years. We begin by discussing prolegomenous reviews of historical perspectives on the use of theoretical modelling as a complementary tool in public health and epidemiology, current biological background motivating the objective of the thesis, and derivations of mathematical models of multi-locus-allele systems for infectious diseases with co-circulating serotypes. We provide detailed analysis of the multi-locus-allele model and its age-specific extension. In particular, we establish the necessary conditions for the local asymptotic stability of the steady states and the existence of oscillatory behaviours. For the age-structured model, results on the existence of a mild solution and stability conditions are presented. Numerical studies of various strain spaces show that the dynamic features are preserved. Specifically, we demonstrate that discrete antigenic forms of pathogens can exhibit three distinct dynamic features, where antigenic variants (i) fully self-organize and co-exist with no strain structure (NSS), (ii) sort themselves into discrete strain structure (DSS) with non-overlapping or minimally overlapping clusters under the principle of competitive exclusion, or (iii) exhibit cyclical strain structure (CSS) where dominant antigenic types are cyclically replaced with sharp epidemics dominated by (1) a single strain dominance with irregular emergence and re-emergence of certain pathogenic forms, (2) ordered alternating appearance of a single antigenic type in periodic or quasi-periodic form similar to periodic travelling waves, (3) erratic appearance and disappearance of synchrony between discrete antigenic types, and (4) phase-synchronization with uncorrelated amplitudes. These analyses allow us to gain insight into the age-specific immunological profile in order to untangle the effects of strain structures as captured by the clustering behaviours, and to provide public health implications. The age-structured model can be used to investigate the effect of age-specific targeting for public health purposes.

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ALTIERI, LAURA. "Risposte di linfociti T CD8+ specifici per antigeni self derivanti da cellule apoptotiche di pazienti affetti da infezione cronica da HIV". Doctoral thesis, Università degli Studi di Roma "Tor Vergata", 2008. http://hdl.handle.net/2108/501.

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L’attivazione immunitaria cronica, che caratterizza le malattie autoimmuni e le patologie infettive, è sostenuta da una persistente iperattivazione del sistema immunitario, da forte infiammazione dei tessuti colpiti dalla malattia e da apoptosi massiva delle cellule degli stessi tessuti. Nel corso di infezione da HIV (o da SIV) questi tre aspetti coesistono.Nell’infezione da HIV è dimostrata, in particolare, l’aumentata apoptosi, spontanea o indotta dall’attivazione, delle cellule T CD4+ e CD8+ ,ma in particolare delle cellule T CD4+ HIV-1 specifiche. I fenomeni alla base dell’attivazione immunitaria cronica nell’infezione da HIV potrebbero contribuire al mantenimento, quindi alla cronicità, dell’infezione stessa. Nel nostro laboratorio erano stati analizzati i profili proteici di cloni di linfociti T vivi o apoptotici, osservando che alcune proteine (tra cui proteine del citosheletro) vengono frammentate durante l’apoptosi. Era stato anche osservato che le caspasi, oltre ad essere necessarie, come era già noto, per la frammentazione delle proteine durante l’apoptosi, lo erano anche nel fenomeno della cross-presentazione delle cellule apoptotiche da parte delle DCs ai linfociti T CD8+ specifici. Ipotizzando che le proteine identificate possano essere immunogeniche, abbiamo sintetizzato un pannello di peptidi, ristretti per HLA-A2, derivati dalle proteine frammentate durante l’apoptosi e li abbiamo utilizzati in test Elispot. Nei pazienti testati esiste un ampio repertorio di linfociti T efCD8+ IFN-gamma+ specifici per diversi peptidi self. Le frequenze delle cellule T CD8+ effettrici specifiche per epitopi apoptotici correlano con la frequenza delle cellule T CD4+ apoptotiche. La citofluorimetria ha confermato l’esistenza, in vivo, di cellule T CD8+ specifiche per epitopi self apoptotici. Il fenotipo effettore di queste cellule è stato confermato dall’espressione di perforina e granzimi in una notevole porzione di cellule fresche CD8+ pentamero+ in tutti i soggetti infettati studiati. Le cellule T CD8+ pentamero+ da soggetti infettati da HIV producevano IFN-gamma , ex vivo, se stimolate con DCs che erano state pulsate con cellule apoptotiche derivate da cloni di cellule T CD95+. Questi dati indicano che, nel repertorio periferico degli individui infettati da HIV, in vivo, sono presenti cellule T efCD8+ IFN-gamma+ specifiche per gli epitopi derivati dal processamento delle proteine apoptotiche.
Chronic immune activation, that characterizes chronic viral or autoimmune diseases, is supported by a persistent hyperactivation of the immune system, by a strong inflammation of the tissues damaged and by a massive apoptosis of the cells in these tissues. During HIV (or SIV) infection these elements co-exist. In particular, it was demonstrated that the spontaneous or activation-induced apoptosis of CD4+ and CD8+ T cells (in particular of CD4+ HIV-1 specific T cells) increases in HIV infection. The phenomena that characterize the chronic immune activation in HIV infection may contribute to the maintenance of the same infection. In our laboratory, we analyzed the protein patterns of live or apoptotic T cell clones, observing that some proteins (for example cytoskeletal proteins) are fragmented during apoptosis. These protein fragments are generated by caspases. We observed that caspases are also important in the cross-presentation of apoptotic cells by DCs to specific CD8+ T cells. Assuming that the identified proteins can be immunogenic, we synthetized a panel of peptides, HLA-A2-restricted, derived from protein fragmentation during apoptosis and we used them in the Elispot test. In the tested patients there is a wide repertoire of efCD8+ IFN-gamma+ T lymphocytes specific to different self peptides. The frequencies of effector CD8+ T cells specific for apoptotic self epitopes are directly correlated with the percentage of apoptotic annexin V+ CD4+ T cells. FACS analysis confirmed, in vivo, the existence of CD8+T cells specific for apoptotic self epitopes. The effector phenotype of these cells was confirmed by perforin and granzyme expression in a considerable proportion of fresh pentamer+CD8+ T cells from all infected subjects studied. Pentamer+ CD8+ T cells from HIV-infected subjects produced IFN-gamma, ex vivo, after stimulation with DCs that had been pulsed with apoptotic cells derived from CD95+ T cell clones. These data indicate that efCD8+ IFN-gamma+ T cells, specific for naturally processed epitopes derived from apoptotic proteins, are present in the peripheral repertoire of HIV-infected individuals in vivo.

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Alami, Harchali Asmae. "Détection par immunephelemetrie sur supports microparticulaires d'autoanticorps anti-thyroïde de spécificité épisodique définie : mise au point de la méthode et applications". Nancy 1, 1994. http://www.theses.fr/1994NAN10286.

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Ce travail a pour objectif d'adapter à la détection et à la caractérisation d'autoanticorps, la technique d'immunonephelemetrie sur supports microparticulaires. Le but est d'affiner le pouvoir discriminant de cette technique jusqu'à l'identification de la spécificité épitopique des anticorps décelés. Un premier groupe d'applications porte sur la détection des autoanticorps anti-thyroglobuline humaine. Un test de détection de ces autoanticorps anti-domaine antigénique deux de la molécule de thyroglobuline, a été développé. Il est basé sur l'aptitude des autoanticorps à inhiber les systèmes agglutinants thyroglobuline-anticorps monoclonaux anti-thyroglobuline ont ainsi été détectés et quantifiés chez tous les patients atteints de thyroïdite d'Hashimoto et dans plus du trois-quarts des patients présentant une maladie de basedow non traitée. Les résultats obtenus se comparent favorablement à ceux de l'immunofluorescence indirecte et de l'hemagglutination passive. Le système mis au point peut aussi se prêter au dosage de la thyroglobuline sérique par inhibition. La détection des autoanticorps anti-thyroperoxydase humaine est calquée dans son principe sur le protocole mis au point pour les anticorps anti-thyroglobuline. Ce test confirme la polyclonalité des autoanticorps anti-thyroperoxydase et leur réactivité préférentielle envers les épitopes localisés sur les domaines antigéniques a et b de la molécule de thyroperoxydase, épitopes impliques dans les maladies thyroïdiennes auto-immunes. Ces mêmes spécificités sont observées chez les patients atteints de thyroïdite d'Hashimoto et de maladie de basedow. Les données immunonephelemetriques sont en accord avec les résultats des autres moyens d'investigation et avec les autres éléments des dossiers cliniques

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DORE, PETIT-MAIRE ISABELLE. "Utilisation des anticorps monoclonaux en virologie vegetale : diagnostic et etudes structurales de quelques tobamovirus". Université Louis Pasteur (Strasbourg) (1971-2008), 1987. http://www.theses.fr/1987STR13097.

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Etude des epitopes reconnus par 18 anticorps monoclonaux diriges contre la proteine de l'enveloppe du virus de la mosaique du tabac, en mesurant leur reactivite vis-a-vis de differents mutants, virus et peptides synthetiques. Visualisation de la liaison entre anticorps monoclonaux et virus par microscopie electronique, dans differents tests elisa. Preparation d'anticorps monoclonaux permettant la detection du virus des taches annulaires de l'odontoglossum et du virus de la mosaique de la tomate

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Misumi, Denise Shimbo. "Validação do Teste de ativação de basófilos no diagnóstico de reações de hipersensibilidade a anti-inflamatórios não esteroidais". Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/5/5146/tde-24062013-152145/.

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Introdução: Atualmente, o diagnóstico das reações de hipersensibilidade a anti-inflamatórios não esteroidais (AINEs) baseia-se na história relatada pelo paciente e, em determinados casos, é realizado o Teste de Provocação. Todavia, este teste pode expor os pacientes a riscos graves, inclusive anafilaxia. Em busca de ferramenta mais segura, tem-se estudado o Teste de Ativação de Basófilos (BAT). Trata-se de um teste in vitro, no qual é possível testar diversos estímulos em uma única amostra de sangue, avaliando a ativação dos basófilos (indicativo de reação de hipersensibilidade), através do aumento da expressão de moléculas na superfície desses leucócitos, como o CD63. Objetivo: Padronizar e validar o BAT para ácido acetilsalicílico (AAS), diclofenaco, dipirona e paracetamol em pacientes com hipersensibilidade a AINEs. Metodologia: Participaram 20 (testados com os quatro AINEs) + 33 (testados somente com AAS) pacientes atendidos no Serviço de Imunologia Clínica e Alergia do HCFMUSP, que apresentaram manifestações cutâneas em até 24 horas após exposição a um ou múltiplos AINEs, bem como 13 (quatro AINEs) + 26 (AAS) controles. A técnica consistiu em incubar sangue total com os AINEs já mencionados e, depois, marcar as amostras com anticorpos monoclonais (CD45, anti-IgE e CD63) para posterior leitura por citometria de fluxo. Os resultados obtidos foram comparados com as histórias clínicas e os testes de provocação oral, quando realizados. Resultados: Utilizando os critérios de positividade do BAT empregados na literatura (isto é, porcentagem de CD45+IgE+highCD63+ e índice de estimulação), a sensibilidade e a especificidade variaram de acordo com o AINE: para ácido acetilsalicílico foram 75,0% e 16,7%, respectivamente, diclofenaco, 100% e 0%, dipirona, 23,5% e 66,7%, paracetamol, 40,0% e 42,9%. Após a realização de curvas dose-resposta e tempo-resposta somente com AAS, foi encontrado novo critério de positividade: média de intensidade de fluorescência (MFI) menor do que 6575 representava BAT positivo; com isso, os valores de sensibilidade e especificidade foram: 84,4% e 34,6%, respectivamente. O BAT foi mais sensível em pacientes cuja última reação ocorreu há menos de um ano da data de execução do BAT (93,7%). Conclusão: Devido aos baixos valores de sensibilidade e/ou especificidade, não foi possível padronizar e, por conseguinte, validar o BAT para ácido acetilsalicílico, diclofenaco, dipirona e paracetamol.
Introduction: Currently, the diagnosis of nonsteroidal antiinflammatory drugs (NSAIDs) hypersensivitity is based on patients´ clinical history and drug provocation tests, which are done in selected cases. Nevertheless, this test may expose patients to severe risks, including anaphylaxis. Looking for a safer tool, Basophil Activation Test (BAT) for allergy diagnosis has been studied in the last years. It is an in vitro method where a wide variety of stimuli can be tested, incubating them with the patient\'s blood sample, and observing basophil activation (indication of hypersensitivity) through upregulation of CD63 (or other basophil activation markers) on this leucocyte\'s membrane. Objective: To standardize and validate BAT stimulated with acetylsalicylic acid (ASA), diclophenac, dipyrone and paracetamol in NSAID hypersensitive patients. Methods: Patients which reported immediate reactions (less than 24 hours) after exposure to one or multiple NSAIDs, with cutaneous symptoms were enrolled from Clinical Immunology and Allergy outpatient clinic from HC-FMUSP. BAT with the four NSAIDs was tested on 20 patients and 13 controls and BAT with ASA only, on 33 patients and 26 controls. BAT consisted of incubating whole blood with NSAIDs, then triple-labeled with monoclonal antibodies (CD45, anti-IgE, CD63) for analysis by flow cytometry. BAT results were compared to clinical history and oral provocation tests, when available. Results: According to literature\'s positivity criteria (percentage of CD45+IgE+highCD63+ and stimulation index), sensitivity and specificity varied according to the NSAID tested: for ASA was 75.0% and 16.7% respectively, diclophenac, 100.0% and 0.0%, dipyrone, 23.5% and 66.7%, paracetamol, 40.0% and 42.9%. A new positivity criterion was possible to be defined after further dose-response and time-response curves only for ASA: Mean Fluorescence Intensity lower than 6575 (positive BAT). Accordingly, new sensitivity and specificity for BAT in ASA hypersensitivity were 84,4% and 34,6%. Patients that presented the last reaction in the last year were more likely to present a positive BAT (93.7%). Conclusion: Due to low values for sensitivity and/or specificity, it was not possible to standardize and validate BAT for ASA, diclophenac, dipyrone and paracetamol.

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Hui-Chuan i 朱慧娟. "Study the promoter specificity of Hepatitis D Virus antigen". Thesis, 2005. http://ndltd.ncl.edu.tw/handle/06716663784063400080.

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碩士
中山醫學大學
醫學分子毒理學研究所
93
In a natural setting, hepatitis delta virus (HDV) is only found in patients that are also infected with hepatitis B virus (HBV). The genome of HDV is composed of a circular single-stranded RNA molecule of 1.7-kb that is the smallest, and only known circular RNA genome of the aminals RNA virus. Sequence analysis of the HDV genome revealed that as many as 70% of nucleotides have to undergo intramolecular base pairing, thus allowing the RNA to fold into a rod-like structure. HDV RNA genome are assembled using the envelope protein (HBsAg) of HBV. From previously study indicated that HDV cDNA contains endogenous promoters both in genomic and antigenomic strands. It has been shown that the antigenomic cDNA promoter-like sequence of HDV was located to a 29-nucleotide region (corresponding to HDV-1.9 nucleotides 999 ~ 1028). Whereas the promoter activity of the genomic HDV cDNA was still unclear. In ours previously study, we known that anti-genomic HDV的cDNA has an endogenous promoter activity and is located in nucleotide 970 ~ 1070（promoter-8）. The activity of this promoter is not restricted by its orientation. In this study, we use luciferase and Green Fluorescent Protein (GFP) as reporter genes that compare with HDV SmAg gene to determine the promoter-8 activity. The results of RT-PCR show this promoter-8 has specific-orientation activity for SmAg. We also use western blotting to comfirm this result. Furthermore, we use Immunofluorescence stain to demonstrate the difference by staining HDV SmAg. Taken together, we propose that promoter-8 has SmAg specific expression activity. These results may have implications for studying HDV RNA replication and transcription mechanisms.

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Sciammas, Roger. "Function and antigen specificity of the TCR [gamma][delta] cell response to HSV-1 infection /". 1997. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:9832198.

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Hagembe, Juliana Liambaya. "Effect of antigenic site mutations on the binding specificity of an anti-hemagglutinin antibody to H3N2 influenza virus isolates". 2009. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:1467107.

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Gaur, Rajneesh Kumar [Verfasser]. "Structural study of human antibody fragments with specificity for mucin-1 antigen / vorgelegt von Rajneesh Kumar Gaur". 2004. http://d-nb.info/972712682/34.

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Lin, Wen-bin, i 林文斌. "Genotype specificity of hepatitis delta virus RNA replication by genotype I and IIb hepatitis delta antigens". Thesis, 2006. http://ndltd.ncl.edu.tw/handle/02856432169139122997.

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Zheng, Yi-Hsuan, i 鄭佾瑄. "Application of Magnetic Nanoparticles in Investigating the Binding Specificity of Chicken Polyclonal Antibodies to NTx Antigens". Thesis, 2014. http://ndltd.ncl.edu.tw/handle/78178664819112978203.

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碩士
東海大學
化學系
102
Osteoporosis is a disease that leads to reduce bone strength and increase the risk of bone fracture. An important assessment for diagnosis of osteoporosis is the analysis of specific biomarkers of bone metabolism. In urine, one such biomarker found is the cross-linked N-telopeptide of type I collagen (NTx) epitope such as P1, P2, and P3 peptides. In this study, chicken polyclonal antibodies were bound on the modified surface of magnetic nanoparticles and then applied immunological reaction combining MALDI-TOF MS and ELISA techniques to detect the immune responses before and after the reaction. Peptide concentrations in the residual solutions were measured for the investigation of binding specificity between the antibodies and the antigens. The results of MALDI-TOF MS analysis showed chicken polyclonal antibodies had significantly binding specificity for P2 peptide. On the other hand, it did not have any binding property for P1 and P3 peptides. In addition, the ELISA results confirmed that the antibodies on the 96-wells plate could grab P2-Ahx-FITC fluorescence peptide and make the absorbance values decreased. Finally, comparing the absorbance values of P2 antibodies binding on the 96-wells plate or on the surface of magnetic nanoparticles, we found the later method showed larger absorbance change which could be used to improve quantitative analysis.

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Groeneveld, Kees. "Haemophilus influenzae infections in chronic obstructive pulomonary disease persistence, antigenic drift and antibody specificity /". 1989. http://catalog.hathitrust.org/api/volumes/oclc/25893475.html.

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Thesis (doctoral)--Universiteit van Amsterdam, 1989.
Summary in Dutch. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

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Petrul, Heike Maria. "Production of recombinant antibody molecules with specificity for proliferation antigens on human endothelium using phage display libraries for the optimization of the therapy of solid tumours and rheumatoid diseases = Herstellung von rekombinanten Antikörpermolekülen mit Spezifität für Proliferationsantigene auf humanen Endothelzellen basierend auf Phagen-Genbanken zur Optimierung der Therapie von soliden Tumoren und rheumatischen Erkrankungen /". 1999. http://www.gbv.de/dms/bs/toc/310687543.pdf.

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