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Guillot, Loic. "Rôle des "toll-like receptor" (TLR) 3 et TLR4 dans l'immunité innée de la muqueuse pulmonaire." Paris 6, 2004. http://www.theses.fr/2004PA066147.
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Hamann, Timothy [Verfasser]. "Interaktion von TLR-3 stimuliertem retinalen Pigmentepithel und retinaler Mikroglia vor dem Hintergrund der altersabhängigen Makuladegeneration / Timothy Hamann." Kiel : Universitätsbibliothek Kiel, 2017. http://d-nb.info/114495519X/34.
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Desnous, Béatrice. "Effets de l'administration intra-hippocampique et intra-péritonéale de l'acide polyinosinique polycytidylique, agoniste des récepteurs TLR-3, sur l'épileptogenèse." Sorbonne Paris Cité, 2015. http://www.theses.fr/2015USPCC289.
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Notre approche expérimentale a pour but d'évaluer le rôle de l'inflammation virale dans l'épileptogenèse. Nous avons choisi de modéliser l'inflammation virale par injection d'un agoniste TLR-3, acide polyinosinique polycytidylique (PIC) soit intra-péritonéale, soit intra-hippocampique, Chaque modélisation inflammatoire était couplée à un modèle d'épileptogenèse électrique le kindling rapide. L'ensemble de notre travail expérimental était réalisé chez le rat Wistar à P14 et à P75. Notre travail a montré que l'injection I. H, de PIC facilitait l'épileptogenèse du cerveau immature et adulte et induisait une augmentation du taux I. H. D'IL-1P à P14 et P75. A l'opposé la minocycline inhibait cette facilitation de l'épileptogenèse sans bloquer l'augmentation I. H. De l'IL-113 aux 2 âges étudiés. Nous avons montré que l'injection I,p, de PIC facilitait l'épileptogenèse du cerveau immature uniquement. Nous avons observé à P14 une réponse immunitaire avec une inflammation périphérique plus importante que chez l'adulte suivi d'une augmentation de l'IL-1ß hippocampique présente uniquement à P14. La BHE avait une perméabilité plus importante chez les P14 prétraités par PIC que chez l'adulte. Ces éléments nous amènent a suggérer un passage de rIL-1p de la périphérie vers le secteur intra-cérébral avec augmentation précoce et transitoire de l'IL-1ß intra-hippocampique,enforcée que nous n'avons<br>Our experimental approach is intended to assess the rote of viral inflammation in epileptogenesis. We chose to model the viral inflammation by 'Meeting a TLR-3 agonist, polyinosinic polycytidylic (PIC) or intraperitoneal or intra-hippocampal, Each inflammatory modeling was coupled to an electric Epileptogenesis mode rapid kindling, All of our experimental work was performed in Wistar rats at P14 and P75. Our work has shown that the injection I. H, PIC facilitated epileptogenesIs immature and adult brain and induced an increase of I. H, levels of IL-1ß to P14 and P75. In contrast minocycline inhibited this facilitation epileptogenesis without blocking I. H. Increase of IL-1ß to 2 ages studied. We have shown that the injection in PIC- facilitated epileptogenesis immature brain only. We observed an immune response to P14 with a. .
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Endoh, Yasumi Medical Sciences Faculty of Medicine UNSW. "New mechanisms modulating S100A8 gene expression." Publisher:University of New South Wales. Medical Sciences, 2008. http://handle.unsw.edu.au/1959.4/42942.
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S100A8 is a highly-expressed calcium-binding protein in neutrophils and activated macrophages, and has proposed roles in myeloid cell differentiation and host defense. Functions of S100A8 are not fully understood, partly because of difficulties in generating S100A8 knockout mice. Attempts to silence S100A8 gene expression in activated macrophages and fibroblasts using RNA interference (RNAi) technology were unsuccessful. Despite establishing validated small interfering RNA (siRNA) systems, enzymaticallysynthesized siRNA targeted to S100A8 suppressed mRNA levels by only 40% in fibroblasts activated with FGF-2+heparin, whereas chemically-synthesized siRNAs suppressed S100A8 driven by an S100A8-expression vector by ~75% in fibroblasts. Suppression of the gene in activated macrophages/fibroblasts was low, and some enzymatically-synthesized siRNAs to S100A8, and unrelated siRNA to GAPDH, induced/enhanced S100A8 expression in macrophages. This indicated that S100A8 may be upregulated by type-1 interferon (IFN). IFN-β enhanced expression, but did not directly induce S100A8. Poly (I:C), a synthetic dsRNA, directly induced S100A8 through IL-10 and IFN-dependent pathways. Induction by dsRNA was dependent on RNA-dependent protein kinase (PKR), but not cyclooxygenase-2, suggesting divergent pathways in LPS- and dsRNA-induced responses. New mechanisms of S100A8 gene regulation are presented, that suggest functions in anti-viral defense. S100A8 expression was confirmed in lungs from influenza virus-infected mice and from a patient with severe acute respiratory syndrome (SARS). Multiple pathways via mitochondria mediated S100A8 induction in LPS-activated macrophages; Generation of reactive oxygen species via the mitochondrial electron transport chain and de novo synthesis of ATP may be involved. This pathway also regulated IL-10 production, possibly via PKR. Extracellular ATP and its metabolites enhanced S100A8 induction. Results support involvement of cell stress, such as transfection, in S100A8 expression. A breast tumor cell line (MCF-7) in which the S100A8 gene was silenced, was established using micro RNA technology; S100A8 induction by oncostatin M was reduced by >90% in stably-transfected cells. This did not alter MCF-7 growth. The new approach to investigate the role of S100A8 in a human tumor cell line may assist in exploring its functions and lead to new studies concerning its role in cancer.
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Fallah, Mosoka Papa. "ROLE OF PI3K-AKT PATHWAY IN THE AGE ASSOCIATED DECLINE IN TLR MEDIATED ACTIVATION OF INNATE AND ADAPTIVE IMMUNE RESPONSES." UKnowledge, 2011. http://uknowledge.uky.edu/gradschool_diss/205.
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Immunosenescence results in reduced immune response to infections with Streptococcus pneumoniae as well as to pneumococcal polysaccharide vaccines. The antibody response to the capsular polysaccharide (CPS) provides protection against S. pneumoniae infection. CPS immunoresponse is T cell independent and needs the macrophage-derived cytokines such as IL-12, IL-6 and IL-1β to elicit an antibody response. We showed a cytokine dysregulation, i.e. a decrease in IL-12, IL-6 and TNF-α but an increase in IL-10, in the aged (18-24 months old comparable to >65 years in human) compared to young adult mouse (8-12 weeks less than 65 years old) splenic macrophages (SM) or bone marrow derived macrophages (BMDM) activated via TLR4, TLR2 or TLR9 as well as heat killed Streptococcus pneumoniae (HKSP). There is also an age-associated defect in splenic B cells in the production of IgG3 upon stimulation with these ligands. A microarray analysis in SM followed by validation by both qt-RTPCR and western blots indicated that this age-associated defect in aged SM, BMDM and B cells was due to a heightened activity of the PI3K-Akt signaling pathway. We hypothesized that the senescence of immune responses in macrophages and B cells is due to an increase in activity of PI3K/Akt and decrease in the activity of GSK-3, the downstream kinase. Inhibition of the PI3-kinase with either LY294002 or Wortmannin restored the TLR2, 4, 9 and HKSP induced cytokine phenotype of the aged to that of the young adult in both the SM and BMDM and an enhanced IgG3 production in aged mice.
We also showed that inhibition of glycogen synthase kinase-3 (GSK-3) the downstream target of the PI3K-Akt signaling pathway with SB216763 in SM, BMDM and B cells resulted in an enhancement in production of IL-10, IL-6 and IL-1β by macrophages and in B cell activation. Treatment of B cells with SB216763 in the presence of ligands for TLR-1/2, 4 or 9 as well as HKSP under in vitro conditions led to enhanced production of IgG3 and IgA, plasma cell formation and a slight increase in the proliferation of the B-cells with no adverse effects on the viability of the cells. Therefore, targeting the PI3K-AKT-GKS-3 signaling pathway could rescue the intrinsic signaling defect in the aged macrophages, increase IL-12 and IL-6, and enhance anti-CPS antibody responses.
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Campbell, Sara J. "Mechanisms of Moraxella catarrhalis Induced Immune Signaling in the Pulmonary Epithelium." University of Toledo Health Science Campus / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=mco1268141520.
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Salisbury, Richard L. Jr. "TCDD represses 3'IghRR activation through an AhR-dependent shift in the NF-κB/Rel protein complexes binding to κB motifs within the hs1,2 and hs4 enhancers". Wright State University / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=wright1401136335.
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Kuzemtseva, Liudmila. "Distribución tisular de los receptores Toll-like (TLR) 3, 7 y 9 en el cerdo y efecto in vitro de la infección por el virus de síndrome respiratorio y reproductivo porcino en su regulación en macrófagos alveolares porcinos." Doctoral thesis, Universitat Autònoma de Barcelona, 2012. http://hdl.handle.net/10803/284490.
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Los receptores Toll-like (TLRs), en particular los que se encuentran en vesículas intracelulares de origen endosomal (TLR3, TLR7 y TLR9), están involucrados en la respuesta innata antivírica. La unión a sus respectivos ligandos conduce a la activación de cascadas intracelulares que resultan en una producción de citoquinas pro-inflamatorias (TNF-α) y antivirales (interferones de tipo I). Existe muy poca información sobre la distribución celular y tisular de estos receptores en la especie porcina así como su regulación en condiciones normales o de infección.
En el primer estudio de la presente tesis se valoró la distribución tisular de los TLRs endosomales en pulmón y tejidos linfoides primarios y secundarios de cerdos sanos de distintas edades. El marcaje del TLR9 se realizó con un anticuerpo comercial con reactividad específica para el porcino. En cambio, en el caso de TLR3 y TLR7 los anticuerpos se dirigían a las moléculas humanas pero, supuestamente, poseían reactividad cruzada con las moléculas de origen porcino. Los resultados obtenidos permitieron valorar la distribución del TLR9 en los distintos tejidos examinados, pero no la de los TLR3 y TLR7 ya que el uso de los anticuerpos dirigidos frente a estos dos últimos receptores no produjo resultados satisfactorios. Así, el marcaje obtenido con el anticuerpo anti-TLR3 fue muy variable en función del tejido utilizado; es decir, en algunos órganos como el pulmón, tonsila o linfonodos parecía ser específico, pero en otros como en el hígado, producía un intenso color de fondo inespecífico. Por el contrario, sí hubo un marcaje específico para el TLR9 que reveló una expresión constitutiva de dicho receptor en células de la periferia de los folículos linfoides de los linfonodos, la tonsila y las placas de Peyer, (células de tipo epitelial, dendríticas, macrófagos o linfocitos) un hecho que sugería que este receptor probablemente puede jugar un papel importante en la activación el sistema inmunitario de los cerdos a partir de las 3 semanas de vida.
El segundo estudio de esta tesis consistió en determinar la variación de la expresión de TLR3, TLR7 y TLR9 a lo largo del tiempo en una población de células presentadoras de antígeno. La población de estudio elegida fue la de macrófagos alveolares porcinos (PAMs). Los resultados de la cinética de expresión mediante citometría de flujo nos mostró que estas células presentaban una expresión basal elevada de TLR3 y TLR9 pero no de TLR7. Una de las explicaciones posibles para este marcaje basal señalaría a la necesaria manipulación de estas células antes de ser congeladas como responsable de esta expresión.
Por otra parte, es difícil conocer con exactitud el ambiente en el cual se encontraban los PAMs en el pulmón antes de ser recogidos (concentración de interleuquinas, quimioquinas, otras moléculas, etc). Dado que los animales donantes estaban sanos, no presentaban ningún tipo de lesión pulmonar y eran libres de los patógenos víricos comunes del cerdo (circovirus porcino de tipo 2, influenza A y virus del PRRS entre otros) la causa de esta elevada expresión no está clara. En cuanto a la expresión de TLR7, apenas se pudo detectar una expresión basal en los PAMs utilizados.
Para el tercer estudio de esta tesis se buscó un modelo de infección con un virus RNA que pudiera influir en la regulación de estos TLRs y además pudiera añadir nuevos conocimientos respecto a la inmunopatogenia de dicha infección. En el campo de las enfermedades infecciosas del porcino, una de las mayores incógnitas inmunológicas del momento la encontramos en la infección con el virus del PRRS. Los resultados de este estudio demostraron que dos cepas del mismo genotipo del virus del PRRS causaban una regulación diferente del TLR3 y del patrón de citoquinas pro-inflamatorias. En concreto, en los estudios de citometría de flujo, la cepa 3262 al inducir la expresión de TLR3 en PAMs, sobre todo a dosis elevadas (m.o.i=1), activaría la producción de TNF-α+; en cambio, la cepa 3267 o la cepa vacunal DV activaron TLR3 con menor intensidad y no inducirían TNF-α; sugiriendo en definitiva, que la regulación del patrón de citoquinas antivirales o pro-inflamatorias en los macrófagos dependería del tipo de cepa utilizada. Resulta interesante señalar que a pesar de las diferencias observadas en la citometría de flujo respecto el porcentaje de células que expresaban TLR3 y en la intensidad de su expresión según el tipo de virus utilizado, la expresión relativa del mRNA no parecía modificarse. Estas diferencias resultan interesantes y apuntan a que distintas cepas de campo de genotipo europeo podrían ejercer un efecto regulador de diferente intensidad sobre moléculas inhibitorias de la cascada de señalización de los TLRs. Además esta regulación parece depender de diferentes factores tales como: la cepa vírica, el tiempo de infección y la dosis infectiva inicial. Nuestros resultados pueden ser útiles para abrir y conducir una nueva línea de investigaciones orientadas hacia el área de la inmunidad innata frente al virus del PRRS.<br>Toll-like receptors (TLRs), particularly those found within intracellular vesicles of endosomal origin (TLR3, TLR7 and TLR9), are involved in the innate antiviral responses. Binding of those receptors to their respective ligands leads to the activation of intracellular cascades resulting in the release of pro-inflammatory cytokines (TNF-α) and antiviral (type I) interferons. The knowledge on the distribution of those receptors in porcine organs, tissues and cells and its regulation in physiological states or in infection is scarce.
In the first study of the present thesis the distribution of endosomal TLRs in lung and primary and secondary lymphoid tissues of healthy pigs of different ages was assessed. Labeling of TLR9 was performed using a commercial antibody with specific reactivity for the porcine TLR9. For TLR3 and TLR7 the antibodies used in the study were directed to human molecules but they were supposed to cross-react with the porcine counterpart molecules. The results allowed the assessment of the distribution of TLR9 in the different tissues examined, but not that of TLR3 and TLR7 since the use of antibodies directed against the latter two receptors did not yield satisfactory results. Thus, labeling obtained with the anti-TLR3 antibody was highly variable depending on the tissue examined, that is, in some organs such as lungs, tonsils or lymph nodes labeling was apparently specific but in others, as in the liver, the se of that antibody resulted in an intense non-specific background. By contrast, TLR9 labeling was specific and revealed a constitutive expression of this receptor in cells of the periphery of lymphoid follicles of lymph nodes, tonsils and Peyer's patches (epithelial cells, dendritic cells, macrophages or lymphocytes) a fact suggesting that this receptor can probably play an important role in activating the immune system of pigs of 3 week-old piglets.
The second study of this thesis was aimed to determine the variation of the expression of TLR3, TLR7 and TLR9 over time in a population of antigen-presenting cells. Porcine alveolar macrophages (PAMs) were used for this purpose. The results of the kinetics of expression as assessed by flow cytometry showed that PAMs had a high basal expression of TLR3 and TLR9 but not of TLR7. A possible explanation for this basal labeling could point to the unavoidable manipulation of PAMs needed for their collection. Moreover, it is difficult to know precisely the environmental conditions in which PAMs were in the lungs before being collected (concentration of interleukins, chemokines, presence of other molecules, etc.).
Since PAM donors were healthy, showed no lung lesions and were demonstrated to be free of common viral pathogens of pigs (porcine circovirus type 2, influenza A and PRRS virus among others) the cause of this elevated expression remains unclear. As for TLR7, basal expression in the PAMs used was low or nil.
The third study of the present thesis aimed to a model of infection with an RNA virus that might influence the regulation of these TLRs and also could add new knowledge regarding the pathogenesis of the infection. In the field of infectious diseases of swine, one of most interesting models of RNA virus infections is PRRS virus for which immunopathogenesis is largely understood. The results of this study showed that two strains of the same genotype of PRRS virus resulted in a different regulation of TLR3 and in a different pattern of pro-inflammatory cytokines. Specifically, in flow cytometry experiments, strain 3262, induced the expression of TLR3 in PAMs, particularly at high multiplicities of infection (m.o.i = 1) and triggered the production of TNF-α+ whereas strain 3267 or the vaccine strain DV resulted in lower TLR3 expression and did not induce TNF-α, suggesting ultimately that the regulation of the antiviral or pro-inflammatory cytokine patterns in macrophages depends on the strain used. Interestingly, despite the differences observed in flow cytometry for TLR3, the relative mRNA expression did not apparently change under different circumstances. This was an interesting observation that suggests that different field strains of genotype I PRRSV might exert a regulatory effect of different intensity on inhibitory molecules of the signaling cascade of TLRs. Furthermore, this regulation seems to depend on various factors such as the viral strain, the time of infection and the multiplicity of infection. Our results may be useful as a basis for further studies in the area of innate immunity against PRRS virus.
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Liljeroos, M. (Mari). "Toll-like receptor 2 (TLR2) and TLR4 signaling in the innate response against bacterial components." Doctoral thesis, University of Oulu, 2008. http://urn.fi/urn:isbn:9789514288111.
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Abstract Toll-like receptors (TLRs) are transmembrane proteins involved in the recognition of specific microbial structures and thus the activation of signaling cascades of innate immunity. Regulation of the innate immune response is a complex biological process involving the combined synergistic and antagonistic effects of distinct signaling mediators. Although TLR signaling has been widely studied in recent years, there remain many unexplored unique features of each TLR signaling pathway. The present study evaluated the activation and regulation of TLR4 and TLR2 signaling with the aim of better understanding the molecular mechanisms that control these inflammatory signaling pathways. In the present study, the signal transduction mechanisms of TLR4 and TLR2 in response to Escherichia coli LPS and Staphylococcus aureus LTA were evaluated in mouse macrophages. The inductions, interactions, and activations of the signaling molecules and mediators in the TLR pathways were studied by using several molecular biology and protein chemistry methods. In addition, the role of TLR4 and TLR2 in the regulation of the hepatic inflammatory reaction during endotoxemia was studied. Mouse macrophages were found to induce central proinflammatory mediators in response to LPS and LTA stimulation. Specific roles for PI 3-kinase and Btk were described. These kinases were found to be activated by LPS and LTA; moreover, PI 3-kinase and Btk were found to form specific interactions with TLRs and their intracellular signaling mediators. In addition, a unique IRF2 signaling pathway for LTA-induced TLR2 was found, resulting in the activation of signal transducers and activators of transcription (Stats) and IFN-α secretion. The secreted IFN-α was shown to regulate the LTA-induced inflammatory responses, thereby combining the LTA-induced IRF proteins into NF-κB pathway. The present study provides insight into the signal transduction mechanisms of TLRs. The understanding of these molecular mechanisms that control the activation of TLR signaling cascades will in the future help to predict predisposition and outcome in infectious diseases, and to control the course of disease at an earlier stage<br>Tiivistelmä Toll:n kaltaiset reseptorit (TLR) ovat solukalvon proteiineja, jotka tunnistavat taudinaiheuttajien eli patogeenien spesifisiä rakenteita johtaen elimistön puolustusjärjestelmän, immuniteetin, aktivoitumiseen. Immuniteetin säätely on monimutkainen biologinen prosessi, joka tapahtuu kudosten, solujen ja erilaisten synnynnäiseen immuniteettiin liittyvien molekyylien vuorovaikutuksina. Tulehdusvasteen säätelyssä tasapaino positiivisten ja negatiivisten säätelysignaalien välillä on erittäin tärkeää, jotta autoimmuunisairauksien, akuuttien tai kroonisten tulehdusten sekä infektiosairauksien synty voitaisiin välttää. Tämän tutkimuksen tavoitteena oli saada lisätietoa TLR2 ja TLR4 proteiinien säätelemistä signaalireiteistä, niiden vasteista tiettyjä patogeenirakenteita vastaan ja ymmärtää paremmin synnynnäisen immuniteetin puolustusmekanismeja. Patogeenirakenteiden aiheuttamaa tulehdusvastetta tutkittiin pääosin soluviljelymallissa. Lisäksi selvitettiin immuunivasteen luonnetta fysiologisessa kokonaisuudessa ja sen korrelaatiota solutasolla nähtyihin vasteisiin käyttäen in vivo hiirimallia. Tutkimus tehtiin käyttäen useita molekyylibiologian ja proteiinikemian menetelmiä proteiini- ja mRNA-ekspressioiden sekä proteiini-interaktioiden tutkimiseen ja erilaisten aktiivisuuksien määrityksiin. Tulehdusvastetta tutkittiin etenkin sytokiinivastetta määrittämällä ja signaaliketjujen toimintaa analysoitiin estämällä spesifisesti niiden toimintaa. Tarkoituksena oli selvittää, mitkä tekijät ovat välttämättömiä kyseisten tulehdusta aiheuttavien bakteerien tunnistuksessa ja puolustusreaktiossa niitä vastaan. Tutkimuksessa havaittiin kahden kinaasin, PI 3-kinaasin ja Brutonin tyrosiinikinaasin, liittyvän oleellisesti TLR signaalireitteihin. Nämä TLR:ien stimulaation seurauksena aktivoituneet kinaasit muodostivat spesifisiä sidoksia TLR:ien ja niiden signaaliketjuihin liittyvien solunsisäisten signaalivälittäjien kanssa. Lisäksi TLR2 signaalireitillä havaittiin aktivoituvan tekijöitä, jotka johtivat interferoni-α välitteiseen tulehdusvasteen säätelyyn. TLR signaalireittien selvittäminen auttaa ymmärtämään tulehdussairauksien patofysiologiaa ja voi siten tulevaisuudessa johtaa parempien hoitomenetelmien kehittämiseen
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Rao, Bhalchandra Shantikumar. "Diverse Biological Functions For 3'-5' Nucleotide Addition Reactions: tRNA Repair to tRNAHis Identity." The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1397425994.
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Eriksson, Tobias, and Erik Ragnarsson. "Uttagsbeskattning : Hur man effektivast tar ut pengar ur fåmansaktiebolag." Thesis, Karlstad University, Faculty of Economic Sciences, Communication and IT, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:kau:diva-1738.
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<p>Uppsatsens syfte har varit att försöka finna ”det effektivaste sättet att ta ut pengar från ett få-mansföretag”. För att kunna göra detta har vi granskat lagtexten i 56-57 kap IL, skatteverkets informationsbroschyrer, tagit fram ett antal beräkningsexempel och genomfört intervjuer med respondenter från de fem största revisionsbyråerna. När en företagare står inför valet hur den-ne ska ta ut pengar från sitt företag kan denne välja på att ta ut lön, göra pensionsavsättningar, ta ut utdelning eller låna in pengar till företaget med ränta.</p><p>Det mest effektiva sättet att ta ut pengar på varierar från företag till företag, men i de flesta fallen är det bäst att först och främst göra uttag genom löneutbetalningar till delägarna. An-ledningen till att delägarna först och främst ska ta ut lön är att den tillsammans med arbetsgi-varavgifterna är avdragsgilla i företaget och att lönen dessutom är pensions-, sjukpennings- och föräldrapenningsgrundande. Löneutbetalningen ska i första hand uppgå till någon av föl-jande gränser: sjukpenningsgrundande inkomst (7,5 prisbasbelopp = 307 500kr), undre skikt-gränsen för statlig inkomstskatt (328 800kr), pensionsgrundande inkomst (8,07 inkomstbasbe-lopp = 387 360kr) eller den inkomst som lönekravet kräver (275 400-688 500kr).</p><p>I andra hand ska företaget göra pensionsavsättningar på ca 7-10 procent av bruttolönerna till de anställda delägarna så de får samma skydd som en vanlig privatanställd tjänsteman. Efter att företaget har betalat ut lön och gjort pensionsavsättningar bör utdelning tas ut upp till gränsbeloppet. Gränsbeloppet bestäms utifrån det högsta av förenklingsregeln och huvudre-geln. Huvudregeln är vanligast förekommande då den ger ett högre gränsbelopp redan då företaget har bruttolöner på 360 000kr, förenklingsregeln ger alltid minsta gränsbelopp på två inkomstbasbelopp (91 800kr). Om utdelningsbara medel i företaget överstiger gränsbeloppet sparas detta belopp till senare år och eventuellt görs extra pensionsinsättningar till delägarna.</p>
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Long, Yicheng. "Characterization of the diverse functions of a family of 3'-5' reverse polymerases." The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1437563497.
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Richard, Benjamin. "Étude des protocoles d'authentification et de dérivation de clefs en 3 parties." Thesis, Rennes 1, 2017. http://www.theses.fr/2017REN1S037/document.
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Dans cette thèse, nous nous sommes intéressés à la sécurité des protocoles d’authentification et de dérivations de clefs dans le cas où une troisième entité intermédiaire, partiellement de confiance, est requise pour différentes raisons pratiques. Dans un premier temps, nous nous sommes focalisés sur le protocole AKA, dont les différentes versions sont utilisées pour établir un canal sécurisé sur la voix radio au sein des réseaux mobiles 3G et 4G. Nous avons d’abord fait état des faiblesses de sécurité et celles concernant le respect de la vie privée des clients mobiles durant l’établissement d’un tel canal sécurisé. Différentes solutions pratiques ont été proposé afin d’assurer les propriétés de sécurité et de vie privée requises par le 3GPP au sein des réseaux 3G, 4G. Dans un second temps, nous avons analysé le protocole Keyless SSL utilisé au sein des CDNs afin d’établir le canal sécurisé requis pour les communications HTTPS. Nous avons proposé un modèle de sécurité calculatoire recoupant l’ensemble des besoins de sécurité et ainsi pointé les différentes faiblesses de sécurité de la proposition Keyless SSL. Par conséquent, une variante basée sur TLS 1.2 a été proposé<br>In this thesis, we study the security of authentication and key exchange protocols when they are proxied through a semi-trusted third party is required. We begin by focusing on the security of the UMTS/LTE AKA protocol, when the different versions of this protocol are used to establish a secure channel across a radio access link in 3G and 4G mobile networks. We first describe some security and privacy weaknesses during the execution of the EPS- and UMTS-AKA protocols. Then, several practical solutions are proposed, guaranteeing better security and privacy for this protocol in both 3G and 4G scenarios. Secondly, we focus on computer networks, more precisely on the use of the Keyless SSL in proxying over HTTPS. A security model including the different various, specific security requirements from the web delivery context has been established. We also identify and discuss various weaknesses in the structure of Keyless SSL. Finally, we propose an improvement of Keyless SSL over TLS 1.2, and describe how Keyless SSL could work securely for the new TLS 1.3 protocol version
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Elco, Christopher. "REGULATION OF dsRNA-INDUCED TRANSCRIPTION BY NFêB AND IRF-3 THROUGH TLR3 AND RIG-I." Case Western Reserve University School of Graduate Studies / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=case1182005526.
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Garcia-Cattaneo, Alejandra. "Régulation du transport, de la maturation et de la signalisation du TLR3." Paris 7, 2001. http://www.theses.fr/2011PA077075.
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TLR3 est un récepteur Toll-like (TLR) endosomal qui active les réponses immunes contre diverses infections virales en se liant à des ARN double brin, produits lors du cycle de réplication de la plupart des virus. TLR3 est abondamment exprimé et peut à la fois activer l' immunité innée et adaptative. Or, le trafic intracellulaire et la maturation du TLR3 sont peu connus. Cette thèse montre que le TLR3 endogène existe sous deux formes à l'état basal: la forme longue (130 kDa) et la courte (70 kDa). L'expression du TLR3 est induite par son ligand: les molécules néosynthétisées transitent par l'appareil de Colgi vers les endosomes où elles sont vite clivées par des cathepsines. Un criblage des cathepsines humaines par ARN d'interférence a montré que les Cathepsines B et H sont responsables de la maturation du TLR3. Le clivage se produit entre les acides aminés 252 et 346. La suppression de 345 acides aminés du N-Terminal produit la forme courte du TLR3 qui est fonctionnel pour la signalisation. Ces données indiquent que la maturation protéolytique du TLR3 est essentielle pour sa fonction, et suggèrent un nouveau mécanisme de régulation de la signalisation des TLR<br>TLR3 is an endosomal Toll-like receptor (TLR) that mediates immune responses against viral infections upon activation by its ligand double stranded RNA, a replication intermediate of most viruses. TLR3 is expressed widely in the body and activates both the innate and adaptive immune Systems. However, little is known about how TLR3 intracellular trafficking and maturation are regulated. Here we show that newly synthesized endogenous TLR3 is transported through the ER and Colgi apparatus to endosomes, where it is rapidly cleaved. TLR3 protein expression is up-regulated by its own ligand leading to the accumulation of its cleaved form. Furthermore, TLR3 signaling and cleavage are sensitive to a cathepsin inhibitor. Screening of the human cathepsin family by RNA interference identified cathepsins B and H as key mediators of TLR3 processing. Cleavage occurs between aa 252 and 346, and results in a functional receptor that signals upon activation. A truncated form of TLR3 lacking the N-terminal 345 amino acids does also signal from acidic compartments in response to ligand activation. Taken together our data indicate that TLR3 proteolytic processing is essential for its function and suggests a mechanism of tight control of TLR3 signaling and thus inflammation
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Heleno, Evandro Fernandes. "Avaliação de câmaras reverberantes através do método numérico TLM." Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/3/3143/tde-01122006-121507/.
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O presente trabalho tem por objetivo avaliar o comportamento dos campos eletromagnéticos no interior de câmaras reverberantes de modos misturados através do método numérico TLM (Transmission Line Matrix). Inicialmente, apresenta-se uma descrição dos diversos tipos de câmaras aplicáveis na avaliação de desempenho de compatibilidade eletromagnética de equipamentos e sistemas elétricos, destacando-se suas principais características físicas e geométricas, com ênfase nas câmaras reverberantes. Os aspectos teóricos relacionados à descrição do método TLM são detalhados e sua aplicação na avaliação do ambiente eletromagnético das câmaras é então abordada. Diversos resultados são apresentados, considerando-se configurações pré-definidas de câmaras reverberantes, ressaltando-se a definição e cálculo de índices de mérito, bem como os principais aspectos relacionados à representação e definição de critérios adotados nas simulações destas.<br>The aim of this report is the evaluation of the behavior of electromagnetic fields inside reverberation chambers by means of Transmission Line Modeling (TLM). Initially, it is presented a description of several kinds of chambers applicable for electromagnetic compatibility tests followed by a more detailed description regarding reverberation chambers. Theoretical aspects of TLM method and its application for electromagnetic fields solution are covered. Some results are presented, considering pre-defined reverberation chambers configurations, highlighting some merit indicators and the main aspects adopted on its simulation.
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Katsura, Yoshichika. "mDia1/3-dependent actin polymerization spatiotemporally controls LAT phosphorylation by Zap70 at the immune synapse." Doctoral thesis, Kyoto University, 2021. http://hdl.handle.net/2433/263571.
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Meijer, Lisa. "Signalling and activation of TLR4 by Gram-negative bacteria in epithelial cells /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-560-3/.
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Elco, Christopher. "Regulation of dsRNA-induced transcription by NFêB and IRF-3 through TLR3 and RIG-1." Connect to text online, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=case1182005526.
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Menager, Pauline. "Role of Toll-like receptor 3 (TLR3) during infection of neuronal cells with rabies virus." Paris 6, 2009. http://www.theses.fr/2009PA066198.
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Toll-like récepteur 3 (TLR3) est un récepteur de l’immunité innée détectant les ARN double brins et pouvant induire une réponse antivirale. TLR3 est fortement exprimé par les neurones humains. Cette étude concerne la localisation et le rôle de TLR3 dans les cellules neuronales lors de l'infection par un virus neurotrope, le virus de la rage (RABV). Nous avons montré que RABV induit une réponse immune indépendante de TLR3 mais qu’il joue un rôle prépondérant dans l’infection rabique : in vivo, le cerveau des souris invalidées pour TLR3 est moins infecté par le virus de la rage que le cerveau des souris sauvages ; les souris déficientes pour TLR3 survivent mieux et présentent des signes cliniques moins sévères. De plus, l’infection induit une relocalisation partielle des molécules TLR3 –associées constitutivement au compartiment endosomal dans les cellules neuronales- dans des inclusions correspondant aux corps de Negri. Ces derniers sont organisés avec en leur centre un agrégat de molécules de TLR3 enchâssées dans une gangue de NC. Ils présentent certaines caractéristiques des aggrésomes et rappellent les structures utilisées par certains virus qui détournent ce type de sous-compartiments cellulaires pour former des usines virales. L'extinction du gène TLR3 s’accompagne de la disparition des corps de Négri. Cette étude établit que le TLR3 exprimé par les neurones joue un rôle important dans l’infection rabique.
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Venkatesh, Amritha K. "Toll-like Receptor 3 Signaling in Breast Cancer Cells and the Recruitment of Leukocytes to the Tumor Microenvironment." Ohio University / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1339093424.
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Lim, Hye Kyung. "Inherited TLR3 deficiency in human : genetic etiology of herpes simplex encephalitis and life-threatening influenza in childhood." Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066639.
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TLR3 est un récepteur endosomal qui détecte les doubles brins d’ARN produits par HSV-1 lors de sa réplication. La majorité des patients déclarés portants des mutations dans le gène TLR3 ont souffert de l’encéphalite herpétique (EH) sans autre phénotype clinique majeur. Nous avons décrit trois patients présentant des mutations dans le gène TLR3. Ici, nous reportons trois nouvelles formes de défaut AD de TLR3: G743D+R811I et L360P, qui chez deux patients confèrent un défaut AD de TLR3 par dominance négative et haplo-insuffisance; et R867Q, qui confère à un patient un défaut partial AR de TLR3. Les fibroblastes des patients présentent une diminution des réponses médiées par TLR3 et sont plus susceptibles à l’infection par le HSV-1. Le défaut de TLR3 est donc présent chez six (5%) patients sur les 120 EH patients étudiés. De plus, de façon surprenante, nous avons identifé deux mutations dans le gène TLR3 chez deux patients présentant des pneumonies sévères dues au virus de l’influenza A (IAV). Deux patients sont hétérozygotes pour les mutations P554S et P680L dans le gène TLR3. Il a été reporté que P554S est délétère et exerte un effet dominant-négatif chez les patients d’EH. P680L est aussi délétère et cause un défaut AD de TLR3 par haplo-insuffisance. Les fibroblastes hétérozygotes pour la mutation P680L ainsi que les cellules épitheliales pulmonaires dérivées de iPSCs présentent une susceptibilité accrue à IAV. Ces résultats suggèrent que le défaut de TLR3 ne cause pas seulement l’EH mais aussi des pneumonies IAV sévères via une diminution des réponses immunitaires dépendantes de TLR3 et médiées par IFN intrinsèques au système nerveux central et aux poumons<br>TLR3 is an endosomal receptor for dsRNA, an intermediate of viral replication. Most of the reported human TLR3 deficiency related to life-threatening HSV-1 encephalitis (HSE), in otherwise healthy children. To date, we have described 3 patients with TLR3 deficiency and 7 patients with TLR3 pathway gene deficiency. We herein report the three novel forms of TLR3 deficiency: G743D+R811I and L360P in two patients underlie AD TLR3 deficiency due to dominant negative (DN) and haploinsufficiency, respectively, and R867Q in one patient leads to a partial AR TLR3 deficiency. The patients’ fibroblasts display impaired TLR3 responses and enhanced HSV-1 susceptibility. TLR3 deficiency is therefore a relatively common in childhood HSE, as it is found in six (5%) of the 120 patients studied. In addition, we surprisingly found two TLR3 mutations in two patients with influenza A virus (IAV) pneumonitis. The pathogenesis of isolated severe influenza is largely unknown, until we recently reported a child with AR IRF7 deficiency. Two patients are each heterozygous for P554S and P680L in TLR3. P554S is previously found to be deleterious and DN in HSE patients. P680L is also deleterious and causes AD TLR3 deficiency by haploinsufficiency. We show that P680L heterozygous fibroblasts fail to produce IFN-β and -λ upon poly(I:C) and IAV infection. Furthermore, both P680L heterozygous and AR TLR3-deficient fibroblasts and iPSCs-derived lung epithelium display enhanced susceptibility to IAV, like IRF7-deficient cells. These findings suggest that TLR3 deficiency underlies not only HSE but also severe influenza due to impaired TLR3-dependent, IFN-mediated, CNS or lung-intrinsic antiviral immunity
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Santos, Cristiane Nascimento. "Estudo de vidros metafosfatos do sistema KPO3 Al(PO3)3 e sua aplicação em dosimetria termoluminescente." Universidade de São Paulo, 2003. http://www.teses.usp.br/teses/disponiveis/76/76132/tde-09122013-110749/.
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Vidros com composição de aluminofosfato vêm sendo estudados por apresentarem elevada durabilidade química. O objetivo do presente trabalho foi estudar as propriedades térmicas e estruturais do sistema vítreo xKPO3 - (100-x)Al(PO3)3, para x = 10, 30 e 50 (% em mol), a fim de determinarmos uma composição que apresentasse uma boa resposta termoluminescente (TL) quando dopada com íons de manganês. As matrizes vítreas não dopadas apresentaram uma boa estabilidade vítrea frente a devitrificação. As fases cristalizadas no sistema foram determinadas por difração de raios X e espectroscopia micro-Raman como KAIP2O7 e AI(PO3)3. A composição KAI(PO3)4 (x = 50 %) apresentou elevada durabilidade química e o menor ponto de fusão, o que facilitou o processo de preparação. Essa composição foi então utilizada para as dopagens com íons de manganês. A composição com 1,0 % em mol de MnO2 apresentou a melhor resposta TL. As propriedades dosimétricas estudadas mostraram que o vidro possui uma resposta linear para raios X no intervalo de dose de 2 mGy a 80 Gy, podendo então ser utilizado em dosimetria clínica e pessoal<br>Aluminophosphate glasses have been studied because of their good chemical resistance. The main purpose of this work was to investigate the structural and thermal properties of glasses in the system xKPO3 - (100-x)AI(PO3)3, with x = 10, 30 e 50 (mol %). The goal was to determine a composition which provided a good thermoluminescence response (TL) when doped with manganese ions. The undoped vitreous matrixes showed a good thermal stability against devitrification. The crystalline phases were identified by X ray diffraction and micro-Raman spectroscopy as KAIP2O7 and Al(PO3)3. The composition KAI(PO3)4 (x = 50 %) showed high chemical resistance and lower melting point. This composition was used for doping with manganese ions. The composition of 1,0 mol % of MnO2 showed the best TL response. The dosimetric properties showed that this glass has a linear response for X-rays in the dose interval of 2 mGy to 80 Gy, and it is a promising material for application as a TLD dosimeter
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Flórez, Martha Johanna Sepúlveda. "Estimativa de desempenho de uma NoC a partir de seu modelo em SYSTEMC-TLM." Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/3/3140/tde-14122006-152854/.
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The wide variety of interconnection structures presently nowadays for SoC (Systemon- Chip), bus and networks-on-Chip NoCs, each of them with a wide set of setup parameters, provides a huge amount of design alternatives. Although the interconnection structure is a key SoC component, there are few design tools in order to set the appropriate configuration parameters for a given application. An efficient SoC project may comply an exploration stage among the possible solutions for the communication structure, during the first steps of the design process. The absence of appropriate tools for that exploration makes critical the designer?s judgment. The present study aims to enhance the communication SoC structure design area, when a NoC is used. This work proposes a methodology that allows the establishment of the NoC communication parameters using a high level model (SystemC TLM timed). Our approach analyzes and evaluates the NoC performance under a wide variety of traffic conditions. The experimental stage was conducted employing a model of a net represented by a SystemC TLM timed (Hermes_Temp). Parametric and pseudo-random generators control the network traffic. The analysis was carried on with a tool designed for these purpose, which generates a group of performance metrics. The results allow to elucidate the global and inner network behavior. The performance values are useful for the heterogeneous and homogeneous NoC design projects, improving the performance evaluation studies scope.<br>The wide variety of interconnection structures presently nowadays for SoC (Systemon- Chip), bus and networks-on-Chip NoCs, each of them with a wide set of setup parameters, provides a huge amount of design alternatives. Although the interconnection structure is a key SoC component, there are few design tools in order to set the appropriate configuration parameters for a given application. An efficient SoC project may comply an exploration stage among the possible solutions for the communication structure, during the first steps of the design process. The absence of appropriate tools for that exploration makes critical the designer?s judgment. The present study aims to enhance the communication SoC structure design area, when a NoC is used. This work proposes a methodology that allows the establishment of the NoC communication parameters using a high level model (SystemC TLM timed). Our approach analyzes and evaluates the NoC performance under a wide variety of traffic conditions. The experimental stage was conducted employing a model of a net represented by a SystemC TLM timed (Hermes_Temp). Parametric and pseudo-random generators control the network traffic. The analysis was carried on with a tool designed for these purpose, which generates a group of performance metrics. The results allow to elucidate the global and inner network behavior. The performance values are useful for the heterogeneous and homogeneous NoC design projects, improving the performance evaluation studies scope.
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Griggs, Caitlin Elizabeth. "Generation of myeloid-derived lymphatic endothelial cell progenitors (M-LECPs) by TLR4-mediated inflammation and de novo VEGFR-3 signaling in breast cancer." OpenSIUC, 2016. https://opensiuc.lib.siu.edu/theses/1902.
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Breast cancer is the second leading cause of cancer-related death in women in the United States. Complications that lead to mortality of cancer patients are associated with tumor metastasis. Specifically, lymphatic metastasis in breast cancer patients strongly correlates with poor patient survival and this process is facilitated by the formation of new tumor lymphatic vessels termed lymphangiogenesis. Previously, our lab reported that lymphangiogenesis was promoted by a distinct subset of bone marrow (BM)-derived myeloid cells that co-express lymphatic-specific markers designated as myeloid-derived endothelial cell progenitors (M-LECPs). Furthermore, our lab has generated M-LECP in vitro from a mouse macrophage cell line (RAW264.7) by LPS stimulation. Taken together, these data suggest that chronically inflamed sites drive M-LECP differentiation and that these cells can contribute to the formation of new lymphatic vessels and promote lymph node metastasis. Evidence supporting this hypothesis was indicated by high levels of circulating M-LECP in peripheral blood of breast cancer patients but undetectable levels in healthy donors, cancer-free donors. Additionally, the generation of M-LECP was prompted through TLR4-signaling pathway, and de novo expression of VEGFR-3 and VEGF-C. This co-expression produces an autocrine loop essential for pro-lymphatic reprogramming in both primary human monocytes and the immature monocytic cell line, THP-1. Taken together, these data indicate the major regulatory role of TLR4 in inflammation-driven lymphangiogenesis involves the recruitment and differentiation of M-LECP, a process that may promote lymphatic metastasis.
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El-Azzem, Mohamed Hassan Abd. "Using 3-D TLM method for the simulation of linear and nonlinear microstrip structures and frequency selective surfaces." Thesis, University of Kent, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.319233.
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Szekely, Thomas. "Synthèse et évaluation d’un candidat vaccin à 3 composantes (Agoniste TLR7-glycopeptoïde-OVA 323-339) dans le cadre d’une application en immunothérapie anti-tumorale." Thesis, Clermont-Ferrand 2, 2014. http://www.theses.fr/2014CLF22476/document.
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Les antigènes saccharidiques associés aux tumeurs (TACAs) sont considérés comme des marqueurs de cellules tumorales. Le développement de candidats vaccins synthétiques capables d'induire des réponses immunitaires robustes dirigées contre ces TACAs est un vaste champ d'investigation depuis de nombreuses années. Dans cette optique, mon travail s'est principalement focalisé sur la conception d'un candidat vaccin à trois composantes qui peut activer spécifiquement les cellules dendritiques, les cellules TH et les cellules B. La première partie de la thèse consistait à effectuer une étude approfondie des méthodes submonomère et monomère en solution pour accéder à une plateforme β-tripeptoïde O-α-GalNAc (épitope des cellules B), servant de mime du cluster trimérique de l'antigène Tn (GalNAc-α-O-Ser/Thr). Pour renforcer la stimulation du système immunitaire, un agoniste du récepteur Toll 7 (TLR7) préalablement synthétisé (exprimé par les cellules dendritiques) a été ensuite couplé à cette plateforme par l'intermédiaire de l'acide amino-caproïque, pris comme espaceur. L'édifice candidat vaccin a ensuite été complété par conjugaison au peptide OVA 323-339 (épitope des cellules TH ) grâce à la réaction de cycloaddition 1,3-dipolaire CuAAC. Enfin, l'aptitude du candidat vaccin à induire une réponse anti-Tn a été évaluée par l'équipe du Pr. C. Leclerc de l'Institut Pasteur de Paris. En parallèle de ces études, nous avons mis au point des conditions de ligation multivalente par couplage thiol-ène (TEC) pour l'obtention de peptoïdes S-glycosylés<br>Tumor-Associated Carbohydrate Antigen (TACAs) are considered as cancer cells markers. The development of synthetic vaccine candidates which are able to induce a robust immune response against these TACAs is a field of great interest since many years. In this context, my work has been focused mainly on the design of a three-component vaccine candidate with the ability to activate specifically dendritic cells, T H cells and B cells. The first part of the thesis consisted in making a deep study on the submonomer and monomer methods for solution-phase synthesis of a β-tripeptoid O-α-GalNAc scaffold (B epitope). Its role is to mimic the Tn (GalNAc-α-O-Ser/Thr) trimeric cluster which is naturally present on tumor cells surface. To strengthen the stimulation of the immune system, a TLR7 agonist (receptor express by dendritic cells) has been, firstly, coupled through an amino-caproic acid spacer. The vaccine candidate has been next completed by conjugation with the OVA 323- 339 peptide (TH epitope) using the Copper-catalized Alkyne-Azide Cycloaddition (CuAAC). Finally, the capacity of this construction to generate anti-Tn response have been evaluated by the groupe of C. Leclerc of Institut Pasteur of Paris. At the same time, we have also developed conditions for multivalent ligations using thiol-ene coupling (TEC) to obtain a β-tripeptoid S-α-GalNAc scaffolds
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Malaplate, Alain. "Radiométrie infrarouge : Développement et validation de méthodes utilisant la bande [3-5um] pour la détermination des paramètres de surface à haute résolution spatiale." Université Louis Pasteur (Strasbourg) (1971-2008), 2001. http://www.theses.fr/2001STR13227.
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Rodrigues, Daniel Brás Rochinha. "Desenvolvimento de sensores baseados em reflectometria no domínio do tempo para análise de combustíveis." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/3/3140/tde-21122016-090032/.
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Este trabalho apresenta um estudo da técnica da Reflectometria no Domínio do Tempo - TDR, para qualificação de álcool combustível. Há grande interesse na qualificação de combustíveis pois a adulteração é uma prática comum no Brasil e tem implicações nocivas no funcionamento do motor, causa maior poluição ambiental e evasão fiscal. O presente estudo foi focado em etanol adulterado com água, utilizando uma sonda comercial e sondas desenvolvidas neste trabalho, tendo sido dividido em três etapas: a primeira etapa consistiu em confirmar a viabilidade da técnica TDR para o tema proposto utilizando o sensor comercial de umidade de solo VG400 da Vegetronix, enquanto que o segundo passo tratou da simulação de sondas dos tipos bifilar, microstrip, coaxial e helicoidal em simulador tridimensional de eletromagnetismo, visando a escolha e otimização do tipo de sonda a ser usada para a qualificação do combustível. O terceiro e último passo consistiu na fabricação das sondas simuladas escolhidas e na realização de ensaios utilizando amostras de etanol com variadas proporções de água. Este estudo mostrou que a sonda helicoidal, que é uma proposta original deste trabalho, apresentou maior sensibilidade entre os modelos escolhidos, mostrando uma variação de resposta entre as amostras de etanol e água puros 12,5% maior que a sonda bifilar, que é a segunda sonda mais sensível dentre as estudadas.<br>This work presents a study of the Time-Domain Reflectometry - TDR technique for ethanol fuel qualification. There is a great interest in fuel qualification since adulteration is a common practice, which brings harmful consequences to the vehicle motor functioning, besides causing higher environmental pollution and tax evasion. The present study is focused on the qualification of ethanol adulterated with water, by using a commercial probe and probes developed in this work. It was divided in three steps: the first step has confirmed the viability of the technique for the proposed theme using a commercial sensor Vegetronix VG400 for soil moisture analysis. The second step was the simulation of bifilar, microstrip, coaxial and helical probe geometries using a 3D eletromagnectics software, leading to the optimization of the probe for fuel qualification. The last step was the fabrication of the simulated probes and the test of their performance into alcohol adulterated with various proportions of water. This study showed that the helical probe, an original proposal of this work, presented higher sensibility among the chosen models. Its response variation between pure alcohol and pure water was 12.5% greater than the bifilar probe, which was the second most sensitive sensor among the studied geometries.
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Backlund, Daniel. "”Sitter det en spik i väggen, väljer jag inte skruvdragaren. Jag tar hammaren.” : En studie om hur lärare inom F-3 använder surfplattor och applikationer i matematikundervisningen." Thesis, Mittuniversitetet, Avdelningen för ämnesdidaktik och matematik, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:miun:diva-32723.
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Denna studie handlar om hur lärare i årskurs 1-3 använder surfplattor i matematikundervisningen. Syftet med studien är att ta reda på hur surfplattor används och hur lärarna arbetar med olika applikationer. För att få svar på det har kvalitativa intervjuer skett med tre lärare. Lärarna använde surfplattan i matematikundervisningen som ett komplement till den ordinarie undervisningen. Trots att surfplattorna användes som komplement förekom verktyget på hälften av alla matematiklektioner. Ingen av lärarna använde applikationerna utifrån utgivarens rekommendationer om sådana fanns. Fördelarna med verktyget var att det var motiverande för eleverna och de kunde göra fler repetitioner och nöta uppgifter. Nackdelarna var tekniska problem som slut på batteri eller nätverkskrångel.
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Genc, Murat. "Design And Digital Implementation Of Thyristor Controlled Reactor Control." Master's thesis, METU, 2007. http://etd.lib.metu.edu.tr/upload/3/12609184/index.pdf.
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In this research work, the control system of 16 MVAr, 13.8 kV TCR will be
designed and digitally implemented. A Real-Time Control System (NI
CompactRIOTM Reconfigurable I/O) and a Digital Platform (NI LabVIEWTM Gcode)
are used in the digital implementation of TCR control system. The digital
control system is composed of reactive power calculation, firing angle
determination and triggering pulse generation blocks. The performance of control
system will be tested in the field. The simulation results will also be compared
with test data.
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Assmann, Taís Silveira. "Estudo da associação de polimorfismos no gene receptor do tipo toll 3 (tlr3) e o diabetes mellitus tipo 1." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2013. http://hdl.handle.net/10183/87172.
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Introdução: O diabetes mellitus tipo 1 (DM1) é uma doença autoimune crônica e progressiva caracterizada por descompensações metabólicas frequentemente acompanhadas por desidratação e cetoacidose. Os agentes virais parecem ter um papel importante no desencadeamento da destruição autoimune que leva ao desenvolvimento do DM1. Entre as cepas virais estudadas, a família dos enterovírus foi associada ao surgimento da doença em humanos. Um dos mediadores do dano viral é o RNA fita dupla (RNAfd) gerado durante a replicação e transcrição do RNA e DNA viral. O gene TLR3 codifica um receptor endoplasmático pertencente à família dos Pattern- Recognition Receptors (PRR), o qual reconhece o RNAfd, tendo um importante papel na resposta imune inata desencadeada por infecção viral. A ligação do RNAfd ao TLR3 desencadeia a liberação de citocinas proinflamatórias, como interferons, as quais exibem uma potente ação anti-viral; assim, protegendo as células não infectadas e induzindo apoptose naquelas já contaminadas. Dessa forma, esse estudo teve como objetivo investigar a associação entre polimorfismos no gene TLR3 e o DM1. Métodos: As frequências dos polimorfismos rs5743313, rs11721827, rs3775291, rs13126816 e rs7668666 no gene TLR3 foram analisadas em 476 pacientes com DM1 e em 507 indivíduos não-diabéticos saudáveis. Os haplótipos construídos a partir da combinação dos cinco polimorfismos estudados e suas frequências foram inferidos utilizando o programa Phase 2.1, o qual implementa o método estatístico bayesiano. Resultados: Todos os genótipos estão de acordo com o esperado pelo Equilíbrio de Hardy-Weinberg. Os polimorfismos rs3775291 e rs13126816 foram associados com risco para DM1 em diferentes modelos de herança, com a associação mais forte sendo observada para o modelo aditivo [OR= 2,3 (IC 95% 1,3-4,1) e OR= 2,1 (IC 95% I 1,4-3,2); respectivamente]. Os demais polimorfismos estudados não foram associados ao DM1. Interessantemente, a frequência de DM1 aumentou quanto maior o número de alelos mutados dos cinco polimorfismos estudados presente nos haplótipos (p-trend= 0,002). Além disso, em pacientes com DM1, os alelos mais raros dos polimorfismos rs5743313 e rs11721827 foram associados com menor idade de diagnóstico do DM1 e a um pior controle glicêmico. Conclusão: Os polimorfismos rs3775291 e rs13126816 no gene TLR3 estão associados com risco para o DM1 em indivíduos do Sul do Brasil, enquanto os polimorfismos rs5743313 e rs11721827 estão associados com idade de diagnóstico precoce e a um pior controle glicêmico. O número de alelos de risco nos haplótipos formados pelos cinco polimorfismos estudados no gene TLR3 parece influenciar o risco para DM1, sugerindo que esses polimorfismos interagem na suscetibilidade para a doença.<br>Introduction: Type 1 diabetes mellitus (T1DM) is a chronic, progressive autoimmune disease characterized by metabolic decompensation often leading to dehydration and ketoacidosis. Viral agents seem to have an important role in triggering the autoimmune destruction that leads to the development of T1DM. Among several viral strains investigate so far, the enterovirus family has been consistently associated with the onset of T1DM in humans. One of the mediators of viral damage is the double-stranded RNA (dsRNA) generated during replication and transcription of viral RNA and DNA. The Toll-like receptor 3 (TLR3) gene codes for an endoplasmic receptor of the patternrecognition receptors (PRRs) family that recognizes dsRNA, playing an important role in the innate immune response triggered by viral infection. Binding of dsRNA to the TLR3 triggers the release of proinflammatory cytokines, such as interferons, which exhibit potent antiviral action; thus, protecting uninfected cells and inducing apoptosis of infected ones. Therefore, this study aimed to investigate whether TLR3 polymorphisms were associated with T1DM. Methods: Frequencies of the TLR3 rs5743313, rs11721827, rs3775291, rs13126816 and rs7668666 polymorphisms were analyzed in 476 T1DM patients and in 507 healthy subjects. Haplotypes constructed from the combination of these polymorphisms were inferred using Bayesian statistical method. Results: All genotypes are in agreement with those predicted by the Hardy-Weinberg equilibrium. The rs3775291 and rs13126816 polymorphisms were associated with T1DM in different inheritance models, with the strongest association being observed for the additive model [OR= 2.3 (95% CI 1.3-4.1) and OR= 2.1 (95% CI 1.4-3.2); respectively]. The other three polymorphisms were not significantly associated with T1DM. Interestingly, the prevalence of T1DM was higher as more risk alleles of the five polymorphisms were present (P trend = 0.002). Moreover, in T1DM patients, the minor alleles of the rs5743313 and rs117221827 polymorphisms were associated with an early age at diagnosis and worse glycemic control. Conclusion: The TLR3 rs3775291 and rs13126816 polymorphisms are associated with risk for T1DM in Southern Brazilian subjects, while the rs5743313 and rs11721827 polymorphisms are associated with age at T1DM diagnosis and worst glycemic control. The number of risk alleles of the five TLR3 polymorphisms in the haplotypes seems to influence the risk for T1DM, suggesting that these polymorphisms might interact in the susceptibility for the disease.
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Goldstein, Evan Zachary. "TLR4-activated microglia have divergent effects on oligodendrocyte lineage cells." The Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1468967532.
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Low, Benjamin. "Design of a 3 axis wear testing device to evaluate the effect of slide to roll ratio on ultra high molecular weight polyethylene wear in total knee replacements." Thesis, University of Canterbury. Mechanical Engineering, 2005. http://hdl.handle.net/10092/1105.
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Multidirectional motion occurs in total knee replacements (TKR), is a major factor in ultra high molecular weight polyethylene (UHMWPE) wear and is a requirement for wear tester and simulators. There are three ways the femoral component can move relative to the tibial component; sliding, rolling and gliding and these are defined by the slide to roll ratio. Previous wear tester research has investigated the effects of multidirectional motion and slide to roll ratio, individually but not combined. The project aim was to design a machine that combined multidirectional motion with variable slide to roll ratio. A three station wear testing machine was designed and built featuring flexion extension, variable anterior posterior translation, variable internal external rotation and a 2KN load per station. The TKR was simplified to a cylinder on flat. Lubrication was 25% bovine serum and each station had its own recirculation system. A million cycle validation test was successfully carried out on non-irradiated UHMWPE samples using a slide to roll ratio of 1 : 0.5 and the mean wear rate was 14.7mg/10^6 cycles. Polished areas and scratches from 3rd body abrasion were observed. Magnification revealed a fine ripple pattern with a 1-2 micron periodicity. Ripples were randomly oriented, perpendicular to the primary direction of motion and a small number were running parallel to the primary direction of motion, indicative of rolling motion. The results from the validation study show that the knee joint wear tester is capable of producing wear rates and wear mechanisms similar to those observed in other wear testers and knee joint simulators and has met the aim of the project.
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Conforti, Rosa. "Traitement anti tumoral par ciblage de TLR3 et découplage des effets opposés des chimiokines pour améliorer l’efficacité des agonistes de TLR3." Thesis, Paris 11, 2011. http://www.theses.fr/2011PA11T067.
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Le rationnel pour l’utilisation des agonistes des Toll-Like Récepteurs (TLR) dans le traitement du cancer repose sur leurs effets bénéfiques au niveau des cellules du système immunitaire permettant une stimulation de la réponse immunitaire innée et adaptative. Cependant, certains types de cellules tumorales expriment les TLRs qui, une fois activés, peuvent déclencher des effets “délétères” comme la tumorigénèse.Pour mieux disséquer les effets biologiques directs et indirects d’un agoniste de TLR3, l’acide polyadenylique-polyurydilique (poly(A:U)), nous avons utilisé deux modèles tumoraux murins exprimant TLR3 et ne répondant pas à la chimiothérapie, mais capables de produire des grandes quantités de CCL5 et CXCL10 en réponse au poly(A:U) et à l’IFN de type I. In vivo, la combinaison chimiothérapie – poly(A:U) n’a permis d’obtenir qu’une faible activité anti tumorale sauf lorsqu’une vaccination contre les antigènes tumoraux est inclue dans le protocole de traitement et le récepteur CCR5 est bloqué (souris Ccr5-/- ou souris sauvages traitées avec MetRANTES). L’efficacité anti tumorale du traitement combiné est associée à l’induction de cellules T CD8+CXCR3+IFNγ+ et est perdue chez les souris nu/nu, Trif-/- et Cxcr3-/-. La source du ligand de CCR5 est constituée par les cellules tumorales dont la voie TLR3 est activée. L’efficacité du traitement combiné sur ces cellules a été améliorée en inhibant la production de CCL5 à l’aide d’un shARN spécifique pour CCL5. Ces résultats soutiennent la notion que le poly(A:U) peut directement agir sur l’épithélium tumoral pour promouvoir la libération de CXCL10 qui a un effet bénéfique (recrutement des LTCs), mais aussi la sécrétion de CCL5 qui a un rôle délétère (action sur des immunosuppresseurs au niveau de l’hôte). Le découplage des effets opposés des chimiokines et la vaccination anti tumorale préalable peuvent permettre aux LTCs dépendant des ligands de CXCR3 d’infirmer l’action d’immunosuppression CCR5 dépendante et devraient être intégrés dans les essais cliniques à venir utilisant les agonistes de TLR3<br>The rationale for the use of Toll –Like Receptor (TLR) agonists in cancer therapy relies upon their “beneficial” effects on immune cells leading to enhanced innate and adaptive immune responses. However, a variety of cancer epithelia express TLRs which, upon triggering, may mediate “deleterious” effects such as tumorigenesis. To further dissect the direct versus indirect biological effects of the TLR3 agonist polyadenylic-polyuridylic acid (poly(A:U)), we took advantage of two murine tumor models expressing TLR3 that failed to respond to chemotherapy but did produce large amounts of CCL5 and CXCL10 in response to the poly(A:U) and type I IFN. In vivo, the combination of chemotherapy and poly(A:U) mediated low tumoricidal activity unless a vaccination against tumor antigens was included in the regimen and the CCR5 receptor was blocked (CCR5 loss-of-function mice or WT animals treated with MetRANTES). The antitumor efficacy of the combination therapy was associated with the elicitation of CD8+CXCR3+IFN+ T cells and abrogated in nu/nu, Trif-/- and Cxcr3-/- mice. The source of CCR5L is the TLR3-activated tumor cells in that stable inhibition of the chemokine production by specific shRNA CCL5 ameliorated the efficacy of the combination therapy. These results support the notion that poly(A:U) can directly act on tumor epithelia to promote the release of beneficial CXCL10 for the recruitment of intratumoral CTLs but also the release of deleterious CCL5 acting on host immunosuppressors. Uncoupling chemokine release and prior vaccination may enable the CXCR3L-dependent CTLs to overrule the CCR5-dependent suppression and may be integrated in future trials using TLR3 agonists
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Gaiarsa, Claudio Martins. "Financiamento da infraestrutura urbana com base na valorização imobiliária: um estudo comparado de mecanismos de quatro países." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/3/3146/tde-17082010-112846/.
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O trabalho é uma análise comparada de cinco mecanismos de política urbana praticados em quatro países diferentes: EUA, França, Colômbia e Brasil. Esses mecanismos têm como característica principal o financiamento de melhorias na infraestrutura urbana, com recursos gerados por parte da valorização imobiliária, e apropriados por meio desses mecanismos. São eles: Transfer of Development Rights (TDR) nos EUA, Leyes de la Plusvalia na Colômbia, Zones d´Aménagement Concertée (ZAC) na França, CEPACs e Outorga Onerosa em São Paulo, Brasil. O objetivo do trabalho é identificar princípios e regras comuns entre eles, e analisar suas diferenças mais significativas, e as razões para isso. Os mecanismos são apresentados individualmente e, em seguida, comparados quanto a suas características principais: histórico e objetivos de sua implantação, estrutura legal, método de formação do preço ou valor a ser pago, momento do pagamento e eficácia na geração de benefícios urbanísticos.<br>This work is a comparative analysis of five different mechanisms or urban policy as they are practiced in four different countries: the USA, France, Colombia and Brazil. The main characteristic these mechanisms have in common is the financing of improvements in the urban infrastructure with resources generated by the increase in value or real estate, and the corresponding capture part of that increase in value. The mechanisms analyzed are: Transfer of Development Rights (TDR) in the USA, Leyes de la Plusvalia, in Colombia, Zones d\'Aménagement Concertée (ZAC) in France, Certificados de Potencial Adicional de Construção (CEPACs) and Outorga Onerosa do Direito de Construir, São Paulo, Brazil. The objective of this work is to identify the principles and rules that they share, analyze the most relevant differences and the reasons for those differences. Each of the mechanisms is presented individually, followed by a comparison of their main characteristics: its objective and history, legal structure, price or value formation, moment of payment, and its effectiveness in generating urban improvement.
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Jonsson, Elizabeth, and Ellen Hamrelius. ""HUR TAR MAN SIG AN EN TEXT?” : En kvalitativ studie av åtta F–3-lärares beskrivningar av sin undervisning i läsförståelse." Thesis, Mälardalens högskola, Akademin för utbildning, kultur och kommunikation, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:mdh:diva-42662.
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Syftet med denna studie är att undersöka hur åtta lärare i årskurserna F–3 beskriver att de arbetar med läsförståelse för att eleverna ska nå målen i svenska och för att förbereda eleverna för nationella proven i årskurs 3. För att studera detta användes semistrukturerade intervjuer som metod. Analysmetoden som användes var innehållsanalys. Resultatet visar att lärarna använder olika metoder för att utveckla elevers läsförståelse. Undervisningen varierar från användning av färdigt material till egenanpassad undervisning. Ingen lärare nämner vetenskaplig forskning kopplat till sin undervisning och det finns en viss omedvetenhet i förhållandet vad de arbetar med, hur de arbetar och varför de arbetar som de gör. Gemensamt är att alla lärare modellerar, arbetar med läsförståelse i flera ämnen, förbereder inför nationella proven och betonar vikten av samarbete.
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Friboulet, Luc. "Contribution de la protéine c-IAP2 à l'oncologenèse des carcinomes nasopharryngés et d'autres tumeurs malignes : Modulation des effets biologiques de TLR3." Paris 11, 2009. http://www.theses.fr/2009PA11T010.
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Wilkie, Tasha Wilkie. "Tumor Commensal Microbiota Activates an S100A7-TLR4-STAT-3 Signaling to Induce Chronic Inflammation and Consequent Growth and Metastasis of Breast Cancer." The Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu1524214470077411.
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Benner, Sarah E. "Characterizing the Role Toll Like Receptor 3 (TLR3) Plays in Viral-Mediated Type 1 Diabetes in Female Non-Obese Diabetic (NOD) Mice." Ohio University / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1547131981099488.
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Kroenke, Samantha E. "A Study of the Herald-Phillipstown Fault in the Wabash Valley using Drillhole and 3-D Seismic Reflection Data." OpenSIUC, 2011. https://opensiuc.lib.siu.edu/theses/676.
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In June 2009, a 2.2 square mile 3-D high resolution seismic reflection survey was shot in southeastern Illinois in the Phillipstown Consolidated oilfield. A well was drilled in the 3-D survey area to tie the seismic to the geological data with a synthetic seismogram from the sonic log. The objectives of the 3-D seismic survey were three-fold: 1.) To image and interpret faulting of the Herald-Phillipstown Fault using drillhole-based geological and seismic cross-sections and structural contour maps created from the drillhole data and seismic reflection data, 2.) To test the effectiveness of imaging the faults by selected seismic attributes, and 3.) To compare spectral decomposition amplitude maps with an isochron map and an isopach map of a selected geologic interval (VTG interval). Drillhole and seismic reflection data show that various formation offsets increase near the main Herald-Phillipstown fault, and that the fault and its large offset subsidiary faults penetrate the Precambrian crystalline basement. A broad, northeast-trending 10,000 feet wide graben is consistently observed in the drillhole data. Both shallow and deep formations in the geological cross-sections reveal small horst and graben features within the broad graben created possibly in response to fault reactivations. The HPF faults have been interpreted as originally Precambrian age high-angle, normal faults reactivated with various amounts and types of offset. Evidence for strike-slip movement is also clear on several faults. Changes in the seismic attribute values in the selected interval and along various time slices throughout the whole dataset correlate with the Herald-Phillipstown faults. Overall, seismic attributes could provide a means of mapping large offset faults in areas with limited or absent drillhole data. Results of the spectral decomposition suggest that if the interval velocity is known for a particular formation or interval, high-resolution 3-D seismic reflection surveys could utilize these amplitudes as an alternative seismic interpretation method for estimating formation thicknesses. A VTG isopach map was compared with an isochron map and a spectral decomposition amplitude map. The results reveal that the isochron map strongly correlates with the isopach map as well as the spectral decomposition map. It was also found that thicker areas in the isopach correlated with higher amplitude values in the spectral decomposition amplitude map. Offsets along the faults appear sharper in these amplitudes and isochron maps than in the isopach map, possibly as a result of increased spatial sampling.
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Aracil-Flügel, Frida. "Hur applicerar lärare Total Physical Response i undervisningen för att utveckla den språkliga förmågan i engelska som andraspråk? : En empiriskstudie om användning av TPR- metoden enligt engelsklärare i årskurserna 1–3." Thesis, Högskolan Dalarna, Pedagogiskt arbete, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:du-26539.
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Total Physical Response, TPR 1, är en inlärningsmetod som bygger på att läraren förmedlar instruktioner på engelska genom aktiviteter där rörelser, lekar, sång eller bilder ingår. Eleverna visar gensvar genom att uttrycka förståelse där kroppsspråket används i form av gester, miner och andra rörelser. Tidigare utländsk forskning indikerar positiv effekt vid användning av TPR i engelskundervisningen därav har ett intresse hos mig väckts för TPR som forskningsområde. Syftet med studien är att undersöka tillämpningen av TPR-metoden i engelskundervisning inom årskurser 1–3. Frågeställningarna är: Hur definierar engelsklärare i studien TPR-metoden? På vilket sätt appliceras TPR i undervisningen inom årskurserna 1–3 enligt engelsklärare i studien? I vilken omfattning beskriver studiens engelsklärare användningen av TPR-metoden i undervisningen inom årskurserna 1–3? Studien utgörs av sju halvstrukturerade intervjuer med verksamma engelsklärare inom årskurserna 1–3 i två kommuner i Svealand. I resultatet framkom det att flera av lärarna i studien saknade vetskap om TPR-metoden men trots det använder sig utav aktiviteter som innefattar rörelser, lekar, sång eller bilder i engelskundervisningen. Hur lärarna applicerar TPR i undervisningen diskuteras utifrån valda teoretiska perspektiv där bland annat filosofen John Deweys uttryckssätt learning by doing använts.<br><p>Engelska</p>
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Aracil-Flügel, Frida. "Total Physical Response – TPR, en metod för att locka fram den språkliga förmågan i engelska som andraspråk. : En litteraturstudie om TPR- metoden hos elever i årskurs F-3." Thesis, Högskolan Dalarna, Pedagogiskt arbete, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:du-25487.
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För att barn ska kunna utveckla en språklig förmåga krävs det att läraren förser eleverna med en undervisning där tillvägagångssättet innefattar de rätta verktygen. Ett av undervisningssättet är att tillämpa TPR- metoden. TPR, står för Total Physical Response och är en metod som bygger på att läraren förmedlar instruktioner på engelska och eleverna visar förståelse genom att använda kroppsspråket i form av gester, miner och andra rörelser. Syftet med den här litteraturstudien är att undersöka vad det finns för tidigare forskning hur TPR, total physical response, kan länkas ihop med språkinlärning, lärares attityd till att använda TPR- metoden samt hur metoden kan stödja elever i lärandet i engelska som andraspråk inom årskurs F-3. Resultatet i litteraturstudien har skett systematiskt vilket innebär en tolkning av vad tidigare forskare har kommit fram till. Det som upptäckts genom analysen är indikationer om positiv effekt av tillämpning av TPR-metoden och att metoden nyttjas bäst när fler kombinationer av aktiviteter som berör TPR får utövas samtidigt. Med hänsyn till examensarbetets resultat kan förslag över vidare forskning handla om elevers reaktioner om tillämpning av TPR- metoden i engelskundervisningen.<br><p>Engelska</p>
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MESQUITA, Adriano Queiroz de. "Associação entre polimorfismos de nucleotídeo único (SNPs) no gene codificador do Toll-like receptor 4 (TLR4) e contagem celular somática." Universidade Federal de Goiás, 2010. http://repositorio.bc.ufg.br/tede/handle/tde/831.
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Made available in DSpace on 2014-07-29T15:07:28Z (GMT). No. of bitstreams: 1
Adriano Queiroz de Mesquita -30-07-2010.pdf: 3684854 bytes, checksum: bc87bf213d6700cac487c2b4580b87a1 (MD5)
Previous issue date: 2010-07-30<br>A mastite tem sido considerada, mundialmente, a doença de maior impacto nos
rebanhos leiteiros, devido à elevada prevalência e aos prejuízos econômicos que
determina. As desordens decorrentes da mastite por agente etiológico de origem
bacteriana são complexas, dependentes do microrganismo envolvido, e
desencadeiam inúmeros processos de reconhecimento. As estruturas
moleculares dos microrganismos são conhecidas como padrões moleculares
associados aos patógenos (PAMPS) e os receptores nas células do hospedeiro
como receptores de reconhecimento de padrões (PRR). O presente trabalho foi
desenvolvido com o objetivo de identificar a presença de polimorfismos de
nucleotídeo único no gene codificador do TLR4 em vacas leiteiras da raça
holandesa em uma propriedade leiteira em Goiás, avaliando a relação dos alelos
identificados, com a ocorrência de mastite subclínica e contagem celular
somática. Foram coletadas 150 amostras de leite individual de vacas para
identificação de microrganismos, contagem celular somática e composição
centesimal, e 150 amostras de sangue para genotipagem em uma propriedade
rural do Estado de Goiás. A discriminação alélica foi realizada por meio da técnica
de PCR em tempo real, baseada em 4 SNPs de referência no gene codificador do
TLR4 depositados no NCBI (rs8193046, rs8193047, rs8193060 e rs29017188).
Os resultados obtidos revelam maior frequência de microrganismos Gram
negativos na propriedade de estudo (52,47%) e que, animais identificados com os
genótipos AACCCC, GGTCGG e GACCGC são os mais indicados para seleção
assistida por marcadores moleculares.<br>Mastitis has been considered, worldwide, the disease of greatest impact in dairy
herds because of the high prevalence and the economic losses that determines.
The disorders caused by mastitis causative agent of bacterial origin are complex,
depending on the microrganism involved, and trigger numerous processes of
recognition. The molecular structures of microrganisms are known as Pathogen-
Associated Molecular Patterns (PAMPs) and the receptors on host cells as pattern
recognition receptors (PRR). This study was developed with the aim of identifying
the presence of single nucleotide polymorphisms in TLR4 in Holstein dairy cows
on a dairy farm in Goiás, evaluating the relationship between identified alleles,
occurrence of subclinical mastitis and somatic cell count. 150 milk samples from
individual cows were collected for identification of microrganisms, somatic cell
count and composition, and 150 blood samples for genotyping on a farm in the
State of Goiás. The allelic discrimination was performed by Real-time PCR, based
on four reference SNPs in TLR4 gene from NCBI (rs8193046, rs8193047,
rs8193060 and rs29017188). The results showed higher frequency of Gram
negative microrganisms (52.47%) and that animals with the genotypes AACCCC,
GGTCGG GACCGC are best suited for marker-assisted selection.
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Verillaud, Benjamin. "Propriétés biologiques du récepteur TLR3 dans les carcinomes des voies aérodigestives supérieures : contribution à l’oncogénèse et intérêt comme cible thérapeutique." Thesis, Paris 11, 2015. http://www.theses.fr/2015PA11T006/document.
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Contexte. Les carcinomes des voies aérodigestives supérieures (VADS) arrivent en 6ème position parmi les cancers les plus fréquents au niveau mondial. La fonction du récepteur TLR3 dans les cellules de carcinomes des VADS est encore très mal comprise. Objectifs et méthodes. 1) Déterminer le niveau d’expression du récepteur TLR3 dans les lignées et les biopsies de carcinomes des VADS par western blot et par immunohistochimie. 2) Etudier le rôle de TLR3 dans la croissance tumorale de ces tumeurs, en utilisant notamment des lignées invalidées de façon conditionnelle pour TLR3. 3) Evaluer in vitro les effets cytotoxiques de ligands artificiels de TLR3 soit seuls, soit utilisés en combinaisons avec un inhibiteur d’IAP (inhibitor of apoptosis protein).Résultats. La protéine TLR3 est détectée à un niveau élevé en western blot dans les lignées de carcinomes des VADS étudiées, comparativement à un panel d’autres tumeurs épithéliales humaines. TLR3 est également constamment détecté en immunohistochimie dans les biopsies. TLR3 semble jouer un rôle dans la croissance tumorale des carcinomes des VADS : dans certaines conditions de culture (culture en hypoxie ou en milieu pauvre en SVF et en nutriments), la stimulation de TLR3 par un ligand exogène, le poly(A:U), favorise la croissance des cellules tumorales. Nous avons étudié l’effet de la stimulation de TLR3 sur le métabolisme glucidique dans ces mêmes cellules en utilisant un appareil de type Seahorse® qui mesure la consommation d’oxygène et la production de protons à partir de cellules cultivées en microplaques. Ces expériences montrent que la stimulation de TLR3 fait augmenter l’activité des voies du métabolisme cellulaire anaérobie (glycolyse extra-mitochondriale). Une étude métabolomique a mis en évidence des différences significatives dans le profil métabolique des cellules tumorales stimulées par le poly(A:U) comparativement aux cellules non traitées. Par ailleurs, nous avons montré que la stimulation de TLR3 permettait de détecter le facteur de transcription HIF1 en Western blot, même en conditions normoxiques. Sachant que des ARN libérés par des cellules en état de nécrose peuvent stimuler TLR3, il est tentant de penser que ce récepteur pourrait favoriser la survie des cellules malignes en zone hypoxique au voisinage de cellules nécrotiques. Néanmoins, l’expression de TLR3 représente aussi un facteur de vulnérabilité pour les cellules de carcinome des VADS : en effet les ligands artificiels de TLR3 utilisés en combinaison avec un inhibiteur d’IAP (Inhibitor of Apoptosis Protein) produisent des effets cytotoxiques sur les lignées de carcinomes des VADS étudiées<br>Background. Head and Neck (HN) carcinomas are the 6th most frequent type of cancer worldwide. The role of the TLR3 receptor in HN carcinomas remains poorly understood.Objectives and Methods. 1) To assess the expression level of TLR3 in HN carcinoma cell lines and biopsies by Western blot and immunohistochemistry, respectively. 2) To study the role of TLR3 in tumour growth using specific cell lines with conditional knock-down of TLR3. 3). To assess in vitro the cytotoxic effects of artificial ligands of TLR3 used either alone or in combination with an IAP (inhibitor of apoptosis protein) inhibitor.Results. TLR3 protein was detected at a high level by Western blot analysis in HN carcinoma cell lines, by comparison with a panel of other human epithelial cancer cell lines. TLR3 was also consistently detected by immunohistochemistry in tumour biopsies. TLR3 seem to play a role in HN carcinoma cell growth: under certain culture conditions (hypoxic or low fetal calf serum/low nutrient culture conditions), TLR3 stimulation by a synthetic ligand, the poly(A:U), favours tumour cell growth. We investigated the effects of TLR3 stimulation on glucose metabolism using a Seahorse® analyzer, which measures the oxygen consumption and the proton production in living cells. Our results indicate that TLR3 stimulation induces an increase in anaerobic metabolism (extra-mitochondrial glycolysis). A metabolomic study revealed significant changes in the metabolic profile of cancer cells treated by poly(A:U) by comparison with untreated cells. We also showed that under TLR3 stimulation, HIF1 became detectable by Western blot analysis, even in normoxia. Given the fact that RNA fragments released by dying cells are able to trigger TLR3, one can assume that TLR3 might favour cancer cell survival in hypoxic areas located near the necrotic core of the tumour. However, TLR3 expression is also a factor of vulnerability for HN carcinoma cells: indeed, the combination of TLR3 artificial ligands with an IAP inhibitor has a strong cytotoxic effect on HN carcinoma cells in vitro
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Odenholm, Jenny. "Hbtq-frågor, varför då? Barnen är ju så små... : En studie om huruvida lärare tar tillvara på hbtq-perspektiv i sin undervisning i årskurs F-3." Thesis, Södertörns högskola, Institutionen för kultur och lärande, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:sh:diva-23429.
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This study investigates whether teachers working with children ages 6 – 9 are including an LGBTQ perspective in their teaching methods. The purpose is to critically examine sexuality and gender as part of the teaching methods in Swedish schools; whether teachers are working with LGBTQ questions in their classes, and if so, how. The following research questions are answered: Are the teachers incorporating an LGBTQ perspective in their classes, and if so, in what sense? Are LGBTQ questions relevant and of interest in the education? Do teachers feel like they have gained the right tools in their pedagogical education and/or in their workplace to work with LGBTQ questions in their class room? And if so, in what way? The method used is qualitative research in the form of interviews and observations. The conclusions reached are that in theory most teachers agree that an LGBTQ perspective is of importance in the classes; however in practice it is not that easy. Most teachers agree that is it difficult to incorporate this perspective. All teachers stress that their pedagogical education lacked in providing an LGBTQ perspective, but a couple teachers point out that they have received it from their workplace instead.
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Arancibia, Zunino Sergio Andrés. "Regulación de moléculas de la inmunidad innata por glucocorticoides : papel de la fosfoinositol 3-quinasa en la vía de señalización del receptor tipo toll 2 (TLR2)." Tesis, Universidad de Chile, 2006. http://repositorio.uchile.cl/handle/2250/105556.
Full textAbstract:
Memoria para optar el título de Bioquímico<br>Los receptores tipo Toll (TLR) son proteínas de transmembrana que reconocen
patrones moleculares asociados a patógenos (PAMPs). El TLR2 reconoce PAMPs de
bacterias gram positivas, los cuales activan una vía de señalización clásica que
involucra el reclutamiento de la proteína MyD88 y una alternativa donde participa la
Fosfoinositol 3-Quinasa (PI3K). A su vez, los glucocorticoides (GCs) son moléculas que
suprimen la inflamación y la inmunidad adaptativa, que recientemente han sido
reportadas como potenciadoras de la expresión de ciertas moléculas de la inmunidad
innata, tales como el TLR2. La importancia de PI3K y los GC en la regulación de la vía
alternativa del TLR2 no ha sido estudiada aún.
El objetivo general fue determinar la participación de PI3K en la producción de
TNFα inducida por agonistas del TLR2 y GCs. Los objetivos específicos fueron: 1)
Analizar el efecto de Pam3Cys-Ser-Lys4 un lipopéptido sintético análogo a la porción
NH2-terminal de lipoproteínas de bacterias gram positivas, y Dexametasona, sobre la
secreción de TNFα y la activación transcripcional de NFκB, en células A549. 2)
Estudiar la participación de PI3K-Akt en la ruta de señalización del TLR2 inducida por
Pam3Cys-Ser-Lys4 y Dexametasona. 3) Determinar la interacción entre TLR2-PI3K y
GR-PI3K.
Los resultados obtenidos muestran que la activación del TLR2 por Pam3Cys-Ser-
Lys4 provocó un aumento en la expresión de TNFα y la activación transcripcional del
TLR2, sin embargo el co-tratamiento con Dexametasona no alteró el efecto del
agonista del TLR2. Al mismo tiempo, PI3K aumenta la expresión de TNFα e inhibe la
transcripción del TLR2, al usar un dominante negativo para PI3K (p85-DN). PI3K activa
la transcripción de genes que responden a la movilización de NFκB y AP-1, ya que
células expuestas a Pam3Cys-Ser-Lys4 y que expresan el constructo p85-DN,
presentan una disminución significativa de la activación transcripcional de NFκB y APLos
resultados indicaron que Pam3Cys-Ser-Lys4 aumentó significativamente la
fosforilación de Akt, como un indicador indirecto de la actividad de PI3K, y
Dexametasona la revirtió. Por otra parte, se determinó la interacción entre p85 con el GR o el TLR2, siendo la
primera modulada exclusivamente por Dexametasona.
Estos resultados demuestran que PI3K presenta diversos mecanismos de
regulación en la vía de señalización del TLR2 y además proponen mecanismos por los
que los GCs intervienen en la ruta transduccional<br>Toll-like receptors (TLRs) are transmembrane proteins that recognize pathogenassociated
molecular patterns (PAMPs). TLR2 identify PAMPs from gram positive
bacteria, which activate a classical signaling pathway involving MyD88 recruitment to
the receptor intracellular domain, and an alternative signaling pathway, which
comprises the activation of the phosphoinositol 3-kinase (PI3K). Moreover,
glucocorticoids (GCs) suppress the inflammation and adaptive immune responses, and
have been recently reported to enhance the TNFα-induced expression of TLR2. The
relevance of GCs in the regulation of the alternative pathway has not yet been
described.
The general aim of this thesis was to determine PI3K participation on TNFα
production induced by TLR2 agonists in the presence or absence of GCs. The specific
aims were: 1) To analyze the effect of Pam3Cys-Ser-Lys4, a specific synthetic ligand
analogue to the NH2-terminal portion of gram positive bacterial lipoproteins, and
Dexamethasone, a synthetic GC, on TNFα expression and NFκB transcriptional
activation,in A549 cells. 2) To study the role of PI3K-Akt in the TLR2 signaling pathway
induced by Pam3Cys-Ser-Lys4 in the presence or absence of Dexamethasone. 3) To
determine the interaction between TLR2-PI3K and GR-PI3K.
The results show that TLR2 activation by Pam3Cys-Ser-Lys4 promotes TNFα
expression and TLR2 transcriptional activity, however co-treatment of cells with
Pam3Cys-Ser-Lys4 and Dexamethasone did not revert TNFα increase. In relation to this
pathway, we investigated if PI3K was involved in TNFα expression and TLR2
transcription activity regulation. Pam3Cys-Ser-Lys4 significantly increased Akt
phosphorylation, as an indicator of PI3K activity, and Dexamethasone reverted to it.
Moreover, by using a PI3K regulatory subunit dominant negative mutant cDNA
(p85-DN) transiently expressed in cells, a remarkably decrease in NFκB and AP-1
transcriptional activation was observed. On the other hand, we determined p85 regulatory PI3K subunit interaction with GR
or TLR2, and we were able to identify interaction between p85-GR in the presence of
Dexamethasone. These results demonstrate that PI3K shows different mechanism of
regulation in the TLR2 signaling and propose pathways in which GCs may be
participating
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Badeva, Diyana. "Elaboration et caractérisation de nanocomposites organiques à matrice de silicium poreux : exemple du Poly (3'-acide acétique -2,2' -5, 2'' ter tiophène) et de ses complexes." Nantes, 2010. http://archive.bu.univ-nantes.fr/pollux/show.action?id=e9a1aa92-93d9-4d34-bd60-d4270722cb24.
Full textAbstract:
Ce travail de thèse est réalisé en cotutelle entre l‟IMN de Nantes (France) et UTCM de Sofia (Bulgarie) dans le cadre d‟une bourse du Gouvernement Français. Il consiste en l‟élaboration et caractérisation de nouveaux nanocomposites à base d‟une matrice de silicium poreux remplie avec des polymères qui présentent des propriétés optique non linéaires pour des applications de télécommunication, pour le traitement du signal optique en mode tout optique ultrarapide. Après une brève bibliographie, nous présentons une première partie de nos études qui consiste en l‟élaboration de la matrice en silicium poreux soit de type dopé p, soit dopé n, qui doit répondre aux besoins optiques : avoir une porosité élevée, des pores dans l‟échelle « mésoporeux » (20-50nm) et une épaisseur de la couche poreuse la plus importante possible. La morphologie et les caractéristiques physico-chimiques sont déterminées par différentes techniques de caractérisation. Une seconde partie traite des possibilités de modifier la nature chimique de la surface poreuse par oxydation et greffage d‟organosilanes fluoré ou aminé, pour optimiser le remplissage de la couche poreuse. Enfin la dernière partie présente la réalisation des nanocomposites à matrice de silicium poreux avec le poly (terthiophène-acide acétique) et ses complexes. Nous avons mis en évidence le remplissage par une nouvelle méthode - à la fusion. Une approche des mesures optiques a été menée pour montrer les propriétés optique non linéaires de ce matériau<br>This work is realized in partnership between IMN in Nantes (France) and UCTM in Sofia (Bulgaria) financed by a French Government Scholarship. It consists in the elaboration and characterization of new nanocomposites based on a porous silicon matrix filled with polymers showing non linear optical properties used in the field of telecommunication. The tendency of communications networks is to use devices for ultrafast optical signal processing. Following à short bibliography, we present the first section of our work, which is the elaboration of porous silicon matrix from p and n doped silicon. This matrix must have a high porous volume, mesoporous diameter (20-50 nm) of the pores and the highest thickness. The morphology and the physicochemical characterization of our matrix are determined by different methods. In the second section we have optimized the chemical properties of the porous silicon surface by oxidation and surface modification with fluorinated and amino organosilanes to enhance the filling of the porous layer. Finally we have obtained a nanocomposite with a porous silicon matrix and poly (terthiophene-acetic-acid) and its complexes. The filling of the porous layer is realized by a new melting-based method. Primary measurements have been carried out to demonstrate the nonlinear optical properties of these nanocomposites
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Åkesson, Marie-Louise, and Engberg Johanna Håkansson. "Vardagsmatematik med barn i åldern 1-3 år : En studie om och hur pedagoger tar tillvara på och arbetar med vardagsmatematiken och hur de synliggör den för barnen." Thesis, Växjö University, School of Mathematics and Systems Engineering, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:vxu:diva-1682.
Full textAbstract:
<p>Syftet med arbetet är att se om pedagoger i Tingsryds kommun arbetar med vardagsmatematiken och om de synliggör den för barnen. Vi har valt att avgränsa oss till pedagoger som arbetar med barn i åldrarna 1-3 år. Arbetet är tänkt att inspirera pedagoger till att ta till vara på den vardagsmatematik som finns och även reflektera över hur de kan synliggöra den i olika aktiviteter för barnen. I litteraturgenomgången ges en historisk genomgång av matematik i förskolan. Här presenteras även vardagsmatematiken i förskolan som är den form av matematik som små barn kommer i kontakt med och använder under en dag på förskolan. Vi har tagit hjälp av enkäter och observationer för att få svar på hur pedagoger arbetar med vardagsmatematik och hur de synliggör den för barnen. Situationerna som observerats är de två aktiviteter som flest pedagoger uppgett i enkäten att de använder och synliggör vardagsmatematik i för barnen. Genom enkätundersökning och observationer har vi blivit medvetna om att pedagogerna ofta använder sig av vardagsmatematik under dagen på förskolan men att de har svårt att synliggöra den för barnen.</p>
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Dieudonné, Audrey. "Infections virales respiratoires et exacerbations de l’asthme : rôles des récepteurs d’épuration et du TLR3 exprimés par l’épithélium bronchique." Thesis, Lille 2, 2010. http://www.theses.fr/2010LIL2S021.
Full textAbstract:
Les virus à tropisme respiratoire, tels que le rhinovirus, le virus respiratoire syncytial et le virus influenza A, ont pour cibles principales les cellules épithéliales bronchiques (CEB) et les cellules dendritiques (DC). Ces virus représentent la cause majeure des exacerbations de l’asthme de l’enfant. L’immunité innée et adaptative jouent un rôle essentiel dans la réponseantivirale et l’allergie. Au niveau bronchique, les CEB et les DC pulmonaires qui coopèrentactivement du fait de leur colocalisation, font partie des principaux acteurs de l’immunitéinnée. Le développement de la réponse immunitaire nécessite à la fois la mobilisation derécepteurs de reconnaissance impliqués dans l’endocytose, parmi lesquels les récepteursd’épuration ou SR, ainsi que des récepteurs de signalisation tels que les Toll-like receptors(TLR) qui coopèrent afin d’ajuster la réponse de l’hôte aux pathogènes. Au cours desinfections virales respiratoires, l’activation des CEB par les ARN double brin (ARNdb)viraux via le TLR3 et les hélicases à ARN constitue un élément clé de la réponse antivirale.Dans ce contexte, notre objectif a consisté à élucider les rôles respectifs du TLR3 et des SR del’épithélium bronchique dans les infections virales du tractus respiratoire et les mécanismescellulaires et moléculaires impliqués dans les exacerbations asthmatiques d’origine virale.L’expression des SR au niveau des CEB étant peu documentée, nous avons tout d’abord misen évidence l’expression de certains SR et leur régulation par le TNF-a. Cette expression estassociée à une internalisation des LDL acétylées, ligands de SR, et d’un ligand protéique:l’ovalbumine maléylée (OVAm) au niveau de l’épithélium bronchique, confirmant lafonctionnalité de ces récepteurs. L’ajout de différents ligands de SR permet de bloquerl’activation des CEB par les ARNdb viraux soulignant le rôle de corécepteur de ces SR. Cesligands de SR agissent en limitant la capture des ARNdb et en bloquant l’activation des voiesde signalisation dépendantes de NF-κB et d’IRF3. In vivo, l’administration de ligand de SRpermet d’inhiber l’action proinflammatoire de l’ARNdb et le développement de la réponseimmune, en limitant la migration des DC vers les ganglions lymphatiques drainants. D’autrepart, nous avons évalué les rôles respectifs des CEB, des DC myéloïdes (mDC) et de la voiede signalisation TRIF, dans un modèle murin d’exacerbation de l’asthme, par administrationd’ARNdb. Nous avons pu démontrer que cette administration induit l’exacerbation de laréaction allergique pulmonaire. L’utilisation de souris invalidées pour le gène trif a permis demontrer que la signalisation dépendante de TLR3/TRIF est indispensable à ce phénomèned’exacerbation de la réaction allergique pulmonaire. Le transfert de mDC dérivées de lamoelle osseuse exposées à l’ovalbumine et à l’ARNdb induit également l’exacerbation de laréaction allergique pulmonaire, soulignant le rôle majeur des mDC dans ce processus. Enfin,nous avons observé qu’en réponse à la stimulation par l’ARNdb, les CEB issues de sourissauvages participent au recrutement des mDC et des cellules inflammatoires via la productionde chimiokines.L’ensemble de ces travaux souligne le rôle des SR dans la réponse de l’épithéliumbronchique à l’ARNdb. Ces résultats permettent d’envisager l’implication de ces SR dans lesinfections virales. D’autre part, nos données révèlent le rôle clé de la voie de signalisationTLR3/TRIF dans un modèle murin d’exacerbation allergique pulmonaire d’origine virale.Elles soulignent également le rôle crucial des CEB qui participent au recrutement des mDC etdes cellules de l’inflammation. Ces observations laissent entrevoir de nouvelles approchesthérapeutiques visant à renforcer ou à contrôler une réponse immune antivirale<br>Viral airway infections by rhinovirus, respiratory syncytial virus and influenza Avirus, mainly target airway epithelial cells and pulmonary dendritic cells (DCs). Theseinfections are the major cause of exacerbations associated with allergic asthma in children.Innate and adaptative immunity have an essential role in the antiviral response and allergy.The main actors in innate immunity of the lung include bronchial epithelial cells (BECs) andDCs, which actively cooperate. Induction of innate immune responses involves patternrecognition receptors (PRRs) implicated in endocytosis such as scavenger receptors (SRs) andsignalling receptors like Toll-like receptors (TLRs), which both cooperate to adjust theresponse to pathogens. During respiratory viral infections, BEC activation by double-strandedRNA (dsRNA) is linked to the mobilization of TLR3 and RNA-helicases and represents a keycomponent of the antiviral response.In this context, our aim was to elucidate TLR3 and SRs functions in BECs in respiratory viralinfections and cellular and molecular mechanisms implicated in asthma exacerbations.Since expression of SRs in BECs is not well-known, we have first demonstrated SRsexpression in these cells and their regulation by TNF-a. This increased expression is relatedwith a higher capacity to bind and to internalize SRs ligands such as acetylated LDL ormaleylated ovalbumin (mOVA). Addition of SRs ligands inhibits dsRNA-induced activation,showing that SRs act as coreceptors for TLR3 and RNA-helicases. Ligands of SRs are able toinhibit viral dsRNA binding and NF-κB and IRF3 signalling pathways. In vivo, administrationof SRs ligand allows to partially control proinflammatory effects of dsRNA and thedevelopment of the immune response by limiting DCs migration towards draining lymphnodes. Next, we defined the role of BECs, myeloid DCs (mDCs) and of the signallingpathways TRIF in a mouse model of lung allergic exacerbation based on the localadministration of dsRNA. Our data demonstrated that treatment with dsRNA induces lungallergic exacerbation. The use of trif -/- mice showed that the TLR3/TRIF pathway was criticalin lung allergic exacerbation induced by dsRNA. Intratracheal transfer of bone marrowdendritic cells (BMDC) primed with IL-4/dsRNA/ovalbumin in wild type mice reproducesexacerbation of the allergic reaction, whereas cells primed with dsRNA/ovalbumin have amore limited effect. These data show the importance of mDCs in this mechanism. The role ofairway epithelium is related to the dsRNA induced production of chemokines which isimplicated within mDCs and inflammatory cell recruitment towards the lung.All these data underline the important role of SRs in BECs response to dsRNA. Theseobservations allow to hypothesize the implication of SRs in infections by respiratory viruses.Moreover, our work reveals the key role of TLR3/TRIF pathway in exacerbation of theallergic reaction and the importance of BECs/mDCs crosstalk in these settings. Theseobservations suggest new therapeutic approaches in order to strengthen or to limit antiviralimmune response