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Engelmann, Ines. "Änderung der Stoffwechselaktivität von BaF3-Zellen durch die Expression von BCR/ABL." Doctoral thesis, Universitätsbibliothek Leipzig, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-163535.
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Die vorliegende Arbeit handelt von einer in vitro Untersuchung der Stoffwechselveränderun-gen durch die Expression von BCR/ABL bei BaF3-Zellen, einer murinen, IL-3-abhängigen B-Zelllinie. Die Zellen wurden in nährstoffreichem Standard- und in durch Titrationen ermittel-tem nährstoffarmem Minimalmedium auf unterschiedliche Stoffwechselaktivität in Abhän-gigkeit von BCR/ABL-Expression untersucht sowie auf die zusätzliche Beeinflussbarkeit durch IL-3. Danach wurden vergleichend zwischen den 2 Zelllinien (BaF3 und BaF3-BCR/ABL) im Minimalmedium und im Standardmedium Metabolite wie Glukose, Laktat und Aminosäuren bestimmt, wobei BaF3-BCR/ABL sowohl mit als auch ohne IL-3 kultiviert wur-de. Um den Einfluss von Nährstoffrestriktion auf die Therapie zu zeigen, wurden anschlie-ßend vergleichend in den beiden Medien die Tyrosinkinaseinhibitoren Imatinib und Nilotinib titriert.
Die Ergebnisse zeigen, dass BaF3-BCR/ABL einen Wachstumsvorteil im Minimalmedium hat, welcher im Standardmedium nicht vorliegt. Während die bereits bekannte Verstärkung der Glukoseaufnahme durch BCR/ABL im Standardmedium bestätigt wurde, konnte im Minimal-medium Gegenteiliges gezeigt werden. Zudem wurde ein Unterschied im Aminosäurestoff-wechsel zwischen BaF3 + IL-3 und BaF3-BCR/ABL + IL-3 im Minimalmedium deutlich. Die therapeutische Relevanz des gezeigten Einflusses der Nährstoffrestriktion konnte anschlie-ßend in der Tyrosinkinaseinhibitortitration dargestellt werden, da die Medikamente in Abhän-gigkeit vom Medium unterschiedliche Wirkungen zeigen.
Insgesamt bieten die Ergebnisse einen metabolischen Erklärungsansatz für das Überleben von Tumorstammzellen in nährstoffarmen Arealen des Knochenmarks unter Therapie und Raum für neue Therapieansätze.
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Engelmann, Ines [Verfasser], Thoralf [Akademischer Betreuer] Lange, and Michael [Akademischer Betreuer] Cross. "Änderung der Stoffwechselaktivität von BaF3-Zellen durch die Expression von BCR/ABL : Änderung der Stoffwechselaktivität von BaF3-Zellen durch die Expression von BCR/ABL / Ines Engelmann ; Thoralf Lange, Michael Cross." Leipzig : Universitätsbibliothek Leipzig, 2015. http://d-nb.info/1239564937/34.
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Groom, Laura R. "Synthesis and reactions of titanium-nitrogen multiple bonds." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:17286f91-a1d9-48dc-baf3-02fbbe30a314.
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This Thesis reports the synthesis and reactions of new hydrazide, alkoxyimide and benzimidamide complexes (L)Ti=NX (X = NAr2, NOtBu or C(Ar)NOtBu; L = dianionic supporting ligand or ligand set). The work is supported by DFT calculations which are used to rationalise the reaction outcomes observed and, in one case, the bonding in alkoxyimide complexes. Chapter One provides a background to hydrazide complexes, starting with their relevance to nitrogen fixation. In addition, Group 4 imide, alkylidene hydrazide and alkoxyimide complexes are also reviewed. The Chapter focuses in particular on the synthesis, structure, and stoichiometric and catalytic reactions of these complexes with unsaturated substrates. Chapter Two describes the development of the virtually unexplored 1,2-diamination reaction. The substrate scope and isolation of the vinylamine products are discussed. The protonation of the vinylimide complex Ti(N2NMe){NC(Ph)C(Me)NPh2}(py) and the overall diamination reaction itself is then explored through an in-depth experimental and computational study. Chapter Three details the synthesis of cyclopentadienyl-amidinate supported alkoxyimide complexes. The first detailed reactivity study, supported by structural and computational studies, of any alkoxyimide complex is reported. Novel reactivity at Ti=Nα and, in one instance, Nα–Oβ reductive bond cleavage is observed. Chapter Four describes the reactivity of the benzimidamide complex Cp*Ti{PhC(NiPr)2}{NC(ArF5)NOtBu} with a range of substrates including heterocumulenes, aldehydes, isonitriles and B(ArF5)3. Novel reactivity at Ti=Nα, and 3-component coupling is presented, and the experimental results supported by structural and computational studies. Chapter Five presents full experimental procedures and characterising data for the new complexes reported.
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Meyer, Stefan [Verfasser], Xiaohua [Akademischer Betreuer] Yu, Bernhard [Akademischer Betreuer] Brümmer, and Thomas [Akademischer Betreuer] Kneib. "Estimation of the Long-Run Food Price Equilibrium in Germany, the U.S. and Europe / Stefan Meyer. Gutachter: Bernhard Brümmer ; Thomas Kneib. Betreuer: Xiaohua Yu." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2013. http://nbn-resolving.de/urn:nbn:de:gbv:7-11858/00-1735-0000-0001-BAF3-7-8.
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Tan, Justin Teng-Tiong. "Mystical anthropology in Gregory of Nyssa's Homilies on the Song of Songs." Thesis, King's College London (University of London), 1995. https://kclpure.kcl.ac.uk/portal/en/theses/mystical-anthropology-in-gregory-of-nyssas-homilies-of-the-song-of-songs(98abf7a5-3380-48cd-baf3-20bbfb9ba285).html.
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The Thesis is an attempt to explicate Gregory of Nyssa's mystical anthropology in one of his most mature of mystical writings, the Homilies to the Song of Songs. Gregory's mystical anthropology draws its basis from his philosophical anthropology, and explores the implication of the nature and destiny of man in terms of the concept of divinisation or the transformation of human nature by the indwelling Christ. Gregory utilises the neo-Platonic concept of the ascent of the soul to its original perfection, but transforms this concept by the biblical doctrine of Grace and Incarnation. Holding to the unbridgeable gulf between the Created and the Uncreated, Gregory proposes the abandonment of all senses and entrance into the darkness where God ist and he postulates the divinisation of human nature without end based on that unbridgeable gulf. Gregory's philosophical anthropology would be incomplete without his mystical anthropology. The divinisation of human nature does not imply an idiosyncratic idea of the soul in flight, "from the alone to the Alone". The soul, as Gregory understands it, is firmly attached to its ecclesiastical community, where it has its space-time existence in a life of imitating its Lord in his love for mankind. Its destiny is ultimately linked with the destiny of the body of Christ, the Church. Gregory's concept is then compared with Origen's, whose ideas are said to have the most influence on Gregory's. Analysis shows that there are extrapolations of Origen's theology in Gregory's, but there are obvious discontinuities. The fact of the Incarnation is stressed by both writers, but the soul in Origen seems to pass beyond faith in the Incarnation in its ascent to God into the light of the full knowledge of God; whereas Gregory places his theology on the faith of the Incarnation throughout the soul's ascent, not into increasing light, but into increasing darkness where God is. An illustration of Gregorys mystical anthropology can be detected in his other writing, the Life of Macrina, where he describes his sister using the familiar imageries from the Song of Songs i. e. virgin, bride, Thecla, refining gold and guidance to her ascetic community. Her ascent in perfection is also described in the language of the doctrine of Epektasis. Gregory seems to see in Macrina a real life paradigm for his mystical anthropology.
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Akhter, Shakil. "Basic needs analysis of participants in social forestry projects in north-west Bangladesh." Thesis, Bangor University, 2001. https://research.bangor.ac.uk/portal/en/theses/basic-needs-analysis-of-participants-in-social-forestry-projects-in-northwest-bangladesh(24d019d4-ed54-42d3-baf3-588cfb7191f8).html.
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Satisfaction of basic needs is among the priority objectives of the Bangladesh government, a priority reflected in the forestry sector. Elaborate programmes have been chalked out in both public and private sectors. This study attempts to assess performance of a public sector social forestry project in Bangladesh in terms of basic needs fulfilment of participating rural farmers. `Thana Afforestation and Nursery Development Project' is a major social forestry project in Bangladesh, covering the whole country except the Sundarbans mangrove forest and the hill forests in the east. The project has several components, major among which are agroforestry (AF) and woodlot (WL) schemes. The project started in revised form in 1991-92. This research attempts to study the consumption pattern of basic needs goods (food and non-food) of participants and the project's contribution to satisfying basic needs. Rajshahi Division comprises north west Bangladesh and supports a large area of social forestry plantations. A stratified multi-stage random design was adopted for sampling participants. Stratification was based on agro-ecological zones (AEZs), while the stages consisted of districts, villages and participants. The sample consisted of 180 participants (90 each from AF and WL) from 32 villages distributed in five districts and in five agro-ecological zones. A household questionnaire survey was administered to participants to apprehend various aspects like socio-economic profile, basic consumption needs, involvement in the project, benefits derived, and knowledge, awareness, attitude and opinions. Tree growth measures of participants' plots were also recorded to estimate expected final return, since no plot has been harvested, despite reaching the rotation age in 1998. Data analyses on socio-economic aspects of participants reveal that most males and females occur in the most economically active age class. 54% are literate with 24% having primary education. Agriculture is the main occupation (54%), while 32% have other occupations like tradespersons and professionals. Seasonal employment is dominant (57%) depending upon the nature of agriculture. Most households (42%) reported monthly income in the range Tk. 1000-2000. AF plots are mostly in the range 0.2-0.4 ha while WL plots are larger (0.4-1.0 ha). Although the project is designed for landless farmers, in reality only 17% of farmers were genuinely landless, the remainder having their own land in the range 0.02-0.11 ha. Own land of AF and WL farmers is highly unequally distributed with Gini concentration ratio (GCR) of 0.60 and 0.61 respectively. 75% of participants have cattle (2 or more head). Food consumption of participants has been studied to some depth, food being the most important basic needs item. Participants consume 1010 gms of food per head per day, rice and vegetables constituting 55% and 22% of average daily food basket. Energy and protein consumption are relatively high in the national context (2427 Kcal and 72.38 gms per head per day). They derive higher food value from all major food items except fish and fruits, which are dearer and less available items in Rajshahi (also explained by income elasticity and regression analysis results). Poverty analysis tells quite an encouraging story: poverty head count ratio (HCR) of 21.4, compared with national HCR of 47.5. AF farmers are less poor (HCR 20.76) than WL farmers (HCR 22.05). Depth of poverty is higher for WL farmers, while severity of poverty is higher for AF farmers. Income inequality of participants is less than both national and rural distributions (GCR of 0.35, compared to 0.43 and 0.38 respectively). WL farmers suffer less income inequality. Incidence of poverty is lowest in TMF zone and highest in LBT zone, although income inequality is lowest in the latter zone. Both schemes are profitable in all AEZs, with the WL scheme promising greater returns per ha and HBT zone showing the highest NPV value. Mean financial IRRs are high: 57% for AF and 48% for WL. Conversely, financial BCRs are higher for WL plots (5.32) than for AF plots (3.32). Altogether, WL plots generate higher financial revenues than AF plots over the project life (8 years). Sensitivity analyses show that both schemes are financially robust under differing site and cost conditions. Per capita per day basic needs income needed to satisfy the minimum caloric requirement, derived from both food and non-food items, has been estimated as Tk. 16.00. Basic needs outcomes of the combined analyses show that both schemes successfully fulfil the basic needs of participants and WL is more promising. LBT zone ranks first in the AF scheme, while HBT zone provides the highest per ha per year basic needs value.
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Tun, Paul Fei-Tun. "BAFF, B cells and tumour immunity." Thesis, University of Oxford, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.534210.
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Bitoun, Samuel. "Mise au point de modèles animaux pour étudier la physiopathologie de la polyarthrite rhumatoïde et le rôle du méthotrexate dans la tolérisation." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS174.
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La polyarthrite rhumatoïde (PR) est une maladie auto-immune (MAI) dans laquelle des anticorps anti-peptides citrullinés (ACPA) sont un outil diagnostique très spécifique. L’un des traitements clé de la PR est le méthotrexate (MTX). En plus de son action directe sur la maladie il renforce l’effet des anti-TNF alpha (aTNF). Ceci pourrait passer par une prévention de la formation d’anticorps anti-médicaments dirigés contre les aTNF ce qui leur fait perdre leur efficacité.Nous avons développé un modèle macaque pour reproduire la maladie humaine par immunisation avec des peptides citrullinés dans le contexte d’un facteur génétique favorisant la PR : l’épitope HLA partagé. L’immunisation de macaques avec divers peptides citrullinés en utilisant un boost intra-articulaire a déclenché une réponse T et B anti-citrulline et a entraîné une mono-arthrite chronique.Le rôle du MTX sur l’immunogénicité des aTNF a été étudié sur un modèle de souris autoimmunes, les souris BAFF transgéniques (tg) qui présentent une MAI. L’utilisation du MTX juste avant l’injection d’aTNF a permis de prévenir l’immunisation contre ce médicament uniquement chez ces souris BAFFtg et pas chez des souris sauvages ou chez des macaques. Nous avons démontré que ces souris BAFFtg surexprimaient CD73, ce qui permettait une sécrétion accrue d’adénosine et de cellules B régulatrices sous l’effet du MTX. L’interaction entre BAFF et le méthotrexate a été confirmée chez l’homme dans la cohorte ABIRISK : le MTX prévient plus efficacement l’immunogénicité chez les patients avec des taux de BAFF élevés.En conclusion, nous avons mis au point deux nouveaux modèles animaux permettant de mieux comprendre la physiopathologie de la PR et d’optimiser l’utilisation des traitements biologiques qui s’étend dans tous les domaines de la médecineTitle : Development of new animal models to study the pathophysiology of RA and the role of methotrexate-induced tolerance.Keywords : Rheumatoid arthritis, shared epitope, ACPA, immunogenicity, methotrexate, TNF inhibitorsAbstract: Rheumatoid arthritis (RA) is an autoimmune disease (AID) where antibodies directed against citrullinated peptides (ACPA) are highly specific for the diagnosis. One of the key treatments of RA is methotrexate. It has an action on both the disease and reinforces the effect of second line TNF inhibitors (TNFi). MTX might act via prevention of anti-drug antibodies (ADAb) directed against TNFi that are implicated in loss of efficacy of TNFi. We have developed a macaque model to recapitulate the human disease by immunization with citrullinated peptides in the context of a genetic factor favoring RA: the shared epitope on the HLA. Immunization of macaques with citrullinated peptides and intra-articular boost cause an anti-citrulline T and B cell response and a chronic monoarthritis.The role of MTX-induced tolerance against TNFI has been studied in autoimmune BAFF transgenic (tg) mice using MTX just before treatment with TNFi we were able to prevent ADAb formation in BAFFtg mice and not wild type mice or macaques. We identified that BAFFtg mice expressed elevated CD73 leading to more adenosine and regulatory B cells as actors in MTX-induced tolerance. This MTX-BAFF interaction was further confirmed in humans in the ABIRISK cohort where MTX was more efficient to prevent ADAb formation in RA patients with elevated BAFF levels.Setting up two new animal models allows better understanding of RA pathophysiology and better use of biologics that extend to other domains of medicine
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Sutherland, Andrew Peter Robert St Vincents Clinical School UNSW. "BAFF regulation of peripheral T cell responses." Awarded by:University of New South Wales. St Vincents Clinical School, 2005. http://handle.unsw.edu.au/1959.4/22788.
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The activation and effector function of CD4+ T cells are critical points of regulation during an antigen specific T cell response. Dysregulation of these processes can lead to the development of human diseases, encompassing both immunodeficiency and autoimmunity. Members of the TNF superfamily have recently emerged as important regulators of T cell responses, with their overexpression causing autoimmune inflammation in animal models. As overproduction of the novel TNF superfamily ligand BAFF is associated with several autoimmune conditions, we sought to examine the potential role of BAFF as a regulator of T cell activation and effector function. We initially demonstrated BAFF costimulation of T cell activation in vitro. Generation of specific monoclonal antibodies identified BAFF-R as the only BAFF receptor present on T cells, and showed that it was expressed in an activation-dependent and subset-specific manner. Impaired BAFF costimulation in BAFF-R deficient mice indicated that BAFF-R was crucial for mediating BAFF effects in T cells. Analysis of T cell responses in vivo revealed that BAFF transgenic mice have increased T cell priming and recall responses to protein antigens, and showed a corresponding increase in the DTH model of Th1 cell-dependent inflammation. In addition, Th2-dependent allergic airway responses are suppressed in BAFF transgenic mice. Crossing to a B cell deficient background revealed that the proinflammatory effects of BAFF on T cell priming and DTH rely on the presence of B cells, while the suppressive effects during allergic airway inflammation are B cell independent. These data demonstrated that BAFF regulated the outcome of T cell responses in vivo and identified BAFF dependent crosstalk between T and B cells. Stimulation of B cells with BAFF induced the upregulation of MHC class II and ICOS-L both in vitro and in vivo. Induction of these cell surface molecules was associated with an increased capacity to induce T cell proliferation, however this effect was independent of ICOS-L expression. Thus it was demonstrated that BAFF regulated T cell activation and effector function both directly, via stimulation of BAFF-R, and indirectly, by altering the function of B cells. These data suggest that BAFF dependent alterations in T cell function may be an additional causative factor in the association between elevated BAFF levels and the generation of autoimmunity.
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Myers, Valerie. "The Role of BAG3 in the Failing Heart." Diss., Temple University Libraries, 2018. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/490584.
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Biomedical SciencesPh.D.
Heart disease has been the leading cause of death in the United States for more than 90 years. The leading cause of death in individuals aged 65 and older has remained diseases of the heart from 1950 to the current time. According to the CDC, once diagnosed with heart disease, individuals have an approximately 50% chance of dying within 5 years, regardless of race. Mortality related to heart disease increased dramatically from the start of the 1900s to 1921, but subsequently experienced a steady decline from the mid-1960’s to 2000. However, when the decrease in heart disease is examined at the level of race it is clear that the decrease is not equally shared. While the leading cause of death among both Caucasian American men and women and African American men and women remains heart disease, the decrease in incidence of coronary heart disease among African American men was only half of the decrease in incidence among Caucasian American men. Genetic variants in BAG3 (Bcl-2 associated athanogene 3), a highly evolutionarily conserved gene that has recently emerged as a major dilated cardiomyopathy locus, are prevalent in isolated populations. This led us to hypothesize that variants in BAG3 might contribute to the increased prevalence of IDC in individuals of African ancestry. Expressed predominantly in the heart, the skeletal muscle and in many cancers, BAG3 has pleotropic effects in the heart. It inhibits apoptosis by binding to Bcl-2, facilitates protein quality control by binding to both large and small heat shock proteins, mediates adrenergic responsiveness by coupling the β-adrenergic receptor and the L-type Ca2+ channel, and maintains the integrity of the sarcomere by anchoring actin filaments to the Z disc. However, a paucity of subjects of African ancestry have been included in cohorts of probands with familial dilated cardiomyopathy whose exomes or genomes have been sequenced. Based on our previous observations and reports from other groups we postulated: 1) that mice with haplo-insufficiency of BAG3 will re-capitulate disease seen in humans and serve as a model for studying the pathogenesis of BAG3. 2) The prevalence or identification of specific BAG3 variants will differ by race and/or ethnicity. 3) SNVs of BAG3 may contribute to disease progression and thereby be pathogenic. Our study points out that we cannot understand population-based differences without enhancing the diversity of populations included in genomic studies. Similarly, in the era of big data, efforts must be undertaken to assess the genetic profile of both probands and their family members as without the ability to measure segregation, penetrance and plasticity we can only ascribe associations to functional genetic variants.
Temple University--Theses
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Sellam, Jérémie. "Etude de nouveaux acteurs impliqués dans la physiopathologie du syndrome de Sjögren primaire : Id3, BAFF, BAFF-R et les microparticules circulantes." Paris 11, 2009. http://www.theses.fr/2009PA11T012.
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Korniat, Agathe. "Etude fonctionnelle des variants moléculaires du gène BAG3 associés à la cardiomyopathie dilatée humaine." Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066716.
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Le gène BAG3 a été identifié comme étant un nouveau gène responsable de cardiomyopathie dilatée (CMD), première cause d'insuffisance cardiaque (IC). La protéine BAG3 est une co-chaperonne qui participe au contrôle de l'homéostasie protéique via son rôle dans l'autophagie, protégeant ainsi les cellules contre la protéotoxicité induite par les protéines dégradées ou mal repliées. L'hypothèse qu'une inactivation de la voie autophagique contrôlée par BAG3 induirait une protéotoxicité cardiomyocytaire à l'origine de la CMD apparait particulièrement attractive et constitue l'hypothèse centrale de ce travail. Nos résultats indiquent que les mutations de BAG3 abolissent l'interaction avec la chaperonne HSP70, une protéine centrale du contrôle qualité des protéines. Nous avons observé une cytotoxicité des mutants BAG3, une altération de la fonction chaperonne HSP70-dépendante et une absence de réponse autophagique en condition de stress (jeun, choc thermique, expression d'une protéine pro-agrégante). In vivo (modèle poisson-zèbre) l'extinction de l'expression de BAG3 ou la surexpression des mutants conduisent à l'apparition d'un phénotype d'insuffisance cardiaque (¿dème péricardique) chez les embryons injectés. Par édition génomique, nous développons également un modèle de cardiomyocytes dérivés de cellules iPS porteurs ou non de la mutation afin d'explorer plus en avant la fonction contractile de ces cellules. Nos résultats confirment donc le rôle de BAG3 dans la CMD et indiquent que l'altération de la fonction protéostasique serait à l'origine de la maladie. Cette nouvelle voie physiopathologique dans la CMD pourrait s'avérer être, plus généralement, une voie centrale dans l'ICThe BAG3 gene was identified as a novel gene responsible for dilated cardiomyopathy (DCM), a major cause of heart failure (HF). The BAG3 protein is a co-chaperone that participates in the control of protein homeostasis via its role in autophagy, protecting cells against the proteotoxicity induced by degraded or misfolded proteins. The hypothesis that inactivation of the autophagic pathway controlled by BAG3 would induce cardiomyocyte proteotoxicity behind the CMD appears particularly attractive and is the central hypothesis of this work. Our results indicate that BAG3 mutations abolish the interaction with the chaperone HSP70, a central actor of the protein quality control. We observed cytotoxicity of BAG3 mutants, an impaired HSP70-dependent chaperone function and absence of autophagic response under stress conditions (starvation, heat shock, expression of a pro-aggregating protein). In vivo (zebrafish model) the extinction of BAG3 expression or mutants overexpression lead to the occurrence of a heart failure phenotype (pericardial edema) in injected embryos. Through genomic edition, we also develop a model of iPS-derived cardiomyocytes carrying or not the mutation in order to further explore the contractile function of these cells. Our results confirm the role of BAG3 in DCM and indicate that the alteration of the proteostasis function is the cause of the disease. This new pathophysiological pathway in DCM may prove to be more generally, a central line in the IC
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Groom, Joanna Ruth School of Medicine UNSW. "Loss of immune regulatory checkpoints in BAFF transgenic mice." Awarded by:University of New South Wales. School of Medicine, 2006. http://handle.unsw.edu.au/1959.4/27281.
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Multiple checkpoints control the survival and activation of auto-reactive B cells. The discovery of the TNF family cytokine BAFF has been crucial to understanding peripheral B cell tolerance mechanisms. Homeostatic levels of BAFF are tightly regulated to maintain tolerance in the periphery. Chronically increased levels of BAFF lead to the survival of autoreactive B cells. Autoimmune patients display elevated serum BAFF levels. BAFF Tg mice model this situation with systemically high levels of BAFF and the subsequent development of two separate but related autoimmune syndromes; systemic lupus erythematosus (SLE) and Sj??gren???s syndrome (SS). The work conducted in this thesis further investigates the defects in tolerance down-stream of self-reactive B cell survival, which may contribute to autoimmune disease development in BAFF Tg mice. Expansion of the Marginal zone (MZ) B cell population correlates with the pathogenesis of several models of autoimmune disease. BAFF Tg mice are unique in that they not only display an increased splenic MZ B cell population, but also MZ B cells are found in the salivary glands of mice developing SS. The examination of genes differentially regulated between MZ and Follicular (Fo) B cells led to the investigation of sphingosine-1-phosphate receptor biology. The expression of S1P receptors was shown to be required for the positioning of MZ B cells in the spleen. Chronic BAFF stimulation alters the retention of MZ B cells through the alteration of S1P receptors and decreased integrin activation. The alteration of S1P receptors and increased ligand sensitivity leads to the accumulation of MZ B cells in the inflamed salivary glands of BAFF Tg mice. This works provides a potential mechanism for the tissue specificity seen in systemic autoimmune disease. The provision of T cell help to auto-reactive B cells is thought to underlie the development of SLE. BAFF Tg mice deficient in T cells surprisingly developed an SLE-like disease indistinguishable from that of BAFF Tg mice. Autoimmunity in BAFF Tg mice did however require signals through the toll-like receptor (TLR)-associated signalling adaptor, MyD88, which controlled the production of pathogenic autoantibodies. Therefore, autoimmunity in BAFF Tg mice results from altered B cell tolerance, which requires TLR signalling and is independent of T cell help. It is likely that autoimmune patients with elevated levels of BAFF show a similar basis for disease.
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Manchen, Steven T. "Characterization and subcellular localization of the human BAT3 protein." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp05/MQ62248.pdf.
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Murphy, Deirdre. "Investigating the BAFF/APRIL cytokine system in atherosclerosis pathology." Thesis, University of Cambridge, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.709281.
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Pereira, Quezia Cristina Campos. "Simulação via dinâmica molecular do Fluoreto de Bário (BaF2)." Universidade Federal do Amazonas, 2013. http://tede.ufam.edu.br/handle/tede/4359.
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The system studied is considered a superionic material type AB2. This shows a variety of interesting properties, not only in academic context, but also in technological applications. However, there are not still many studies about its behavior and dynamics. The computational method used in this work is the method of Molecular Dynamics (MD), a technique able to generate the trajectories in phase space of N particles that interacting with each other. The system in question is which is composed of 1500 particles, with 1000 of Barium and 500 of Fluoride. The …rst step is to provide simulation system its initial conditions and from there use an algorithm, appropriate to the system under study, to make the numerical integrations of the forces and the calculations of the positions and velocities of the particles. Complied all these steps is then started the simulation in fact. The system under consideration in steps of illness started time _t as the addition initially temperature while the system pressure was kept constant and equal to zero. The ensembles isoentalpic-isobaric (N, P, H), in which the volume ensemble acts as a dynamic variable, and ensemble microcanonic were used (N, V, E), where the calculations of statistical averages were performed. The potential chosen to describe our system has the potential pairs proposed by Vashishta-Rahman. From there we started the simulation via DM Barium ‡uoride BaF2. The temperature of the system was to vary from an initial temperature of 300K to a …nal temperature of 3000K in increments of 50K. From there, they were possible to plot graphs with T dependence of this parameter as well as the graphs of the pair correlation g(r) and coordination number c(r), the density function of vibrational states G(w) functions, and peaks selected from G(w) function that shows the relation of the frequency temperature T. The next step in the simulation was to investigate, from the application of pressure, as the system would behave. The system su¤ered compression 0GPa 3GPa up in increments of 0.5 GPa and temperature of 300K. The superionic phase of the compound is con…rmed and its melting temperature.
O sistema em estudo é considerado um material superiônico do tipo AB2. Este exibe uma variedade de propriedades interessantes, não apenas no contexto acadêmico, mas também em aplicações tecnológicas. Contudo, não se encontra ainda muitos estudos a respeito de seu comportamento e dinâmica. O método computacional utilizado nesse trabalho é o método de Dinâmica Molecular (DM), uma técnica capaz de gerar as tra-jetórias no espaço de fase de N partículas que interagem entre si. O sistema em questão é contituído por 1500 partículas, sendo 1000 de Flúor e 500 de Bário. A primeira etapa da simulação é fornecer ao sistema sua condições inicias e a partir daí utilizar um algoritmo, apropriado ao sistema em estudo, para fazer as integrações numéricas das forças e os cálculos das velocidades e posições das partículas. Obedecidas todas essas etapas é então iniciada a simulação de fato. O sistema em estudo evoluia em passos de tempos, _t, conforme o acréscimo, inicialmente, da temperatura enquanto a pressão no sistema era mantida constante. Foram usados os ensembles isobárico-isoentálpico (N, P, H), ensemble no qual o volume funciona como uma variável dinâmica, e o ensemble microcanônico (N, V, E), onde os cálculos das médias estatísticas foram realizadas. O potencial escolhido para descrever nosso sistema foi o potencial de pares proposto por Vashishta-Rahman. A partir daí, iniciamos a simulação via DM do ‡uoreto de Bário BaF2. A temperatura do sistema passou a variar de uma temperatura inicial de 300K até uma temperatura …nal de 3000K, com incrementos de 50K. A partir daí, foi possível plotar os grá…cos com de-pendência deste parâmetro T, bem como os grá…cos das funções correlação de pares g(r) e número de coordenação c(r), da função densidade de estados vibracionais G(w), e dos picos escolhidos da função G(w) que apresenta a relação da frequência pela temperatura T. O próximo passo na simulação foi investigar, a partir da aplicação de pressão, como se comporta o sistema. O sistema sofreu compressão de 0GPa até 3GPa em incrementos de 0,5GPa, e temperatura igual a 300K. A fase superiônica do composto é comprovada bem como sua temperatura de fusão.
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Lahiri, Ayan. "The complexity of the BAFF forms and their functional implications." Thesis, Brest, 2014. http://www.theses.fr/2014BRES0006/document.
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BAFF, «facteur d'activation des lymphocytes B (LB) » contribue à l'expansion des LB autoréactifs de faible affinité lors de la mise en place de la tolérance. Cependant, les mécanismes menant à la surexpression de BAFF dans les maladies auto-immunes ne sont pas compris. Nous avons découvert un nouveau variant de BAFF, 4BAFF (dans lequel l'exon 4 est épissé), qui agit comme un facteur de transcription de son propre gène et participe à sa régulation. Ainsi, 4BAFF est préférentiellement observé dans les cellules isolées de patients atteints de maladies auto-immunes. De plus, 4BAFF régule un grand nombre de gènes associés à la réponse immunitaire innée et à la régulation de l’apoptose. Une autre constatation importante est que 4BAFF est un élément clé pour comprendre l’activité des LB régulateurs. Notre travail présente un concept entièrement nouveau suggérant qu'une cytokine peut être régulée par l'activité de l'un de ses variants d'épissage. Par ailleurs, nous avons observé que les cellules épithéliales expriment le récepteur de BAFF : BR3. Le blocage de BR3 se traduit par la translocation nucléaire de PKC et l'apoptose des cellules épithéliales. Par un effet autocrine, nous démontrons que seules certaines formes de BAFF participent à la survie des cellules épithéliales. Enfin , nous avons étudié les conséquences de l'expression du TLR9 à la surface des LB et démontrons que ce TLR9 membranaire ne fixe pas le CpG et agit comme un co-récepteur négatif du BCR. En effet, l'activation des LB par le CpG capté au niveau endosomal, est inhibée par l’action d’un anticorps anti-TLR9 se fixant au niveau membranaire. Tous ces résultats contribuent à une meilleure compréhension des mécanismes impliqués dans l'immunopathologie des maladies autoimmunes avec des applications potentielles en thérapeutiqueElevated expression of ‘B cell activating factor’ (BAFF), a potent B cell survival factor contributes to the expansion of low-affinity self-reactive B cells during the establishment of tolerance. However, mechanisms leading to BAFF over-expression in autoimmune diseases are not understood. We reported the discovery of a new variant for BAFF, 4BAFF in humans (in which exon 4 is excised) or 5BAFF in mice (in which exon 5 is excised), which acts as a transcription factor of the full-length form of BAFF, and which is preferentially found in cells isolated from patients with autoimmune diseases. When transfected in human B cells, D4BAFF upregulates a large number of genes associated with immune response and especially innate immunity and regulation of apoptotis. Furthermore D4BAFF acts, in association with p50 from the NF- B pathway, as a transcription factor for its own parent gene. Another important finding is that 4BAFF is an important component of the efficacy of regulatory B cell activity. Our work introduces an entirely novel concept in biology suggesting that a human cytokine gene can be transcriptionally regulated by the activity of one of its own splice variants.We have also tried to understand the complexity of the various forms of BAFF. We observed that epithelial cells expressed BAFF-receptor (BR3) and produce BAFF suggesting autocrine properties. Blocking BR3 results in nuclear translocation of PKC promoting epithelial cell apoptosis.Furthermore, only some forms of BAFF are required for epithelial cell survival. Finally, we studied the consequences of the expression of TLR9 on the B cell surface and demonstrated that TLR9 acts as a co-receptor of the B cell receptor to influence B cell fate independently of CpG binding. We show that CpG activation of B cells, acting synergistically with BCR signals, was inhibited by anti-TLR9 stimulation. Induction of CD25 expression and proliferation of B cells were thus down-regulated by engagement of cell surface TLR9. Overall, our results indicate that TLR9 expressed on B cell plasma membrane might be a negative regulator of endosomal TLR9, and could provide a novel control by which activation of autoreactive B cells is restrained. All these findings contribute to a better understanding on immunopathology of autoimmune diseases with potential applications in therapy
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Mendoza, Espinosa Leopoldo Guillermo. "Upflow and downflow biological aerated filters (BAFs) for wastewater treatment." Thesis, Cranfield University, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.268131.
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Nakamura, Gerson Hiroshi de Godoy. "Análise térmica e equilíbrios de fase no sistema BaF2 - YF3." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/85/85134/tde-17082009-091300/.
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Realizou-se, neste trabalho, uma investigação do sistema binário BaF2-YF3 com o objetivo de esclarecer o comportamento térmico e os equilíbrios de fase em torno do composto BaY2F8, um requisito importante para a obtenção de cristais de alta qualidade. Diversas amostras mistas de composições entre 58 e 80 mol% YF3 foram sintetizadas mediante fusão sob atmosfera reativa; os fluoretos de partida foram obtidos através da hidrofluorinação de óxido de ítrio e de carbonato de bário de alta pureza. Empregou-se análise térmica diferencial, calorimetria exploratória diferencial, termogravimetria, difração de raios-X, microscopia eletrônica de varredura e espectroscopia de energia dispersiva para caracterizar as amostras. Experiências de crescimento de cristais pelo método da fusão por zona também foram realizadas para examinar o diagrama de fases do sistema. Devido à grande vulnerabilidade do YF3 à contaminação por oxigênio e do problema da sobreposição dos eventos térmicos que ocorrem próximos à fusão do BaY2F8, antes de ser possível investigar o sistema em si através de análise térmica foi necessário determinar as condições ótimas para os ensaios com estas técnicas. O método de Rietveld foi empregado para determinação quantitativa das fases presentes nas amostras a partir dos difratogramas correspondentes, e para o cálculo dos parâmetros de rede do BaY2F8. Foram observadas importantes discrepâncias entre os resultados obtidos através das várias técnicas de caracterização e os diagramas de fase encontrados na literatura: foram detectadas diferenças nas temperaturas de transições de fase e encontrou-se evidências de que o BaY2F8 funde incongruentemente. Com base nestes resultados, propôs-se um diagrama de fases parcial do sistema que engloba a faixa de composições estudada no trabalho e que leva em consideração as discrepâncias observadas.An investigation of the BaF2-YF3 binary system was performed in this work with the objective of clarifying the thermal behavior and phase equilibria surrounding the BaY2F8 compound, an important requisite for obtaining high quality crystals. Several mixed samples of compositions ranging between 58 and 80 mol% YF3 were synthesized under a reactive atmosphere; the starting compounds were obtained through the hydrofluorination of high purity yttrium oxide and barium carbonate. Differential thermal analysis, differential scanning calorimetry, thermogravimetry, X-ray diffraction, scanning electron microscopy and energy-dispersive X-ray spectroscopy were employed in order to characterize the samples. Crystal growth through the zone melting method was also performed in order to examine the systems phase diagram. An assessment of the optimal experimental conditions for thermal analysis was required prior to the investigation of the system itself due to the strong vulnerability of YF3 to oxygen contamination and the problem of the overlapping of thermal events near the melting of BaY2F8. The Rietveld method was used for the quantitative determination of the phases present in the samples based on the corresponding diffraction patterns, and for the calculation of BaY2F8s lattice parameters. Important discrepancies between results from the many characterization techniques and the phase diagrams found in the literature were observed: differences in the phase transition temperatures were detected and evidence that BaY2F8 melts incongruently was found. A partial phase diagram that cover the composition range studied in this work and which reflects the observed discrepancies was proposed based on these results.
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Fountain, Kathryn. "The role of the BAFF receptor in B cell survival." Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/10040551/.
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Signalling through the BAFF receptor (BAFFR) is critical for the development and survival of B cells. The binding of BAFF to BAFFR leads to the recruitment and subsequent degradation of TRAF3, which results in the accumulation of NIK and induction of signalling through the non-canonical NFκB pathway. However, recent studies have shown that IKK1, a component of the alternative NFκB pathway, is required for B cell development, but not B cell survival. Concurrently, a number of other signalling molecules were shown to be of importance of B cell survival, including SYK, PI3K and the classical NFκB pathway. However, the mechanisms through which BAFFR transduces signals to these pathways remains unclear. The experiments described in this thesis sought to further understand the role of the BAFFR in controlling B cell survival. I have used inducible deletions to delete BAFFR and TRAF3 in mature B cells to determine their role in B cell survival. I have shown that TRAF3 deletion is only partially able to rescue B cell survival in BAFFR-deficient B cells, suggesting that there are additional interactors of BAFFR that transduce survival signals. To further understand how BAFFR transduces survival signals, I sought to identify novel proteins that interact with BAFFR. I generated a modified tandem affinity purification (moTAP)-BAFF, a tagged version of BAFF that can be used to stimulate and affinity purify BAFFR. Preliminary experiments have shown that, as expected, TRAF3 is one of the most enriched proteins in the BAFFR interactome. BAFF stimulation also leads to the recruitment of CD19 to BAFFR. It is hoped that further analysis of the BAFFR interactome will give insight into the receptor proximal events that control B cell survival. Finally, I developed a B cells survival assay to screen a panel of kinase inhibitors in order to identify novel kinases that are involved in B cell survival.
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Saidoune, Fanny. "Rôle de BAFF dans l'athérome accéléré associé au lupus systémique." Thesis, Université de Paris (2019-....), 2020. http://www.theses.fr/2020UNIP7011.
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Le lupus érythémateux systémique (LES) est une maladie auto-immune caractérisée par des anomalies du système immunitaire inné et adaptatif. Les événements cardiovasculaires sont aujourd’hui la première cause de mortalité des sujets ayant un LES. Ces événements cardiovasculaires, en lien avec l’athérome, sont plus précoces que dans la population générale et ne sont pas complètement expliqués par les facteurs de risque cardiovasculaire classiques. Cet athérome accéléré trouve peut-être une partie de son explication dans l’immunopathogenèse du LES.Les lymphocytes B, par leur capacité à produire des auto-anticorps pathogènes, jouent un rôle causal dans le LES. Les lymphocytes B matures sont dépendants pour leur activation, leur prolifération et leur survie, de la cytokine BAFF. Chez l’homme, le Belimumab (GSK), un anticorps monoclonal spécifiquement dirigé contre BAFF, est la seule biothérapie ayant une AMM en France dans le LES. Le rôle joué par BAFF dans l’athérogenèse est démontré par l’athéroprotection induite par l’invalidation génétique du récepteur de BAFF dans les modèles murins pro-athéromateux. Mon projet de thèse consiste en l’étude de la contribution de BAFF dans l’athérome accéléré associé au lupus.Nous avons tout d’abord montré que, la souris ApoE-/-D227K constituait, contrairement à la souris ApoE-/- pristane, un modèle approprié pour l’étude de l’athérome associé au lupus.Nous avons ensuite montré que, dans le modèle ApoE-/-D227K, la neutralisation de BAFF au moyen d’un anticorps ciblant spécifiquement cette cytokine, traitait efficacement le lupus en induisant la déplétion des lymphocytes B matures au sein des organes lymphoïdes secondaires. En revanche, l’effet athéroprotecteur de la neutralisation de BAFF n’était apparent, malgré la déplétion des lymphocytes B présents au sein des organes lymphoïdes tertiaires aortiques, que pour des taux sériques de cholestérol bas. Pour des taux sériques de cholestérol haut, la neutralisation de BAFF tendait à aggraver les lésions athéromateuses en favorisant la spumification des macrophages exprimant TACI.Nous avons poursuivi nos travaux expérimentaux chez l’humain, en montrant, de façon congruente à ce que nous observions chez la souris, une corrélation positive des taux sériques de BAFF, et de l’expansion périphérique des lymphocytes B avec la progression de la maladie athéromateuse infraclinique chez des patients lupiques à faible risque cardiovasculaire apparent. L’effet du traitement par Belimumab sur l’athérome était également analysé ex vivo et in vitro chez un petit nombre de patients et montrait que la neutralisation de BAFF en contexte lupique pouvait promouvoir ou ralentir le développement de la maladie athéromateuse en fonction de l’indice de masse corporel (IMC).En conclusion, nos travaux montrent 1- que les lymphocytes B matures et BAFF jouent un rôle pathogénique dans l’athérome associé au lupus et 2- que BAFF peut être athéroprotecteur ou athéroaggravant en fonction de la nature des mécanismes impliqués. En l’absence de facteurs de risque cardiovasculaire classiques (dyslipidémie, surpoids), les lymphocytes B jouent un rôle important dans l’athérogenèse associée au lupus et les thérapies neutralisant BAFF, en inhibant l’interaction BAFF/BAFFR sur les lymphocytes B, induisent une déplétion B athéroprotectrice dans les organes lymphoïdes tertiaires. En présence de facteurs de risque cardiovasculaire classiques, les lymphocytes B ne jouent plus qu’un rôle marginal dans l’athérogenèse et les thérapies neutralisant BAFF, en inhibant l’interaction BAFF/TACI sur les macrophages, favorisent la transformation spumeuse athéroaggravante des macrophagesAccelerated atherosclerosis is now recognized as the main cause of death in SLE patients. Of note, the increased prevalence of premature atherosclerosis in SLE is not fully explained by traditional cardiovascular risk factors. Although we and others showed that lupus immunopathogenesis may promote accelerated atherosclerosis, the mechanisms by which SLE pathogenesis might contribute to accelerate atherosclerosis remains elusive.B cells, by their ability to produce pathogenic autoantibodies, play a causative role in SLE. Consistently, there are strong evidence to connect B-cell activating factor (BAFF), a cytokine required for maturation and survival of B2 B cells, to lupus. Belimumab (GSK), a monoclonal antibody specifically directed against BAFF, is the only approved biotherapy for SLE treatment. BAFF is involved in atherosclerosis and atherosclerosis-prone mice in which hematopoietic cells did not express the receptor for the pro-B2 BAFF cytokine displayed a significant reduction in atherosclerotic lesion development. My thesis project consists of studying the contribution of BAFF in accelerated atherosclerosis associated with SLE.We first showed that ApoE-/-D227K mice were an appropriate model for the study of lupus associated atherosclerosis, when compared to the ApoE-/- pristane treated mice.We then demonstrated that, in the ApoE-/-D227K model, the neutralization of BAFF by using an antibody specifically targeting this cytokine, efficiently treated lupus by inducing the depletion of mature B cells in the secondary lymphoid organs. On the other hand, the atheroprotective effect of the BAFF neutralization, despite the depletion of B cells in the aortic tertiary lymphoid organs, was apparent in mice with low cholesterol levels, only. For high cholesterol levels, the neutralization of BAFF tended to aggravate atherosclerotic lesions by promoting the foam cell transformation of macrophages that expressed TACI.We then asked whether the observations made in our mouse model were relevant to human atherosclerosis associated with SLE and observed a positive correlation between BAFF serum levels, peripheral expansion of B lymphocytes and progression of subclinical atherosclerosis in lupus patients at apparent low risk for cardiovascular events. The effect of Belimumab treatment on atherosclerosis was also analyzed ex vivo and in vitro in a small number of patients and we showed that BAFF neutralization in lupus could enhance or dampen the development of atherosclerosis according to the body mass index (BMI).In conclusion, our work shows 1- that B cells and BAFF play a pathogenic role in atherosclerosis associated with lupus and 2-that BAFF can be atheroprotective or atheroaggravative depending on the mechanisms involved. In absence of classical cardiovascular risk factors (such as dysplipidemia or overweight), BAFF neutralizing therapy, by disrupting the BAFF/BAFFR interaction on B cells, depletes mature B cells in tertiary lymphoid organs and is atheroprotective. In the presence of classical cardiovascular risk factors, BAFF neutralizing therapy, by disrupting the BAFF/TACI interaction on macrophages, promotes the foam cell transformation of macrophages and aggravates atherosclerosis
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Gunzert-Marx, Konstanze. "Nachweis leichter Fragmente aus Schwerionenreaktionen mit einem BaF2-Teleskop-Detektor." Phd thesis, [S.l.] : [s.n.], 2004. http://tuprints.ulb.tu-darmstadt.de/416/1/Diss_KGM_A.pdf.
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Kernfragmentierung führt bei der Schwerionentherapie dazu, daß der Primärstrahl beim Eindringen in Materie abgeschwächt wird und leichte Fragmente mit geringeren Kernladungen gebildet werden. Diese haben in der Regel größere Reichweiten als die Primärionen und erzeugen deshalb einen Dosisbeitrag hinter dem Bragg-Peak der 12C-Ionen. Da außerdem auch die biologische Wirksamkeit der Fragmente sich von derjenigen der Primärionen unterscheidet, ist die Kenntnis der Fragmentierung sowohl für die Berechnung der RBW als auch für die Bestrahlungsplanung sehr wichtig. Die Abschwächung des Primärstrahls und die Erzeugung geladener Teilchen durch Fragmentierung von 12C- und 20Ne-Ionen in gewebeäquivalenten Targets wurde sowohl in Berkeley als auch an der GSI in Darmstadt untersucht. Bezüglich der Neutronenproduktion in solchen Targets gibt es jedoch nur Messungen mit 4He-Ionen in Wasser, die von Cecil et al. durchgeführt wurden. Ziel dieser Arbeit war es deshalb, sowohl die Energie- und Winkelverteilungen als auch die Ausbeuten von Neutronen zu messen, die durch das Abstoppen von Kohlenstoffstrahlen einer in der Therapie häufig verwendeten Energie (200 AMeV) in gewebeäquivalenten Targets (13 cm Wasser) entstehen. Die nach vorn emittierten leichten Fragmente wurden mit einem BaF2-Teleskop-Detektor nachgewiesen. Durch die Aufzeichnung der Flugzeiten konnten die Energieverteilungen der Neutronen und der geladenen Fragmente bei verschiedenen Winkeln hinter dem Wassertarget bestimmt werden. Die Ausbeute im gesamten vorderen Halbraum wurde durch Integration der Winkelverteilungen berechnet und ergab pro Kohlenstoffion 0,5 Neutronen, 0,31 Wasserstoff-Ionen und 0,13 Helium-Ionen. Beruhend auf diesen Ausbeuten wurden die Dosisbeiträge der Fragmente bei einer typischen Patientenbestrahlung abgeschätzt und es konnte gezeigt werden, daß der Dosisbeitrag schneller Neutronen (>10 MeV) weniger als 1% der Dosis im Zielvolumen entspricht und verglichen mit den Dosen der geladenen Fragmente gering ist. Die Vergleichbarkeit der Messungen an gewebeäquivalenten Targets mit tatsächlichen Patientenbestrahlungen wurde dadurch verifiziert, daß mit demselben Versuchsaufbau auch Messungen parallel zur Patientenbestrahlung durchgeführt wurden. Hierbei wurde auch die Energie der 12C-Ionen protokolliert, wodurch die hinter dem bestrahlten Patienten aufgezeichneten Teilchenfelder, Winkelverteilungen und Fragmentausbeuten getrennt nach den Energie der Primärionen analysiert werden konnten. Der BaF2-Teleskop-Detektor besteht aus einem BaF2-Szintillator, der mit einem dünnen Plastikszintillator kombiniert wurde, um in gemischten Teilchenfeldern Neutronen und geladene Fragmente aufgrund ihres Energieverlusts zu identifizieren. Der BaF2-Szintillator zeichnete sich durch seine hohe Neutroneneffizienz von 20% für Neutronen mit Energien oberhalb von 100 MeV aus. Die Neutroneneffizienz wurde experimentell in kalibrierten, quasi--monoenergetischen Neutronenstrahlen am UCL in Belgien und an den iThemba LABS in Südafrika ermittelt. Das im Rahmen dieser Arbeit kalibrierte Detektor-Teleskop wurde auch eingesetzt, um Daten zu reproduzieren, die in Chiba (Japan) ermittelt wurden (400 AMeV 12C-Ionen auf 20 cm Graphit). Die existierenden Messungen wurden zudem um die Energie- und Winkelverteilungen der geladenen Fragmente erweitert. Außerdem wurde im Hinblick auf das Zukunftsprojekt der GSI in Zusammenarbeit mit der Abteilung für Strahlenschutz auch die Teilchenemission aus 20 cm dicken Eisentargets untersucht, in denen 1 AGeV 12C- und 238U-Ionen abgestoppt wurden. Durch diese Messungen konnte das emittierte Teilchenfeld charakterisiert werden, das entsteht, wenn ein Schwerionenstrahl in einem Strahlführungselement abgestoppt wird oder wenn kosmische Teilchen auf die Abschirmung von Raumschiffen treffen. Diese Untersuchungen erlauben somit die Konstruktion von Abschirmungen beruhend auf experimentell bestimmten Quelldaten.
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Peña, Oyarzún Daniel. "Rol de BAG3 en la regulación del metabolismo muscular esquelético." Tesis, Universidad de Chile, 2014. http://repositorio.uchile.cl/handle/2250/134613.
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Memoria para optar el título de BioquímicoAutor no autoriza el acceso a texto completo de su documento hasta diciembre de 2015
La proteína co-chaperona Bag3 es un factor clave en el control de la autofagia selectiva, un proceso de degradación de proteínas y organelos activado en respuesta a distintos estresores, en tejidos altamente diferenciados, como el músculo esquelético. Este último tejido transforma la energía química del ATP en energía mecánica para la contracción, por lo que el control del metabolismo de la glucosa resulta fundamental para mantener su función fisiológica. En este sentido, insulina, a través de sus efectores intracelulares Akt y mTORC1, promueve el ingreso y metabolismo de la glucosa. No obstante, en condiciones de estrés nutricional la proteína AMPK activa la autofagia para aumentar el metabolismo celular por degradación de diversas macromoléculas. Prueba de esta relación funcional entre metabolismo y autofagia es que la inhibición de la autofagia lleva a resistencia a la insulina en células musculares esqueléticas. Por otro lado, existe evidencia que los ratones knock-out para Bag3 presentan una disminución en los niveles de glucosa e insulina circulantes, y mueren a las 3 semanas de nacimiento con deterioro muscular progresivo. Sin embargo, hasta hoy se desconoce si Bag3 regula el metabolismo energético de la célula, y si las vías que controlan ese metabolismo se relacionan con la autofagia. En vista de estos antecedentes, se investigó si Bag3 altera la señalización de la vía Akt-AMPK-mTORC1, produciendo efectos metabólicos y de autofagia en miotubos L6 (línea celular: músculo esquelético de rata). A través de ensayos de captura de 3H-2-desoxiglucosa, consumo de oxígeno y detección densitométrica de GLUT4-myc en superficie, se determinó que las células con niveles reducidos de Bag3 (RNA interferente) y sin insulina en el sistema, incorporaron mayor cantidad de glucosa por un incremento de transportadores Glut-4 en la membrana celular junto con una mayor capacidad oxidativa mitocondrial. Lo anterior es debido a un aumento de la activación basal de Akt, evidenciado por Western blot contra Fosfo-Ser-473. Además, estas células presentaron una menor capacidad de activar la autofagia debido a un procesamiento disminuido de LC3, además de una menor activación de AMPK (Fosfo-Thr-172) y una sobre-activación de mTORC1 (Fosfo-Ser-2448). Finalmente, en presencia de insulina (100 nM, 20 min), las células con niveles reducidos de Bag3 presentaron una incorporación deficiente de glucosa para la cantidad de transportador Glut-4 exportado a la membrana, y una menor capacidad oxidativa mitocondrial. En estas condiciones, Akt se activó de forma normal ante insulina, observándose sin embargo que AMPK y mTORC1 se activó e inactivó, respectivamente; comportamiento inverso respecto a lo normal. Con estos datos, se propone a Bag3 como un novedoso regulador del metabolismo y la autofagia muscular esquelética
The co-chaperone protein Bag3 is a key factor for the control of selective autophagy, a degradation process of proteins and organelles activated in response to stress, in highly differentiated tissues, as the skeletal muscle. The role of the latter is to transform the chemical energy from ATP into mechanical energy for contraction, thus the metabolism control of glucose is important to keep its biological function. In that way, the hormone insulin, by its intracellular effectors Akt and mTORC1, promotes the uptake and metabolism of glucose. However, in nutritional stress conditions the AMPK protein activate autophagy in order to increase cellular metabolism by macromolecular degradation. Proof of this functional relationship between metabolism and autophagy is that autophagy abrogation leads to insulin resistance in muscle cells. On the other hand, there is evidence that shows that Bag3 Knock-out mice present diminished glucose and insulin in blood, and die after 3 weeks from birth with progressive muscle wasting. However, it is not known yet whether Bag3 regulates energy metabolism in the cell, nor whether the pathways that control that metabolism are related with Bag3 mediated autophagy. With this in mind, we decided to determine if Bag3 was able to alter the Akt-AMPK-mTORC1 signaling pathway, leading to metabolic and autophagy effects, in L6 myotubes (cell line: skeletal muscle from rat). By 3H-2-desoxyglucose uptake, oxygen consumption and GLUT4-myc surface detection assays, we were able to determine that cells with reduced levels of Bag3 (interference RNA), and without insulin in the system, had increased glucose uptake because of an augmented Glut-4 translocation to the cell membrane, along with an enhanced mitochondrial oxidative capacity. This is explained by an increased Akt basal activation, evidenced by Phospho-Ser-473 western blot. Furthermore, these cells showed a diminished capacity to produce autophagy, because of a decreased LC3 processing, along with a diminished activation of AMPK (Phospho-Thr-172) and an over activation of mTORC1 (Phospho-Ser-2448). Finally, in the presence of insulin (100 nM, 20 minutes), cells with diminished levels of Bag3 showed a deficient glucose uptake for the amount of Glut-4 transporter exported to cell membrane, and a decreased mitochondrial oxidative capacity. Under these conditions, Akt protein increased its activation, as normal, but AMPK was activated and mTORC1 was inactivated, an inverted behavior with respect to normal metabolism. With these data, we propose Bag3 as a novel regulator of metabolism and autophagy in muscle
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Schröter, Thomas. "Charakterisierung der ba3 Chinoloxidase aus Paracoccus denitrificans." [S.l. : s.n.], 2000. http://deposit.ddb.de/cgi-bin/dokserv?idn=961246944.
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Fogel, William. "Elaboration de cristaux de BaF₂ pour scintillateurs." Grenoble INPG, 1989. http://www.theses.fr/1989INPG0028.
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Nous avons étudié les influences respectives de la poudre et des conditions de cristallogenèse sur l’apparition des défauts dans les cristaux de BaF₂. […] Un mécanisme de formation des inclusions gazeuses a été développé en accord avec nos expérimentations expérimentales. Nous avons montré que les inclusions contiennent uniquement de l’argon, principal constituant de l’atmosphère de croissance. Ce gaz, peu soluble dans BaF₂solide, est repoussé à l’état dissous dans le liquide proche de l’interface. […] La formation des inclusions est favorisée, d’une part par la présence d’impuretés (composés oxygénés) et par l’emploi de vitesse de solidification élevés et/ou de grands diamètres de cristaux. […] La voie de synthèse choisie est la précipitation en milieu aqueux : Fluoration de Ba(NO₃)₂ par NH₄F. La poudre est séchée à 350°C, puis traitée à 160°C par un courant de fluor gazeux dilué à 5% dans N₂, en vue d’abaisser la teneur résiduelle en ions OH⁻, O²⁻, NO₃⁻ et CO₃²⁻. […] Divers essais de cristallogenèse réalisés avec nos poudres nous ont permis de séparer les contributions de la poudre et des conditions de cristallogenèse sur l’apparition des défauts. Nous avons confirmé qu’un traitement de la poudre par le fluor empêchait la formation des inclusions. La qualité optique a ensuite été améliorée par un affinage du bain fondu à une température suffisamment élevée (~ 1530 -1560°C) pour obtenir une bonne efficacité de fluoration par CF₄ de l’atmosphère de croissance. Nous avons pu élaboré des cristaux de grandes dimensions (diamètre = 40 mm) à vitesse de solidification élevée (15 mm/h), sans inclusions et de bonne qualité optique (transmittance de 80% à 220 mm sur une épaisseur de 35 mm). Ces cristaux ont donc les qualités requises pour être employés comme scintillateurs. […]
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Wördehoff, Judith Friederike [Verfasser]. "Regulation des Cochaperons BAG3 durch Phosphorylierung und Dephosphorylierung / Judith Friederike Wördehoff." Bonn : Universitäts- und Landesbibliothek Bonn, 2020. http://d-nb.info/1225793106/34.
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Sebti, Salwa. "Rôle de la protéine BAT3 dans la signalisation cellulaire de l'autophagie." Thesis, Montpellier 1, 2013. http://www.theses.fr/2013MON1T028.
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L'autophagie est un processus d'autodigestion qui se produit dans toutes les cellules eucaryotes et conduit à la dégradation d'éléments du cytoplasme (organites, macromolécules) par le lysosome. Ce mécanisme, qui se produit de manière basale, permet le renouvellement du contenu cytoplasmique mais également la survie cellulaire lorsqu'il est induit par différents stress (carence nutritionnelle, hypoxie…). L'autophagie est alors impliquée dans diverses pathologies comme les maladies neurodégénératives et le cancer car sa dérégulation peut grandement perturber l'homéostasie cellulaire. Le but de ma thèse est de déterminer le rôle de la protéine nucléaire et cytoplasmique BAT3 dans l'autophagie et d'étudier son mécanisme de régulation. Cette protéine de 150 kDa, également appelée BAG6 ou Scythe, est composée de nombreux domaines protéiques (UBL, Prolin-rich, NLS, BAG) qui lui permettent d'interagir avec de multiples partenaires. Sa fonction majeure réside dans le contrôle qualité du cytoplasme mais BAT3 est aussi impliquée dans l'immunité ou l'apoptose. Ce travail identifie la protéine BAT3 comme essentiel pour l'autophagie basale et induite. Nous montrons que son mécanisme d'action passe par la régulation de la localisation de l'acétyltransférase p300 et l'acétylation de ces substrats : p53 et une protéine de la machinerie de l'autophagie : ATG7. En effet, BAT3 (i) limite la présence de p300 dans le cytosol en (ii) maintenant un faible et régulable niveau d'acétylation d'ATG7 et (iii) permet l'acétylation de p53 dans le noyau au cours de la carence nutritionnelle, événement indispensable à l'induction de l'autophagieAutophagy, literally meaning self-eating, is a highly evolutionary conserved process in eukaryotes in which parts of the cytoplasm (organelles, macromolecules) are degraded by lysosomes. Basal autophagy is a quality control mechanism allowing the renewal of the cytoplasm but autophagy is also induced by cellular stress (starvation, hypoxia…) to improve cell survival. Autophagy has been implicated in several physiopathologies such as cancer or neurodegenerative diseases. Deregulations of autophagy may profoundly affect homeostasis.The purpose of my thesis is to explore the role of the nucleo-cytoplasmic shuttling protein BAT3 in autophagy and the mechanism of BAT3-dependent autophagy.Also known as BAG6 or Scythe, this 150 kDa protein is composed of various domain (UBL, Prolin-Rich, NLS, BAG) by which BAT3 interacts with multiple partners. The major of role BAT3 seems to be the protein quality control but BAT3 is also implicated in immunity and apoptosis. Our work demonstrates that the protein BAT3 is essential for basal and starvation-induced autophagy. We show that BAT3 regulation of autophagy is mediated by the modulation of p300 acetyltransferase intracellular localization and acetylation of two subtrates: p53 and the autophagy-related protein ATG7. Indeed, Bat3 allows: (i) the limitation of p300 into cytosol resulting in (ii) the maintenance of a low level of ATG7 acetylation and (iii) the increase of the starvation-induced p53 autophagy leading to the induction of autophagy
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Chhabra, Manu. "Targeting the BAFF/April signalling axis for prevention of humoral rejection." Thesis, University of Cambridge, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708468.
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Aranha, Carolina Pereira. "Estudo das propriedades microestruturais e ópticas do sistema BaO-BaF2-B2O3." Universidade Federal do Maranhão, 2011. http://tedebc.ufma.br:8080/jspui/handle/tede/728.
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Previous issue date: 2011-08-10The objective this work is study the system BaO-B2O3 glassy-BaF2 and phases obtained from the process of controlled crystallization of it in pursuit of obtain the β-phase BaB2O4,. We studied samples containing between 0% and 40% barium fluoride. The evaluation of the microstructural and optical properties were performed using the techniques of Differential Scanning Analysis (DSC), X-ray diffraction(XRD), optical microscopy, microhardness, and absorption in the visible and ultraviolet (UV). The study of microhardness of the samples revealed an increase in tensile strength with increasing fluoride content in the sample. Increasing the fluoride content in the sample is also related to a decrease in Tg, as verified by DSC. The study of XRD patterns of crystallized samples showed that the prevalence of β-phase is BaB2O4 reduced as the fluoride content exceeds 10% of the sample, and for the sample containing 40% fluoride, the XRD patterns revealed the predominance of phase Ba2B5O9F, and samples with 20% and 40% of fluoride showed the lowest optical absorption in the visible.
Este trabalho teve por objetivo o estudo do sistema vítreo BaO-B2O3-BaF2 e das fases obtidas a partir do processo de cristalização controlada do mesmo, em busca da obtenção da fase β-BaB2O4. Foram estudadas amostras contendo entre 0% e 40% de fluoreto de Bário. A avaliação das propriedades microestruturais e ópticas foram realizadas através das técnicas de Análise Térmica Diferencial (DSC), Difração de raios-X, Microscopia Óptica, Microdureza, e absorção no visível e no Ultravioleta (UV). O estudo da microdureza das amostras revelou o aumento da resistência à tensão, com o aumento do teor de fluoreto na amostra. O aumento do teor de fluoreto na amostra também está relacionado com uma diminuição na Tg, verificada através da medida de DSC. O estudo dos difratogramas das amostras na forma de pó cristalizadas mostrou que a predominância da fase β-BaB2O4 é reduzida à proporção em que o teor de fluoreto excede os 10% na amostra, e para a amostra contendo 40% de fluoreto, os difratogramas das amostras em pó cristalizadas não-isotermicamente. Revelaram a predominância da fase Ba2B5O9F, e as amostras com 20% e 40% de fluoreto apresentaram menor absorção óptica no visível.
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Rodríguez, Villarroel Andrea Elizabeth. "Estudio de los mecanismos de regulación de la autofagia por BAG3." Tesis, Universidad de Chile, 2015. http://repositorio.uchile.cl/handle/2250/136770.
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Doctora en BioquímicaAutor no autoriza el acceso a texto completo de su documento
La macroautofagia (autofagia) es una vía de reciclaje caracterizada por la formación de vesículas de doble membrana denominadas autofagosomas que secuestran estructuras citoplasmáticas marcadas para su degradación. La formación del autofagosoma requiere la actividad de proteínas relacionadas con la autofagia (Atg) que median algunas de las cuatro etapas principales de la autofagia: iniciación, nucleación, expansión y cierre. La proteína MAP1LC3B (referida sólo como LC3) es una de las Atg más importantes ya que ayuda a elongar la membrana y reclutar al cargo. Su forma lipidada (LC3-II) se encuentra en ambas superficies del autofagosoma (externa e interna) donde se degrada con su cargo cuando el autofagosoma se fusiona con el lisosoma. La autofagia se regula principalmente por modificaciones post-traduccionales y modificaciones lipídicas de las proteínas Atg. Además, en algunos escenarios, la inducción de la autofagia se acompaña de aumentos en los niveles de mRNA de ciertos genes asociados a la autofagia, como LC3, ATG5 o ATG12. Sin embargo, prácticamente se desconocen los mecanismos que controlan la traducción de las proteínas Atg. Estudios recientes con la cochaperona Bag3 han mostrado controlar la degradación selectiva de proteínas mal plegadas a través de autofagia, incluyendo huntingtina con expansiones de poli-Q y SOD1 mutante. El mecanismo involucra la asociación de Bag3 a dineína y microtúbulos para el transporte de proteínas mal plegadas a los agresomas, facilitando su eliminación por la autofagia. Además del papel en el plegamiento y degradación de proteínas, recientemente se ha descrito que la chaperona Hsp70 regula la traducción de proteínas. Los últimos trabajos muestran que Bag3 es una proteína que induce la lipidación LC3 pero no hay antecedentes sobre el mecanismo utilizado. En esta tesis se estudió cómo Bag3 controla la autofagia en células HeLa. Para este fin Bag3 se silenció con un siRNA ó shRNA, o se expresó con plasmidios. Los niveles de mRNA, proteínas y estado de fosforilación de varias proteínas Atg, particularmente de LC3I y LC3II, mTOR y AMPK. Además, se determinó si Bag3 es necesaria para la inducción de la autofagia en condiciones de estrés como la privación de nutrientes e inhibición del proteasoma. Los resultados mostraron que Bag3 mantiene los niveles basales de la proteína LC3 en células HeLa, controlando la traducción de su mRNA. El efecto de Bag3 es aparentemente específico para LC3 dado que otras proteínas Atg no fueron afectadas. De hecho, la conversión de LC3I a LC3II por inductores autofagia, como la privación de nutrientes y la inhibición del proteosoma, no se observó afectada. Se concluye que Bag3 regula niveles proteicos totales de LC3, manteniendo su traducción
Macroautophagy (autophagy) is a recycling pathway characterized by the formation of double-membrane vesicles called autophagosomes, which sequester cytoplasmic structures targeted for destruction. Autophagosome formation requires the activity of autophagy-related proteins (Atg), which are shown to participate in the four major steps: initiation, nucleation, expansion and closure. MAP1LC3B (referred only as LC3) is most important Atg protein, aiding to elongate the membrane and recruit the cargo. The lipidated form of LC3 (LC3-II) lies on both surfaces of autophagosome (external and internal) where it degrades with its cargo when the autophagosome fuses with the lysosome. Autophagy is mainly regulated by post-translational modifications and lipid modifications of Atg proteins. Moreover, in some scenarios, the induction of autophagy is accompanied by an increase in the mRNA levels of certain genes associated to autophagy, such as LC3, ATG5 or ATG12. However, less work has done on the study of mechanisms controlling translation of the Atg proteins. In recent studies, Bag3 has shown to control the selective degradation of misfolded proteins by autophagy, including polyQ-expanded huntingtin and mutant SOD1. The mechanism involves Bag3 association to dynein and microtubules to transport misfolded proteins to the aggresomes and facilitates their clearance by autophagy. Besides the role in folding and degradation of proteins, recently has shown a role of the Hsp70 chaperone in the regulation of the translation of proteins. The last reports show that Bag3 is a protein that induces LC3 lipidation but little is known about the mechanisms used. In the present work, we study how Bag3 controls the autophagy pathway in HeLa cells. Bag3 was knockdown with siRNA or shRNA, or expressed with plasmids. mRNA levels, protein levels and phosphorylation status of several Atg, particularly of LC3I and LC3II, mTOR and AMPK were evaluated. In addition, it was determined whether Bag3 is required for the induction of autophagy in stress conditions such as nutrient deprivation and inhibition of the proteasome. Our results showed that Bag3 maintains the basal protein levels of LC3 in HeLa cells, controlling the translation of its mRNA. This effect was apparently specific for LC3 because the levels of other Atg proteins remained unchanged. The LC3I conversion to LC3II did not alter by autophagy inductors such as nutrient deprivation or proteasome inhibition. We concluded that Bag3 maintains the basal protein levels of LC3, controlling the translation of its mRNA
Conicyt Fondecyt Fondap Proyecto Anillo ACT 1111
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Ittah, Marc. "Lien entre l'immunité innée, la cytokine BAFF (B-cell activating factor of TNF family) et l'auto-immunité." Paris 11, 2009. http://www.theses.fr/2009PA11T037.
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Kothlow, Sonja. "Charakterisierung des Zytokins BAFF als wichtiger Regulator der B-Zellfunktion beim Haushuhn." Diss., lmu, 2004. http://nbn-resolving.de/urn:nbn:de:bvb:19-25222.
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Gohlke, Paul Reid Matsushima Glenn K. "The role of MerTK and BAFF in dendritic cell-B cell interactions." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2007. http://dc.lib.unc.edu/u?/etd,1231.
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Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2007.Title from electronic title page (viewed Mar. 26, 2008). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Microbiology and Immunology." Discipline: Microbiology and Immunology; Department/School: Medicine.
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Schwarz, Mario [Verfasser]. "Untersuchung autophagischer Prozesse mit Fokus auf BAG3 und seine Interaktoren. / Mario Schwarz." Mainz : Universitätsbibliothek der Johannes Gutenberg-Universität Mainz, 2021. http://d-nb.info/1225796059/34.
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Zeidler, Claudia [Verfasser]. "Functional Characterization of Interaction Partners of the Co-Chaperone BAG3 / Claudia Zeidler." Bonn : Universitäts- und Landesbibliothek Bonn, 2018. http://d-nb.info/116059452X/34.
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Bergamin, Fabio. "Antigen-presenting cells and BAFF in porcine B-cell responses against FMDV /." Bern : [s.n.], 2007. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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Welzel, Oliver Patrick. "Transport measurements of Cá́₃Ru₂O₇ and BaFe₂As₂ using micropatterned anvils." Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609486.
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Rauch, Melanie. "The role of FLT3L and BAFF in B cell development and homeostasis /." [S.l.] : [s.n.], 2009. http://edoc.unibas.ch/diss/DissB_8751.
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Ribeiro, Luis Sousa. "Bafo: Ensaios sobre a duplicidade de º, o humano e técnica terapêutica." Master's thesis, Instituto Superior de Psicologia Aplicada, 1993. http://hdl.handle.net/10400.12/851.
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Allen, Jessica L. "Inhibition by Proxy: Modulation of TLR4-driven B cell responses by RP105." University of Cincinnati / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1275658195.
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Faber, Hans. "Die Therapie der Multiplen Sklerose mit IFN-b induziert den B-Zellüberlebensfaktor BAFF." Diss., lmu, 2008. http://nbn-resolving.de/urn:nbn:de:bvb:19-89236.
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Richter, Katharina [Verfasser]. "BAFF- und APRIL-Expression im Synovialgewebe von Patienten mit Rheumatoider Arthritis / Katharina Richter." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2015. http://d-nb.info/1071088785/34.
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Visvikis, Dimitrios. "The development of a unique whole body BaF2-TMAE positron camera for oncology." Thesis, Institute of Cancer Research (University Of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.363045.
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Suárez, Emilio Heredia. "Propriedades estruturais e ópticas de amostras de EuTe e PbEuTe crescidas sobre BaF2." Instituto Nacional de Pesquisas Espaciais (INPE), 2012. http://urlib.net/sid.inpe.br/mtc-m19/2012/11.28.14.50.
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A pesquisa sobre semicondutores magnéticos é de relevância na atualidade, devido a possíveis aplicações em dispositivo magneto ópticos e spintrônicos. O EuTe foi um dos primeiros semicondutores magnéticos intrínsecos a ser descoberto e tem sido amplamente estudado, porém, até hoje, as suas propriedades ópticas e eletrônicas não são completamente conhecidas ou compreendidas. Adicionalmente, quando o átomo de Eu é parcialmente substituído por Pb na liga Pb$_{x}$Eu$_{1-x}$Te aparecem novas e interessantes propriedades. Neste trabalho, foram investigadas as propriedades estruturais de ilhas e filmes finos de EuTe e as propriedades ópticas de filmes finos de EuTe e Pb(x)Eu(1-x)Te com até 20 \% de Pb, crescidos por epitaxia de feixes moleculares sobre substratos de BaF$_{2}$ (111). O estudo por difração de raios-x das ilhas de EuTe mostrou que, quando são utilizadas baixas temperaturas do substrato durante o crescimento, as mesmas apresentam parâmetros de rede no plano maiores do que a do EuTe relaxado, mesmo estando sobre um substrato de parâmetro de rede menor. Tal efeito, chamado de super compensação do descasamento de parâmetro de rede, nunca tinha sido observado experimentalmente em nenhum material e isto pode ter aplicações práticas, por exemplo, na engenharia de estruturas de bandas de semicondutores. O estudo das propriedades ópticas, por outro lado, revelou que quando se utilizam altas densidades de potência de excitação, os espectros de PL da liga PbEuTe (com até 5 \% de Pb) apresentam uma nova banda de emissão centrada em energias maiores do que às das bandas excitônicas conhecidas como MXs, observadas nos trabalhos anteriores publicados na literatura. Com a aplicação de campos magnéticos, em filmes de EuTe a nova banda se desloca para energias menores com uma taxa de $\sim$40 meV/T na geometria de Faraday, valor superior ao das demais bandas de emissão mencionadas na literatura. Adicionalmente, nas amostras com Pb, para campos magnéticos aplicados relativamente altos, esta banda se desdobra em até 3 sub-bandas com taxas de deslocamento diferentes. O comportamento da nova banda em função da temperatura também é diferente ao das bandas MXs, em particular a nova banda é visível a temperaturas de nitrogênio líquido e superiores, o que aumenta o intervalo de temperaturas em que poderiam operar dispositivos opto eletrônicos e spintrônicos baseados em PbEuTe. As possíveis origens da nova banda de PL no EuTe e PbEuTe são discutidas no trabalho. O estudo do espalhamento Raman para amostras de EuTe e PbEuTe também revelou diferenças nos espectros com e sem adição de chumbo. Essencialmente, a presença de Pb na estrutura, substituindo o Eu, muda a simetria dos modos de vibração alterando a regra de seleção, o que pode ter provocado a mudança nos espectros Raman entre EuTe e PbEuTe. Estes e outros resultados discutidos no trabalho incrementam o nosso conhecimento sobre as propriedades do EuTe e PbEuTe e podem contribuir para estimular novas investigações teóricas e experimentais nesses materiais.The research on magnetic semiconductors is now more relevant than has ever been, due to their potential applications in magneto optic and spintronic devices. EuTe was one of the first intrinsic magnetic semiconductors to be discovered, and has been extensively studied since then. Nevertheless, still today its electronic and optical properties are not completely known or understood. Furthermore, when Eu is partially substituted by Pb in the alloy Pb(x)Eu(1-x)Te, new and interesting properties appear. The present work reports the investigation of the structural properties of EuTe islands and thin films, and of the optical properties of EuTe and Pb(x)Eu(1-x)Te (x up to 20 \% Pb) thin films, grown by molecular beam epitaxy over BaF$_{2}$ (111). The x-ray diffraction investigation of the EuTe islands shows that if low substrate temperatures are used during growth, the islands have in-plane lattices parameters bigger than relaxed EuTe (they are effectively under tensile strain), while compressive strain is expected for epitaxial growths on substrates with smaller lattice parameters. This effect, known as mismatch overcompensation, had never been experimentally observed and could find practical applications, for instance, in the engineering of semiconductor nanostructures energy levels. Also, it was observed that the photoluminescence spectra of EuTe and Pb(x)Eu(1-x)Te thin films (with x up to 5 \%), obtained under high excitation power densities at low temperatures, shows a new band. The new band is centered at energies higher than the previously reported MXs bands and with, applied magnetic field, shifts to lower energies at rates even higher than the MXs (in EuTe, $\sim$ 40 meV/T in Faraday geometry). Additionally, in the alloy, the new band is clearly split into 2 or 3 sub bands (depending on the Pb content) with different shift rates by the application of a relatively strong magnetic field (B > 1 T). The new band and MXs behaviors with temperature also differ. For instance, the new band is visible at liquid nitrogen temperatures and up, while the MXs vanish at $\sim$40 K. This finding in particular, increases the range of operating temperature of potential optoelectronic and spintronics devices based on EuTe. The possible origin of the new high-energy band in EuTe and PbEuTe is discussed in the text. The Raman spectra of EuTe and PbEuTe samples are also different. Essentially, the presence of Pb in the crystal lattice changes the symmetry of the vibration modes observed during the scattering process, thus making new peaks appear on the spectra. The new peaks in the spectra of the alloy come presumably from TO and mixed-mode phonons, while only peaks due to LO modes appear in pure EuTe. In addition, the intensity of the 1$^{th}$ order Raman scattering, relative to the 2$^{nd}$ order, increases with increasing Pb content, probably due to the relaxation of the Raman selection-rules by chemical disorder. These results and others discussed in this work, increase our knowledge on the basic properties of EuTe and PbEuTe, and might also contribute towards finding new practical applications for these interesting materials. Nevertheless, there is much more to learn about them, and based in the findings that have been made, further research in this area would be promising.
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Chan, Calvin. "Uncovering an Adipocyte’s Perspective of Inflammation and Immunity in Obesity." University of Cincinnati / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1560866472579872.
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François, Antoine. "Rôle du "B-cell activating factor" (BAFF) et des lymphocites B dans la fibrose pulmonaire et cutanée dans la sclérodermie systémique." Thesis, Strasbourg, 2013. http://www.theses.fr/2013STRAJ056/document.
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La sclérodermie systémique (ScS) est une maladie autoimmune rare qui se caractérise par une fibrose cutanée et parfois pulmonaire. Nous avons tout d’abord évalué le rôle de BAFF, une cytokine impliquée dans le développement des lymphocytes B (LB), dans la fibrose pulmonaire induite par la bléomycine chez la souris. Nous avons démontré que BAFF était augmenté en réponse à la bléomycine et que les souris BAFF-/- ou traitées par le BAFF-R-Ig sont protégées de la fibrose pulmonaire. Ensuite, nous avons évalué si les LB et BAFF pouvaient moduler la production de collagène par des fibroblastes de peau isolés de patients atteints de ScS. Nous avons démontré que les LB augmentent la production de collagène et de cytokines impliquées dans la fibrose cutanée et l’ajout de BAFF augmente cet effet des LB sur les fibroblastes. Enfin, nous avons étudié la régulation de l’expression de BAFF par les microARNs. Nos résultats montrent que les miR-30a*, d* et e* ciblent directement l’ARNm de BAFFSystemic sclerosis (SSc) is a rare autoimmune disease characterized by skin fibrosis and occasionally pulmonary fibrosis. We first assessed the role of BAFF, a cytokine involved in B cell maturation, in bleomycin-induced pulmonary fibrosis in mice. We showed that BAFF was increased in response to bleomycin and that BAFF-/- mice or BAFF-R-Igtreated mice are protected from pulmonary fibrosis. Then, we assessed whether B cells and BAFF could regulate collagen production by skin fibroblasts isolated from SSc patients. We demonstrated that B cells increase collagen production and cytokines involved in skin fibrosis. The addition of BAFF increases the effect of B cells on fibroblasts. Lastly, we studied the regulation of BAFF expression by microRNAs. Our results show that miR-30a*, d* and e* directly target the BAFF mRNA
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Matei, Ion. "Electrochemical studies of MBE-grown CaF 2 /BaF 2 heterolayers." Kostenfrei, 2007. http://nbn-resolving.de/urn:nbn:de:bsz:93-opus-32888.
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Lanoue, Vanessa. "Rôle du récepteur BAI3 dans le développement neuronal - Études in vitro et in vivo -." Phd thesis, Université Pierre et Marie Curie - Paris VI, 2012. http://tel.archives-ouvertes.fr/tel-00865692.
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La dendritogenèse et la spinogenèse sont des étapes clés du développement neuronal. Elles impliquent de nombreuses protéines jouant un rôle essentiel dans la réorganisation du cytosquelette d'actine via les RhoGTPases. Des défauts dans ces processus peuvent mener à des maladies neurodéveloppementales comme l'autisme ou la schizophrénie. Les récepteurs BAI appartiennent à la famille des RCPG d'Adhésion et ont été identifiés dans des préparations biochimiques de densités postsynaptiques. BAI1 module la RhoGTPase Rac1 via son interaction avec la protéine ELMO1. De plus, les protéines sécrétées C1q-like ont récemment été identifiées comme ligands du récepteur BAI3 in vitro et cette interaction régulerait la synaptogenèse. Nous avons émis l'hypothèse que le récepteur BAI3 pourrait réguler le développement neuronal, en particulier la dendritogenèse et la spinogenèse, en interagissant avec ELMO1. Nos travaux ont montré que BAI3 est localisé dans les dendrites, et chez les neurones matures dans les épines dendritiques. Des études morphométriques nous ont permis de montrer son rôle dans la croissance et la complexification de l'arbre dendritique des neurones in vitro. Nos données in vivo sont en accord avec un rôle du récepteur BAI3 dans la morphogenèse des cellules de Purkinje du cervelet et la mise en place de leur innervation excitatrice. Le rôle de BAI3 dans la morphogenèse dendritique semble dépendre en partie de son interaction avec ELMO1. Par ailleurs, BAI3 module l'étalement cellulaire, suggérant son implication dans la régulation des RhoGTPases. L'ensemble de nos résultats met en lumière un nouveau rôle des récepteurs BAI comme régulateurs de la dendritogenèse et de la formation des synapses, en partie via la voie de signalisation ELMO1/Rac1. Nos résultats identifient les récepteurs BAI comme de nouveaux acteurs de la morphogenèse neuronale et, au vu du lien génétique existant entre BAI3 et certains symptômes de la schizophrénie, offrent de nouvelles perspectives dans l'étude des maladies neurodéveloppementales.
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Farahmand, Bafi Nima [Verfasser], and Siegfried [Akademischer Betreuer] Dietrich. "Tricritical Casimir forces in 3He -4He wetting films / Nima Farahmand Bafi ; Betreuer: Siegfried Dietrich." Stuttgart : Universitätsbibliothek der Universität Stuttgart, 2017. http://d-nb.info/1133074898/34.
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Jami, Morteza School of Biological Earth & Environmental Sciences UNSW. "Geology, geochemistry and evolution of the Esfordi Phosphate - Iron Deposit, Bafq Area, Central Iran." Awarded by:University of New South Wales. School of Biological, Earth and Environmental Sciences, 2005. http://handle.unsw.edu.au/1959.4/32745.
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Esfordi is a Kiruna-type Fe???P oxide deposit in the Bafq district of Iran. It formed within a predominantly rhyolitic volcanic sequence that formed in a continental margin tectonic regime and is of Cambrian age. The gently dipping, stratabound ore body is lenticular and displays a well-developed mineralogical zonal pattern. The Fe-oxide rich core contains a central zone of massive magnetite and a more hematitic brecciated rim. The overlying P-rich ore body contains massive and brecciated, apatite-rich variants with accessory hematite and actinolite. A zone of apatite-bearing veins and disseminations envelopes the Fe-oxide and P-rich zones and extends into overlying volcaniclastics that contain detrital magnetite ?? apatite clasts. The main ore zones are surrounded by Ca-rich alteration, dominated by actinolite, extending ~100 m into the more permeable overlying volcaniclastics. Beyond this envelope is widespread development of secondary K-feldspar. Mesoscopic and microscopic observations reveal a paragenetic sequence containing four generations of apatite. The early stage is a LREE-rich apatite 1 that occurs within the massive and brecciated magnetite core. The second generation is large and brecciated apatite 2, associated with hematite and actinolite. Both apatite 1 and 2 exhibit widespread dissolution and reprecipitation to form a LREE-poor granular apatite that is generally associated with quartz-carbonate??REE minerals. The final stage involved an overprint of LREE-poor apatite 3-carbonate-quartz-actinolite-chlorite-epidote??bastnaesite??synchesite extending into the host rocks. Fluid inclusions in apatite 1 have homogenisation temperatures of 375-425oC and indicate salinities of 14???18 wt. % NaCl. The magnetite displays low ???????O of -0.1???1.7 ???, suggesting precipitation from fluids with ???????O of 7.8???9.6 ??? at ~400oC, consistent with a magmatic source. Fluid inclusions in apatite 2 homogenise between 195???295oC with indicated salinities of 13???19 wt. % NaCl. The associated hematite displays ???????O of -0.2???2.3 ??? which would be in equilibrium with fluids having a ???????O of 10.7???13.0 ??? at ~250oC. Such enriched isotopic fluids suggest interaction of magmatic fluids with cooler saline fluids that were probably derived from the underlying carbonate-rich sequences. Fluid inclusions in apatite 3 and quartz homogenise at 145???155oC and, together with a quartz ???????O of 16.0???17.1 ???, suggests precipitation from a fluid with ???????O of -0.7???2.1 ??? that is likely to have resulted from the introduction of a cooler, less saline and isotopically depleted fluid (such as sea water). The results of this study clearly indicate a significant role for fluids in the evolution of the Esfordi deposit but do not preclude a role for immiscible Fe-oxide???P-rich melts in the initial stages of the mineralising process.